MDedge Psychiatry

This transcript has been edited for clarity. 

Hi. I’m Art Caplan. I’m at the Division of Medical Ethics at New York University Grossman School of Medicine in New York City. 

There are many things screwy with our healthcare system. Many of you [reading] this are dealing with bureaucracy, paperwork, all sorts of constraints, restraints, and requirements that sometimes make the practice of medicine, or even nursing, difficult.

I don’t think I’ve seen anything screwier, from a moral point of view, than the system we have that allows for preauthorization by third-party payers, or insurers, in order to give care to patients. It’s pretty clear that a third-party payer has a conflict of interest. It’s simple: They don’t want to spend money.

Their goal as profit-making companies is to reduce what it is that they’re going to authorize. That clearly is driving how the preauthorization process works. We’re not getting a neutral review by third parties of the appropriateness of treatment recommendations or somebody saying, this is the standard of care and this is what ought to happen.

We’re letting the people who have the pocketbooks and the wallets have prior approval of what the doctor thinks is correct. That is really not the way to practice medicine. 

We now have more evidence about what really is going on. A doctor was recently interviewed by ProPublica and said that she had worked for Cigna as a reviewer. Basically, the message she got from that insurer was to speed it up, go fast, and basically “deny, deny, deny” when she got requests. Those are her words, not mine.

We get a peek under the tent of how this works, and Dr. Day is basically saying she had to leave because she just didn’t feel that it was evidence-driven. It was driven by concerns about who’s going to lose money or make money.

If you want to check to see whether something is appropriate, the question becomes, who ought to do prior review? 

Who does it now? Sometimes doctors. Sometimes nurses who aren’t in the specialty where the request is coming in for preapproval. I’ve even seen situations where some companies use nurses in other countries, such as the Philippines, to do preapproval. They send them information, like a clip, to use to deny things that basically is boilerplate language, whatever the request is.

Looming up now, some insurers are starting to think, well, maybe artificial intelligence could do it. Just review the written request, trigger certain responses on the part of the artificial intelligence — it can deny the claims just as well as a human — and maybe it’s even cheaper to set up that system for the insurer.

This is ethically nuts. We need to have a system where doctors’ judgments drive what patients get. You listen to doctors, as I do, about preapproval access and they say patients sometimes give up trying to get what they think is needed. Continuity of care is interrupted if they have to keep making requests all the time.

There are adverse events when the thing that the doctor thought was most appropriate isn’t approved and something else is used that is less safe or less efficacious. It isn’t in patient interest to have the person with the wallet saying, this is what we think you need, and then having unqualified people or even automated intelligence with no accountability and no transparency get involved in preauthorization.

This system costs us money because middlemen are doing all this work. It basically becomes one of the huge scandals, in my view, of our health system, that doctors don’t ultimately decide what the patient needs. A preauthorizing third party or robot, without transparency, without accountability, and behind closed doors second-guesses what’s going on.

I’m Art Caplan at the Division of Medical Ethics at the New York University Grossman School of Medicine.

Arthur L. Caplan, Director, Division of Medical Ethics, New York University Langone Medical Center, New York, New York, has disclosed the following relevant financial relationships: Served as a director, officer, partner, employee, advisor, consultant, or trustee for Johnson & Johnson’s Panel for Compassionate Drug Use (unpaid position). Serves as a contributing author and advisor for Medscape.

A version of this article first appeared on Medscape.com.

This transcript has been edited for clarity. 

Hi. I’m Art Caplan. I’m at the Division of Medical Ethics at New York University Grossman School of Medicine in New York City. 

There are many things screwy with our healthcare system. Many of you [reading] this are dealing with bureaucracy, paperwork, all sorts of constraints, restraints, and requirements that sometimes make the practice of medicine, or even nursing, difficult.

I don’t think I’ve seen anything screwier, from a moral point of view, than the system we have that allows for preauthorization by third-party payers, or insurers, in order to give care to patients. It’s pretty clear that a third-party payer has a conflict of interest. It’s simple: They don’t want to spend money.

Their goal as profit-making companies is to reduce what it is that they’re going to authorize. That clearly is driving how the preauthorization process works. We’re not getting a neutral review by third parties of the appropriateness of treatment recommendations or somebody saying, this is the standard of care and this is what ought to happen.

We’re letting the people who have the pocketbooks and the wallets have prior approval of what the doctor thinks is correct. That is really not the way to practice medicine. 

We now have more evidence about what really is going on. A doctor was recently interviewed by ProPublica and said that she had worked for Cigna as a reviewer. Basically, the message she got from that insurer was to speed it up, go fast, and basically “deny, deny, deny” when she got requests. Those are her words, not mine.

We get a peek under the tent of how this works, and Dr. Day is basically saying she had to leave because she just didn’t feel that it was evidence-driven. It was driven by concerns about who’s going to lose money or make money.

If you want to check to see whether something is appropriate, the question becomes, who ought to do prior review? 

Who does it now? Sometimes doctors. Sometimes nurses who aren’t in the specialty where the request is coming in for preapproval. I’ve even seen situations where some companies use nurses in other countries, such as the Philippines, to do preapproval. They send them information, like a clip, to use to deny things that basically is boilerplate language, whatever the request is.

Looming up now, some insurers are starting to think, well, maybe artificial intelligence could do it. Just review the written request, trigger certain responses on the part of the artificial intelligence — it can deny the claims just as well as a human — and maybe it’s even cheaper to set up that system for the insurer.

This is ethically nuts. We need to have a system where doctors’ judgments drive what patients get. You listen to doctors, as I do, about preapproval access and they say patients sometimes give up trying to get what they think is needed. Continuity of care is interrupted if they have to keep making requests all the time.

There are adverse events when the thing that the doctor thought was most appropriate isn’t approved and something else is used that is less safe or less efficacious. It isn’t in patient interest to have the person with the wallet saying, this is what we think you need, and then having unqualified people or even automated intelligence with no accountability and no transparency get involved in preauthorization.

This system costs us money because middlemen are doing all this work. It basically becomes one of the huge scandals, in my view, of our health system, that doctors don’t ultimately decide what the patient needs. A preauthorizing third party or robot, without transparency, without accountability, and behind closed doors second-guesses what’s going on.

I’m Art Caplan at the Division of Medical Ethics at the New York University Grossman School of Medicine.

Arthur L. Caplan, Director, Division of Medical Ethics, New York University Langone Medical Center, New York, New York, has disclosed the following relevant financial relationships: Served as a director, officer, partner, employee, advisor, consultant, or trustee for Johnson & Johnson’s Panel for Compassionate Drug Use (unpaid position). Serves as a contributing author and advisor for Medscape.

A version of this article first appeared on Medscape.com.

This transcript has been edited for clarity. 

Hi. I’m Art Caplan. I’m at the Division of Medical Ethics at New York University Grossman School of Medicine in New York City. 

There are many things screwy with our healthcare system. Many of you [reading] this are dealing with bureaucracy, paperwork, all sorts of constraints, restraints, and requirements that sometimes make the practice of medicine, or even nursing, difficult.

I don’t think I’ve seen anything screwier, from a moral point of view, than the system we have that allows for preauthorization by third-party payers, or insurers, in order to give care to patients. It’s pretty clear that a third-party payer has a conflict of interest. It’s simple: They don’t want to spend money.

Their goal as profit-making companies is to reduce what it is that they’re going to authorize. That clearly is driving how the preauthorization process works. We’re not getting a neutral review by third parties of the appropriateness of treatment recommendations or somebody saying, this is the standard of care and this is what ought to happen.

We’re letting the people who have the pocketbooks and the wallets have prior approval of what the doctor thinks is correct. That is really not the way to practice medicine. 

We now have more evidence about what really is going on. A doctor was recently interviewed by ProPublica and said that she had worked for Cigna as a reviewer. Basically, the message she got from that insurer was to speed it up, go fast, and basically “deny, deny, deny” when she got requests. Those are her words, not mine.

We get a peek under the tent of how this works, and Dr. Day is basically saying she had to leave because she just didn’t feel that it was evidence-driven. It was driven by concerns about who’s going to lose money or make money.

If you want to check to see whether something is appropriate, the question becomes, who ought to do prior review? 

Who does it now? Sometimes doctors. Sometimes nurses who aren’t in the specialty where the request is coming in for preapproval. I’ve even seen situations where some companies use nurses in other countries, such as the Philippines, to do preapproval. They send them information, like a clip, to use to deny things that basically is boilerplate language, whatever the request is.

Looming up now, some insurers are starting to think, well, maybe artificial intelligence could do it. Just review the written request, trigger certain responses on the part of the artificial intelligence — it can deny the claims just as well as a human — and maybe it’s even cheaper to set up that system for the insurer.

This is ethically nuts. We need to have a system where doctors’ judgments drive what patients get. You listen to doctors, as I do, about preapproval access and they say patients sometimes give up trying to get what they think is needed. Continuity of care is interrupted if they have to keep making requests all the time.

There are adverse events when the thing that the doctor thought was most appropriate isn’t approved and something else is used that is less safe or less efficacious. It isn’t in patient interest to have the person with the wallet saying, this is what we think you need, and then having unqualified people or even automated intelligence with no accountability and no transparency get involved in preauthorization.

This system costs us money because middlemen are doing all this work. It basically becomes one of the huge scandals, in my view, of our health system, that doctors don’t ultimately decide what the patient needs. A preauthorizing third party or robot, without transparency, without accountability, and behind closed doors second-guesses what’s going on.

I’m Art Caplan at the Division of Medical Ethics at the New York University Grossman School of Medicine.

Arthur L. Caplan, Director, Division of Medical Ethics, New York University Langone Medical Center, New York, New York, has disclosed the following relevant financial relationships: Served as a director, officer, partner, employee, advisor, consultant, or trustee for Johnson & Johnson’s Panel for Compassionate Drug Use (unpaid position). Serves as a contributing author and advisor for Medscape.

A version of this article first appeared on Medscape.com.

PHILADELPHIA – Nearly half of dementia cases worldwide could theoretically be prevented or delayed by eliminating 14 modifiable risk factors during an individual’s lifetime, a report from the Lancet Commission on dementia prevention, intervention, and care.

The report adds two new modifiable risk factors for dementia — high cholesterol and vision loss — to the 12 risk factors identified in the 2020 Lancet Commission report, which were linked to about 40% of all dementia cases. 

The original Lancet Commission report, published in 2017, identified nine modifiable risk factors that were estimated to be responsible for one third of dementia cases. 

“Our new report reveals that there is much more that can and should be done to reduce the risk of dementia. It’s never too early or too late to act, with opportunities to make an impact at any stage of life,” lead author Gill Livingston, MD, from University College London in England, said in a statement. 

The 57-page report was published online in The Lancet Neurology (to coincide with its presentation at the 2024 Alzheimer’s Association International Conference (AAIC).
 

‘Compelling’ New Evidence 

The 12 risk factors cited in the 2020 report are lower levels of education, hearing loss, hypertension, smoking, obesity, depression, physical inactivity, diabetes, excessive alcohol consumption, traumatic brain injury (TBI), air pollution, and social isolation. 

According to the authors of the current report, there is “new compelling evidence” that untreated vision loss and elevated low-density lipoprotein (LDL) cholesterol are also risk factors for dementia.

These two added risk factors are associated with 9% of all dementia cases — with an estimated 7% of cases caused by high LDL cholesterol from about age 40 years, and 2% of cases caused by untreated vision loss in later life, the authors said.

Out of all 14 risk factors, those tied to the greatest proportion of dementia in the global population are hearing impairment and high LDL cholesterol (7% each), along with less education in early life, and social isolation in later life (5% each), the report estimates. 

The new report also outlines 13 recommendations aimed at individuals and governments to help guard against dementia. They include preventing and treating hearing loss, vision loss, and depression; being cognitively active throughout life; using head protection in contact sports; reducing vascular risk factors (high cholesterol, diabetes, obesity, hypertension); improving air quality; and providing supportive community environments to increase social contact. 

Tara Spires-Jones, PhD, president of the British Neuroscience Association, emphasized that, while this research doesn’t directly link specific factors to dementia, it supports evidence that a healthy lifestyle — encompassing education, social activities, exercise, cognitive engagement, and avoiding head injuries and harmful factors for heart and lung health — can enhance brain resilience and prevent dementia.

In an interview, Heather M. Snyder, PhD, senior vice president of medical and scientific relations, Alzheimer’s Association, said: “Our brains are complex and what happens throughout our lives may increase or decrease our risk for dementia as we age. Protecting brain health as we age requires a comprehensive approach that includes discussions on diet, exercise, heart health, hearing, and vision.”

Also weighing in on the new report, Shaheen Lakhan, MD, PhD, neurologist and researcher based in Miami, Florida, said the addition of high cholesterol is “particularly noteworthy as it reinforces the intricate connection between vascular health and brain health — a link we’ve long suspected but can now target more effectively.”

As for vision loss, “it’s not just a matter of seeing clearly; it’s a matter of thinking clearly. Untreated vision loss can lead to social isolation, reduced physical activity, and cognitive decline,” said Dr. Lakhan. 
 

Dementia Is Not Inevitable

In his view, “the potential to prevent or delay nearly half of dementia cases by addressing these risk factors is nothing short of revolutionary. It shifts our perspective from viewing dementia as an inevitable part of aging to seeing it as a condition we can actively work to prevent,” Dr. Lakhan added.

He said the report’s emphasis on health equity is also important. 

“Dementia risk factors disproportionately affect socioeconomically disadvantaged groups and low- and middle-income countries. Addressing these disparities isn’t just a matter of fairness in the fight against dementia, equality in prevention is as important as equality in treatment,” Dr. Lakhan commented.

While the report offers hope, it also presents a challenge, he said. 

Implementing the recommended preventive measures requires a “coordinated effort from individuals, healthcare systems, and policymakers. The potential benefits, both in terms of quality of life and economic savings, make this effort not just worthwhile but imperative. Preventing dementia is not just a medical imperative — it’s an economic and humanitarian one,” Dr. Lakhan said. 

Masud Husain, PhD, with the University of Oxford in England, agreed. 

The conclusions in this report are “very important for all of us, but particularly for health policy makers and government,” he said. 

“If we did simple things well such as screening for some of the factors identified in this report, with adequate resources to perform this, we have the potential to prevent dementia on a national scale. This would be far more cost effective than developing high-tech treatments, which so far have been disappointing in their impacts on people with established dementia,” Dr. Husain said. 

The Lancet Commission was funded by University College London, Alzheimer’s Society, Alzheimer’s Research UK, and the Economic and Social Research Council. A complete list of author disclosures is available with the original article. Dr. Snyder, Dr. Lakhan, Dr. Husain and Dr. Spires-Jones have no relevant disclosures.

A version of this article appeared on Medscape.com.

PHILADELPHIA – Nearly half of dementia cases worldwide could theoretically be prevented or delayed by eliminating 14 modifiable risk factors during an individual’s lifetime, a report from the Lancet Commission on dementia prevention, intervention, and care.

The report adds two new modifiable risk factors for dementia — high cholesterol and vision loss — to the 12 risk factors identified in the 2020 Lancet Commission report, which were linked to about 40% of all dementia cases. 

The original Lancet Commission report, published in 2017, identified nine modifiable risk factors that were estimated to be responsible for one third of dementia cases. 

“Our new report reveals that there is much more that can and should be done to reduce the risk of dementia. It’s never too early or too late to act, with opportunities to make an impact at any stage of life,” lead author Gill Livingston, MD, from University College London in England, said in a statement. 

The 57-page report was published online in The Lancet Neurology (to coincide with its presentation at the 2024 Alzheimer’s Association International Conference (AAIC).
 

‘Compelling’ New Evidence 

The 12 risk factors cited in the 2020 report are lower levels of education, hearing loss, hypertension, smoking, obesity, depression, physical inactivity, diabetes, excessive alcohol consumption, traumatic brain injury (TBI), air pollution, and social isolation. 

According to the authors of the current report, there is “new compelling evidence” that untreated vision loss and elevated low-density lipoprotein (LDL) cholesterol are also risk factors for dementia.

These two added risk factors are associated with 9% of all dementia cases — with an estimated 7% of cases caused by high LDL cholesterol from about age 40 years, and 2% of cases caused by untreated vision loss in later life, the authors said.

Out of all 14 risk factors, those tied to the greatest proportion of dementia in the global population are hearing impairment and high LDL cholesterol (7% each), along with less education in early life, and social isolation in later life (5% each), the report estimates. 

The new report also outlines 13 recommendations aimed at individuals and governments to help guard against dementia. They include preventing and treating hearing loss, vision loss, and depression; being cognitively active throughout life; using head protection in contact sports; reducing vascular risk factors (high cholesterol, diabetes, obesity, hypertension); improving air quality; and providing supportive community environments to increase social contact. 

Tara Spires-Jones, PhD, president of the British Neuroscience Association, emphasized that, while this research doesn’t directly link specific factors to dementia, it supports evidence that a healthy lifestyle — encompassing education, social activities, exercise, cognitive engagement, and avoiding head injuries and harmful factors for heart and lung health — can enhance brain resilience and prevent dementia.

In an interview, Heather M. Snyder, PhD, senior vice president of medical and scientific relations, Alzheimer’s Association, said: “Our brains are complex and what happens throughout our lives may increase or decrease our risk for dementia as we age. Protecting brain health as we age requires a comprehensive approach that includes discussions on diet, exercise, heart health, hearing, and vision.”

Also weighing in on the new report, Shaheen Lakhan, MD, PhD, neurologist and researcher based in Miami, Florida, said the addition of high cholesterol is “particularly noteworthy as it reinforces the intricate connection between vascular health and brain health — a link we’ve long suspected but can now target more effectively.”

As for vision loss, “it’s not just a matter of seeing clearly; it’s a matter of thinking clearly. Untreated vision loss can lead to social isolation, reduced physical activity, and cognitive decline,” said Dr. Lakhan. 
 

Dementia Is Not Inevitable

In his view, “the potential to prevent or delay nearly half of dementia cases by addressing these risk factors is nothing short of revolutionary. It shifts our perspective from viewing dementia as an inevitable part of aging to seeing it as a condition we can actively work to prevent,” Dr. Lakhan added.

He said the report’s emphasis on health equity is also important. 

“Dementia risk factors disproportionately affect socioeconomically disadvantaged groups and low- and middle-income countries. Addressing these disparities isn’t just a matter of fairness in the fight against dementia, equality in prevention is as important as equality in treatment,” Dr. Lakhan commented.

While the report offers hope, it also presents a challenge, he said. 

Implementing the recommended preventive measures requires a “coordinated effort from individuals, healthcare systems, and policymakers. The potential benefits, both in terms of quality of life and economic savings, make this effort not just worthwhile but imperative. Preventing dementia is not just a medical imperative — it’s an economic and humanitarian one,” Dr. Lakhan said. 

Masud Husain, PhD, with the University of Oxford in England, agreed. 

The conclusions in this report are “very important for all of us, but particularly for health policy makers and government,” he said. 

“If we did simple things well such as screening for some of the factors identified in this report, with adequate resources to perform this, we have the potential to prevent dementia on a national scale. This would be far more cost effective than developing high-tech treatments, which so far have been disappointing in their impacts on people with established dementia,” Dr. Husain said. 

The Lancet Commission was funded by University College London, Alzheimer’s Society, Alzheimer’s Research UK, and the Economic and Social Research Council. A complete list of author disclosures is available with the original article. Dr. Snyder, Dr. Lakhan, Dr. Husain and Dr. Spires-Jones have no relevant disclosures.

A version of this article appeared on Medscape.com.

PHILADELPHIA – Nearly half of dementia cases worldwide could theoretically be prevented or delayed by eliminating 14 modifiable risk factors during an individual’s lifetime, a report from the Lancet Commission on dementia prevention, intervention, and care.

The report adds two new modifiable risk factors for dementia — high cholesterol and vision loss — to the 12 risk factors identified in the 2020 Lancet Commission report, which were linked to about 40% of all dementia cases. 

The original Lancet Commission report, published in 2017, identified nine modifiable risk factors that were estimated to be responsible for one third of dementia cases. 

“Our new report reveals that there is much more that can and should be done to reduce the risk of dementia. It’s never too early or too late to act, with opportunities to make an impact at any stage of life,” lead author Gill Livingston, MD, from University College London in England, said in a statement. 

The 57-page report was published online in The Lancet Neurology (to coincide with its presentation at the 2024 Alzheimer’s Association International Conference (AAIC).
 

‘Compelling’ New Evidence 

The 12 risk factors cited in the 2020 report are lower levels of education, hearing loss, hypertension, smoking, obesity, depression, physical inactivity, diabetes, excessive alcohol consumption, traumatic brain injury (TBI), air pollution, and social isolation. 

According to the authors of the current report, there is “new compelling evidence” that untreated vision loss and elevated low-density lipoprotein (LDL) cholesterol are also risk factors for dementia.

These two added risk factors are associated with 9% of all dementia cases — with an estimated 7% of cases caused by high LDL cholesterol from about age 40 years, and 2% of cases caused by untreated vision loss in later life, the authors said.

Out of all 14 risk factors, those tied to the greatest proportion of dementia in the global population are hearing impairment and high LDL cholesterol (7% each), along with less education in early life, and social isolation in later life (5% each), the report estimates. 

The new report also outlines 13 recommendations aimed at individuals and governments to help guard against dementia. They include preventing and treating hearing loss, vision loss, and depression; being cognitively active throughout life; using head protection in contact sports; reducing vascular risk factors (high cholesterol, diabetes, obesity, hypertension); improving air quality; and providing supportive community environments to increase social contact. 

Tara Spires-Jones, PhD, president of the British Neuroscience Association, emphasized that, while this research doesn’t directly link specific factors to dementia, it supports evidence that a healthy lifestyle — encompassing education, social activities, exercise, cognitive engagement, and avoiding head injuries and harmful factors for heart and lung health — can enhance brain resilience and prevent dementia.

In an interview, Heather M. Snyder, PhD, senior vice president of medical and scientific relations, Alzheimer’s Association, said: “Our brains are complex and what happens throughout our lives may increase or decrease our risk for dementia as we age. Protecting brain health as we age requires a comprehensive approach that includes discussions on diet, exercise, heart health, hearing, and vision.”

Also weighing in on the new report, Shaheen Lakhan, MD, PhD, neurologist and researcher based in Miami, Florida, said the addition of high cholesterol is “particularly noteworthy as it reinforces the intricate connection between vascular health and brain health — a link we’ve long suspected but can now target more effectively.”

As for vision loss, “it’s not just a matter of seeing clearly; it’s a matter of thinking clearly. Untreated vision loss can lead to social isolation, reduced physical activity, and cognitive decline,” said Dr. Lakhan. 
 

Dementia Is Not Inevitable

In his view, “the potential to prevent or delay nearly half of dementia cases by addressing these risk factors is nothing short of revolutionary. It shifts our perspective from viewing dementia as an inevitable part of aging to seeing it as a condition we can actively work to prevent,” Dr. Lakhan added.

He said the report’s emphasis on health equity is also important. 

“Dementia risk factors disproportionately affect socioeconomically disadvantaged groups and low- and middle-income countries. Addressing these disparities isn’t just a matter of fairness in the fight against dementia, equality in prevention is as important as equality in treatment,” Dr. Lakhan commented.

While the report offers hope, it also presents a challenge, he said. 

Implementing the recommended preventive measures requires a “coordinated effort from individuals, healthcare systems, and policymakers. The potential benefits, both in terms of quality of life and economic savings, make this effort not just worthwhile but imperative. Preventing dementia is not just a medical imperative — it’s an economic and humanitarian one,” Dr. Lakhan said. 

Masud Husain, PhD, with the University of Oxford in England, agreed. 

The conclusions in this report are “very important for all of us, but particularly for health policy makers and government,” he said. 

“If we did simple things well such as screening for some of the factors identified in this report, with adequate resources to perform this, we have the potential to prevent dementia on a national scale. This would be far more cost effective than developing high-tech treatments, which so far have been disappointing in their impacts on people with established dementia,” Dr. Husain said. 

The Lancet Commission was funded by University College London, Alzheimer’s Society, Alzheimer’s Research UK, and the Economic and Social Research Council. A complete list of author disclosures is available with the original article. Dr. Snyder, Dr. Lakhan, Dr. Husain and Dr. Spires-Jones have no relevant disclosures.

A version of this article appeared on Medscape.com.

Increasingly recognized as a multifactorial disease, obesity demands an approach that involves multiple healthcare professionals. For psychologist Andréa Levy, coordinator and founder of the nongovernmental organization Obesity Brazil, addressing the patient’s “psychological weight” is crucial.

In an interview with this news organization, Ms. Levy, who was one of the speakers at the International Congress on Obesity in 2024, emphasized the importance of integrating emotional and behavioral aspects into treatment, because these factors often influence eating habits and weight gain.

She also highlighted the essential collaboration between endocrinologists, nutritionists, psychiatrists, and psychologists, who must work together to provide comprehensive and effective care to patients.
 

How do psychological factors affect the treatment of obesity?

Psychological factors are important triggers for weight gain. As the degree of obesity increases, so does the predisposition to mental health problems such as anxiety, mood disorders, personality disorders, and eating disorders. Understanding these factors is important because accurate psychodiagnosis is essential for effective disease treatment.

Without a proper diagnosis, the treatment may be incomplete and omit relevant factors. For example, a person with undiagnosed depression who is starting treatment for weight loss may feel discouraged and low on energy. He or she may wrongly attribute these symptoms to the diet or surgery. Similarly, someone undergoing bariatric surgery may confuse malnutrition symptoms with depression, resulting in inadequate treatment with antidepressants and possible iatrogenic complications.

Furthermore, psychotherapy and psychological follow-up are essential to help the individual organize better and understand the treatment and the disease itself. This is especially important in stigmatized diseases and those subject to prejudice such as obesity, where understanding and acceptance are often challenging, which affects treatment adherence.

Is the collaboration between psychologist and psychiatrist always necessary?

Often, it is necessary to have the support of both a psychologist and a psychiatrist. The process generally begins with a good psychodiagnosis. Initially, there may not be a case that requires treatment, but it is important to perform this evaluation to rule out any issues.

The follow-up, unlike weekly psychotherapy, can be monthly or at an interval agreed on with the patient. It is crucial to help him or her navigate the various stages of obesity treatment. For example, the patient may be going through a period of mourning or separation, or a happier moment, such as the beginning of a relationship or the birth of a child in the family. These moments affect eating habits and need to be well managed.

Depending on the degree of the pathology, such as depression, severe binge-eating disorder, or personality disorders, the psychologist works in conjunction with the psychiatrist. When we talk about obesity, we are possibly also talking about a psychiatric population because it is a disease that, besides being highly recurrent, involves many other factors, such as the gaze of others, difficulty with dressing, body pains, mobility, and relationships. Therefore, having this disease alone is already a trigger for disorders such as depression.
 

What is the main evidence regarding the psychological follow-up of patients with obesity?

Several studies have investigated the relationship between obesity and mental health. Research indicates that the greater the obesity, the higher the likelihood of a positive diagnosis for a psychiatric disorder. Additionally, there is evidence of the benefits of psychological treatment for patients with obesity.

A study published in the Journal of Clinical Endocrinology and Metabolism addressed the impact of cognitive-behavioral therapy (CBT), which helps patients manage goals and treat maladaptive behaviors such as binge-eating disorders. CBT has a modest effect on weight loss, but its integration as part of a lifestyle modification amplifies the results of this loss.

Recent research also shows that weight loss through bariatric surgery offers significant psychological benefits. In the past, it was believed that this procedure could cause depression and other severe psychiatric disorders, but it is now more than proven that weight loss, when done properly and without misconduct or malnutrition, improves psychological and psychiatric issues.
 

How does psychological follow-up affect the use of medication during obesity treatment?

Many people who take medications, such as corticosteroids for chronic pain or psychiatric medications, may experience weight gain. It is essential to discuss these issues with the psychiatrist because if the patient already has a predisposition to weight gain, medication X should be chosen instead of medication Y, or the dosage should be adjusted. The psychiatrist needs to understand obesity to medicate correctly. Other types of medication, such as chemotherapeutics, may also cause weight gain, often resulting in more abdominal obesity.

There is also lipedema, a hormone-dependent disease that is different from obesity. In this disease, the person gains weight mainly in the legs and arms. In this case, bariatric surgery may result in weight loss only in specific areas, causing disproportionality and difficulty in understanding for the patient. Therefore, when treating obesity, it is important to analyze the patient from all angles: psychological, physiologic, and physical, considering the diversity of the body, its functioning, and hormonal reactions.

Although psychologists do not prescribe medications, they often explain their functioning to the patient. For example, if a patient is taking a glucagon-like peptide 1 analog and experiences initial nausea, he or she may stop using the treatment because the wrong dose had been started. In this case, the psychologist can explain how the medication works and encourage the patient to discuss adjustments with the doctor, avoiding premature discontinuation.
 

How has the mental health follow-up of patients with obesity evolved over the years?

I started working with people with obesity 25 years ago, when I myself underwent bariatric surgery. At that time, surgeons were used to “solving” the problem and sending the person home. Often, the patient did not even return for surgical follow-up because, in theory, the problem was solved.

Over time, I believe that surgeons learned to talk to the patient, understanding that there is a whole process that even involves creating a bond with the individual who underwent the surgical procedure. Within this process, the importance of the mental health of patients was recognized, and how common it is to confuse a degree of malnutrition with a mental disorder.

Even though I am not a nutritionist, I need to know the difference between a case of malnutrition and depression. So, it is a whole set of factors that needs to be worked on like an orchestra. It is not necessary for this work to be done in the same physical space, but dialogue is important.

Of course, there are things that the patient will only share with the psychologist or with the surgeon, but there are also pieces of information that need to be shared for positive management. I have had patients who were afraid to go back to the nutritionist because they did not lose weight. If they are afraid, it is because the professional is guiding them incorrectly.
 

What tips would you give to clinicians regarding the psychological approach to people with obesity?

Accessibility is crucial. When someone tells me they are dealing with obesity and depression, I usually ask, “Did you know you have two chronic diseases?” It is essential to explain these concepts because the patient may often think they are free after a successful diet and weight loss, which is not true because of the high relapse associated with obesity. Depression and anxiety follow similar patterns. If the same person wears prescription glasses, I interact by saying, “Did you know you have three chronic diseases?” This question often causes surprise. “I hadn’t thought of that.”

It is essential to use accessible language for the patient to understand the functioning of the disease. More important than choosing a treatment approach is understanding the pathophysiology of obesity and its psychological impact. This avoids a one-size-fits-all approach for all patients.

For example, the impact on someone who developed obesity in childhood after suffering physical, moral, or sexual abuse will probably be deeper than on someone in a healthy family who gained weight after becoming sedentary. Each life story requires a personalized approach.

Sometimes, a patient with mild obesity (grade 1) may not seem to need specific interventions at first glance, but it is crucial to listen to his or her story. Similarly, patients with severe obesity (grades 3 or 4) who resist surgery are entitled to other treatment options, and this is perfectly valid. Therefore, it is always important to ask, “Who is this person? What does obesity represent in their story?” Then propose the most appropriate treatment.

Ms. Levy reported having no relevant financial relationships.
 

This story was translated from the Medscape Portuguese edition using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

Increasingly recognized as a multifactorial disease, obesity demands an approach that involves multiple healthcare professionals. For psychologist Andréa Levy, coordinator and founder of the nongovernmental organization Obesity Brazil, addressing the patient’s “psychological weight” is crucial.

In an interview with this news organization, Ms. Levy, who was one of the speakers at the International Congress on Obesity in 2024, emphasized the importance of integrating emotional and behavioral aspects into treatment, because these factors often influence eating habits and weight gain.

She also highlighted the essential collaboration between endocrinologists, nutritionists, psychiatrists, and psychologists, who must work together to provide comprehensive and effective care to patients.
 

How do psychological factors affect the treatment of obesity?

Psychological factors are important triggers for weight gain. As the degree of obesity increases, so does the predisposition to mental health problems such as anxiety, mood disorders, personality disorders, and eating disorders. Understanding these factors is important because accurate psychodiagnosis is essential for effective disease treatment.

Without a proper diagnosis, the treatment may be incomplete and omit relevant factors. For example, a person with undiagnosed depression who is starting treatment for weight loss may feel discouraged and low on energy. He or she may wrongly attribute these symptoms to the diet or surgery. Similarly, someone undergoing bariatric surgery may confuse malnutrition symptoms with depression, resulting in inadequate treatment with antidepressants and possible iatrogenic complications.

Furthermore, psychotherapy and psychological follow-up are essential to help the individual organize better and understand the treatment and the disease itself. This is especially important in stigmatized diseases and those subject to prejudice such as obesity, where understanding and acceptance are often challenging, which affects treatment adherence.

Is the collaboration between psychologist and psychiatrist always necessary?

Often, it is necessary to have the support of both a psychologist and a psychiatrist. The process generally begins with a good psychodiagnosis. Initially, there may not be a case that requires treatment, but it is important to perform this evaluation to rule out any issues.

The follow-up, unlike weekly psychotherapy, can be monthly or at an interval agreed on with the patient. It is crucial to help him or her navigate the various stages of obesity treatment. For example, the patient may be going through a period of mourning or separation, or a happier moment, such as the beginning of a relationship or the birth of a child in the family. These moments affect eating habits and need to be well managed.

Depending on the degree of the pathology, such as depression, severe binge-eating disorder, or personality disorders, the psychologist works in conjunction with the psychiatrist. When we talk about obesity, we are possibly also talking about a psychiatric population because it is a disease that, besides being highly recurrent, involves many other factors, such as the gaze of others, difficulty with dressing, body pains, mobility, and relationships. Therefore, having this disease alone is already a trigger for disorders such as depression.
 

What is the main evidence regarding the psychological follow-up of patients with obesity?

Several studies have investigated the relationship between obesity and mental health. Research indicates that the greater the obesity, the higher the likelihood of a positive diagnosis for a psychiatric disorder. Additionally, there is evidence of the benefits of psychological treatment for patients with obesity.

A study published in the Journal of Clinical Endocrinology and Metabolism addressed the impact of cognitive-behavioral therapy (CBT), which helps patients manage goals and treat maladaptive behaviors such as binge-eating disorders. CBT has a modest effect on weight loss, but its integration as part of a lifestyle modification amplifies the results of this loss.

Recent research also shows that weight loss through bariatric surgery offers significant psychological benefits. In the past, it was believed that this procedure could cause depression and other severe psychiatric disorders, but it is now more than proven that weight loss, when done properly and without misconduct or malnutrition, improves psychological and psychiatric issues.
 

How does psychological follow-up affect the use of medication during obesity treatment?

Many people who take medications, such as corticosteroids for chronic pain or psychiatric medications, may experience weight gain. It is essential to discuss these issues with the psychiatrist because if the patient already has a predisposition to weight gain, medication X should be chosen instead of medication Y, or the dosage should be adjusted. The psychiatrist needs to understand obesity to medicate correctly. Other types of medication, such as chemotherapeutics, may also cause weight gain, often resulting in more abdominal obesity.

There is also lipedema, a hormone-dependent disease that is different from obesity. In this disease, the person gains weight mainly in the legs and arms. In this case, bariatric surgery may result in weight loss only in specific areas, causing disproportionality and difficulty in understanding for the patient. Therefore, when treating obesity, it is important to analyze the patient from all angles: psychological, physiologic, and physical, considering the diversity of the body, its functioning, and hormonal reactions.

Although psychologists do not prescribe medications, they often explain their functioning to the patient. For example, if a patient is taking a glucagon-like peptide 1 analog and experiences initial nausea, he or she may stop using the treatment because the wrong dose had been started. In this case, the psychologist can explain how the medication works and encourage the patient to discuss adjustments with the doctor, avoiding premature discontinuation.
 

How has the mental health follow-up of patients with obesity evolved over the years?

I started working with people with obesity 25 years ago, when I myself underwent bariatric surgery. At that time, surgeons were used to “solving” the problem and sending the person home. Often, the patient did not even return for surgical follow-up because, in theory, the problem was solved.

Over time, I believe that surgeons learned to talk to the patient, understanding that there is a whole process that even involves creating a bond with the individual who underwent the surgical procedure. Within this process, the importance of the mental health of patients was recognized, and how common it is to confuse a degree of malnutrition with a mental disorder.

Even though I am not a nutritionist, I need to know the difference between a case of malnutrition and depression. So, it is a whole set of factors that needs to be worked on like an orchestra. It is not necessary for this work to be done in the same physical space, but dialogue is important.

Of course, there are things that the patient will only share with the psychologist or with the surgeon, but there are also pieces of information that need to be shared for positive management. I have had patients who were afraid to go back to the nutritionist because they did not lose weight. If they are afraid, it is because the professional is guiding them incorrectly.
 

What tips would you give to clinicians regarding the psychological approach to people with obesity?

Accessibility is crucial. When someone tells me they are dealing with obesity and depression, I usually ask, “Did you know you have two chronic diseases?” It is essential to explain these concepts because the patient may often think they are free after a successful diet and weight loss, which is not true because of the high relapse associated with obesity. Depression and anxiety follow similar patterns. If the same person wears prescription glasses, I interact by saying, “Did you know you have three chronic diseases?” This question often causes surprise. “I hadn’t thought of that.”

It is essential to use accessible language for the patient to understand the functioning of the disease. More important than choosing a treatment approach is understanding the pathophysiology of obesity and its psychological impact. This avoids a one-size-fits-all approach for all patients.

For example, the impact on someone who developed obesity in childhood after suffering physical, moral, or sexual abuse will probably be deeper than on someone in a healthy family who gained weight after becoming sedentary. Each life story requires a personalized approach.

Sometimes, a patient with mild obesity (grade 1) may not seem to need specific interventions at first glance, but it is crucial to listen to his or her story. Similarly, patients with severe obesity (grades 3 or 4) who resist surgery are entitled to other treatment options, and this is perfectly valid. Therefore, it is always important to ask, “Who is this person? What does obesity represent in their story?” Then propose the most appropriate treatment.

Ms. Levy reported having no relevant financial relationships.
 

This story was translated from the Medscape Portuguese edition using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

Increasingly recognized as a multifactorial disease, obesity demands an approach that involves multiple healthcare professionals. For psychologist Andréa Levy, coordinator and founder of the nongovernmental organization Obesity Brazil, addressing the patient’s “psychological weight” is crucial.

In an interview with this news organization, Ms. Levy, who was one of the speakers at the International Congress on Obesity in 2024, emphasized the importance of integrating emotional and behavioral aspects into treatment, because these factors often influence eating habits and weight gain.

She also highlighted the essential collaboration between endocrinologists, nutritionists, psychiatrists, and psychologists, who must work together to provide comprehensive and effective care to patients.
 

How do psychological factors affect the treatment of obesity?

Psychological factors are important triggers for weight gain. As the degree of obesity increases, so does the predisposition to mental health problems such as anxiety, mood disorders, personality disorders, and eating disorders. Understanding these factors is important because accurate psychodiagnosis is essential for effective disease treatment.

Without a proper diagnosis, the treatment may be incomplete and omit relevant factors. For example, a person with undiagnosed depression who is starting treatment for weight loss may feel discouraged and low on energy. He or she may wrongly attribute these symptoms to the diet or surgery. Similarly, someone undergoing bariatric surgery may confuse malnutrition symptoms with depression, resulting in inadequate treatment with antidepressants and possible iatrogenic complications.

Furthermore, psychotherapy and psychological follow-up are essential to help the individual organize better and understand the treatment and the disease itself. This is especially important in stigmatized diseases and those subject to prejudice such as obesity, where understanding and acceptance are often challenging, which affects treatment adherence.

Is the collaboration between psychologist and psychiatrist always necessary?

Often, it is necessary to have the support of both a psychologist and a psychiatrist. The process generally begins with a good psychodiagnosis. Initially, there may not be a case that requires treatment, but it is important to perform this evaluation to rule out any issues.

The follow-up, unlike weekly psychotherapy, can be monthly or at an interval agreed on with the patient. It is crucial to help him or her navigate the various stages of obesity treatment. For example, the patient may be going through a period of mourning or separation, or a happier moment, such as the beginning of a relationship or the birth of a child in the family. These moments affect eating habits and need to be well managed.

Depending on the degree of the pathology, such as depression, severe binge-eating disorder, or personality disorders, the psychologist works in conjunction with the psychiatrist. When we talk about obesity, we are possibly also talking about a psychiatric population because it is a disease that, besides being highly recurrent, involves many other factors, such as the gaze of others, difficulty with dressing, body pains, mobility, and relationships. Therefore, having this disease alone is already a trigger for disorders such as depression.
 

What is the main evidence regarding the psychological follow-up of patients with obesity?

Several studies have investigated the relationship between obesity and mental health. Research indicates that the greater the obesity, the higher the likelihood of a positive diagnosis for a psychiatric disorder. Additionally, there is evidence of the benefits of psychological treatment for patients with obesity.

A study published in the Journal of Clinical Endocrinology and Metabolism addressed the impact of cognitive-behavioral therapy (CBT), which helps patients manage goals and treat maladaptive behaviors such as binge-eating disorders. CBT has a modest effect on weight loss, but its integration as part of a lifestyle modification amplifies the results of this loss.

Recent research also shows that weight loss through bariatric surgery offers significant psychological benefits. In the past, it was believed that this procedure could cause depression and other severe psychiatric disorders, but it is now more than proven that weight loss, when done properly and without misconduct or malnutrition, improves psychological and psychiatric issues.
 

How does psychological follow-up affect the use of medication during obesity treatment?

Many people who take medications, such as corticosteroids for chronic pain or psychiatric medications, may experience weight gain. It is essential to discuss these issues with the psychiatrist because if the patient already has a predisposition to weight gain, medication X should be chosen instead of medication Y, or the dosage should be adjusted. The psychiatrist needs to understand obesity to medicate correctly. Other types of medication, such as chemotherapeutics, may also cause weight gain, often resulting in more abdominal obesity.

There is also lipedema, a hormone-dependent disease that is different from obesity. In this disease, the person gains weight mainly in the legs and arms. In this case, bariatric surgery may result in weight loss only in specific areas, causing disproportionality and difficulty in understanding for the patient. Therefore, when treating obesity, it is important to analyze the patient from all angles: psychological, physiologic, and physical, considering the diversity of the body, its functioning, and hormonal reactions.

Although psychologists do not prescribe medications, they often explain their functioning to the patient. For example, if a patient is taking a glucagon-like peptide 1 analog and experiences initial nausea, he or she may stop using the treatment because the wrong dose had been started. In this case, the psychologist can explain how the medication works and encourage the patient to discuss adjustments with the doctor, avoiding premature discontinuation.
 

How has the mental health follow-up of patients with obesity evolved over the years?

I started working with people with obesity 25 years ago, when I myself underwent bariatric surgery. At that time, surgeons were used to “solving” the problem and sending the person home. Often, the patient did not even return for surgical follow-up because, in theory, the problem was solved.

Over time, I believe that surgeons learned to talk to the patient, understanding that there is a whole process that even involves creating a bond with the individual who underwent the surgical procedure. Within this process, the importance of the mental health of patients was recognized, and how common it is to confuse a degree of malnutrition with a mental disorder.

Even though I am not a nutritionist, I need to know the difference between a case of malnutrition and depression. So, it is a whole set of factors that needs to be worked on like an orchestra. It is not necessary for this work to be done in the same physical space, but dialogue is important.

Of course, there are things that the patient will only share with the psychologist or with the surgeon, but there are also pieces of information that need to be shared for positive management. I have had patients who were afraid to go back to the nutritionist because they did not lose weight. If they are afraid, it is because the professional is guiding them incorrectly.
 

What tips would you give to clinicians regarding the psychological approach to people with obesity?

Accessibility is crucial. When someone tells me they are dealing with obesity and depression, I usually ask, “Did you know you have two chronic diseases?” It is essential to explain these concepts because the patient may often think they are free after a successful diet and weight loss, which is not true because of the high relapse associated with obesity. Depression and anxiety follow similar patterns. If the same person wears prescription glasses, I interact by saying, “Did you know you have three chronic diseases?” This question often causes surprise. “I hadn’t thought of that.”

It is essential to use accessible language for the patient to understand the functioning of the disease. More important than choosing a treatment approach is understanding the pathophysiology of obesity and its psychological impact. This avoids a one-size-fits-all approach for all patients.

For example, the impact on someone who developed obesity in childhood after suffering physical, moral, or sexual abuse will probably be deeper than on someone in a healthy family who gained weight after becoming sedentary. Each life story requires a personalized approach.

Sometimes, a patient with mild obesity (grade 1) may not seem to need specific interventions at first glance, but it is crucial to listen to his or her story. Similarly, patients with severe obesity (grades 3 or 4) who resist surgery are entitled to other treatment options, and this is perfectly valid. Therefore, it is always important to ask, “Who is this person? What does obesity represent in their story?” Then propose the most appropriate treatment.

Ms. Levy reported having no relevant financial relationships.
 

This story was translated from the Medscape Portuguese edition using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

PHILADELPHIA – A new study supports the potential to repurpose glucagon-like peptide 1 (GLP-1) receptor agonists, used to treat type 2 diabetes and obesity, for dementia prevention.

In the phase 2b ELAD clinical trial, adults with early-stage Alzheimer’s disease taking the GLP-1 receptor agonist liraglutide exhibited slower decline in memory and thinking and experienced less brain atrophy over 12 months, compared with placebo.

“The slower loss of brain volume suggests liraglutide protects the brain, much like statins protect the heart,” study chief Paul Edison, MD, PhD, with Imperial College London, London, England, said in a statement.

“While further research is needed, liraglutide may work through various mechanisms, such as reducing inflammation in the brain, lowering insulin resistance and the toxic effects of Alzheimer’s biomarkers amyloid beta and tau, and improving how the brain’s nerve cells communicate,” Dr. Edison said.

He presented the study results at the 2024 Alzheimer’s Association International Conference (AAIC).

Brain Benefits

Liraglutide has previously demonstrated promising neuroprotective effects in animal models of Alzheimer’s disease and epidemiologic studies. 

In ELAD, 204 patients with mild to moderate Alzheimer’s disease were randomly allocated (1:1) to a daily subcutaneous injection of up to 1.8 mg of liraglutide or placebo for 12 months; 80 patients in the liraglutide group and 89 in the placebo group completed the study. 

Brain MRI was performed at baseline and at 12 months, along with neuropsychometric evaluation and 18F-fludeoxyglucose PET. 

The study’s primary endpoint — change in the cerebral glucose metabolic rate in the cortical regions of the brain (hippocampus, medial temporal lobe, and posterior cingulate) — was not met. 

However, patients taking liraglutide experienced a significant slowing of cognitive decline, compared with placebo group (P = .01), which was a key secondary outcome, calculated as a composite score of 18 different tests of memory, comprehension, language, and spatial orientation. 

Although the study was not powered to assess cognitive changes, adults taking liraglutide had an 18% slower decline in cognitive function over 12 months, compared with those on placebo, Dr. Edison reported. 

In addition, patients treated with liraglutide had nearly 50% less volume loss in several areas of the brain involved in memory, language, and decision-making, including frontal, temporal, parietal, and total gray matter, as measured by MRI. 

Liraglutide daily subcutaneous injections were safe and well tolerated in patients with Alzheimer’s disease, Dr. Edison reported. There were 25 serious side effects — 18 in the placebo group and 7 in the liraglutide group — and most were considered unlikely to be related to the study treatment. There were no deaths. 
 

Promising, Preliminary

This study shows a positive effect of liraglutide on the brain in terms of “slowing down of brain atrophy and slowing down the rate of cognitive decline,” said Howard Fillit, MD, founding executive director of the Alzheimer’s Drug Discovery Foundation, who wasn’t involved in the study.

Heather Snyder, PhD, vice-president of medical and scientific relations at the Alzheimer’s Association, said it’s “interesting” to see slowing of brain volume loss and some cognitive benefit “especially as the study was not powered necessarily to see some of those changes. The fact that they did see these changes in this small study provides a window into what may happen, but we certainly need larger phase 3 studies.”

In a statement from the UK nonprofit Science Media Centre, Tara Spires-Jones, PhD, president of the British Neuroscience Association and group leader at the UK Dementia Research Institute, called the data “promising.”

“There are clear links from strong data in the field between vascular risk factors including diabetes and obesity being associated with increased risk of dementia. The GLP-1 drug should help reduce these risk factors as well as potentially directly protecting brain cells,” Dr. Spires-Jones said. 

However, she said “more research in bigger trials is needed to confirm whether this type of treatment will be effective in people with Alzheimer’s disease.”

Stephen Evans, MSc, emeritus professor, London School of Hygiene and Tropical Medicine, noted that the repurposing of drugs is “an important avenue of research but there is a lot of uncertainty here.”

He cautioned that the “50% brain volume change may not translate to important cognitive effects, and reporting only on those who completed the full 52 weeks of treatment could bring bias into the results. It sounds like it is worth pursuing a larger trial, but these results cannot demonstrate that liraglutide can protect against dementia.”

The ongoing phase 3 EVOKE trial is investigating the effects of the GLP-1 receptor agonist semaglutide in early Alzheimer’s disease.

Funding for the study was provided by Alzheimer’s Society UK, Alzheimer’s Drug Discovery Foundation, Novo Nordisk, John and Lucille Van Geest Foundation, and the National Institute for Health and Care Research Biomedical Research Centre. Dr. Edison, Dr. Fillit, Dr. Snyder, Mr. Evans, and Dr. Spires-Jones had no relevant conflicts of interest.

A version of this article first appeared on Medscape.com.

PHILADELPHIA – A new study supports the potential to repurpose glucagon-like peptide 1 (GLP-1) receptor agonists, used to treat type 2 diabetes and obesity, for dementia prevention.

In the phase 2b ELAD clinical trial, adults with early-stage Alzheimer’s disease taking the GLP-1 receptor agonist liraglutide exhibited slower decline in memory and thinking and experienced less brain atrophy over 12 months, compared with placebo.

“The slower loss of brain volume suggests liraglutide protects the brain, much like statins protect the heart,” study chief Paul Edison, MD, PhD, with Imperial College London, London, England, said in a statement.

“While further research is needed, liraglutide may work through various mechanisms, such as reducing inflammation in the brain, lowering insulin resistance and the toxic effects of Alzheimer’s biomarkers amyloid beta and tau, and improving how the brain’s nerve cells communicate,” Dr. Edison said.

He presented the study results at the 2024 Alzheimer’s Association International Conference (AAIC).

Brain Benefits

Liraglutide has previously demonstrated promising neuroprotective effects in animal models of Alzheimer’s disease and epidemiologic studies. 

In ELAD, 204 patients with mild to moderate Alzheimer’s disease were randomly allocated (1:1) to a daily subcutaneous injection of up to 1.8 mg of liraglutide or placebo for 12 months; 80 patients in the liraglutide group and 89 in the placebo group completed the study. 

Brain MRI was performed at baseline and at 12 months, along with neuropsychometric evaluation and 18F-fludeoxyglucose PET. 

The study’s primary endpoint — change in the cerebral glucose metabolic rate in the cortical regions of the brain (hippocampus, medial temporal lobe, and posterior cingulate) — was not met. 

However, patients taking liraglutide experienced a significant slowing of cognitive decline, compared with placebo group (P = .01), which was a key secondary outcome, calculated as a composite score of 18 different tests of memory, comprehension, language, and spatial orientation. 

Although the study was not powered to assess cognitive changes, adults taking liraglutide had an 18% slower decline in cognitive function over 12 months, compared with those on placebo, Dr. Edison reported. 

In addition, patients treated with liraglutide had nearly 50% less volume loss in several areas of the brain involved in memory, language, and decision-making, including frontal, temporal, parietal, and total gray matter, as measured by MRI. 

Liraglutide daily subcutaneous injections were safe and well tolerated in patients with Alzheimer’s disease, Dr. Edison reported. There were 25 serious side effects — 18 in the placebo group and 7 in the liraglutide group — and most were considered unlikely to be related to the study treatment. There were no deaths. 
 

Promising, Preliminary

This study shows a positive effect of liraglutide on the brain in terms of “slowing down of brain atrophy and slowing down the rate of cognitive decline,” said Howard Fillit, MD, founding executive director of the Alzheimer’s Drug Discovery Foundation, who wasn’t involved in the study.

Heather Snyder, PhD, vice-president of medical and scientific relations at the Alzheimer’s Association, said it’s “interesting” to see slowing of brain volume loss and some cognitive benefit “especially as the study was not powered necessarily to see some of those changes. The fact that they did see these changes in this small study provides a window into what may happen, but we certainly need larger phase 3 studies.”

In a statement from the UK nonprofit Science Media Centre, Tara Spires-Jones, PhD, president of the British Neuroscience Association and group leader at the UK Dementia Research Institute, called the data “promising.”

“There are clear links from strong data in the field between vascular risk factors including diabetes and obesity being associated with increased risk of dementia. The GLP-1 drug should help reduce these risk factors as well as potentially directly protecting brain cells,” Dr. Spires-Jones said. 

However, she said “more research in bigger trials is needed to confirm whether this type of treatment will be effective in people with Alzheimer’s disease.”

Stephen Evans, MSc, emeritus professor, London School of Hygiene and Tropical Medicine, noted that the repurposing of drugs is “an important avenue of research but there is a lot of uncertainty here.”

He cautioned that the “50% brain volume change may not translate to important cognitive effects, and reporting only on those who completed the full 52 weeks of treatment could bring bias into the results. It sounds like it is worth pursuing a larger trial, but these results cannot demonstrate that liraglutide can protect against dementia.”

The ongoing phase 3 EVOKE trial is investigating the effects of the GLP-1 receptor agonist semaglutide in early Alzheimer’s disease.

Funding for the study was provided by Alzheimer’s Society UK, Alzheimer’s Drug Discovery Foundation, Novo Nordisk, John and Lucille Van Geest Foundation, and the National Institute for Health and Care Research Biomedical Research Centre. Dr. Edison, Dr. Fillit, Dr. Snyder, Mr. Evans, and Dr. Spires-Jones had no relevant conflicts of interest.

A version of this article first appeared on Medscape.com.

PHILADELPHIA – A new study supports the potential to repurpose glucagon-like peptide 1 (GLP-1) receptor agonists, used to treat type 2 diabetes and obesity, for dementia prevention.

In the phase 2b ELAD clinical trial, adults with early-stage Alzheimer’s disease taking the GLP-1 receptor agonist liraglutide exhibited slower decline in memory and thinking and experienced less brain atrophy over 12 months, compared with placebo.

“The slower loss of brain volume suggests liraglutide protects the brain, much like statins protect the heart,” study chief Paul Edison, MD, PhD, with Imperial College London, London, England, said in a statement.

“While further research is needed, liraglutide may work through various mechanisms, such as reducing inflammation in the brain, lowering insulin resistance and the toxic effects of Alzheimer’s biomarkers amyloid beta and tau, and improving how the brain’s nerve cells communicate,” Dr. Edison said.

He presented the study results at the 2024 Alzheimer’s Association International Conference (AAIC).

Brain Benefits

Liraglutide has previously demonstrated promising neuroprotective effects in animal models of Alzheimer’s disease and epidemiologic studies. 

In ELAD, 204 patients with mild to moderate Alzheimer’s disease were randomly allocated (1:1) to a daily subcutaneous injection of up to 1.8 mg of liraglutide or placebo for 12 months; 80 patients in the liraglutide group and 89 in the placebo group completed the study. 

Brain MRI was performed at baseline and at 12 months, along with neuropsychometric evaluation and 18F-fludeoxyglucose PET. 

The study’s primary endpoint — change in the cerebral glucose metabolic rate in the cortical regions of the brain (hippocampus, medial temporal lobe, and posterior cingulate) — was not met. 

However, patients taking liraglutide experienced a significant slowing of cognitive decline, compared with placebo group (P = .01), which was a key secondary outcome, calculated as a composite score of 18 different tests of memory, comprehension, language, and spatial orientation. 

Although the study was not powered to assess cognitive changes, adults taking liraglutide had an 18% slower decline in cognitive function over 12 months, compared with those on placebo, Dr. Edison reported. 

In addition, patients treated with liraglutide had nearly 50% less volume loss in several areas of the brain involved in memory, language, and decision-making, including frontal, temporal, parietal, and total gray matter, as measured by MRI. 

Liraglutide daily subcutaneous injections were safe and well tolerated in patients with Alzheimer’s disease, Dr. Edison reported. There were 25 serious side effects — 18 in the placebo group and 7 in the liraglutide group — and most were considered unlikely to be related to the study treatment. There were no deaths. 
 

Promising, Preliminary

This study shows a positive effect of liraglutide on the brain in terms of “slowing down of brain atrophy and slowing down the rate of cognitive decline,” said Howard Fillit, MD, founding executive director of the Alzheimer’s Drug Discovery Foundation, who wasn’t involved in the study.

Heather Snyder, PhD, vice-president of medical and scientific relations at the Alzheimer’s Association, said it’s “interesting” to see slowing of brain volume loss and some cognitive benefit “especially as the study was not powered necessarily to see some of those changes. The fact that they did see these changes in this small study provides a window into what may happen, but we certainly need larger phase 3 studies.”

In a statement from the UK nonprofit Science Media Centre, Tara Spires-Jones, PhD, president of the British Neuroscience Association and group leader at the UK Dementia Research Institute, called the data “promising.”

“There are clear links from strong data in the field between vascular risk factors including diabetes and obesity being associated with increased risk of dementia. The GLP-1 drug should help reduce these risk factors as well as potentially directly protecting brain cells,” Dr. Spires-Jones said. 

However, she said “more research in bigger trials is needed to confirm whether this type of treatment will be effective in people with Alzheimer’s disease.”

Stephen Evans, MSc, emeritus professor, London School of Hygiene and Tropical Medicine, noted that the repurposing of drugs is “an important avenue of research but there is a lot of uncertainty here.”

He cautioned that the “50% brain volume change may not translate to important cognitive effects, and reporting only on those who completed the full 52 weeks of treatment could bring bias into the results. It sounds like it is worth pursuing a larger trial, but these results cannot demonstrate that liraglutide can protect against dementia.”

The ongoing phase 3 EVOKE trial is investigating the effects of the GLP-1 receptor agonist semaglutide in early Alzheimer’s disease.

Funding for the study was provided by Alzheimer’s Society UK, Alzheimer’s Drug Discovery Foundation, Novo Nordisk, John and Lucille Van Geest Foundation, and the National Institute for Health and Care Research Biomedical Research Centre. Dr. Edison, Dr. Fillit, Dr. Snyder, Mr. Evans, and Dr. Spires-Jones had no relevant conflicts of interest.

A version of this article first appeared on Medscape.com.

PHILADELPHIA – Higher intake of processed red meat, including bacon, hot dogs, and sausages, is associated with an elevated dementia risk, preliminary research shows.

Study participants who consumed 0.25 or more servings of processed meat per day, or roughly two servings per week, had a 15% higher risk for dementia, compared with those who consumed less than 0.10 serving per day, which is about three servings per month. 

“Our study found a higher intake of red meat — particularly processed red meat — was associated with a higher risk of developing dementia, as well as worse cognition,” said study author Yuhan Li, MHS, research assistant, Channing Division of Network Medicine, Brigham and Women’s Hospital, Boston, Massachusetts.

However, the study also showed that replacing processed red meat with nuts and legumes could potentially lower this increased risk.

The findings were presented on at the 2024 Alzheimer’s Association International Conference (AAIC).

Inconsistent Research 

Previous studies have shown an inconsistent association between red meat intake and cognitive health.

To assess the relationship between diet and dementia, the researchers used data from the Nurses’ Health Study, which began recruiting female registered nurses aged 30-55 years in 1976, and the Health Professionals Follow-Up Study, which began recruiting male health professionals aged 40-75 in 1986.

They assessed processed red meat intake by validated semi-quantitative food frequency questionnaires administered every 2-4 years. Participants were asked how often they consumed a serving of processed red meat.

Investigators also assessed intake of unprocessed red meat, including beef, pork, or lamb as a main dish, in a sandwich or hamburger, or in a mixed dish. 

The investigators also looked at participants’ intake of nuts and legumes.

Dementia outcome was a composite endpoint of self-reported dementia and dementia-related death. “Specifically, participants reported a physician diagnosis of Alzheimer’s disease or other forms of dementia by questionnaire. Deaths were identified through state vital statistics records, the National Death Index, family reports, and the postal system,” said Ms. Li.
 

Three Cognitive Outcomes

Researchers examined three outcomes: dementia, subjective cognitive decline, and objective cognitive function. For dementia, they ascertained incident cases in 87,424 individuals in the UK’s National Health Service database without Parkinson’s disease or baseline dementia, stroke, or cancer. 

They longitudinally collected information on subjective cognitive decline from 33,908 Nurses’ Health Study participants and 10,058 participants in the Health Professionals Follow-Up Study.

Cognitive function was assessed using the Telephone Interview for Cognitive Status (1995-2008) in a subset of 17,458 Nurses’ Health Study participants.

Over a follow-up of 38 years (1980-2018), there were 6856 dementia cases in the Nurses’ Health Study. Participants with processed red meat intake of 0.25 or more serving/day, compared with less than 0.10 serving/day, had 15% higher risk for dementia (hazard ratio [HR], 1.15; 95% CI, 1.08-1.23; P < .001). 

In addition to an increased risk for dementia, intake of processed red meat was associated with accelerated cognitive aging in global cognition (1.61 years per 1–serving/day increment; 95% CI, 0.20, 3.03) and verbal memory (1.69 years per 1–serving/day increment; 95% CI, 0.13, 3.25; both P = .03).

Participants with processed red meat intake of 0.25 or more serving/day had a 14% higher likelihood of subjective cognitive decline, compared with those with intake less than 0.10 serving/day (odds ratio [OR], 1.14; 95% CI, 1.04-1.24; P = .004). 

For unprocessed red meat, consuming 1.00 or more serving/day versus less than 0.50 serving/day was associated with a 16% higher likelihood of subjective cognitive decline (OR, 1.16; 95% CI, 1.04-1.30; P = .02). 
 

Substitution Analysis

Researchers modeled the effects of replacing 1 serving/day of processed red meat with 1 serving/day of nuts and legumes on cognitive outcomes. They did this by treating food intakes as continuous variables and calculating the differences in coefficients of the two food items.

They found that substituting legumes and nuts was associated with a 23% lower risk for dementia (HR, 0.77; 95% CI, 0.69-0.86), 1.37 fewer years of cognitive aging (95% CI, –2.49 to –0.25), and 20% lower odds of subjective cognitive decline (OR, 0.80, 95% CI, 0.69-0.92).

The research cannot determine whether it’s the processing method itself or the type of red meat that affects cognition, Ms. Li cautioned. 

“Our study is an epidemiologic study, not a biological mechanism study, but based on our findings, red meat may be related to worse cognition, and processed red meat may add additional risk,” she said. 

She also noted that because the study focused solely on red meats, the study cannot determine the potential on the impact of other processed meats on cognition.

Although the study doesn’t address a possible mechanism linking processed red meat with cognition, Ms. Li said it’s possible such meats have high levels of relatively harmful substances, such as nitrites, N-nitroso compounds, and sodium, and that “these carry the additional risk to brain health.”

There are currently no specific guidelines regarding the “safe” amount of processed meat consumption specifically related to cognition, she said.

The study is important because of its large sample size, long follow-up period, and inclusion of repeated measurements of diet, the investigators noted. In addition, researchers assessed both processed and unprocessed red meat and evaluated multiple cognitive outcomes.

The investigators plan to assess the association between other modifiable factors and cognitive health.
 

Experts Weigh In 

In a comment, Claire Sexton, DPhil, senior director of scientific programs and outreach at the Alzheimer’s Association, agreed past studies on the topic have been “mixed,” with only some studies reporting links between cognition or dementia and processed red meat. 

Another unique aspect of the study, said Dr. Sexton, was the replacement analysis showing the brain benefits of eating nuts and legumes in place of processed red meat. “So, it’s not just suggesting to people what not to do, but also what they can be doing instead.”

That’s why this large study with more than 130,000 adults that tracked individuals for close to 40 years in some cases “is so valuable,” she added.

In a release from the Science Media Centre in the United Kingdom, several other experts commented on the study. Among them, Kevin McConway, PhD, emeritus professor of applied statistics at the Open University, Milton Keynes, England, said that “it’s pretty well impossible to get a clear message from the information that is available so far about this research. It is a conference paper, and all we have seen so far is a press release, a brief summary of the research, and a diagram. There isn’t a detailed, peer-reviewed research report, not yet anyway. Putting out limited information like this isn’t the right way to report science.”

Dr. McConway also noted that the observational study recorded participants’ diets and dementia diagnoses over several years without assigning specific diets. Those who ate more red processed meat had higher rates of dementia and cognitive decline. However, it’s unclear if these differences are caused by red meat consumption or other factors, such as diet, age, ethnicity, or location.

Researchers typically adjust for these factors, but the available information doesn’t specify what adjustments were made or their impact, he noted, and without detailed data, it’s impossible to evaluate the study’s quality. Although eating more red processed meat might increase dementia risk, more research is needed to confirm this, Dr. McConway added. 

Also commenting, Sebastian Walsh, a National Institute for Health and Care Research doctoral fellow who researches population-level approaches to dementia risk reduction at University of Cambridge, Cambridge, England, said that without seeing the full paper, it’s difficult to know exactly what to make of the study’s findings. 

“On the surface, this is a large and long study. But it isn’t clear how the analysis was done — specifically what other factors were taken into account when looking at this apparent relationship between red meat and dementia.

“Despite a lot of research looking at specific foods and different diseases, the basic public health advice that eating a healthy, balanced diet is good for health is essentially unchanged. Most people know and accept this. What is most important is to find ways of supporting people, particularly those from poorer backgrounds, to follow this advice and address the obesity epidemic,” said Mr. Walsh. 

The study was funded by a National Institutes of Health research grant. Ms. Li reports no relevant conflicts of interest. Dr. Sexton, Dr. McConway, and Mr. Walsh report no relevant disclosures.

A version of this article first appeared on Medscape.com.

PHILADELPHIA – Higher intake of processed red meat, including bacon, hot dogs, and sausages, is associated with an elevated dementia risk, preliminary research shows.

Study participants who consumed 0.25 or more servings of processed meat per day, or roughly two servings per week, had a 15% higher risk for dementia, compared with those who consumed less than 0.10 serving per day, which is about three servings per month. 

“Our study found a higher intake of red meat — particularly processed red meat — was associated with a higher risk of developing dementia, as well as worse cognition,” said study author Yuhan Li, MHS, research assistant, Channing Division of Network Medicine, Brigham and Women’s Hospital, Boston, Massachusetts.

However, the study also showed that replacing processed red meat with nuts and legumes could potentially lower this increased risk.

The findings were presented on at the 2024 Alzheimer’s Association International Conference (AAIC).

Inconsistent Research 

Previous studies have shown an inconsistent association between red meat intake and cognitive health.

To assess the relationship between diet and dementia, the researchers used data from the Nurses’ Health Study, which began recruiting female registered nurses aged 30-55 years in 1976, and the Health Professionals Follow-Up Study, which began recruiting male health professionals aged 40-75 in 1986.

They assessed processed red meat intake by validated semi-quantitative food frequency questionnaires administered every 2-4 years. Participants were asked how often they consumed a serving of processed red meat.

Investigators also assessed intake of unprocessed red meat, including beef, pork, or lamb as a main dish, in a sandwich or hamburger, or in a mixed dish. 

The investigators also looked at participants’ intake of nuts and legumes.

Dementia outcome was a composite endpoint of self-reported dementia and dementia-related death. “Specifically, participants reported a physician diagnosis of Alzheimer’s disease or other forms of dementia by questionnaire. Deaths were identified through state vital statistics records, the National Death Index, family reports, and the postal system,” said Ms. Li.
 

Three Cognitive Outcomes

Researchers examined three outcomes: dementia, subjective cognitive decline, and objective cognitive function. For dementia, they ascertained incident cases in 87,424 individuals in the UK’s National Health Service database without Parkinson’s disease or baseline dementia, stroke, or cancer. 

They longitudinally collected information on subjective cognitive decline from 33,908 Nurses’ Health Study participants and 10,058 participants in the Health Professionals Follow-Up Study.

Cognitive function was assessed using the Telephone Interview for Cognitive Status (1995-2008) in a subset of 17,458 Nurses’ Health Study participants.

Over a follow-up of 38 years (1980-2018), there were 6856 dementia cases in the Nurses’ Health Study. Participants with processed red meat intake of 0.25 or more serving/day, compared with less than 0.10 serving/day, had 15% higher risk for dementia (hazard ratio [HR], 1.15; 95% CI, 1.08-1.23; P < .001). 

In addition to an increased risk for dementia, intake of processed red meat was associated with accelerated cognitive aging in global cognition (1.61 years per 1–serving/day increment; 95% CI, 0.20, 3.03) and verbal memory (1.69 years per 1–serving/day increment; 95% CI, 0.13, 3.25; both P = .03).

Participants with processed red meat intake of 0.25 or more serving/day had a 14% higher likelihood of subjective cognitive decline, compared with those with intake less than 0.10 serving/day (odds ratio [OR], 1.14; 95% CI, 1.04-1.24; P = .004). 

For unprocessed red meat, consuming 1.00 or more serving/day versus less than 0.50 serving/day was associated with a 16% higher likelihood of subjective cognitive decline (OR, 1.16; 95% CI, 1.04-1.30; P = .02). 
 

Substitution Analysis

Researchers modeled the effects of replacing 1 serving/day of processed red meat with 1 serving/day of nuts and legumes on cognitive outcomes. They did this by treating food intakes as continuous variables and calculating the differences in coefficients of the two food items.

They found that substituting legumes and nuts was associated with a 23% lower risk for dementia (HR, 0.77; 95% CI, 0.69-0.86), 1.37 fewer years of cognitive aging (95% CI, –2.49 to –0.25), and 20% lower odds of subjective cognitive decline (OR, 0.80, 95% CI, 0.69-0.92).

The research cannot determine whether it’s the processing method itself or the type of red meat that affects cognition, Ms. Li cautioned. 

“Our study is an epidemiologic study, not a biological mechanism study, but based on our findings, red meat may be related to worse cognition, and processed red meat may add additional risk,” she said. 

She also noted that because the study focused solely on red meats, the study cannot determine the potential on the impact of other processed meats on cognition.

Although the study doesn’t address a possible mechanism linking processed red meat with cognition, Ms. Li said it’s possible such meats have high levels of relatively harmful substances, such as nitrites, N-nitroso compounds, and sodium, and that “these carry the additional risk to brain health.”

There are currently no specific guidelines regarding the “safe” amount of processed meat consumption specifically related to cognition, she said.

The study is important because of its large sample size, long follow-up period, and inclusion of repeated measurements of diet, the investigators noted. In addition, researchers assessed both processed and unprocessed red meat and evaluated multiple cognitive outcomes.

The investigators plan to assess the association between other modifiable factors and cognitive health.
 

Experts Weigh In 

In a comment, Claire Sexton, DPhil, senior director of scientific programs and outreach at the Alzheimer’s Association, agreed past studies on the topic have been “mixed,” with only some studies reporting links between cognition or dementia and processed red meat. 

Another unique aspect of the study, said Dr. Sexton, was the replacement analysis showing the brain benefits of eating nuts and legumes in place of processed red meat. “So, it’s not just suggesting to people what not to do, but also what they can be doing instead.”

That’s why this large study with more than 130,000 adults that tracked individuals for close to 40 years in some cases “is so valuable,” she added.

In a release from the Science Media Centre in the United Kingdom, several other experts commented on the study. Among them, Kevin McConway, PhD, emeritus professor of applied statistics at the Open University, Milton Keynes, England, said that “it’s pretty well impossible to get a clear message from the information that is available so far about this research. It is a conference paper, and all we have seen so far is a press release, a brief summary of the research, and a diagram. There isn’t a detailed, peer-reviewed research report, not yet anyway. Putting out limited information like this isn’t the right way to report science.”

Dr. McConway also noted that the observational study recorded participants’ diets and dementia diagnoses over several years without assigning specific diets. Those who ate more red processed meat had higher rates of dementia and cognitive decline. However, it’s unclear if these differences are caused by red meat consumption or other factors, such as diet, age, ethnicity, or location.

Researchers typically adjust for these factors, but the available information doesn’t specify what adjustments were made or their impact, he noted, and without detailed data, it’s impossible to evaluate the study’s quality. Although eating more red processed meat might increase dementia risk, more research is needed to confirm this, Dr. McConway added. 

Also commenting, Sebastian Walsh, a National Institute for Health and Care Research doctoral fellow who researches population-level approaches to dementia risk reduction at University of Cambridge, Cambridge, England, said that without seeing the full paper, it’s difficult to know exactly what to make of the study’s findings. 

“On the surface, this is a large and long study. But it isn’t clear how the analysis was done — specifically what other factors were taken into account when looking at this apparent relationship between red meat and dementia.

“Despite a lot of research looking at specific foods and different diseases, the basic public health advice that eating a healthy, balanced diet is good for health is essentially unchanged. Most people know and accept this. What is most important is to find ways of supporting people, particularly those from poorer backgrounds, to follow this advice and address the obesity epidemic,” said Mr. Walsh. 

The study was funded by a National Institutes of Health research grant. Ms. Li reports no relevant conflicts of interest. Dr. Sexton, Dr. McConway, and Mr. Walsh report no relevant disclosures.

A version of this article first appeared on Medscape.com.

PHILADELPHIA – Higher intake of processed red meat, including bacon, hot dogs, and sausages, is associated with an elevated dementia risk, preliminary research shows.

Study participants who consumed 0.25 or more servings of processed meat per day, or roughly two servings per week, had a 15% higher risk for dementia, compared with those who consumed less than 0.10 serving per day, which is about three servings per month. 

“Our study found a higher intake of red meat — particularly processed red meat — was associated with a higher risk of developing dementia, as well as worse cognition,” said study author Yuhan Li, MHS, research assistant, Channing Division of Network Medicine, Brigham and Women’s Hospital, Boston, Massachusetts.

However, the study also showed that replacing processed red meat with nuts and legumes could potentially lower this increased risk.

The findings were presented on at the 2024 Alzheimer’s Association International Conference (AAIC).

Inconsistent Research 

Previous studies have shown an inconsistent association between red meat intake and cognitive health.

To assess the relationship between diet and dementia, the researchers used data from the Nurses’ Health Study, which began recruiting female registered nurses aged 30-55 years in 1976, and the Health Professionals Follow-Up Study, which began recruiting male health professionals aged 40-75 in 1986.

They assessed processed red meat intake by validated semi-quantitative food frequency questionnaires administered every 2-4 years. Participants were asked how often they consumed a serving of processed red meat.

Investigators also assessed intake of unprocessed red meat, including beef, pork, or lamb as a main dish, in a sandwich or hamburger, or in a mixed dish. 

The investigators also looked at participants’ intake of nuts and legumes.

Dementia outcome was a composite endpoint of self-reported dementia and dementia-related death. “Specifically, participants reported a physician diagnosis of Alzheimer’s disease or other forms of dementia by questionnaire. Deaths were identified through state vital statistics records, the National Death Index, family reports, and the postal system,” said Ms. Li.
 

Three Cognitive Outcomes

Researchers examined three outcomes: dementia, subjective cognitive decline, and objective cognitive function. For dementia, they ascertained incident cases in 87,424 individuals in the UK’s National Health Service database without Parkinson’s disease or baseline dementia, stroke, or cancer. 

They longitudinally collected information on subjective cognitive decline from 33,908 Nurses’ Health Study participants and 10,058 participants in the Health Professionals Follow-Up Study.

Cognitive function was assessed using the Telephone Interview for Cognitive Status (1995-2008) in a subset of 17,458 Nurses’ Health Study participants.

Over a follow-up of 38 years (1980-2018), there were 6856 dementia cases in the Nurses’ Health Study. Participants with processed red meat intake of 0.25 or more serving/day, compared with less than 0.10 serving/day, had 15% higher risk for dementia (hazard ratio [HR], 1.15; 95% CI, 1.08-1.23; P < .001). 

In addition to an increased risk for dementia, intake of processed red meat was associated with accelerated cognitive aging in global cognition (1.61 years per 1–serving/day increment; 95% CI, 0.20, 3.03) and verbal memory (1.69 years per 1–serving/day increment; 95% CI, 0.13, 3.25; both P = .03).

Participants with processed red meat intake of 0.25 or more serving/day had a 14% higher likelihood of subjective cognitive decline, compared with those with intake less than 0.10 serving/day (odds ratio [OR], 1.14; 95% CI, 1.04-1.24; P = .004). 

For unprocessed red meat, consuming 1.00 or more serving/day versus less than 0.50 serving/day was associated with a 16% higher likelihood of subjective cognitive decline (OR, 1.16; 95% CI, 1.04-1.30; P = .02). 
 

Substitution Analysis

Researchers modeled the effects of replacing 1 serving/day of processed red meat with 1 serving/day of nuts and legumes on cognitive outcomes. They did this by treating food intakes as continuous variables and calculating the differences in coefficients of the two food items.

They found that substituting legumes and nuts was associated with a 23% lower risk for dementia (HR, 0.77; 95% CI, 0.69-0.86), 1.37 fewer years of cognitive aging (95% CI, –2.49 to –0.25), and 20% lower odds of subjective cognitive decline (OR, 0.80, 95% CI, 0.69-0.92).

The research cannot determine whether it’s the processing method itself or the type of red meat that affects cognition, Ms. Li cautioned. 

“Our study is an epidemiologic study, not a biological mechanism study, but based on our findings, red meat may be related to worse cognition, and processed red meat may add additional risk,” she said. 

She also noted that because the study focused solely on red meats, the study cannot determine the potential on the impact of other processed meats on cognition.

Although the study doesn’t address a possible mechanism linking processed red meat with cognition, Ms. Li said it’s possible such meats have high levels of relatively harmful substances, such as nitrites, N-nitroso compounds, and sodium, and that “these carry the additional risk to brain health.”

There are currently no specific guidelines regarding the “safe” amount of processed meat consumption specifically related to cognition, she said.

The study is important because of its large sample size, long follow-up period, and inclusion of repeated measurements of diet, the investigators noted. In addition, researchers assessed both processed and unprocessed red meat and evaluated multiple cognitive outcomes.

The investigators plan to assess the association between other modifiable factors and cognitive health.
 

Experts Weigh In 

In a comment, Claire Sexton, DPhil, senior director of scientific programs and outreach at the Alzheimer’s Association, agreed past studies on the topic have been “mixed,” with only some studies reporting links between cognition or dementia and processed red meat. 

Another unique aspect of the study, said Dr. Sexton, was the replacement analysis showing the brain benefits of eating nuts and legumes in place of processed red meat. “So, it’s not just suggesting to people what not to do, but also what they can be doing instead.”

That’s why this large study with more than 130,000 adults that tracked individuals for close to 40 years in some cases “is so valuable,” she added.

In a release from the Science Media Centre in the United Kingdom, several other experts commented on the study. Among them, Kevin McConway, PhD, emeritus professor of applied statistics at the Open University, Milton Keynes, England, said that “it’s pretty well impossible to get a clear message from the information that is available so far about this research. It is a conference paper, and all we have seen so far is a press release, a brief summary of the research, and a diagram. There isn’t a detailed, peer-reviewed research report, not yet anyway. Putting out limited information like this isn’t the right way to report science.”

Dr. McConway also noted that the observational study recorded participants’ diets and dementia diagnoses over several years without assigning specific diets. Those who ate more red processed meat had higher rates of dementia and cognitive decline. However, it’s unclear if these differences are caused by red meat consumption or other factors, such as diet, age, ethnicity, or location.

Researchers typically adjust for these factors, but the available information doesn’t specify what adjustments were made or their impact, he noted, and without detailed data, it’s impossible to evaluate the study’s quality. Although eating more red processed meat might increase dementia risk, more research is needed to confirm this, Dr. McConway added. 

Also commenting, Sebastian Walsh, a National Institute for Health and Care Research doctoral fellow who researches population-level approaches to dementia risk reduction at University of Cambridge, Cambridge, England, said that without seeing the full paper, it’s difficult to know exactly what to make of the study’s findings. 

“On the surface, this is a large and long study. But it isn’t clear how the analysis was done — specifically what other factors were taken into account when looking at this apparent relationship between red meat and dementia.

“Despite a lot of research looking at specific foods and different diseases, the basic public health advice that eating a healthy, balanced diet is good for health is essentially unchanged. Most people know and accept this. What is most important is to find ways of supporting people, particularly those from poorer backgrounds, to follow this advice and address the obesity epidemic,” said Mr. Walsh. 

The study was funded by a National Institutes of Health research grant. Ms. Li reports no relevant conflicts of interest. Dr. Sexton, Dr. McConway, and Mr. Walsh report no relevant disclosures.

A version of this article first appeared on Medscape.com.

Plasma phosphorylated (p)-tau217 testing can help identify preclinical Alzheimer’s disease, which could aid clinical trial recruitment.

Recruiting preclinical Alzheimer’s disease participants for clinical research is challenging, owing to a lack of symptoms and the high cost and invasiveness of cerebrospinal fluid (CSF) tests and brain amyloid PET imaging.

Plasma p-tau217 has consistently shown high performance in detecting Alzheimer’s disease pathology in patients with mild cognitive impairment and dementia, but there has been concern that it may have lower accuracy in cognitively unimpaired adults, said lead investigator Gemma Salvadó, PhD, with the Clinical Memory Research Unit, Lund University, Lund, Sweden.

However, “our study shows that plasma p-tau217, alone or in combination with invasive tests, can be used accurately to assess amyloid positivity in cognitively unimpaired participants, to streamline the inclusion of these participants in preventive clinical trials,” she said. 

The findings were presented at the 2024 Alzheimer’s Association International Conference (AAIC).
 

Correlation to CSF, PET Amyloid Status

The investigators assessed the clinical accuracy of plasma p-tau217 as a prescreening method in 2917 cognitively unimpaired adults (mean age, 67 years; 57% women) across 12 independent cohorts who had available plasma p-tau217 and amyloid beta PET imaging or CSF samples. 

They found that plasma p-tau217 levels correlated with amyloid beta CSF status and PET load. 

As a standalone test, plasma p-tau217 identified amyloid beta PET–positive cognitively normal adults with a positive predictive value of 80% or greater. 

The positive predictive value increased to 95% or greater when amyloid beta CSF or PET was used to confirm a positive plasma p-tau217 result. 

As a first step, plasma p-tau217 could significantly reduce the number of invasive tests performed because only individuals with a positive p-tau217 test would go on to PET imaging or CSF sampling, Dr. Salvadó told conference attendees. This may reduce trial recruitment costs and get more patients enrolled. 

Although the study had a large sample size, “these results should be replicated in independent studies, [in] more heterogeneous participants, and coming from the clinical setting instead of observational studies to avoid possible bias,” Dr. Salvadó added. 
 

A New Diagnostic Era 

Commenting on the research, Heather Snyder, PhD, vice president of medical and scientific relations at the Alzheimer’s Association, said what’s particularly interesting about this study is that the researchers examined multiple cohorts of cognitively unimpaired individuals and “consistently” found that plasma p-tau217 could identify individuals with amyloid-positive PET and CSF with high accuracy. 

“This may reduce the need for more expensive and more invasive scans or lumbar punctures to confirm if an individual has the biology,” Dr. Snyder said. 

“Blood tests are revolutionizing Alzheimer’s detection, diagnosis and ultimately treatment,” added Howard Fillit, MD, cofounder and chief science officer of the Alzheimer’s Drug Discovery Foundation. 

He predicted that blood tests will “soon replace more invasive and costly PET scans as the standard of care and serve as the first line of defense in diagnosing the disease.”

“After many years of research, the field is in a place where we have novel biomarkers and diagnostics to support a diagnosis,” the way cholesterol is used to help detect heart disease, said Dr. Fillit. 

“The diagnostic framework for Alzheimer’s — an incredibly complex disease — is constantly evolving. As we usher in the new era of care, we are moving closer to the day when blood tests will be complemented by digital tools to provide precise and timely diagnoses and risk assessments backed by numerous data points, complementing existing cognitive tests,” he added. 

Funding for the study was provided by the Alzheimer’s Association, the European Union’s Horizon 2020 Research and Innovation Program, Alzheimerfonden, and Strategic Research Area MultiPark. Dr. Salvadó, Dr. Snyder, and Dr. Fillit have no relevant disclosures.

A version of this article appeared on Medscape.com.

Plasma phosphorylated (p)-tau217 testing can help identify preclinical Alzheimer’s disease, which could aid clinical trial recruitment.

Recruiting preclinical Alzheimer’s disease participants for clinical research is challenging, owing to a lack of symptoms and the high cost and invasiveness of cerebrospinal fluid (CSF) tests and brain amyloid PET imaging.

Plasma p-tau217 has consistently shown high performance in detecting Alzheimer’s disease pathology in patients with mild cognitive impairment and dementia, but there has been concern that it may have lower accuracy in cognitively unimpaired adults, said lead investigator Gemma Salvadó, PhD, with the Clinical Memory Research Unit, Lund University, Lund, Sweden.

However, “our study shows that plasma p-tau217, alone or in combination with invasive tests, can be used accurately to assess amyloid positivity in cognitively unimpaired participants, to streamline the inclusion of these participants in preventive clinical trials,” she said. 

The findings were presented at the 2024 Alzheimer’s Association International Conference (AAIC).
 

Correlation to CSF, PET Amyloid Status

The investigators assessed the clinical accuracy of plasma p-tau217 as a prescreening method in 2917 cognitively unimpaired adults (mean age, 67 years; 57% women) across 12 independent cohorts who had available plasma p-tau217 and amyloid beta PET imaging or CSF samples. 

They found that plasma p-tau217 levels correlated with amyloid beta CSF status and PET load. 

As a standalone test, plasma p-tau217 identified amyloid beta PET–positive cognitively normal adults with a positive predictive value of 80% or greater. 

The positive predictive value increased to 95% or greater when amyloid beta CSF or PET was used to confirm a positive plasma p-tau217 result. 

As a first step, plasma p-tau217 could significantly reduce the number of invasive tests performed because only individuals with a positive p-tau217 test would go on to PET imaging or CSF sampling, Dr. Salvadó told conference attendees. This may reduce trial recruitment costs and get more patients enrolled. 

Although the study had a large sample size, “these results should be replicated in independent studies, [in] more heterogeneous participants, and coming from the clinical setting instead of observational studies to avoid possible bias,” Dr. Salvadó added. 
 

A New Diagnostic Era 

Commenting on the research, Heather Snyder, PhD, vice president of medical and scientific relations at the Alzheimer’s Association, said what’s particularly interesting about this study is that the researchers examined multiple cohorts of cognitively unimpaired individuals and “consistently” found that plasma p-tau217 could identify individuals with amyloid-positive PET and CSF with high accuracy. 

“This may reduce the need for more expensive and more invasive scans or lumbar punctures to confirm if an individual has the biology,” Dr. Snyder said. 

“Blood tests are revolutionizing Alzheimer’s detection, diagnosis and ultimately treatment,” added Howard Fillit, MD, cofounder and chief science officer of the Alzheimer’s Drug Discovery Foundation. 

He predicted that blood tests will “soon replace more invasive and costly PET scans as the standard of care and serve as the first line of defense in diagnosing the disease.”

“After many years of research, the field is in a place where we have novel biomarkers and diagnostics to support a diagnosis,” the way cholesterol is used to help detect heart disease, said Dr. Fillit. 

“The diagnostic framework for Alzheimer’s — an incredibly complex disease — is constantly evolving. As we usher in the new era of care, we are moving closer to the day when blood tests will be complemented by digital tools to provide precise and timely diagnoses and risk assessments backed by numerous data points, complementing existing cognitive tests,” he added. 

Funding for the study was provided by the Alzheimer’s Association, the European Union’s Horizon 2020 Research and Innovation Program, Alzheimerfonden, and Strategic Research Area MultiPark. Dr. Salvadó, Dr. Snyder, and Dr. Fillit have no relevant disclosures.

A version of this article appeared on Medscape.com.

Plasma phosphorylated (p)-tau217 testing can help identify preclinical Alzheimer’s disease, which could aid clinical trial recruitment.

Recruiting preclinical Alzheimer’s disease participants for clinical research is challenging, owing to a lack of symptoms and the high cost and invasiveness of cerebrospinal fluid (CSF) tests and brain amyloid PET imaging.

Plasma p-tau217 has consistently shown high performance in detecting Alzheimer’s disease pathology in patients with mild cognitive impairment and dementia, but there has been concern that it may have lower accuracy in cognitively unimpaired adults, said lead investigator Gemma Salvadó, PhD, with the Clinical Memory Research Unit, Lund University, Lund, Sweden.

However, “our study shows that plasma p-tau217, alone or in combination with invasive tests, can be used accurately to assess amyloid positivity in cognitively unimpaired participants, to streamline the inclusion of these participants in preventive clinical trials,” she said. 

The findings were presented at the 2024 Alzheimer’s Association International Conference (AAIC).
 

Correlation to CSF, PET Amyloid Status

The investigators assessed the clinical accuracy of plasma p-tau217 as a prescreening method in 2917 cognitively unimpaired adults (mean age, 67 years; 57% women) across 12 independent cohorts who had available plasma p-tau217 and amyloid beta PET imaging or CSF samples. 

They found that plasma p-tau217 levels correlated with amyloid beta CSF status and PET load. 

As a standalone test, plasma p-tau217 identified amyloid beta PET–positive cognitively normal adults with a positive predictive value of 80% or greater. 

The positive predictive value increased to 95% or greater when amyloid beta CSF or PET was used to confirm a positive plasma p-tau217 result. 

As a first step, plasma p-tau217 could significantly reduce the number of invasive tests performed because only individuals with a positive p-tau217 test would go on to PET imaging or CSF sampling, Dr. Salvadó told conference attendees. This may reduce trial recruitment costs and get more patients enrolled. 

Although the study had a large sample size, “these results should be replicated in independent studies, [in] more heterogeneous participants, and coming from the clinical setting instead of observational studies to avoid possible bias,” Dr. Salvadó added. 
 

A New Diagnostic Era 

Commenting on the research, Heather Snyder, PhD, vice president of medical and scientific relations at the Alzheimer’s Association, said what’s particularly interesting about this study is that the researchers examined multiple cohorts of cognitively unimpaired individuals and “consistently” found that plasma p-tau217 could identify individuals with amyloid-positive PET and CSF with high accuracy. 

“This may reduce the need for more expensive and more invasive scans or lumbar punctures to confirm if an individual has the biology,” Dr. Snyder said. 

“Blood tests are revolutionizing Alzheimer’s detection, diagnosis and ultimately treatment,” added Howard Fillit, MD, cofounder and chief science officer of the Alzheimer’s Drug Discovery Foundation. 

He predicted that blood tests will “soon replace more invasive and costly PET scans as the standard of care and serve as the first line of defense in diagnosing the disease.”

“After many years of research, the field is in a place where we have novel biomarkers and diagnostics to support a diagnosis,” the way cholesterol is used to help detect heart disease, said Dr. Fillit. 

“The diagnostic framework for Alzheimer’s — an incredibly complex disease — is constantly evolving. As we usher in the new era of care, we are moving closer to the day when blood tests will be complemented by digital tools to provide precise and timely diagnoses and risk assessments backed by numerous data points, complementing existing cognitive tests,” he added. 

Funding for the study was provided by the Alzheimer’s Association, the European Union’s Horizon 2020 Research and Innovation Program, Alzheimerfonden, and Strategic Research Area MultiPark. Dr. Salvadó, Dr. Snyder, and Dr. Fillit have no relevant disclosures.

A version of this article appeared on Medscape.com.

PHILADELPHIA — Amyloid beta (Abeta) and tau protein blood biomarkers are highly accurate in identifying Alzheimer’s disease in patients with cognitive symptoms attending primary and secondary care clinics, new research showed.

Accurate early diagnosis of Alzheimer’s disease is important because two monoclonal antibodies donanemab (Kisunla) and lecanemab (Leqembi) are now approved by the Food and Drug Administration (FDA) for early-stage Alzheimer’s disease. However, the use of these agents requires amyloid confirmation.

A key finding of the study was that primary care physicians had a diagnostic accuracy of 61%, and dementia specialists had an accuracy of 73%, after completing standard clinical evaluations and before seeing results of the blood test or other Alzheimer’s disease biomarkers, while the blood test used in the study had an accuracy of 91% for correctly classifying clinical, biomarker-verified Alzheimer’s disease.

“This underscores the potential improvement in diagnostic accuracy, especially in primary care, when implementing such a blood test,” said study investigator Sebastian Palmqvist, MD, PhD, associate professor of neurology at Lund University, Lund, and a consultant at Skåne University Hospital, Malmö, Sweden. “It also highlights the challenges in accurately identifying Alzheimer’s disease based solely on clinical evaluation and cognitive testing, even for specialists.”

The findings were presented at the 2024 Alzheimer’s Association International Conference (AAIC) and simultaneously published online in JAMA.

The study included two cohorts from primary and secondary care clinics in Sweden. Researchers analyzed plasma samples together at one time point in a single batch.

It also included two cohorts from Swedish primary and secondary care clinics where the plasma samples were analyzed prospectively (biweekly) in batches throughout the enrollment period, which more closely resembles clinical practice.

Primary care physicians and dementia specialists documented whether they believed their patients had Alzheimer’s disease pathology, basing the diagnoses on the standard evaluation that includes clinical examination, cognitive testing, and a CT scan prior to seeing any Alzheimer’s disease biomarker results.

They reported their certainty of the presence of Alzheimer’s disease pathology on a scale from 0 (not at all certain) to 10 (completely certain).

Plasma analyses were performed by personnel blinded to all clinical or biomarker data. Mass spectrometry assays were used to analyze Abeta42, Abeta40, phosphorylated tau 217 (p-tau217), and non–p-tau217.

Biomarkers used in the study included the percentage of plasma p-tau217, which is the ratio of p-tau217 relative to non–p-tau217, and the Abeta42 to Abeta40 ratio (the amyloid probability score 2 [APS2]). Researchers determined p-tau217 alone and when combined with the APS2.

The study included 1213 patients with cognitive symptoms — mean age 74.2 years and 48% women. Researchers applied biomarker cutoff values to the primary care cohort (n = 307) and the secondary care cohort (n = 300) and then evaluated the blood test prospectively in the primary care cohort (n = 208) and the secondary care cohort (n = 398).

The blood biomarker cutoff value was set at 90% specificity for Alzheimer’s disease pathology (the 1 cutoff-value approach). A 2 cutoff-value approach (using 1 upper and 1 lower cutoff value) was also used with values corresponding to 95% sensitivity and 95% specificity.

The primary outcome was presence of Alzheimer’s disease pathology. A positive finding of the Abeta biomarker was defined according to the FDA-approved cutoff value (≤ 0.072). A positive finding of the tau biomarker was defined as a p-tau217 level > 11.42 pg/mL in cerebrospinal fluid.

Researchers calculated the positive predictive value (PPV), negative predictive value (NPV), and diagnostic accuracy, as well as area under the curve (AUC) values.
 

Accuracy in Specialty Versus Primary Care

When the plasma samples were analyzed in a single batch in the primary care cohort, the AUC was 0.97 when the APS2 was used. In the secondary care cohort, the AUC was 0.96 when the APS2 was used.

When plasma samples were analyzed prospectively (biweekly) in the primary care cohort, the AUC was 0.96 when the APS2 was used. In the secondary care cohort, the AUC was 0.97 when the APS2 was used.

The 2 cutoff-value approach achieved PPVs of 97%-99% in patients with cognitive impairment, which is the target population of currently available antiamyloid treatments.

Although NPVs were slightly lower in these patients (87%-92% using the APS2), “we argue that a very high positive predictive value is probably more important in diagnosing patients as having Alzheimer’s disease, especially before initiating costly and burdensome antiamyloid treatment,” the investigators noted.

The PPVs were less than optimal for accurate identification of Alzheimer’s disease pathology in patients with subjective cognitive decline regardless of the cutoff-value approach used. The researchers pointed out that this could be a disadvantage for clinical trials that include patients with presymptomatic Alzheimer’s disease but not in clinical practice because there are no clinical criteria for diagnosing Alzheimer’s disease at the subjective cognitive decline stage.

The NPVs were higher in patients with subjective cognitive decline (91%-94% for the APS2 or percentage of p-tau217 alone). This indicates the blood test would be more useful for ruling out underlying Alzheimer’s disease when only subtle symptoms are present, the researchers noted.

As for doctors identifying clinical Alzheimer’s disease, primary care physicians had a diagnostic accuracy of 61% (95% CI, 53%-69%) versus 91% (95% CI, 86%-96%) using the APS2. Dementia specialists had a diagnostic accuracy of 73% (95% CI, 68%-79%) versus 91% (95% CI, 86%-95%) using the APS2.

In the overall population, the diagnostic accuracy using the APS2 (90%; 95% CI, 88%-92%) was not different from that using the percentage of p-tau217 alone (90%; 95% CI, 88%-91%).

Very little was known about how a blood test would perform in a primary care setting, said Dr. Palmqvist. “Seeing that the test was just as accurate in primary care (about 90%) as it was in secondary care is really encouraging, especially since primary care is the first, and often final, point of entry into the healthcare system for cognitive evaluations.”

He said he was surprised the biomarkers performed so well in prospective, biweekly analyses throughout the study. “Previous studies have only demonstrated their effectiveness when all collected samples are analyzed at a single time point, which does not reflect how a blood test is used in clinical practice.”

He added that he was surprised that the tests were just as accurate in primary care as in a memory clinic setting with referred patients. This, despite older age and higher prevalence of comorbidities in primary care, such as chronic kidney disease (present in 26% of the primary care cohort), can be a confounding factor causing increased concentrations of p-tau217.
 

Next Steps

The diagnostic accuracy of the blood tests is on par with FDA-cleared cerebrospinal fluid biomarkers, noted the investigators, led by senior author Oskar Hansson, MD, PhD, Clinical Memory Research Unit, Department of Clinical Sciences Malmö, Faculty of Medicine, Lund University, Lund, Sweden.

As blood tests are “more time effective, cost effective, and convenient” for patients, “they could also potentially replace cerebrospinal fluid tests and PET,” they added.

Dr. Palmqvist emphasized that these tests should not be used as stand-alone diagnostic tools for Alzheimer’s disease but should complement the standard clinical evaluation that includes cognitive testing and a thorough interview with the patient and a spouse or relative.

“This is crucial because Alzheimer’s disease pathology can be asymptomatic for many years, and cognitive symptoms in some patients with Alzheimer’s disease pathology may primarily result from other conditions. Misinterpreting a positive Alzheimer’s disease blood test could lead to underdiagnosis of common non–Alzheimer’s disease conditions.”

With new antiamyloid treatments possibly slowing disease progression by 30%-40% when initiated early on, a blood test for Alzheimer’s disease could lead to more people receiving an accurate and earlier diagnosis, said Dr. Palmqvist. “This could potentially result in a better response to treatment. Results from drug trials clearly indicate that the earlier treatment begins, the more effectively it can slow disease progression.”

The test used in the study is already available in the United States, the investigators said, and a similar test will be accessible in Sweden within a few months. “However, the rollout will probably be gradual and will depend on how international and national guidelines recommend their use, so developing these guidelines will be a crucial next step for widespread implementation, particularly in primary care,” said Dr. Palmqvist.

He also underlined the importance of replicating the findings in more diverse populations. “This will help ensure the tests’ reliability and effectiveness across various demographic and clinical contexts.”

An important next research step is to examine how implementing a blood test for Alzheimer’s disease affects patient care. “This includes looking at changes in management, such as referrals, other examinations, and the initiation of appropriate treatments,” said Dr. Palmqvist.

Another study presented at the meeting showed that a highly accurate blood test could significantly reduce diagnostic wait times.
 

Convincing Research

In an accompanying editorial, Stephen Salloway, MD, Departments of Psychiatry and Neurology, Warren Alpert Medical School, Brown University, Providence, Rhode Island, and colleagues said the study “makes the case convincingly that highly sensitive blood measures of Alzheimer’s disease can be integrated into the clinical decision-making process, including in the primary care setting.”

These tests, they wrote, “can be used to enhance the ability of clinicians to accurately identify individuals with cognitive impairment and dementia due to Alzheimer’s disease.

“Current practice should focus on using these blood biomarkers in individuals with cognitive impairment rather than in those with normal cognition or subjective cognitive decline until further research demonstrates effective interventions for individuals considered cognitively normal with elevated levels of amyloid.”

A key limitation of the study was the lack of diversity in the study sample. This makes it difficult to generalize the results across other ethnic and racial groups, the editorialists noted. Plasma assays for Alzheimer’s disease in the United States will require approval from the FDA and coverage by the Centers for Medicare & Medicaid Services to be widely adopted.

The editorialists also pointed out that advances in the diagnosis and treatment of Alzheimer’s disease will require important changes to healthcare models, including providing additional resources and staffing.

The study was supported by the Alzheimer’s Association, National Institute on Aging, European Research Council, Swedish Research Council, the GHR Foundation, and other groups. The study was conducted as an academic collaboration between Lund University and C2N Diagnostics in the United States. Lund University or its affiliated researchers received no funding or compensation from C2N Diagnostics. C2N Diagnostics performed the plasma analyses blinded to any biomarker or clinical data and had no role in the statistical analysis or results. Dr. Palmqvist reported receiving institutional research support from ki:elements, Alzheimer’s Drug Discovery Foundation, and Avid Radiopharmaceuticals and consultancy or speaker fees from BioArctic, Biogen, Esai, Eli Lilly, and Roche. Dr. Hansson reported receiving personal fees from AC Immune, ALZpath, BioArctic, Biogen, Cerveau, Eisai, Eli Lilly, Fujirebio, Roche, Bristol-Myers Squibb, Merck, Novartis, Novo Nordisk, Roche, Sanofi, and Siemens and institutional research support from ADX, AVID Radiopharmaceuticals, Biogen, Eli Lilly, Eisai, Fujirebio, GE Healthcare, Pfizer, and Roche. Dr. Salloway reported receiving grants from Biogen, Roche, Lilly, Genentech, Eisai, and Novartis; personal fees from Biogen, Roche, Lilly, Genentech, Eisai, Novo Nordisk, Prothena, AbbVie, Acumen, and Kisbee; and nonfinancial support (travel expenses for conference attendance) from Biogen, Roche, Lilly, and Acumen.

A version of this article appeared on Medscape.com.

PHILADELPHIA — Amyloid beta (Abeta) and tau protein blood biomarkers are highly accurate in identifying Alzheimer’s disease in patients with cognitive symptoms attending primary and secondary care clinics, new research showed.

Accurate early diagnosis of Alzheimer’s disease is important because two monoclonal antibodies donanemab (Kisunla) and lecanemab (Leqembi) are now approved by the Food and Drug Administration (FDA) for early-stage Alzheimer’s disease. However, the use of these agents requires amyloid confirmation.

A key finding of the study was that primary care physicians had a diagnostic accuracy of 61%, and dementia specialists had an accuracy of 73%, after completing standard clinical evaluations and before seeing results of the blood test or other Alzheimer’s disease biomarkers, while the blood test used in the study had an accuracy of 91% for correctly classifying clinical, biomarker-verified Alzheimer’s disease.

“This underscores the potential improvement in diagnostic accuracy, especially in primary care, when implementing such a blood test,” said study investigator Sebastian Palmqvist, MD, PhD, associate professor of neurology at Lund University, Lund, and a consultant at Skåne University Hospital, Malmö, Sweden. “It also highlights the challenges in accurately identifying Alzheimer’s disease based solely on clinical evaluation and cognitive testing, even for specialists.”

The findings were presented at the 2024 Alzheimer’s Association International Conference (AAIC) and simultaneously published online in JAMA.

The study included two cohorts from primary and secondary care clinics in Sweden. Researchers analyzed plasma samples together at one time point in a single batch.

It also included two cohorts from Swedish primary and secondary care clinics where the plasma samples were analyzed prospectively (biweekly) in batches throughout the enrollment period, which more closely resembles clinical practice.

Primary care physicians and dementia specialists documented whether they believed their patients had Alzheimer’s disease pathology, basing the diagnoses on the standard evaluation that includes clinical examination, cognitive testing, and a CT scan prior to seeing any Alzheimer’s disease biomarker results.

They reported their certainty of the presence of Alzheimer’s disease pathology on a scale from 0 (not at all certain) to 10 (completely certain).

Plasma analyses were performed by personnel blinded to all clinical or biomarker data. Mass spectrometry assays were used to analyze Abeta42, Abeta40, phosphorylated tau 217 (p-tau217), and non–p-tau217.

Biomarkers used in the study included the percentage of plasma p-tau217, which is the ratio of p-tau217 relative to non–p-tau217, and the Abeta42 to Abeta40 ratio (the amyloid probability score 2 [APS2]). Researchers determined p-tau217 alone and when combined with the APS2.

The study included 1213 patients with cognitive symptoms — mean age 74.2 years and 48% women. Researchers applied biomarker cutoff values to the primary care cohort (n = 307) and the secondary care cohort (n = 300) and then evaluated the blood test prospectively in the primary care cohort (n = 208) and the secondary care cohort (n = 398).

The blood biomarker cutoff value was set at 90% specificity for Alzheimer’s disease pathology (the 1 cutoff-value approach). A 2 cutoff-value approach (using 1 upper and 1 lower cutoff value) was also used with values corresponding to 95% sensitivity and 95% specificity.

The primary outcome was presence of Alzheimer’s disease pathology. A positive finding of the Abeta biomarker was defined according to the FDA-approved cutoff value (≤ 0.072). A positive finding of the tau biomarker was defined as a p-tau217 level > 11.42 pg/mL in cerebrospinal fluid.

Researchers calculated the positive predictive value (PPV), negative predictive value (NPV), and diagnostic accuracy, as well as area under the curve (AUC) values.
 

Accuracy in Specialty Versus Primary Care

When the plasma samples were analyzed in a single batch in the primary care cohort, the AUC was 0.97 when the APS2 was used. In the secondary care cohort, the AUC was 0.96 when the APS2 was used.

When plasma samples were analyzed prospectively (biweekly) in the primary care cohort, the AUC was 0.96 when the APS2 was used. In the secondary care cohort, the AUC was 0.97 when the APS2 was used.

The 2 cutoff-value approach achieved PPVs of 97%-99% in patients with cognitive impairment, which is the target population of currently available antiamyloid treatments.

Although NPVs were slightly lower in these patients (87%-92% using the APS2), “we argue that a very high positive predictive value is probably more important in diagnosing patients as having Alzheimer’s disease, especially before initiating costly and burdensome antiamyloid treatment,” the investigators noted.

The PPVs were less than optimal for accurate identification of Alzheimer’s disease pathology in patients with subjective cognitive decline regardless of the cutoff-value approach used. The researchers pointed out that this could be a disadvantage for clinical trials that include patients with presymptomatic Alzheimer’s disease but not in clinical practice because there are no clinical criteria for diagnosing Alzheimer’s disease at the subjective cognitive decline stage.

The NPVs were higher in patients with subjective cognitive decline (91%-94% for the APS2 or percentage of p-tau217 alone). This indicates the blood test would be more useful for ruling out underlying Alzheimer’s disease when only subtle symptoms are present, the researchers noted.

As for doctors identifying clinical Alzheimer’s disease, primary care physicians had a diagnostic accuracy of 61% (95% CI, 53%-69%) versus 91% (95% CI, 86%-96%) using the APS2. Dementia specialists had a diagnostic accuracy of 73% (95% CI, 68%-79%) versus 91% (95% CI, 86%-95%) using the APS2.

In the overall population, the diagnostic accuracy using the APS2 (90%; 95% CI, 88%-92%) was not different from that using the percentage of p-tau217 alone (90%; 95% CI, 88%-91%).

Very little was known about how a blood test would perform in a primary care setting, said Dr. Palmqvist. “Seeing that the test was just as accurate in primary care (about 90%) as it was in secondary care is really encouraging, especially since primary care is the first, and often final, point of entry into the healthcare system for cognitive evaluations.”

He said he was surprised the biomarkers performed so well in prospective, biweekly analyses throughout the study. “Previous studies have only demonstrated their effectiveness when all collected samples are analyzed at a single time point, which does not reflect how a blood test is used in clinical practice.”

He added that he was surprised that the tests were just as accurate in primary care as in a memory clinic setting with referred patients. This, despite older age and higher prevalence of comorbidities in primary care, such as chronic kidney disease (present in 26% of the primary care cohort), can be a confounding factor causing increased concentrations of p-tau217.
 

Next Steps

The diagnostic accuracy of the blood tests is on par with FDA-cleared cerebrospinal fluid biomarkers, noted the investigators, led by senior author Oskar Hansson, MD, PhD, Clinical Memory Research Unit, Department of Clinical Sciences Malmö, Faculty of Medicine, Lund University, Lund, Sweden.

As blood tests are “more time effective, cost effective, and convenient” for patients, “they could also potentially replace cerebrospinal fluid tests and PET,” they added.

Dr. Palmqvist emphasized that these tests should not be used as stand-alone diagnostic tools for Alzheimer’s disease but should complement the standard clinical evaluation that includes cognitive testing and a thorough interview with the patient and a spouse or relative.

“This is crucial because Alzheimer’s disease pathology can be asymptomatic for many years, and cognitive symptoms in some patients with Alzheimer’s disease pathology may primarily result from other conditions. Misinterpreting a positive Alzheimer’s disease blood test could lead to underdiagnosis of common non–Alzheimer’s disease conditions.”

With new antiamyloid treatments possibly slowing disease progression by 30%-40% when initiated early on, a blood test for Alzheimer’s disease could lead to more people receiving an accurate and earlier diagnosis, said Dr. Palmqvist. “This could potentially result in a better response to treatment. Results from drug trials clearly indicate that the earlier treatment begins, the more effectively it can slow disease progression.”

The test used in the study is already available in the United States, the investigators said, and a similar test will be accessible in Sweden within a few months. “However, the rollout will probably be gradual and will depend on how international and national guidelines recommend their use, so developing these guidelines will be a crucial next step for widespread implementation, particularly in primary care,” said Dr. Palmqvist.

He also underlined the importance of replicating the findings in more diverse populations. “This will help ensure the tests’ reliability and effectiveness across various demographic and clinical contexts.”

An important next research step is to examine how implementing a blood test for Alzheimer’s disease affects patient care. “This includes looking at changes in management, such as referrals, other examinations, and the initiation of appropriate treatments,” said Dr. Palmqvist.

Another study presented at the meeting showed that a highly accurate blood test could significantly reduce diagnostic wait times.
 

Convincing Research

In an accompanying editorial, Stephen Salloway, MD, Departments of Psychiatry and Neurology, Warren Alpert Medical School, Brown University, Providence, Rhode Island, and colleagues said the study “makes the case convincingly that highly sensitive blood measures of Alzheimer’s disease can be integrated into the clinical decision-making process, including in the primary care setting.”

These tests, they wrote, “can be used to enhance the ability of clinicians to accurately identify individuals with cognitive impairment and dementia due to Alzheimer’s disease.

“Current practice should focus on using these blood biomarkers in individuals with cognitive impairment rather than in those with normal cognition or subjective cognitive decline until further research demonstrates effective interventions for individuals considered cognitively normal with elevated levels of amyloid.”

A key limitation of the study was the lack of diversity in the study sample. This makes it difficult to generalize the results across other ethnic and racial groups, the editorialists noted. Plasma assays for Alzheimer’s disease in the United States will require approval from the FDA and coverage by the Centers for Medicare & Medicaid Services to be widely adopted.

The editorialists also pointed out that advances in the diagnosis and treatment of Alzheimer’s disease will require important changes to healthcare models, including providing additional resources and staffing.

The study was supported by the Alzheimer’s Association, National Institute on Aging, European Research Council, Swedish Research Council, the GHR Foundation, and other groups. The study was conducted as an academic collaboration between Lund University and C2N Diagnostics in the United States. Lund University or its affiliated researchers received no funding or compensation from C2N Diagnostics. C2N Diagnostics performed the plasma analyses blinded to any biomarker or clinical data and had no role in the statistical analysis or results. Dr. Palmqvist reported receiving institutional research support from ki:elements, Alzheimer’s Drug Discovery Foundation, and Avid Radiopharmaceuticals and consultancy or speaker fees from BioArctic, Biogen, Esai, Eli Lilly, and Roche. Dr. Hansson reported receiving personal fees from AC Immune, ALZpath, BioArctic, Biogen, Cerveau, Eisai, Eli Lilly, Fujirebio, Roche, Bristol-Myers Squibb, Merck, Novartis, Novo Nordisk, Roche, Sanofi, and Siemens and institutional research support from ADX, AVID Radiopharmaceuticals, Biogen, Eli Lilly, Eisai, Fujirebio, GE Healthcare, Pfizer, and Roche. Dr. Salloway reported receiving grants from Biogen, Roche, Lilly, Genentech, Eisai, and Novartis; personal fees from Biogen, Roche, Lilly, Genentech, Eisai, Novo Nordisk, Prothena, AbbVie, Acumen, and Kisbee; and nonfinancial support (travel expenses for conference attendance) from Biogen, Roche, Lilly, and Acumen.

A version of this article appeared on Medscape.com.

PHILADELPHIA — Amyloid beta (Abeta) and tau protein blood biomarkers are highly accurate in identifying Alzheimer’s disease in patients with cognitive symptoms attending primary and secondary care clinics, new research showed.

Accurate early diagnosis of Alzheimer’s disease is important because two monoclonal antibodies donanemab (Kisunla) and lecanemab (Leqembi) are now approved by the Food and Drug Administration (FDA) for early-stage Alzheimer’s disease. However, the use of these agents requires amyloid confirmation.

A key finding of the study was that primary care physicians had a diagnostic accuracy of 61%, and dementia specialists had an accuracy of 73%, after completing standard clinical evaluations and before seeing results of the blood test or other Alzheimer’s disease biomarkers, while the blood test used in the study had an accuracy of 91% for correctly classifying clinical, biomarker-verified Alzheimer’s disease.

“This underscores the potential improvement in diagnostic accuracy, especially in primary care, when implementing such a blood test,” said study investigator Sebastian Palmqvist, MD, PhD, associate professor of neurology at Lund University, Lund, and a consultant at Skåne University Hospital, Malmö, Sweden. “It also highlights the challenges in accurately identifying Alzheimer’s disease based solely on clinical evaluation and cognitive testing, even for specialists.”

The findings were presented at the 2024 Alzheimer’s Association International Conference (AAIC) and simultaneously published online in JAMA.

The study included two cohorts from primary and secondary care clinics in Sweden. Researchers analyzed plasma samples together at one time point in a single batch.

It also included two cohorts from Swedish primary and secondary care clinics where the plasma samples were analyzed prospectively (biweekly) in batches throughout the enrollment period, which more closely resembles clinical practice.

Primary care physicians and dementia specialists documented whether they believed their patients had Alzheimer’s disease pathology, basing the diagnoses on the standard evaluation that includes clinical examination, cognitive testing, and a CT scan prior to seeing any Alzheimer’s disease biomarker results.

They reported their certainty of the presence of Alzheimer’s disease pathology on a scale from 0 (not at all certain) to 10 (completely certain).

Plasma analyses were performed by personnel blinded to all clinical or biomarker data. Mass spectrometry assays were used to analyze Abeta42, Abeta40, phosphorylated tau 217 (p-tau217), and non–p-tau217.

Biomarkers used in the study included the percentage of plasma p-tau217, which is the ratio of p-tau217 relative to non–p-tau217, and the Abeta42 to Abeta40 ratio (the amyloid probability score 2 [APS2]). Researchers determined p-tau217 alone and when combined with the APS2.

The study included 1213 patients with cognitive symptoms — mean age 74.2 years and 48% women. Researchers applied biomarker cutoff values to the primary care cohort (n = 307) and the secondary care cohort (n = 300) and then evaluated the blood test prospectively in the primary care cohort (n = 208) and the secondary care cohort (n = 398).

The blood biomarker cutoff value was set at 90% specificity for Alzheimer’s disease pathology (the 1 cutoff-value approach). A 2 cutoff-value approach (using 1 upper and 1 lower cutoff value) was also used with values corresponding to 95% sensitivity and 95% specificity.

The primary outcome was presence of Alzheimer’s disease pathology. A positive finding of the Abeta biomarker was defined according to the FDA-approved cutoff value (≤ 0.072). A positive finding of the tau biomarker was defined as a p-tau217 level > 11.42 pg/mL in cerebrospinal fluid.

Researchers calculated the positive predictive value (PPV), negative predictive value (NPV), and diagnostic accuracy, as well as area under the curve (AUC) values.
 

Accuracy in Specialty Versus Primary Care

When the plasma samples were analyzed in a single batch in the primary care cohort, the AUC was 0.97 when the APS2 was used. In the secondary care cohort, the AUC was 0.96 when the APS2 was used.

When plasma samples were analyzed prospectively (biweekly) in the primary care cohort, the AUC was 0.96 when the APS2 was used. In the secondary care cohort, the AUC was 0.97 when the APS2 was used.

The 2 cutoff-value approach achieved PPVs of 97%-99% in patients with cognitive impairment, which is the target population of currently available antiamyloid treatments.

Although NPVs were slightly lower in these patients (87%-92% using the APS2), “we argue that a very high positive predictive value is probably more important in diagnosing patients as having Alzheimer’s disease, especially before initiating costly and burdensome antiamyloid treatment,” the investigators noted.

The PPVs were less than optimal for accurate identification of Alzheimer’s disease pathology in patients with subjective cognitive decline regardless of the cutoff-value approach used. The researchers pointed out that this could be a disadvantage for clinical trials that include patients with presymptomatic Alzheimer’s disease but not in clinical practice because there are no clinical criteria for diagnosing Alzheimer’s disease at the subjective cognitive decline stage.

The NPVs were higher in patients with subjective cognitive decline (91%-94% for the APS2 or percentage of p-tau217 alone). This indicates the blood test would be more useful for ruling out underlying Alzheimer’s disease when only subtle symptoms are present, the researchers noted.

As for doctors identifying clinical Alzheimer’s disease, primary care physicians had a diagnostic accuracy of 61% (95% CI, 53%-69%) versus 91% (95% CI, 86%-96%) using the APS2. Dementia specialists had a diagnostic accuracy of 73% (95% CI, 68%-79%) versus 91% (95% CI, 86%-95%) using the APS2.

In the overall population, the diagnostic accuracy using the APS2 (90%; 95% CI, 88%-92%) was not different from that using the percentage of p-tau217 alone (90%; 95% CI, 88%-91%).

Very little was known about how a blood test would perform in a primary care setting, said Dr. Palmqvist. “Seeing that the test was just as accurate in primary care (about 90%) as it was in secondary care is really encouraging, especially since primary care is the first, and often final, point of entry into the healthcare system for cognitive evaluations.”

He said he was surprised the biomarkers performed so well in prospective, biweekly analyses throughout the study. “Previous studies have only demonstrated their effectiveness when all collected samples are analyzed at a single time point, which does not reflect how a blood test is used in clinical practice.”

He added that he was surprised that the tests were just as accurate in primary care as in a memory clinic setting with referred patients. This, despite older age and higher prevalence of comorbidities in primary care, such as chronic kidney disease (present in 26% of the primary care cohort), can be a confounding factor causing increased concentrations of p-tau217.
 

Next Steps

The diagnostic accuracy of the blood tests is on par with FDA-cleared cerebrospinal fluid biomarkers, noted the investigators, led by senior author Oskar Hansson, MD, PhD, Clinical Memory Research Unit, Department of Clinical Sciences Malmö, Faculty of Medicine, Lund University, Lund, Sweden.

As blood tests are “more time effective, cost effective, and convenient” for patients, “they could also potentially replace cerebrospinal fluid tests and PET,” they added.

Dr. Palmqvist emphasized that these tests should not be used as stand-alone diagnostic tools for Alzheimer’s disease but should complement the standard clinical evaluation that includes cognitive testing and a thorough interview with the patient and a spouse or relative.

“This is crucial because Alzheimer’s disease pathology can be asymptomatic for many years, and cognitive symptoms in some patients with Alzheimer’s disease pathology may primarily result from other conditions. Misinterpreting a positive Alzheimer’s disease blood test could lead to underdiagnosis of common non–Alzheimer’s disease conditions.”

With new antiamyloid treatments possibly slowing disease progression by 30%-40% when initiated early on, a blood test for Alzheimer’s disease could lead to more people receiving an accurate and earlier diagnosis, said Dr. Palmqvist. “This could potentially result in a better response to treatment. Results from drug trials clearly indicate that the earlier treatment begins, the more effectively it can slow disease progression.”

The test used in the study is already available in the United States, the investigators said, and a similar test will be accessible in Sweden within a few months. “However, the rollout will probably be gradual and will depend on how international and national guidelines recommend their use, so developing these guidelines will be a crucial next step for widespread implementation, particularly in primary care,” said Dr. Palmqvist.

He also underlined the importance of replicating the findings in more diverse populations. “This will help ensure the tests’ reliability and effectiveness across various demographic and clinical contexts.”

An important next research step is to examine how implementing a blood test for Alzheimer’s disease affects patient care. “This includes looking at changes in management, such as referrals, other examinations, and the initiation of appropriate treatments,” said Dr. Palmqvist.

Another study presented at the meeting showed that a highly accurate blood test could significantly reduce diagnostic wait times.
 

Convincing Research

In an accompanying editorial, Stephen Salloway, MD, Departments of Psychiatry and Neurology, Warren Alpert Medical School, Brown University, Providence, Rhode Island, and colleagues said the study “makes the case convincingly that highly sensitive blood measures of Alzheimer’s disease can be integrated into the clinical decision-making process, including in the primary care setting.”

These tests, they wrote, “can be used to enhance the ability of clinicians to accurately identify individuals with cognitive impairment and dementia due to Alzheimer’s disease.

“Current practice should focus on using these blood biomarkers in individuals with cognitive impairment rather than in those with normal cognition or subjective cognitive decline until further research demonstrates effective interventions for individuals considered cognitively normal with elevated levels of amyloid.”

A key limitation of the study was the lack of diversity in the study sample. This makes it difficult to generalize the results across other ethnic and racial groups, the editorialists noted. Plasma assays for Alzheimer’s disease in the United States will require approval from the FDA and coverage by the Centers for Medicare & Medicaid Services to be widely adopted.

The editorialists also pointed out that advances in the diagnosis and treatment of Alzheimer’s disease will require important changes to healthcare models, including providing additional resources and staffing.

The study was supported by the Alzheimer’s Association, National Institute on Aging, European Research Council, Swedish Research Council, the GHR Foundation, and other groups. The study was conducted as an academic collaboration between Lund University and C2N Diagnostics in the United States. Lund University or its affiliated researchers received no funding or compensation from C2N Diagnostics. C2N Diagnostics performed the plasma analyses blinded to any biomarker or clinical data and had no role in the statistical analysis or results. Dr. Palmqvist reported receiving institutional research support from ki:elements, Alzheimer’s Drug Discovery Foundation, and Avid Radiopharmaceuticals and consultancy or speaker fees from BioArctic, Biogen, Esai, Eli Lilly, and Roche. Dr. Hansson reported receiving personal fees from AC Immune, ALZpath, BioArctic, Biogen, Cerveau, Eisai, Eli Lilly, Fujirebio, Roche, Bristol-Myers Squibb, Merck, Novartis, Novo Nordisk, Roche, Sanofi, and Siemens and institutional research support from ADX, AVID Radiopharmaceuticals, Biogen, Eli Lilly, Eisai, Fujirebio, GE Healthcare, Pfizer, and Roche. Dr. Salloway reported receiving grants from Biogen, Roche, Lilly, Genentech, Eisai, and Novartis; personal fees from Biogen, Roche, Lilly, Genentech, Eisai, Novo Nordisk, Prothena, AbbVie, Acumen, and Kisbee; and nonfinancial support (travel expenses for conference attendance) from Biogen, Roche, Lilly, and Acumen.

A version of this article appeared on Medscape.com.

As disease-modifying treatments for Alzheimer’s disease (AD) become available, equipping primary care physicians with a highly accurate blood test could significantly reduce diagnostic wait times. Currently, the patient diagnostic journey is often prolonged owing to the limited number of AD specialists, causing concern among healthcare providers and patients alike. Now, a new study suggests that use of high-performing blood tests in primary care could identify potential patients with AD much earlier, possibly reducing wait times for specialist care and receipt of treatment.

“We need to triage in primary care and send preferentially the ones that actually could be eligible for treatment, and not those who are just worried because their grandmother reported that she has Alzheimer’s,” lead researcher Soeren Mattke, MD, DSc, told this news organization.

“By combining a brief cognitive test with an accurate blood test of Alzheimer’s pathology in primary care, we can reduce unnecessary referrals, and shorten appointment wait times,” said Dr. Mattke, director of the Brain Health Observatory at the University of Southern California in Los Angeles.

The findings were presented at the Alzheimer’s Association International Conference (AAIC) 2024.
 

Projected Wait Times 100 Months by 2033

The investigators used a Markov model to estimate wait times for patients eligible for AD treatment, taking into account constrained capacity for specialist visits.

The model included the projected US population of people aged 55 years or older from 2023 to 2032. It assumed that individuals would undergo a brief cognitive assessment in primary care and, if suggestive of early-stage cognitive impairment, be referred to a AD specialist under three scenarios: no blood test, blood test to rule out AD pathology, and blood test to confirm AD pathology.

According to the model, without an accurate blood test for AD pathology, projected wait times to see a specialist are about 12 months in 2024 and will increase to more than 100 months in 2033, largely owing to a lack of specialist appointments.

In contrast, with the availability of an accurate blood test to rule out AD, average wait times would be just 3 months in 2024 and increase to only about 13 months in 2033, because far fewer patients would need to see a specialist.

Availability of a blood test to rule in AD pathology in primary care would have a limited effect on wait times because 50% of patients would still undergo confirmatory testing based on expert assumptions, the model suggests.
 

Prioritizing Resources 

“Millions of people have mild memory complaints, and if they all start coming to neurologists, it could completely flood the system and create long wait times for everybody,” Dr. Mattke told this news organization.

The problem, he said, is that brief cognitive tests performed in primary care are not particularly specific for mild cognitive impairment.

“They work pretty well for manifest advanced dementia but for mild cognitive impairment, which is a very subtle, symptomatic disease, they are only about 75% accurate. One quarter are false-positives. That’s a lot of people,” Dr. Mattke said.

He also noted that although earlier blood tests were about 75% accurate, they are now about 90% accurate, “so we are getting to a level where we can pretty much say with confidence that this is likely Alzheimer’s,” Dr. Mattke said.

Commenting on this research for this news organization, Heather Snyder, PhD, vice president of medical and scientific relations at the Alzheimer’s Association, said it is clear that blood tests, “once confirmed, could have a significant impact on the wait times” for dementia assessment. 

“After an initial blood test, we might be able to rule out or rule in individuals who should go to a specialist for further follow-up and testing. This allows us to really ensure that we’re prioritizing resources accordingly,” said Dr. Snyder, who was not involved in the study. 

This project was supported by a research contract from C2N Diagnostics LLC to USC. Dr. Mattke serves on the board of directors of Senscio Systems Inc. and the scientific advisory board of ALZPath and Boston Millennia Partners and has received consulting fees from Biogen, C2N, Eisai, Eli Lilly, Novartis, and Roche/Genentech. Dr. Snyder has no relevant disclosures.

A version of this article first appeared on Medscape.com.

As disease-modifying treatments for Alzheimer’s disease (AD) become available, equipping primary care physicians with a highly accurate blood test could significantly reduce diagnostic wait times. Currently, the patient diagnostic journey is often prolonged owing to the limited number of AD specialists, causing concern among healthcare providers and patients alike. Now, a new study suggests that use of high-performing blood tests in primary care could identify potential patients with AD much earlier, possibly reducing wait times for specialist care and receipt of treatment.

“We need to triage in primary care and send preferentially the ones that actually could be eligible for treatment, and not those who are just worried because their grandmother reported that she has Alzheimer’s,” lead researcher Soeren Mattke, MD, DSc, told this news organization.

“By combining a brief cognitive test with an accurate blood test of Alzheimer’s pathology in primary care, we can reduce unnecessary referrals, and shorten appointment wait times,” said Dr. Mattke, director of the Brain Health Observatory at the University of Southern California in Los Angeles.

The findings were presented at the Alzheimer’s Association International Conference (AAIC) 2024.
 

Projected Wait Times 100 Months by 2033

The investigators used a Markov model to estimate wait times for patients eligible for AD treatment, taking into account constrained capacity for specialist visits.

The model included the projected US population of people aged 55 years or older from 2023 to 2032. It assumed that individuals would undergo a brief cognitive assessment in primary care and, if suggestive of early-stage cognitive impairment, be referred to a AD specialist under three scenarios: no blood test, blood test to rule out AD pathology, and blood test to confirm AD pathology.

According to the model, without an accurate blood test for AD pathology, projected wait times to see a specialist are about 12 months in 2024 and will increase to more than 100 months in 2033, largely owing to a lack of specialist appointments.

In contrast, with the availability of an accurate blood test to rule out AD, average wait times would be just 3 months in 2024 and increase to only about 13 months in 2033, because far fewer patients would need to see a specialist.

Availability of a blood test to rule in AD pathology in primary care would have a limited effect on wait times because 50% of patients would still undergo confirmatory testing based on expert assumptions, the model suggests.
 

Prioritizing Resources 

“Millions of people have mild memory complaints, and if they all start coming to neurologists, it could completely flood the system and create long wait times for everybody,” Dr. Mattke told this news organization.

The problem, he said, is that brief cognitive tests performed in primary care are not particularly specific for mild cognitive impairment.

“They work pretty well for manifest advanced dementia but for mild cognitive impairment, which is a very subtle, symptomatic disease, they are only about 75% accurate. One quarter are false-positives. That’s a lot of people,” Dr. Mattke said.

He also noted that although earlier blood tests were about 75% accurate, they are now about 90% accurate, “so we are getting to a level where we can pretty much say with confidence that this is likely Alzheimer’s,” Dr. Mattke said.

Commenting on this research for this news organization, Heather Snyder, PhD, vice president of medical and scientific relations at the Alzheimer’s Association, said it is clear that blood tests, “once confirmed, could have a significant impact on the wait times” for dementia assessment. 

“After an initial blood test, we might be able to rule out or rule in individuals who should go to a specialist for further follow-up and testing. This allows us to really ensure that we’re prioritizing resources accordingly,” said Dr. Snyder, who was not involved in the study. 

This project was supported by a research contract from C2N Diagnostics LLC to USC. Dr. Mattke serves on the board of directors of Senscio Systems Inc. and the scientific advisory board of ALZPath and Boston Millennia Partners and has received consulting fees from Biogen, C2N, Eisai, Eli Lilly, Novartis, and Roche/Genentech. Dr. Snyder has no relevant disclosures.

A version of this article first appeared on Medscape.com.

As disease-modifying treatments for Alzheimer’s disease (AD) become available, equipping primary care physicians with a highly accurate blood test could significantly reduce diagnostic wait times. Currently, the patient diagnostic journey is often prolonged owing to the limited number of AD specialists, causing concern among healthcare providers and patients alike. Now, a new study suggests that use of high-performing blood tests in primary care could identify potential patients with AD much earlier, possibly reducing wait times for specialist care and receipt of treatment.

“We need to triage in primary care and send preferentially the ones that actually could be eligible for treatment, and not those who are just worried because their grandmother reported that she has Alzheimer’s,” lead researcher Soeren Mattke, MD, DSc, told this news organization.

“By combining a brief cognitive test with an accurate blood test of Alzheimer’s pathology in primary care, we can reduce unnecessary referrals, and shorten appointment wait times,” said Dr. Mattke, director of the Brain Health Observatory at the University of Southern California in Los Angeles.

The findings were presented at the Alzheimer’s Association International Conference (AAIC) 2024.
 

Projected Wait Times 100 Months by 2033

The investigators used a Markov model to estimate wait times for patients eligible for AD treatment, taking into account constrained capacity for specialist visits.

The model included the projected US population of people aged 55 years or older from 2023 to 2032. It assumed that individuals would undergo a brief cognitive assessment in primary care and, if suggestive of early-stage cognitive impairment, be referred to a AD specialist under three scenarios: no blood test, blood test to rule out AD pathology, and blood test to confirm AD pathology.

According to the model, without an accurate blood test for AD pathology, projected wait times to see a specialist are about 12 months in 2024 and will increase to more than 100 months in 2033, largely owing to a lack of specialist appointments.

In contrast, with the availability of an accurate blood test to rule out AD, average wait times would be just 3 months in 2024 and increase to only about 13 months in 2033, because far fewer patients would need to see a specialist.

Availability of a blood test to rule in AD pathology in primary care would have a limited effect on wait times because 50% of patients would still undergo confirmatory testing based on expert assumptions, the model suggests.
 

Prioritizing Resources 

“Millions of people have mild memory complaints, and if they all start coming to neurologists, it could completely flood the system and create long wait times for everybody,” Dr. Mattke told this news organization.

The problem, he said, is that brief cognitive tests performed in primary care are not particularly specific for mild cognitive impairment.

“They work pretty well for manifest advanced dementia but for mild cognitive impairment, which is a very subtle, symptomatic disease, they are only about 75% accurate. One quarter are false-positives. That’s a lot of people,” Dr. Mattke said.

He also noted that although earlier blood tests were about 75% accurate, they are now about 90% accurate, “so we are getting to a level where we can pretty much say with confidence that this is likely Alzheimer’s,” Dr. Mattke said.

Commenting on this research for this news organization, Heather Snyder, PhD, vice president of medical and scientific relations at the Alzheimer’s Association, said it is clear that blood tests, “once confirmed, could have a significant impact on the wait times” for dementia assessment. 

“After an initial blood test, we might be able to rule out or rule in individuals who should go to a specialist for further follow-up and testing. This allows us to really ensure that we’re prioritizing resources accordingly,” said Dr. Snyder, who was not involved in the study. 

This project was supported by a research contract from C2N Diagnostics LLC to USC. Dr. Mattke serves on the board of directors of Senscio Systems Inc. and the scientific advisory board of ALZPath and Boston Millennia Partners and has received consulting fees from Biogen, C2N, Eisai, Eli Lilly, Novartis, and Roche/Genentech. Dr. Snyder has no relevant disclosures.

A version of this article first appeared on Medscape.com.

This transcript has been edited for clarity.

Tardive dyskinesia is a chronic, potentially irreversible, hyperkinetic movement disorder. And the challenge with tardive dyskinesia is that it’s underdiagnosed and undertreated. With the expanded use of dopamine receptor–blocking agents, there are about 7.5 million Americans who are now exposed and at risk for tardive dyskinesia.

It’s thought that about 500,000-750,000 of these patients may in fact have tardive dyskinesia, but only 15% are treated. So why are people not being treated for tardive dyskinesia? Well, there are a number of possible answers.

Until a few years ago, there were no Food and Drug Administration (FDA)–approved treatments for tardive dyskinesia, and these antipsychotic medications that the patients were taking, in many cases, were potentially lifesaving drugs, so they couldn’t simply be stopped. As a result of that, I think physicians developed a certain psychic blindness to identifying tardive dyskinesia, because it was their drugs that were causing the disease and yet they couldn’t be stopped. So, there really wasn’t much they could do in terms of making the diagnosis.

In addition, they were trained that tardive dyskinesia doesn’t have much impact on patients. But we now know, through surveys and other studies, that tardive dyskinesia can have a tremendous impact on patients and on your ability to treat the patient’s underlying mental health issues. It’s estimated that 50% of patients with tardive dyskinesia actually reduce the amount of antipsychotic medication they’re taking on their own, and about 40% may in fact stop their antipsychotic medication altogether.

Thirty-five percent of patients stopped seeing their doctor after they developed tardive dyskinesia, and about 20% of patients actually told other patients not to take their antipsychotic medication. So, tardive dyskinesia is impacting your ability to treat patients. In addition, it impacts the patients themselves. Nearly three out of four patients with tardive dyskinesia said, in surveys, that it caused severe impact on their psychosocial functioning.

It also impacted caregivers, with 70% of caregivers saying that the patients with tardive dyskinesia made them more anxious and limited them socially. So, we have this tremendous impact from tardive dyskinesia.

In addition, physicians sometimes don’t identify tardive dyskinesia correctly. They mistake it for another movement disorder: drug-induced parkinsonism. Or it falls under the rubric of extrapyramidal symptoms (EPS), and they were trained that you treat EPS with benztropine. The challenge with that is that benztropine is only indicated for acute dystonia or for drug-induced parkinsonism. It actually makes tardive dyskinesia worse. And, in the product insert for benztropine, it’s recommended that it should not be used in tardive dyskinesia. So if you have a patient whom you suspect has tardive dyskinesia, you have to discontinue the benztropine. That’s a really important first step.

And then, what else should you do? There are now two FDA-approved treatments for tardive dyskinesia. These are valbenazine and deutetrabenazine. Both of these drugs have been demonstrated in large double-blind, placebo-controlled studies to reduce tardive dyskinesia, as measured by the Abnormal Involuntary Movement Scale, by about 30%. These drugs have been demonstrated to be safe and well tolerated, with the main side effect being somnolence.

Some people can also develop parkinsonism. Why could there be Parkinsonism? This is because vesicular monoamine transporter 2 (VMAT2) inhibitors work by reducing the amount of dopamine that can be packaged in the presynaptic neuron. That means that less dopamine is available to the synapse, and this reduces movement. The American Psychiatric Association has issued guidelines for the treatment of tardive dyskinesia and has said that moderate to severe tardive dyskinesia should be treated first-line with VMAT2 inhibitors and that mild tardive dyskinesia should also be treated with VMAT2 inhibitors if the tardive dyskinesia is impacting the patient.

Given the impact that tardive dyskinesia has on patients and caregivers, and the physician’s ability to treat these patients’ mental health issues, we need to become aggressive and treat the tardive dyskinesia so that patients can improve and be able to have their movements treated without impacting their underlying mental health issues.

Daniel Kremens, professor, Department of Neurology, Sidney Kimmel Medical College, Thomas Jefferson University, codirector, Parkinson’s Disease and Movement Disorders Division, Jack and Vickie Farber Center for Neuroscience, Thomas Jefferson University Hospital, Philadelphia, Pennsylvania, has disclosed relevant financial relationships with Teva Pharmaceuticals, AbbVie, Merz, Allergan, Bial, Cerevel, Amneal, Acadia, Supernus, Adamas, Acorda, Kyowa Kirin, and Neurocrine.

A version of this article first appeared on Medscape.com.

This transcript has been edited for clarity.

Tardive dyskinesia is a chronic, potentially irreversible, hyperkinetic movement disorder. And the challenge with tardive dyskinesia is that it’s underdiagnosed and undertreated. With the expanded use of dopamine receptor–blocking agents, there are about 7.5 million Americans who are now exposed and at risk for tardive dyskinesia.

It’s thought that about 500,000-750,000 of these patients may in fact have tardive dyskinesia, but only 15% are treated. So why are people not being treated for tardive dyskinesia? Well, there are a number of possible answers.

Until a few years ago, there were no Food and Drug Administration (FDA)–approved treatments for tardive dyskinesia, and these antipsychotic medications that the patients were taking, in many cases, were potentially lifesaving drugs, so they couldn’t simply be stopped. As a result of that, I think physicians developed a certain psychic blindness to identifying tardive dyskinesia, because it was their drugs that were causing the disease and yet they couldn’t be stopped. So, there really wasn’t much they could do in terms of making the diagnosis.

In addition, they were trained that tardive dyskinesia doesn’t have much impact on patients. But we now know, through surveys and other studies, that tardive dyskinesia can have a tremendous impact on patients and on your ability to treat the patient’s underlying mental health issues. It’s estimated that 50% of patients with tardive dyskinesia actually reduce the amount of antipsychotic medication they’re taking on their own, and about 40% may in fact stop their antipsychotic medication altogether.

Thirty-five percent of patients stopped seeing their doctor after they developed tardive dyskinesia, and about 20% of patients actually told other patients not to take their antipsychotic medication. So, tardive dyskinesia is impacting your ability to treat patients. In addition, it impacts the patients themselves. Nearly three out of four patients with tardive dyskinesia said, in surveys, that it caused severe impact on their psychosocial functioning.

It also impacted caregivers, with 70% of caregivers saying that the patients with tardive dyskinesia made them more anxious and limited them socially. So, we have this tremendous impact from tardive dyskinesia.

In addition, physicians sometimes don’t identify tardive dyskinesia correctly. They mistake it for another movement disorder: drug-induced parkinsonism. Or it falls under the rubric of extrapyramidal symptoms (EPS), and they were trained that you treat EPS with benztropine. The challenge with that is that benztropine is only indicated for acute dystonia or for drug-induced parkinsonism. It actually makes tardive dyskinesia worse. And, in the product insert for benztropine, it’s recommended that it should not be used in tardive dyskinesia. So if you have a patient whom you suspect has tardive dyskinesia, you have to discontinue the benztropine. That’s a really important first step.

And then, what else should you do? There are now two FDA-approved treatments for tardive dyskinesia. These are valbenazine and deutetrabenazine. Both of these drugs have been demonstrated in large double-blind, placebo-controlled studies to reduce tardive dyskinesia, as measured by the Abnormal Involuntary Movement Scale, by about 30%. These drugs have been demonstrated to be safe and well tolerated, with the main side effect being somnolence.

Some people can also develop parkinsonism. Why could there be Parkinsonism? This is because vesicular monoamine transporter 2 (VMAT2) inhibitors work by reducing the amount of dopamine that can be packaged in the presynaptic neuron. That means that less dopamine is available to the synapse, and this reduces movement. The American Psychiatric Association has issued guidelines for the treatment of tardive dyskinesia and has said that moderate to severe tardive dyskinesia should be treated first-line with VMAT2 inhibitors and that mild tardive dyskinesia should also be treated with VMAT2 inhibitors if the tardive dyskinesia is impacting the patient.

Given the impact that tardive dyskinesia has on patients and caregivers, and the physician’s ability to treat these patients’ mental health issues, we need to become aggressive and treat the tardive dyskinesia so that patients can improve and be able to have their movements treated without impacting their underlying mental health issues.

Daniel Kremens, professor, Department of Neurology, Sidney Kimmel Medical College, Thomas Jefferson University, codirector, Parkinson’s Disease and Movement Disorders Division, Jack and Vickie Farber Center for Neuroscience, Thomas Jefferson University Hospital, Philadelphia, Pennsylvania, has disclosed relevant financial relationships with Teva Pharmaceuticals, AbbVie, Merz, Allergan, Bial, Cerevel, Amneal, Acadia, Supernus, Adamas, Acorda, Kyowa Kirin, and Neurocrine.

A version of this article first appeared on Medscape.com.

This transcript has been edited for clarity.

Tardive dyskinesia is a chronic, potentially irreversible, hyperkinetic movement disorder. And the challenge with tardive dyskinesia is that it’s underdiagnosed and undertreated. With the expanded use of dopamine receptor–blocking agents, there are about 7.5 million Americans who are now exposed and at risk for tardive dyskinesia.

It’s thought that about 500,000-750,000 of these patients may in fact have tardive dyskinesia, but only 15% are treated. So why are people not being treated for tardive dyskinesia? Well, there are a number of possible answers.

Until a few years ago, there were no Food and Drug Administration (FDA)–approved treatments for tardive dyskinesia, and these antipsychotic medications that the patients were taking, in many cases, were potentially lifesaving drugs, so they couldn’t simply be stopped. As a result of that, I think physicians developed a certain psychic blindness to identifying tardive dyskinesia, because it was their drugs that were causing the disease and yet they couldn’t be stopped. So, there really wasn’t much they could do in terms of making the diagnosis.

In addition, they were trained that tardive dyskinesia doesn’t have much impact on patients. But we now know, through surveys and other studies, that tardive dyskinesia can have a tremendous impact on patients and on your ability to treat the patient’s underlying mental health issues. It’s estimated that 50% of patients with tardive dyskinesia actually reduce the amount of antipsychotic medication they’re taking on their own, and about 40% may in fact stop their antipsychotic medication altogether.

Thirty-five percent of patients stopped seeing their doctor after they developed tardive dyskinesia, and about 20% of patients actually told other patients not to take their antipsychotic medication. So, tardive dyskinesia is impacting your ability to treat patients. In addition, it impacts the patients themselves. Nearly three out of four patients with tardive dyskinesia said, in surveys, that it caused severe impact on their psychosocial functioning.

It also impacted caregivers, with 70% of caregivers saying that the patients with tardive dyskinesia made them more anxious and limited them socially. So, we have this tremendous impact from tardive dyskinesia.

In addition, physicians sometimes don’t identify tardive dyskinesia correctly. They mistake it for another movement disorder: drug-induced parkinsonism. Or it falls under the rubric of extrapyramidal symptoms (EPS), and they were trained that you treat EPS with benztropine. The challenge with that is that benztropine is only indicated for acute dystonia or for drug-induced parkinsonism. It actually makes tardive dyskinesia worse. And, in the product insert for benztropine, it’s recommended that it should not be used in tardive dyskinesia. So if you have a patient whom you suspect has tardive dyskinesia, you have to discontinue the benztropine. That’s a really important first step.

And then, what else should you do? There are now two FDA-approved treatments for tardive dyskinesia. These are valbenazine and deutetrabenazine. Both of these drugs have been demonstrated in large double-blind, placebo-controlled studies to reduce tardive dyskinesia, as measured by the Abnormal Involuntary Movement Scale, by about 30%. These drugs have been demonstrated to be safe and well tolerated, with the main side effect being somnolence.

Some people can also develop parkinsonism. Why could there be Parkinsonism? This is because vesicular monoamine transporter 2 (VMAT2) inhibitors work by reducing the amount of dopamine that can be packaged in the presynaptic neuron. That means that less dopamine is available to the synapse, and this reduces movement. The American Psychiatric Association has issued guidelines for the treatment of tardive dyskinesia and has said that moderate to severe tardive dyskinesia should be treated first-line with VMAT2 inhibitors and that mild tardive dyskinesia should also be treated with VMAT2 inhibitors if the tardive dyskinesia is impacting the patient.

Given the impact that tardive dyskinesia has on patients and caregivers, and the physician’s ability to treat these patients’ mental health issues, we need to become aggressive and treat the tardive dyskinesia so that patients can improve and be able to have their movements treated without impacting their underlying mental health issues.

Daniel Kremens, professor, Department of Neurology, Sidney Kimmel Medical College, Thomas Jefferson University, codirector, Parkinson’s Disease and Movement Disorders Division, Jack and Vickie Farber Center for Neuroscience, Thomas Jefferson University Hospital, Philadelphia, Pennsylvania, has disclosed relevant financial relationships with Teva Pharmaceuticals, AbbVie, Merz, Allergan, Bial, Cerevel, Amneal, Acadia, Supernus, Adamas, Acorda, Kyowa Kirin, and Neurocrine.

A version of this article first appeared on Medscape.com.

Using a large, real-world population, researchers have developed models that predict cognitive decline in amyloid-positive patients with either mild cognitive impairment (MCI) or mild dementia.

The models may help clinicians better answer common questions from their patients about their rate of cognitive decline, noted the investigators, led by Pieter J. van der Veere, MD, Alzheimer Center and Department of Neurology, Amsterdam Neuroscience, VU University Medical Center, Amsterdam, the Netherlands.

The findings were published online in Neurology.
 

Easy-to-Use Prototype

On average, it takes 4 years for MCI to progress to dementia. While new disease-modifying drugs targeting amyloid may slow progression, whether this effect is clinically meaningful is debatable, the investigators noted.

Earlier published models predicting cognitive decline either are limited to patients with MCI or haven’t been developed for easy clinical use, they added.

For the single-center study, researchers selected 961 amyloid-positive patients, mean age 65 years, who had at least two longitudinal Mini-Mental State Examinations (MMSEs). Of these, 310 had MCI, and 651 had mild dementia; 48% were women, and over 90% were White.

Researchers used linear mixed modeling to predict MMSE over time. They included age, sex, baseline MMSE, apolipoprotein E epsilon 4 status, cerebrospinal fluid (CSF) beta-amyloid (Aß) 1-42 and plasma phosphorylated-tau markers, and MRI total brain and hippocampal volume measures in the various models, including the final biomarker prediction models.

At follow-up, investigators found that the yearly decline in MMSEs increased in patients with both MCI and mild dementia. In MCI, the average MMSE declined from 26.4 (95% confidence interval [CI], 26.2-26.7) at baseline to 21.0 (95% CI, 20.2-21.7) after 5 years.

In mild dementia, the average MMSE declined from 22.4 (95% CI, 22.0-22.7) to 7.8 (95% CI, 6.8-8.9) at 5 years.

The predicted mean time to reach an MMSE of 20 (indicating mild dementia) for a hypothetical patient with MCI and a baseline MMSE of 28 and CSF Aß 1-42 of 925 pg/mL was 6 years (95% CI, 5.4-6.7 years).

However, with a hypothetical drug treatment that reduces the rate of decline by 30%, the patient would not reach the stage of moderate dementia for 8.6 years.

For a hypothetical patient with mild dementia with a baseline MMSE of 20 and CSF Aß 1-42 of 625 pg/mL, the predicted mean time to reach an MMSE of 15 was 2.3 years (95% CI, 2.1-2.5), or 3.3 years if decline is reduced by 30% with drug treatment.

External validation of the prediction models using data from the Alzheimer’s Disease Neuroimaging Initiative, a longitudinal cohort of patients not cognitively impaired or with MCI or dementia, showed comparable performance between the model-building approaches.

Researchers have incorporated the models in an easy-to-use calculator as a prototype tool that physicians can use to discuss prognosis, the uncertainty surrounding the predictions, and the impact of intervention strategies with patients.

Future prediction models may be able to predict patient-reported outcomes such as quality of life and daily functioning, the researchers noted.

“Until then, there is an important role for clinicians in translating the observed and predicted cognitive functions,” they wrote.

Compared with other studies predicting the MMSE decline using different statistical techniques, these new models showed similar or even better predictive performance while requiring less or similar information, the investigators noted.

The study used MMSE as a measure of cognition, but there may be intraindividual variation in these measures among cognitively normal patients, and those with cognitive decline may score lower if measurements are taken later in the day. Another study limitation was that the models were built for use in memory clinics, so generalizability to the general population could be limited.

The study was supported by Eisai, ZonMW, and Health~Holland Top Sector Life Sciences & Health. See paper for financial disclosures.

A version of this article first appeared on Medscape.com.

Using a large, real-world population, researchers have developed models that predict cognitive decline in amyloid-positive patients with either mild cognitive impairment (MCI) or mild dementia.

The models may help clinicians better answer common questions from their patients about their rate of cognitive decline, noted the investigators, led by Pieter J. van der Veere, MD, Alzheimer Center and Department of Neurology, Amsterdam Neuroscience, VU University Medical Center, Amsterdam, the Netherlands.

The findings were published online in Neurology.
 

Easy-to-Use Prototype

On average, it takes 4 years for MCI to progress to dementia. While new disease-modifying drugs targeting amyloid may slow progression, whether this effect is clinically meaningful is debatable, the investigators noted.

Earlier published models predicting cognitive decline either are limited to patients with MCI or haven’t been developed for easy clinical use, they added.

For the single-center study, researchers selected 961 amyloid-positive patients, mean age 65 years, who had at least two longitudinal Mini-Mental State Examinations (MMSEs). Of these, 310 had MCI, and 651 had mild dementia; 48% were women, and over 90% were White.

Researchers used linear mixed modeling to predict MMSE over time. They included age, sex, baseline MMSE, apolipoprotein E epsilon 4 status, cerebrospinal fluid (CSF) beta-amyloid (Aß) 1-42 and plasma phosphorylated-tau markers, and MRI total brain and hippocampal volume measures in the various models, including the final biomarker prediction models.

At follow-up, investigators found that the yearly decline in MMSEs increased in patients with both MCI and mild dementia. In MCI, the average MMSE declined from 26.4 (95% confidence interval [CI], 26.2-26.7) at baseline to 21.0 (95% CI, 20.2-21.7) after 5 years.

In mild dementia, the average MMSE declined from 22.4 (95% CI, 22.0-22.7) to 7.8 (95% CI, 6.8-8.9) at 5 years.

The predicted mean time to reach an MMSE of 20 (indicating mild dementia) for a hypothetical patient with MCI and a baseline MMSE of 28 and CSF Aß 1-42 of 925 pg/mL was 6 years (95% CI, 5.4-6.7 years).

However, with a hypothetical drug treatment that reduces the rate of decline by 30%, the patient would not reach the stage of moderate dementia for 8.6 years.

For a hypothetical patient with mild dementia with a baseline MMSE of 20 and CSF Aß 1-42 of 625 pg/mL, the predicted mean time to reach an MMSE of 15 was 2.3 years (95% CI, 2.1-2.5), or 3.3 years if decline is reduced by 30% with drug treatment.

External validation of the prediction models using data from the Alzheimer’s Disease Neuroimaging Initiative, a longitudinal cohort of patients not cognitively impaired or with MCI or dementia, showed comparable performance between the model-building approaches.

Researchers have incorporated the models in an easy-to-use calculator as a prototype tool that physicians can use to discuss prognosis, the uncertainty surrounding the predictions, and the impact of intervention strategies with patients.

Future prediction models may be able to predict patient-reported outcomes such as quality of life and daily functioning, the researchers noted.

“Until then, there is an important role for clinicians in translating the observed and predicted cognitive functions,” they wrote.

Compared with other studies predicting the MMSE decline using different statistical techniques, these new models showed similar or even better predictive performance while requiring less or similar information, the investigators noted.

The study used MMSE as a measure of cognition, but there may be intraindividual variation in these measures among cognitively normal patients, and those with cognitive decline may score lower if measurements are taken later in the day. Another study limitation was that the models were built for use in memory clinics, so generalizability to the general population could be limited.

The study was supported by Eisai, ZonMW, and Health~Holland Top Sector Life Sciences & Health. See paper for financial disclosures.

A version of this article first appeared on Medscape.com.

Using a large, real-world population, researchers have developed models that predict cognitive decline in amyloid-positive patients with either mild cognitive impairment (MCI) or mild dementia.

The models may help clinicians better answer common questions from their patients about their rate of cognitive decline, noted the investigators, led by Pieter J. van der Veere, MD, Alzheimer Center and Department of Neurology, Amsterdam Neuroscience, VU University Medical Center, Amsterdam, the Netherlands.

The findings were published online in Neurology.
 

Easy-to-Use Prototype

On average, it takes 4 years for MCI to progress to dementia. While new disease-modifying drugs targeting amyloid may slow progression, whether this effect is clinically meaningful is debatable, the investigators noted.

Earlier published models predicting cognitive decline either are limited to patients with MCI or haven’t been developed for easy clinical use, they added.

For the single-center study, researchers selected 961 amyloid-positive patients, mean age 65 years, who had at least two longitudinal Mini-Mental State Examinations (MMSEs). Of these, 310 had MCI, and 651 had mild dementia; 48% were women, and over 90% were White.

Researchers used linear mixed modeling to predict MMSE over time. They included age, sex, baseline MMSE, apolipoprotein E epsilon 4 status, cerebrospinal fluid (CSF) beta-amyloid (Aß) 1-42 and plasma phosphorylated-tau markers, and MRI total brain and hippocampal volume measures in the various models, including the final biomarker prediction models.

At follow-up, investigators found that the yearly decline in MMSEs increased in patients with both MCI and mild dementia. In MCI, the average MMSE declined from 26.4 (95% confidence interval [CI], 26.2-26.7) at baseline to 21.0 (95% CI, 20.2-21.7) after 5 years.

In mild dementia, the average MMSE declined from 22.4 (95% CI, 22.0-22.7) to 7.8 (95% CI, 6.8-8.9) at 5 years.

The predicted mean time to reach an MMSE of 20 (indicating mild dementia) for a hypothetical patient with MCI and a baseline MMSE of 28 and CSF Aß 1-42 of 925 pg/mL was 6 years (95% CI, 5.4-6.7 years).

However, with a hypothetical drug treatment that reduces the rate of decline by 30%, the patient would not reach the stage of moderate dementia for 8.6 years.

For a hypothetical patient with mild dementia with a baseline MMSE of 20 and CSF Aß 1-42 of 625 pg/mL, the predicted mean time to reach an MMSE of 15 was 2.3 years (95% CI, 2.1-2.5), or 3.3 years if decline is reduced by 30% with drug treatment.

External validation of the prediction models using data from the Alzheimer’s Disease Neuroimaging Initiative, a longitudinal cohort of patients not cognitively impaired or with MCI or dementia, showed comparable performance between the model-building approaches.

Researchers have incorporated the models in an easy-to-use calculator as a prototype tool that physicians can use to discuss prognosis, the uncertainty surrounding the predictions, and the impact of intervention strategies with patients.

Future prediction models may be able to predict patient-reported outcomes such as quality of life and daily functioning, the researchers noted.

“Until then, there is an important role for clinicians in translating the observed and predicted cognitive functions,” they wrote.

Compared with other studies predicting the MMSE decline using different statistical techniques, these new models showed similar or even better predictive performance while requiring less or similar information, the investigators noted.

The study used MMSE as a measure of cognition, but there may be intraindividual variation in these measures among cognitively normal patients, and those with cognitive decline may score lower if measurements are taken later in the day. Another study limitation was that the models were built for use in memory clinics, so generalizability to the general population could be limited.

The study was supported by Eisai, ZonMW, and Health~Holland Top Sector Life Sciences & Health. See paper for financial disclosures.

A version of this article first appeared on Medscape.com.