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Hospital programs tackle mental health effects of long COVID
There’s little doubt that long COVID is real. Even as doctors and federal agencies struggle to define the syndrome, hospitals and health care systems are opening long COVID specialty treatment programs. As of July 25, there’s at least one long COVID center in almost every state – 48 out of 50, according to the patient advocacy group Survivor Corps.
Among the biggest challenges will be treating the mental health effects of long COVID. 
Specialized centers will be tackling these problems even as the United States struggles to deal with mental health needs.
One study of COVID patients found more than one-third of them had symptoms of depression, anxiety, or PTSD 3-6 months after their initial infection. Another analysis of 30 previous studies of long COVID patients found roughly one in eight of them had severe depression – and that the risk was similar regardless of whether people were hospitalized for COVID-19.
“Many of these symptoms can emerge months into the course of long COVID illness,” said Jordan Anderson, DO, a neuropsychiatrist who sees patients at the Long COVID-19 Program at Oregon Health & Science University, Portland. Psychological symptoms are often made worse by physical setbacks like extreme fatigue and by challenges of working, caring for children, and keeping up with daily routines, he said.
“This impact is not only severe, but also chronic for many,” he said.
Like dozens of hospitals around the country, Oregon Health & Science opened its center for long COVID as it became clear that more patients would need help for ongoing physical and mental health symptoms. Today, there’s at least one long COVID center – sometimes called post-COVID care centers or clinics – in every state but Kansas and South Dakota, Survivor Corps said.
Many long COVID care centers aim to tackle both physical and mental health symptoms, said Tracy Vannorsdall, PhD, a neuropsychologist with the Johns Hopkins Post-Acute COVID-19 Team program. One goal at Hopkins is to identify patients with psychological issues that might otherwise get overlooked.
A sizable minority of patients at the Johns Hopkins center – up to about 35% – report mental health problems that they didn’t have until after they got COVID-19, Dr. Vannorsdall says. The most common mental health issues providers see are depression, anxiety, and trauma-related distress.
“Routine assessment is key,” Dr. Vannorsdall said. “If patients are not asked about their mental health symptoms, they may not spontaneously report them to their provider due to fear of stigma or simply not appreciating that there are effective treatments available for these issues.”
Fear that doctors won’t take symptoms seriously is common, says Heather Murray MD, a senior instructor in psychiatry at the University of Colorado at Denver, Aurora.
“Many patients worry their physicians, loved ones, and society will not believe them or will minimize their symptoms and suffering,” said Dr. Murray, who treats patients at the UCHealth Post-COVID Clinic.
Diagnostic tests in long COVID patients often don’t have conclusive results, which can lead doctors and patients themselves to question whether symptoms are truly “physical versus psychosomatic,” she said. “It is important that providers believe their patients and treat their symptoms, even when diagnostic tests are unrevealing.”
Growing mental health crisis
Patients often find their way to academic treatment centers after surviving severe COVID-19 infections. But a growing number of long COVID patients show up at these centers after milder cases. These patients were never hospitalized for COVID-19 but still have persistent symptoms like fatigue, thinking problems, and mood disorders.
Among the major challenges is a shortage of mental health care providers to meet the surging need for care since the start of the pandemic. Around the world, anxiety and depression surged 25% during the first year of the pandemic, according to the World Health Organization.
In the United States, 40% of adults report feelings of anxiety and depression, and one in three high school students have feelings of sadness and hopelessness, according to a March 2022 statement from the White House.
Despite this surging need for care, almost half of Americans live in areas with a severe shortage of mental health care providers, according to the Health Resources and Services Administration. As of 2019, the United States had a shortage of about 6,790 mental health providers. Since then, the shortage has worsened; it’s now about 7,500 providers.
“One of the biggest challenges for hospitals and clinics in treating mental health disorders in long COVID is the limited resources and long wait times to get in for evaluations and treatment,” said Nyaz Didehbani, PhD, a neuropsychologist who treats long COVID patients at the COVID Recover program at the University of Texas Southwestern Medical Center, Dallas.
These delays can lead to worse outcomes, Dr. Didehbani said. “Additionally, patients do not feel that they are being heard, as many providers are not aware of the mental health impact and relationship with physical and cognitive symptoms.” .
Even when doctors recognize that psychological challenges are common with long COVID, they still have to think creatively to come up with treatments that meet the unique needs of these patients, said Thida Thant, MD, an assistant professor of psychiatry at the University of Colorado who treats patients at the UCHealth Post-COVID Clinic.
“There are at least two major factors that make treating psychological issues in long COVID more complex: The fact that the pandemic is still ongoing and still so divisive throughout society, and the fact that we don’t know a single best way to treat all symptoms of long COVID,” she said.
Some common treatments for anxiety and depression, like psychotherapy and medication, can be used for long COVID patients with these conditions. But another intervention that can work wonders for many people with mood disorders – exercise – doesn’t always work for long COVID patients. That’s because many of them struggle with physical challenges like chronic fatigue and what’s known as postexertional malaise, or a worsening of symptoms after even limited physical effort.
“While we normally encourage patients to be active, have a daily routine, and to engage in physical activity as part of their mental health treatment, some long COVID patients find that their symptoms worsen after increased activity,” Dr. Vannorsdall said.
Patients who are able to reach long COVID care centers are much more apt to get mental health problems diagnosed and treated, doctors at many programs around the country agree. But many patients hardest hit by the pandemic – the poor and racial and ethnic minorities – are also less likely to have ready access to hospitals that offer these programs, said Dr. Anderson.
“Affluent, predominantly White populations are showing up in these clinics, while we know that non-White populations have disproportionally high rates of acute infection, hospitalization, and death related to the virus,” he said.
Clinics are also concentrated in academic medical centers and in urban areas, limiting options for people in rural communities who may have to drive for hours to access care, Dr. Anderson said.
“Even before long COVID, we already knew that many people live in areas where there simply aren’t enough mental health services available,” said John Zulueta, MD, an assistant professor of clinical psychiatry at the University of Illinois at Chicago who provides mental health evaluations at the UI Health Post-COVID Clinic.
“As more patients develop mental health issues associated with long COVID, it’s going to put more stress on an already stressed system,” he said.
A version of this article first appeared on WebMD.com.
There’s little doubt that long COVID is real. Even as doctors and federal agencies struggle to define the syndrome, hospitals and health care systems are opening long COVID specialty treatment programs. As of July 25, there’s at least one long COVID center in almost every state – 48 out of 50, according to the patient advocacy group Survivor Corps.
Among the biggest challenges will be treating the mental health effects of long COVID.
Specialized centers will be tackling these problems even as the United States struggles to deal with mental health needs.
One study of COVID patients found more than one-third of them had symptoms of depression, anxiety, or PTSD 3-6 months after their initial infection. Another analysis of 30 previous studies of long COVID patients found roughly one in eight of them had severe depression – and that the risk was similar regardless of whether people were hospitalized for COVID-19.
“Many of these symptoms can emerge months into the course of long COVID illness,” said Jordan Anderson, DO, a neuropsychiatrist who sees patients at the Long COVID-19 Program at Oregon Health & Science University, Portland. Psychological symptoms are often made worse by physical setbacks like extreme fatigue and by challenges of working, caring for children, and keeping up with daily routines, he said.
“This impact is not only severe, but also chronic for many,” he said.
Like dozens of hospitals around the country, Oregon Health & Science opened its center for long COVID as it became clear that more patients would need help for ongoing physical and mental health symptoms. Today, there’s at least one long COVID center – sometimes called post-COVID care centers or clinics – in every state but Kansas and South Dakota, Survivor Corps said.
Many long COVID care centers aim to tackle both physical and mental health symptoms, said Tracy Vannorsdall, PhD, a neuropsychologist with the Johns Hopkins Post-Acute COVID-19 Team program. One goal at Hopkins is to identify patients with psychological issues that might otherwise get overlooked.
A sizable minority of patients at the Johns Hopkins center – up to about 35% – report mental health problems that they didn’t have until after they got COVID-19, Dr. Vannorsdall says. The most common mental health issues providers see are depression, anxiety, and trauma-related distress.
“Routine assessment is key,” Dr. Vannorsdall said. “If patients are not asked about their mental health symptoms, they may not spontaneously report them to their provider due to fear of stigma or simply not appreciating that there are effective treatments available for these issues.”
Fear that doctors won’t take symptoms seriously is common, says Heather Murray MD, a senior instructor in psychiatry at the University of Colorado at Denver, Aurora.
“Many patients worry their physicians, loved ones, and society will not believe them or will minimize their symptoms and suffering,” said Dr. Murray, who treats patients at the UCHealth Post-COVID Clinic.
Diagnostic tests in long COVID patients often don’t have conclusive results, which can lead doctors and patients themselves to question whether symptoms are truly “physical versus psychosomatic,” she said. “It is important that providers believe their patients and treat their symptoms, even when diagnostic tests are unrevealing.”
Growing mental health crisis
Patients often find their way to academic treatment centers after surviving severe COVID-19 infections. But a growing number of long COVID patients show up at these centers after milder cases. These patients were never hospitalized for COVID-19 but still have persistent symptoms like fatigue, thinking problems, and mood disorders.
Among the major challenges is a shortage of mental health care providers to meet the surging need for care since the start of the pandemic. Around the world, anxiety and depression surged 25% during the first year of the pandemic, according to the World Health Organization.
In the United States, 40% of adults report feelings of anxiety and depression, and one in three high school students have feelings of sadness and hopelessness, according to a March 2022 statement from the White House.
Despite this surging need for care, almost half of Americans live in areas with a severe shortage of mental health care providers, according to the Health Resources and Services Administration. As of 2019, the United States had a shortage of about 6,790 mental health providers. Since then, the shortage has worsened; it’s now about 7,500 providers.
“One of the biggest challenges for hospitals and clinics in treating mental health disorders in long COVID is the limited resources and long wait times to get in for evaluations and treatment,” said Nyaz Didehbani, PhD, a neuropsychologist who treats long COVID patients at the COVID Recover program at the University of Texas Southwestern Medical Center, Dallas.
These delays can lead to worse outcomes, Dr. Didehbani said. “Additionally, patients do not feel that they are being heard, as many providers are not aware of the mental health impact and relationship with physical and cognitive symptoms.” .
Even when doctors recognize that psychological challenges are common with long COVID, they still have to think creatively to come up with treatments that meet the unique needs of these patients, said Thida Thant, MD, an assistant professor of psychiatry at the University of Colorado who treats patients at the UCHealth Post-COVID Clinic.
“There are at least two major factors that make treating psychological issues in long COVID more complex: The fact that the pandemic is still ongoing and still so divisive throughout society, and the fact that we don’t know a single best way to treat all symptoms of long COVID,” she said.
Some common treatments for anxiety and depression, like psychotherapy and medication, can be used for long COVID patients with these conditions. But another intervention that can work wonders for many people with mood disorders – exercise – doesn’t always work for long COVID patients. That’s because many of them struggle with physical challenges like chronic fatigue and what’s known as postexertional malaise, or a worsening of symptoms after even limited physical effort.
“While we normally encourage patients to be active, have a daily routine, and to engage in physical activity as part of their mental health treatment, some long COVID patients find that their symptoms worsen after increased activity,” Dr. Vannorsdall said.
Patients who are able to reach long COVID care centers are much more apt to get mental health problems diagnosed and treated, doctors at many programs around the country agree. But many patients hardest hit by the pandemic – the poor and racial and ethnic minorities – are also less likely to have ready access to hospitals that offer these programs, said Dr. Anderson.
“Affluent, predominantly White populations are showing up in these clinics, while we know that non-White populations have disproportionally high rates of acute infection, hospitalization, and death related to the virus,” he said.
Clinics are also concentrated in academic medical centers and in urban areas, limiting options for people in rural communities who may have to drive for hours to access care, Dr. Anderson said.
“Even before long COVID, we already knew that many people live in areas where there simply aren’t enough mental health services available,” said John Zulueta, MD, an assistant professor of clinical psychiatry at the University of Illinois at Chicago who provides mental health evaluations at the UI Health Post-COVID Clinic.
“As more patients develop mental health issues associated with long COVID, it’s going to put more stress on an already stressed system,” he said.
A version of this article first appeared on WebMD.com.
There’s little doubt that long COVID is real. Even as doctors and federal agencies struggle to define the syndrome, hospitals and health care systems are opening long COVID specialty treatment programs. As of July 25, there’s at least one long COVID center in almost every state – 48 out of 50, according to the patient advocacy group Survivor Corps.
Among the biggest challenges will be treating the mental health effects of long COVID.
Specialized centers will be tackling these problems even as the United States struggles to deal with mental health needs.
One study of COVID patients found more than one-third of them had symptoms of depression, anxiety, or PTSD 3-6 months after their initial infection. Another analysis of 30 previous studies of long COVID patients found roughly one in eight of them had severe depression – and that the risk was similar regardless of whether people were hospitalized for COVID-19.
“Many of these symptoms can emerge months into the course of long COVID illness,” said Jordan Anderson, DO, a neuropsychiatrist who sees patients at the Long COVID-19 Program at Oregon Health & Science University, Portland. Psychological symptoms are often made worse by physical setbacks like extreme fatigue and by challenges of working, caring for children, and keeping up with daily routines, he said.
“This impact is not only severe, but also chronic for many,” he said.
Like dozens of hospitals around the country, Oregon Health & Science opened its center for long COVID as it became clear that more patients would need help for ongoing physical and mental health symptoms. Today, there’s at least one long COVID center – sometimes called post-COVID care centers or clinics – in every state but Kansas and South Dakota, Survivor Corps said.
Many long COVID care centers aim to tackle both physical and mental health symptoms, said Tracy Vannorsdall, PhD, a neuropsychologist with the Johns Hopkins Post-Acute COVID-19 Team program. One goal at Hopkins is to identify patients with psychological issues that might otherwise get overlooked.
A sizable minority of patients at the Johns Hopkins center – up to about 35% – report mental health problems that they didn’t have until after they got COVID-19, Dr. Vannorsdall says. The most common mental health issues providers see are depression, anxiety, and trauma-related distress.
“Routine assessment is key,” Dr. Vannorsdall said. “If patients are not asked about their mental health symptoms, they may not spontaneously report them to their provider due to fear of stigma or simply not appreciating that there are effective treatments available for these issues.”
Fear that doctors won’t take symptoms seriously is common, says Heather Murray MD, a senior instructor in psychiatry at the University of Colorado at Denver, Aurora.
“Many patients worry their physicians, loved ones, and society will not believe them or will minimize their symptoms and suffering,” said Dr. Murray, who treats patients at the UCHealth Post-COVID Clinic.
Diagnostic tests in long COVID patients often don’t have conclusive results, which can lead doctors and patients themselves to question whether symptoms are truly “physical versus psychosomatic,” she said. “It is important that providers believe their patients and treat their symptoms, even when diagnostic tests are unrevealing.”
Growing mental health crisis
Patients often find their way to academic treatment centers after surviving severe COVID-19 infections. But a growing number of long COVID patients show up at these centers after milder cases. These patients were never hospitalized for COVID-19 but still have persistent symptoms like fatigue, thinking problems, and mood disorders.
Among the major challenges is a shortage of mental health care providers to meet the surging need for care since the start of the pandemic. Around the world, anxiety and depression surged 25% during the first year of the pandemic, according to the World Health Organization.
In the United States, 40% of adults report feelings of anxiety and depression, and one in three high school students have feelings of sadness and hopelessness, according to a March 2022 statement from the White House.
Despite this surging need for care, almost half of Americans live in areas with a severe shortage of mental health care providers, according to the Health Resources and Services Administration. As of 2019, the United States had a shortage of about 6,790 mental health providers. Since then, the shortage has worsened; it’s now about 7,500 providers.
“One of the biggest challenges for hospitals and clinics in treating mental health disorders in long COVID is the limited resources and long wait times to get in for evaluations and treatment,” said Nyaz Didehbani, PhD, a neuropsychologist who treats long COVID patients at the COVID Recover program at the University of Texas Southwestern Medical Center, Dallas.
These delays can lead to worse outcomes, Dr. Didehbani said. “Additionally, patients do not feel that they are being heard, as many providers are not aware of the mental health impact and relationship with physical and cognitive symptoms.” .
Even when doctors recognize that psychological challenges are common with long COVID, they still have to think creatively to come up with treatments that meet the unique needs of these patients, said Thida Thant, MD, an assistant professor of psychiatry at the University of Colorado who treats patients at the UCHealth Post-COVID Clinic.
“There are at least two major factors that make treating psychological issues in long COVID more complex: The fact that the pandemic is still ongoing and still so divisive throughout society, and the fact that we don’t know a single best way to treat all symptoms of long COVID,” she said.
Some common treatments for anxiety and depression, like psychotherapy and medication, can be used for long COVID patients with these conditions. But another intervention that can work wonders for many people with mood disorders – exercise – doesn’t always work for long COVID patients. That’s because many of them struggle with physical challenges like chronic fatigue and what’s known as postexertional malaise, or a worsening of symptoms after even limited physical effort.
“While we normally encourage patients to be active, have a daily routine, and to engage in physical activity as part of their mental health treatment, some long COVID patients find that their symptoms worsen after increased activity,” Dr. Vannorsdall said.
Patients who are able to reach long COVID care centers are much more apt to get mental health problems diagnosed and treated, doctors at many programs around the country agree. But many patients hardest hit by the pandemic – the poor and racial and ethnic minorities – are also less likely to have ready access to hospitals that offer these programs, said Dr. Anderson.
“Affluent, predominantly White populations are showing up in these clinics, while we know that non-White populations have disproportionally high rates of acute infection, hospitalization, and death related to the virus,” he said.
Clinics are also concentrated in academic medical centers and in urban areas, limiting options for people in rural communities who may have to drive for hours to access care, Dr. Anderson said.
“Even before long COVID, we already knew that many people live in areas where there simply aren’t enough mental health services available,” said John Zulueta, MD, an assistant professor of clinical psychiatry at the University of Illinois at Chicago who provides mental health evaluations at the UI Health Post-COVID Clinic.
“As more patients develop mental health issues associated with long COVID, it’s going to put more stress on an already stressed system,” he said.
A version of this article first appeared on WebMD.com.
Metabolic syndrome raises dementia risk in under-60s
The more components of metabolic syndrome a person has in midlife seems to raise their risk of dementia, although that relationship seems to go away after age 70, a post hoc analysis of data from a major European cohort study has found.
A team of European researchers reported online in the journal Diabetes Care that the follow-up of the Whitehall II cohort study, a study of more than 10,000 civil servants in London that was established in the late 1980s, also found that cardiovascular disease (CVD) may only partially contribute to the risk of dementia in study participants.
They found that each additional metabolic syndrome component before age 60 years was linked to a 13% rise in the risk of dementia (hazard ratio, 1.13; 95% confidence interval [CI], 1.05-1.23) and, from age 60 to 70, the risk rose 8% (HR, 1.08; 95% CI, 1.00-1.16). However, in people aged 70 years and older, the relationship wasn’t statistically significant (HR, 1.04; 95% CI, 0.96-1.13]).
The study used “the latest harmonized definition” of metabolic syndrome; that is, participants were classified as having metabolic syndrome if they had three or more of the five components. As lead author Marcos D. Machado-Fragua, PhD, noted in an email interview, those components are abdominal obesity, high triglycerides, low HDL cholesterol levels, high blood pressure, and high fasting glucose.
“Our research question was on the association between metabolic syndrome and late-life dementia. We found that the presence of one metabolic syndrome component and the presence of metabolic risk before age 60, but not after, is associated with higher risk of dementia,” said Dr. Machado-Fragua, a post-doctoral researcher at the French Institute for Health and Medical Research in Paris.
The study cohort consisted of 10,308 London-based civil servants aged 35-55 years. Every 4-5 years after enrollment, from 1991 through 2016, they completed a questionnaire and had a clinical examination. The U.K. National Health Service electronic health record system tracked outcomes for all but 10 participants through March 2019.
The study identified the individual metabolic syndrome components that posed the highest risk for dementia in these three age groups:
- Age < 60 years: elevated waist circumference (HR 1.39 [95% CI 1.07, 1.81]), low HDL-C, (HR 1.30 [95% CI 1.02, 1.66]), and elevated blood pressure (HR 1.34 [95% CI 1.09, 1.63]).
- Age 60-70 years: low HDL-C (HR 1.26 [95% CI 1.02, 1.57]) and elevated fasting glucose (HR 1.40 [95% CI 1.12, 1.74]).
- Age >70 years: elevated fasting glucose (HR 1.38 [95% CI 1.07, 1.79]).
The study found that the dementia risk was significantly high in study participants under age 60 who had at least one (HR 1.99 [95% CI 1.08, 3.66]) or two (HR 1.69 [95% CI 1.12, 2.56]) metabolic syndrome components even when they didn’t have CVD.
“The present study adds to the understanding of the association between metabolic syndrome and dementia due to three novel features,” Dr. Machado-Fragua said. “First, we tested alternative thresholds to define ‘high metabolic risk,’ and findings show increased risk of dementia to start with the presence of one metabolic syndrome component. Second, assessment of metabolic syndrome components in midlife and later life allowed the examination of the role of age at prevalence of metabolic risk for incident dementia at older ages. Third, our findings showed high dementia risk in those free of cardiovascular disease during follow-up, suggesting that the association between high metabolic risk and incident dementia is not fully explained by cardiovascular disease.”
Dr. Machado-Fragua added, “For now, a cure for dementia remains elusive, making it important to think of prevention strategies. Our findings support targeting the components of the metabolic syndrome in midlife, even in those who have fewer than three of the metabolic syndrome components.”
Applicability ‘confusing’
In an interview, Yehuda Handelsman, MD, questioned the applicability of the study findings in the clinic. “Metabolic syndrome is a clinical manifestation of insulin resistance,” he said. “The more metabolic syndrome criteria a person has, the more insulin resistant that person will be. There is literature that is [suggesting] that insulin resistance is an important cause of dementia.”
The finding of a higher dementia risk before age 70, compared to afterward, makes the applicability “even more confusing,” he said. The results are even more muddled for U.S. physicians, who have moved away from the term metabolic syndrome in favor of cardiometabolic syndrome, said Dr. Handelsman, medical director and principal investigator at the Metabolic Institute of America and president of the Diabetes CardioRenal & Metabolism Institute, both in Tarzana, Calif.
Confusion also surrounds one of the components of metabolic syndrome: Waist circumference, per the harmonized definition the study used, and body mass index, which the more traditional definition uses.
Nonetheless, metabolic syndrome can be used as “kind of a risk calculator” for CVD, diabetes, and dementia, he said. One strength of the study, Dr. Handelsman said, is its size and scope, following 28 years of data. But a weakness was its observational design. “It doesn’t evaluate any true intervention to modify risk,” he said.
Dr. Machado-Fragua and coauthors have no disclosures.
The more components of metabolic syndrome a person has in midlife seems to raise their risk of dementia, although that relationship seems to go away after age 70, a post hoc analysis of data from a major European cohort study has found.
A team of European researchers reported online in the journal Diabetes Care that the follow-up of the Whitehall II cohort study, a study of more than 10,000 civil servants in London that was established in the late 1980s, also found that cardiovascular disease (CVD) may only partially contribute to the risk of dementia in study participants.
They found that each additional metabolic syndrome component before age 60 years was linked to a 13% rise in the risk of dementia (hazard ratio, 1.13; 95% confidence interval [CI], 1.05-1.23) and, from age 60 to 70, the risk rose 8% (HR, 1.08; 95% CI, 1.00-1.16). However, in people aged 70 years and older, the relationship wasn’t statistically significant (HR, 1.04; 95% CI, 0.96-1.13]).
The study used “the latest harmonized definition” of metabolic syndrome; that is, participants were classified as having metabolic syndrome if they had three or more of the five components. As lead author Marcos D. Machado-Fragua, PhD, noted in an email interview, those components are abdominal obesity, high triglycerides, low HDL cholesterol levels, high blood pressure, and high fasting glucose.
“Our research question was on the association between metabolic syndrome and late-life dementia. We found that the presence of one metabolic syndrome component and the presence of metabolic risk before age 60, but not after, is associated with higher risk of dementia,” said Dr. Machado-Fragua, a post-doctoral researcher at the French Institute for Health and Medical Research in Paris.
The study cohort consisted of 10,308 London-based civil servants aged 35-55 years. Every 4-5 years after enrollment, from 1991 through 2016, they completed a questionnaire and had a clinical examination. The U.K. National Health Service electronic health record system tracked outcomes for all but 10 participants through March 2019.
The study identified the individual metabolic syndrome components that posed the highest risk for dementia in these three age groups:
- Age < 60 years: elevated waist circumference (HR 1.39 [95% CI 1.07, 1.81]), low HDL-C, (HR 1.30 [95% CI 1.02, 1.66]), and elevated blood pressure (HR 1.34 [95% CI 1.09, 1.63]).
- Age 60-70 years: low HDL-C (HR 1.26 [95% CI 1.02, 1.57]) and elevated fasting glucose (HR 1.40 [95% CI 1.12, 1.74]).
- Age >70 years: elevated fasting glucose (HR 1.38 [95% CI 1.07, 1.79]).
The study found that the dementia risk was significantly high in study participants under age 60 who had at least one (HR 1.99 [95% CI 1.08, 3.66]) or two (HR 1.69 [95% CI 1.12, 2.56]) metabolic syndrome components even when they didn’t have CVD.
“The present study adds to the understanding of the association between metabolic syndrome and dementia due to three novel features,” Dr. Machado-Fragua said. “First, we tested alternative thresholds to define ‘high metabolic risk,’ and findings show increased risk of dementia to start with the presence of one metabolic syndrome component. Second, assessment of metabolic syndrome components in midlife and later life allowed the examination of the role of age at prevalence of metabolic risk for incident dementia at older ages. Third, our findings showed high dementia risk in those free of cardiovascular disease during follow-up, suggesting that the association between high metabolic risk and incident dementia is not fully explained by cardiovascular disease.”
Dr. Machado-Fragua added, “For now, a cure for dementia remains elusive, making it important to think of prevention strategies. Our findings support targeting the components of the metabolic syndrome in midlife, even in those who have fewer than three of the metabolic syndrome components.”
Applicability ‘confusing’
In an interview, Yehuda Handelsman, MD, questioned the applicability of the study findings in the clinic. “Metabolic syndrome is a clinical manifestation of insulin resistance,” he said. “The more metabolic syndrome criteria a person has, the more insulin resistant that person will be. There is literature that is [suggesting] that insulin resistance is an important cause of dementia.”
The finding of a higher dementia risk before age 70, compared to afterward, makes the applicability “even more confusing,” he said. The results are even more muddled for U.S. physicians, who have moved away from the term metabolic syndrome in favor of cardiometabolic syndrome, said Dr. Handelsman, medical director and principal investigator at the Metabolic Institute of America and president of the Diabetes CardioRenal & Metabolism Institute, both in Tarzana, Calif.
Confusion also surrounds one of the components of metabolic syndrome: Waist circumference, per the harmonized definition the study used, and body mass index, which the more traditional definition uses.
Nonetheless, metabolic syndrome can be used as “kind of a risk calculator” for CVD, diabetes, and dementia, he said. One strength of the study, Dr. Handelsman said, is its size and scope, following 28 years of data. But a weakness was its observational design. “It doesn’t evaluate any true intervention to modify risk,” he said.
Dr. Machado-Fragua and coauthors have no disclosures.
The more components of metabolic syndrome a person has in midlife seems to raise their risk of dementia, although that relationship seems to go away after age 70, a post hoc analysis of data from a major European cohort study has found.
A team of European researchers reported online in the journal Diabetes Care that the follow-up of the Whitehall II cohort study, a study of more than 10,000 civil servants in London that was established in the late 1980s, also found that cardiovascular disease (CVD) may only partially contribute to the risk of dementia in study participants.
They found that each additional metabolic syndrome component before age 60 years was linked to a 13% rise in the risk of dementia (hazard ratio, 1.13; 95% confidence interval [CI], 1.05-1.23) and, from age 60 to 70, the risk rose 8% (HR, 1.08; 95% CI, 1.00-1.16). However, in people aged 70 years and older, the relationship wasn’t statistically significant (HR, 1.04; 95% CI, 0.96-1.13]).
The study used “the latest harmonized definition” of metabolic syndrome; that is, participants were classified as having metabolic syndrome if they had three or more of the five components. As lead author Marcos D. Machado-Fragua, PhD, noted in an email interview, those components are abdominal obesity, high triglycerides, low HDL cholesterol levels, high blood pressure, and high fasting glucose.
“Our research question was on the association between metabolic syndrome and late-life dementia. We found that the presence of one metabolic syndrome component and the presence of metabolic risk before age 60, but not after, is associated with higher risk of dementia,” said Dr. Machado-Fragua, a post-doctoral researcher at the French Institute for Health and Medical Research in Paris.
The study cohort consisted of 10,308 London-based civil servants aged 35-55 years. Every 4-5 years after enrollment, from 1991 through 2016, they completed a questionnaire and had a clinical examination. The U.K. National Health Service electronic health record system tracked outcomes for all but 10 participants through March 2019.
The study identified the individual metabolic syndrome components that posed the highest risk for dementia in these three age groups:
- Age < 60 years: elevated waist circumference (HR 1.39 [95% CI 1.07, 1.81]), low HDL-C, (HR 1.30 [95% CI 1.02, 1.66]), and elevated blood pressure (HR 1.34 [95% CI 1.09, 1.63]).
- Age 60-70 years: low HDL-C (HR 1.26 [95% CI 1.02, 1.57]) and elevated fasting glucose (HR 1.40 [95% CI 1.12, 1.74]).
- Age >70 years: elevated fasting glucose (HR 1.38 [95% CI 1.07, 1.79]).
The study found that the dementia risk was significantly high in study participants under age 60 who had at least one (HR 1.99 [95% CI 1.08, 3.66]) or two (HR 1.69 [95% CI 1.12, 2.56]) metabolic syndrome components even when they didn’t have CVD.
“The present study adds to the understanding of the association between metabolic syndrome and dementia due to three novel features,” Dr. Machado-Fragua said. “First, we tested alternative thresholds to define ‘high metabolic risk,’ and findings show increased risk of dementia to start with the presence of one metabolic syndrome component. Second, assessment of metabolic syndrome components in midlife and later life allowed the examination of the role of age at prevalence of metabolic risk for incident dementia at older ages. Third, our findings showed high dementia risk in those free of cardiovascular disease during follow-up, suggesting that the association between high metabolic risk and incident dementia is not fully explained by cardiovascular disease.”
Dr. Machado-Fragua added, “For now, a cure for dementia remains elusive, making it important to think of prevention strategies. Our findings support targeting the components of the metabolic syndrome in midlife, even in those who have fewer than three of the metabolic syndrome components.”
Applicability ‘confusing’
In an interview, Yehuda Handelsman, MD, questioned the applicability of the study findings in the clinic. “Metabolic syndrome is a clinical manifestation of insulin resistance,” he said. “The more metabolic syndrome criteria a person has, the more insulin resistant that person will be. There is literature that is [suggesting] that insulin resistance is an important cause of dementia.”
The finding of a higher dementia risk before age 70, compared to afterward, makes the applicability “even more confusing,” he said. The results are even more muddled for U.S. physicians, who have moved away from the term metabolic syndrome in favor of cardiometabolic syndrome, said Dr. Handelsman, medical director and principal investigator at the Metabolic Institute of America and president of the Diabetes CardioRenal & Metabolism Institute, both in Tarzana, Calif.
Confusion also surrounds one of the components of metabolic syndrome: Waist circumference, per the harmonized definition the study used, and body mass index, which the more traditional definition uses.
Nonetheless, metabolic syndrome can be used as “kind of a risk calculator” for CVD, diabetes, and dementia, he said. One strength of the study, Dr. Handelsman said, is its size and scope, following 28 years of data. But a weakness was its observational design. “It doesn’t evaluate any true intervention to modify risk,” he said.
Dr. Machado-Fragua and coauthors have no disclosures.
FROM DIABETES CARE
Understanding the neuroscience of narcissism
Editor’s Note: The study covered in this summary was published on ResearchSquare.com as a preprint and has not yet been peer reviewed.
Key takeaway
Why this matters
The cognitive features and phenotypic diversity of narcissism subtypes are partially unknown.
This study integrates both grandiose and vulnerable narcissism into a common framework with cognitive components connected to these traits.
Study design
This study enrolled 478 participants (397 female and 4 did not reveal their gender).
The average age of participants was 35 years (standard deviation, 14.97), with a range of 18-76 years.
A 25-item version of the Narcissistic Personality Inventory (NPI), a 40-item self-report measure of narcissism traits, was used to assess the level of authority, grandiose exhibitionism, and entitlement/exploitativeness characteristics of study participants.
The Maladaptive Covert Narcissism Scale, an expanded version of the 23-item self-report Hypersensitive Narcissism Scale, was used to assess the level of hypersensitivity, vulnerability, and entitlement of study participants.
The Rosenberg Self-Esteem Scale, a 10-item self-report scale, was used to assess the level of self-esteem of study participants.
The Young Schema Questionnaire is a 244-item measure of 19 different maladaptive schemas and was used to observe Emotional Deprivation, Vulnerability to Harm and Illness, and Entitlement schemas of study participants.
The Empathizing Quotient is a self-report measure and was used to assess the emotional intelligence of study participants.
Key results
Moderate correlation between grandiose and vulnerable narcissism and the Entitlement schema was observed.
A moderate/strong connection was observed between vulnerable narcissism and the Vulnerability to Harm and Illness schema and a moderate connection with the Emotional Deprivation schema.
No significant correlation was observed between grandiose narcissism and the Emotional Deprivation schema.
A moderate, negative correlation between vulnerable narcissism and emotional skills was observed.
A positive, weak connection between grandiose narcissism and self-esteem; and a negative, moderate connection between vulnerable narcissism and self-esteem were observed.
Gender and age were associated with empathic skills, and age was weakly/moderately connected with self-esteem and vulnerable narcissism.
Limitations
This was a cross-sectional analysis investigating a temporally specific state of personality and cognitive functioning.
The gender ratio was shifted toward women in this study.
Conclusions drawn from connections between observed components are interchangeable and cause/effect connections cannot be discerned.
Disclosures
The study was supported by the National Research, Development, and Innovation Office (Grant No. NRDI–138040) and by the Human Resource Development Operational Program – Comprehensive developments at the University of Pécs for the implementation of intelligent specialization (EFOP-3.6.1-16-2016-00004). First author Dorian Vida’s work was supported by the Collegium Talentum Programme of Hungary. None of the authors disclosed any competing interests.
This is a summary of a preprint research study, “In the mind of Narcissus: the mediating role of emotional regulation in the emergence of distorted cognitions,” written by Dorian Vida from the University of Pécs, Hungary and colleagues on ResearchSquare.com. This study has not yet been peer reviewed. The full text of the study can be found on ResearchSquare.com.
A version of this article first appeared on Medscape.com
Editor’s Note: The study covered in this summary was published on ResearchSquare.com as a preprint and has not yet been peer reviewed.
Key takeaway
Why this matters
The cognitive features and phenotypic diversity of narcissism subtypes are partially unknown.
This study integrates both grandiose and vulnerable narcissism into a common framework with cognitive components connected to these traits.
Study design
This study enrolled 478 participants (397 female and 4 did not reveal their gender).
The average age of participants was 35 years (standard deviation, 14.97), with a range of 18-76 years.
A 25-item version of the Narcissistic Personality Inventory (NPI), a 40-item self-report measure of narcissism traits, was used to assess the level of authority, grandiose exhibitionism, and entitlement/exploitativeness characteristics of study participants.
The Maladaptive Covert Narcissism Scale, an expanded version of the 23-item self-report Hypersensitive Narcissism Scale, was used to assess the level of hypersensitivity, vulnerability, and entitlement of study participants.
The Rosenberg Self-Esteem Scale, a 10-item self-report scale, was used to assess the level of self-esteem of study participants.
The Young Schema Questionnaire is a 244-item measure of 19 different maladaptive schemas and was used to observe Emotional Deprivation, Vulnerability to Harm and Illness, and Entitlement schemas of study participants.
The Empathizing Quotient is a self-report measure and was used to assess the emotional intelligence of study participants.
Key results
Moderate correlation between grandiose and vulnerable narcissism and the Entitlement schema was observed.
A moderate/strong connection was observed between vulnerable narcissism and the Vulnerability to Harm and Illness schema and a moderate connection with the Emotional Deprivation schema.
No significant correlation was observed between grandiose narcissism and the Emotional Deprivation schema.
A moderate, negative correlation between vulnerable narcissism and emotional skills was observed.
A positive, weak connection between grandiose narcissism and self-esteem; and a negative, moderate connection between vulnerable narcissism and self-esteem were observed.
Gender and age were associated with empathic skills, and age was weakly/moderately connected with self-esteem and vulnerable narcissism.
Limitations
This was a cross-sectional analysis investigating a temporally specific state of personality and cognitive functioning.
The gender ratio was shifted toward women in this study.
Conclusions drawn from connections between observed components are interchangeable and cause/effect connections cannot be discerned.
Disclosures
The study was supported by the National Research, Development, and Innovation Office (Grant No. NRDI–138040) and by the Human Resource Development Operational Program – Comprehensive developments at the University of Pécs for the implementation of intelligent specialization (EFOP-3.6.1-16-2016-00004). First author Dorian Vida’s work was supported by the Collegium Talentum Programme of Hungary. None of the authors disclosed any competing interests.
This is a summary of a preprint research study, “In the mind of Narcissus: the mediating role of emotional regulation in the emergence of distorted cognitions,” written by Dorian Vida from the University of Pécs, Hungary and colleagues on ResearchSquare.com. This study has not yet been peer reviewed. The full text of the study can be found on ResearchSquare.com.
A version of this article first appeared on Medscape.com
Editor’s Note: The study covered in this summary was published on ResearchSquare.com as a preprint and has not yet been peer reviewed.
Key takeaway
Why this matters
The cognitive features and phenotypic diversity of narcissism subtypes are partially unknown.
This study integrates both grandiose and vulnerable narcissism into a common framework with cognitive components connected to these traits.
Study design
This study enrolled 478 participants (397 female and 4 did not reveal their gender).
The average age of participants was 35 years (standard deviation, 14.97), with a range of 18-76 years.
A 25-item version of the Narcissistic Personality Inventory (NPI), a 40-item self-report measure of narcissism traits, was used to assess the level of authority, grandiose exhibitionism, and entitlement/exploitativeness characteristics of study participants.
The Maladaptive Covert Narcissism Scale, an expanded version of the 23-item self-report Hypersensitive Narcissism Scale, was used to assess the level of hypersensitivity, vulnerability, and entitlement of study participants.
The Rosenberg Self-Esteem Scale, a 10-item self-report scale, was used to assess the level of self-esteem of study participants.
The Young Schema Questionnaire is a 244-item measure of 19 different maladaptive schemas and was used to observe Emotional Deprivation, Vulnerability to Harm and Illness, and Entitlement schemas of study participants.
The Empathizing Quotient is a self-report measure and was used to assess the emotional intelligence of study participants.
Key results
Moderate correlation between grandiose and vulnerable narcissism and the Entitlement schema was observed.
A moderate/strong connection was observed between vulnerable narcissism and the Vulnerability to Harm and Illness schema and a moderate connection with the Emotional Deprivation schema.
No significant correlation was observed between grandiose narcissism and the Emotional Deprivation schema.
A moderate, negative correlation between vulnerable narcissism and emotional skills was observed.
A positive, weak connection between grandiose narcissism and self-esteem; and a negative, moderate connection between vulnerable narcissism and self-esteem were observed.
Gender and age were associated with empathic skills, and age was weakly/moderately connected with self-esteem and vulnerable narcissism.
Limitations
This was a cross-sectional analysis investigating a temporally specific state of personality and cognitive functioning.
The gender ratio was shifted toward women in this study.
Conclusions drawn from connections between observed components are interchangeable and cause/effect connections cannot be discerned.
Disclosures
The study was supported by the National Research, Development, and Innovation Office (Grant No. NRDI–138040) and by the Human Resource Development Operational Program – Comprehensive developments at the University of Pécs for the implementation of intelligent specialization (EFOP-3.6.1-16-2016-00004). First author Dorian Vida’s work was supported by the Collegium Talentum Programme of Hungary. None of the authors disclosed any competing interests.
This is a summary of a preprint research study, “In the mind of Narcissus: the mediating role of emotional regulation in the emergence of distorted cognitions,” written by Dorian Vida from the University of Pécs, Hungary and colleagues on ResearchSquare.com. This study has not yet been peer reviewed. The full text of the study can be found on ResearchSquare.com.
A version of this article first appeared on Medscape.com
Neuroscientist alleges irregularities in Alzheimer’s research
A U.S. neuroscientist claims that some of the studies of the experimental agent, simufilam (Cassava Sciences), a drug that targets amyloid beta (Abeta) in Alzheimer’s disease (AD), are flawed, and, as a result, has taken his concerns to the National Institutes of Health.
Matthew Schrag, MD, PhD, department of neurology, Vanderbilt University Medical Center, Nashville, Tenn., uncovered what he calls inconsistencies in major studies examining the drug.
to support the hypothesis that buildup of amyloid in the brain causes AD. The NIH has funded research into Abeta as a potential cause of AD to the tune of millions of dollars for years.
“This hypothesis has been the central dominant thinking of the field,” Dr. Schrag told this news organization. “A lot of the therapies that have been developed and tested clinically over the last decade focused on the amyloid hypothesis in one formulation or another. So, it’s an important component of the way we think about Alzheimer’s disease,” he added.
In an in-depth article published in Science and written by investigative reporter Charles Piller, Dr. Schrag said he became involved after a colleague suggested he work with an attorney investigating simufilam. The lawyer paid Dr. Schrag $18,000 to investigate the research behind the agent. Cassava Sciences denies any misconduct, according to the article.
Dr. Schrag ran many AD studies through sophisticated imaging software. The effort revealed multiple Western blot images – which scientists use to detect the presence and amount of proteins in a sample – that appeared to be altered.
High stakes
Dr. Schrag found “apparently altered or duplicated images in dozens of journal articles,” the Science article states.
“A lot is at stake in terms of getting this right and it’s also important to acknowledge the limitations of what we can do. We were working with what’s published, what’s publicly available, and I think that it raises quite a lot of red flags, but we’ve also not reviewed the original material because it’s simply not available to us,” Dr. Schrag said in an interview.
However, he added that despite these limitations he believes “there’s enough here that it’s important for regulatory bodies to take a closer look at it to make sure that the data is right.”
Science reports that it launched its own independent review, asking several neuroscience experts to also review the research. They agreed with Dr. Schrag’s overall conclusions that something was amiss.
Many of the studies questioned in the whistleblower report involve Sylvain Lesné, PhD, who runs The Lesné Laboratory at the University of Minnesota, Minneapolis, and is an associate professor of neuroscience. His colleague Karen Ashe, MD, PhD, a professor of neurology at the same institution, was also mentioned in the whistleblower report. She was coauthor of a 2006 report in Nature that identified an Abeta subtype as a potential culprit behind AD.
This news organization reached out to Dr. Lesné and Dr. Ashe for comment, but has not received a response.
However, an email from a University of Minnesota spokesperson said the institution is “aware that questions have arisen regarding certain images used in peer-reviewed research publications authored by University faculty Dr. Ashe and Dr. Lesné. The University will follow its processes to review the questions any claims have raised. At this time, we have no further information to provide.”
A matter of trust
Dr. Schrag noted the “important trust relationship between patients, physicians and scientists. When we’re exploring diseases that we don’t have good treatments for.” He added that when patients agree to participate in trials and accept the associated risks, “we owe them a very high degree of integrity regarding the foundational data.”
Dr. Schrag also pointed out that there are limited resources to study these diseases. “There is some potential for that to be misdirected. It’s important for us to pay attention to data integrity issues, to make sure that we’re investing in the right places.”
The term “fraud” does not appear in Dr. Schrag’s whistleblower report, nor does he claim misconduct in the report. However, his work has spurred some independent, ongoing investigation into the claims by several journals that published the works in question, including Nature and Science Signaling.
Dr. Schrag said that if his findings are validated through an investigation he would like to see the scientific record corrected.
“Ultimately, I’d like to see a new set of hypotheses given a chance to look at this disease from a new perspective,” he added.
Dr. Schrag noted that the work described in the Science article was performed outside of his employment with Vanderbilt University Medical Center and that his opinions do not necessarily represent the views of Vanderbilt University or Vanderbilt University Medical Center.
A version of this article first appeared on Medscape.com.
A U.S. neuroscientist claims that some of the studies of the experimental agent, simufilam (Cassava Sciences), a drug that targets amyloid beta (Abeta) in Alzheimer’s disease (AD), are flawed, and, as a result, has taken his concerns to the National Institutes of Health.
Matthew Schrag, MD, PhD, department of neurology, Vanderbilt University Medical Center, Nashville, Tenn., uncovered what he calls inconsistencies in major studies examining the drug.
to support the hypothesis that buildup of amyloid in the brain causes AD. The NIH has funded research into Abeta as a potential cause of AD to the tune of millions of dollars for years.
“This hypothesis has been the central dominant thinking of the field,” Dr. Schrag told this news organization. “A lot of the therapies that have been developed and tested clinically over the last decade focused on the amyloid hypothesis in one formulation or another. So, it’s an important component of the way we think about Alzheimer’s disease,” he added.
In an in-depth article published in Science and written by investigative reporter Charles Piller, Dr. Schrag said he became involved after a colleague suggested he work with an attorney investigating simufilam. The lawyer paid Dr. Schrag $18,000 to investigate the research behind the agent. Cassava Sciences denies any misconduct, according to the article.
Dr. Schrag ran many AD studies through sophisticated imaging software. The effort revealed multiple Western blot images – which scientists use to detect the presence and amount of proteins in a sample – that appeared to be altered.
High stakes
Dr. Schrag found “apparently altered or duplicated images in dozens of journal articles,” the Science article states.
“A lot is at stake in terms of getting this right and it’s also important to acknowledge the limitations of what we can do. We were working with what’s published, what’s publicly available, and I think that it raises quite a lot of red flags, but we’ve also not reviewed the original material because it’s simply not available to us,” Dr. Schrag said in an interview.
However, he added that despite these limitations he believes “there’s enough here that it’s important for regulatory bodies to take a closer look at it to make sure that the data is right.”
Science reports that it launched its own independent review, asking several neuroscience experts to also review the research. They agreed with Dr. Schrag’s overall conclusions that something was amiss.
Many of the studies questioned in the whistleblower report involve Sylvain Lesné, PhD, who runs The Lesné Laboratory at the University of Minnesota, Minneapolis, and is an associate professor of neuroscience. His colleague Karen Ashe, MD, PhD, a professor of neurology at the same institution, was also mentioned in the whistleblower report. She was coauthor of a 2006 report in Nature that identified an Abeta subtype as a potential culprit behind AD.
This news organization reached out to Dr. Lesné and Dr. Ashe for comment, but has not received a response.
However, an email from a University of Minnesota spokesperson said the institution is “aware that questions have arisen regarding certain images used in peer-reviewed research publications authored by University faculty Dr. Ashe and Dr. Lesné. The University will follow its processes to review the questions any claims have raised. At this time, we have no further information to provide.”
A matter of trust
Dr. Schrag noted the “important trust relationship between patients, physicians and scientists. When we’re exploring diseases that we don’t have good treatments for.” He added that when patients agree to participate in trials and accept the associated risks, “we owe them a very high degree of integrity regarding the foundational data.”
Dr. Schrag also pointed out that there are limited resources to study these diseases. “There is some potential for that to be misdirected. It’s important for us to pay attention to data integrity issues, to make sure that we’re investing in the right places.”
The term “fraud” does not appear in Dr. Schrag’s whistleblower report, nor does he claim misconduct in the report. However, his work has spurred some independent, ongoing investigation into the claims by several journals that published the works in question, including Nature and Science Signaling.
Dr. Schrag said that if his findings are validated through an investigation he would like to see the scientific record corrected.
“Ultimately, I’d like to see a new set of hypotheses given a chance to look at this disease from a new perspective,” he added.
Dr. Schrag noted that the work described in the Science article was performed outside of his employment with Vanderbilt University Medical Center and that his opinions do not necessarily represent the views of Vanderbilt University or Vanderbilt University Medical Center.
A version of this article first appeared on Medscape.com.
A U.S. neuroscientist claims that some of the studies of the experimental agent, simufilam (Cassava Sciences), a drug that targets amyloid beta (Abeta) in Alzheimer’s disease (AD), are flawed, and, as a result, has taken his concerns to the National Institutes of Health.
Matthew Schrag, MD, PhD, department of neurology, Vanderbilt University Medical Center, Nashville, Tenn., uncovered what he calls inconsistencies in major studies examining the drug.
to support the hypothesis that buildup of amyloid in the brain causes AD. The NIH has funded research into Abeta as a potential cause of AD to the tune of millions of dollars for years.
“This hypothesis has been the central dominant thinking of the field,” Dr. Schrag told this news organization. “A lot of the therapies that have been developed and tested clinically over the last decade focused on the amyloid hypothesis in one formulation or another. So, it’s an important component of the way we think about Alzheimer’s disease,” he added.
In an in-depth article published in Science and written by investigative reporter Charles Piller, Dr. Schrag said he became involved after a colleague suggested he work with an attorney investigating simufilam. The lawyer paid Dr. Schrag $18,000 to investigate the research behind the agent. Cassava Sciences denies any misconduct, according to the article.
Dr. Schrag ran many AD studies through sophisticated imaging software. The effort revealed multiple Western blot images – which scientists use to detect the presence and amount of proteins in a sample – that appeared to be altered.
High stakes
Dr. Schrag found “apparently altered or duplicated images in dozens of journal articles,” the Science article states.
“A lot is at stake in terms of getting this right and it’s also important to acknowledge the limitations of what we can do. We were working with what’s published, what’s publicly available, and I think that it raises quite a lot of red flags, but we’ve also not reviewed the original material because it’s simply not available to us,” Dr. Schrag said in an interview.
However, he added that despite these limitations he believes “there’s enough here that it’s important for regulatory bodies to take a closer look at it to make sure that the data is right.”
Science reports that it launched its own independent review, asking several neuroscience experts to also review the research. They agreed with Dr. Schrag’s overall conclusions that something was amiss.
Many of the studies questioned in the whistleblower report involve Sylvain Lesné, PhD, who runs The Lesné Laboratory at the University of Minnesota, Minneapolis, and is an associate professor of neuroscience. His colleague Karen Ashe, MD, PhD, a professor of neurology at the same institution, was also mentioned in the whistleblower report. She was coauthor of a 2006 report in Nature that identified an Abeta subtype as a potential culprit behind AD.
This news organization reached out to Dr. Lesné and Dr. Ashe for comment, but has not received a response.
However, an email from a University of Minnesota spokesperson said the institution is “aware that questions have arisen regarding certain images used in peer-reviewed research publications authored by University faculty Dr. Ashe and Dr. Lesné. The University will follow its processes to review the questions any claims have raised. At this time, we have no further information to provide.”
A matter of trust
Dr. Schrag noted the “important trust relationship between patients, physicians and scientists. When we’re exploring diseases that we don’t have good treatments for.” He added that when patients agree to participate in trials and accept the associated risks, “we owe them a very high degree of integrity regarding the foundational data.”
Dr. Schrag also pointed out that there are limited resources to study these diseases. “There is some potential for that to be misdirected. It’s important for us to pay attention to data integrity issues, to make sure that we’re investing in the right places.”
The term “fraud” does not appear in Dr. Schrag’s whistleblower report, nor does he claim misconduct in the report. However, his work has spurred some independent, ongoing investigation into the claims by several journals that published the works in question, including Nature and Science Signaling.
Dr. Schrag said that if his findings are validated through an investigation he would like to see the scientific record corrected.
“Ultimately, I’d like to see a new set of hypotheses given a chance to look at this disease from a new perspective,” he added.
Dr. Schrag noted that the work described in the Science article was performed outside of his employment with Vanderbilt University Medical Center and that his opinions do not necessarily represent the views of Vanderbilt University or Vanderbilt University Medical Center.
A version of this article first appeared on Medscape.com.
Cognitive impairment may predict physical disability in MS
, new research suggests. In an analysis of more than 1,600 patients with secondary-progressive MS (SPMS), the likelihood of needing a wheelchair was almost doubled in those who had the worst scores on cognitive testing measures, compared with their counterparts who had the best scores.
“These findings should change our world view of MS,” study investigator Gavin Giovannoni, PhD, professor of neurology, Blizard Institute, Faculty of Medicine and Dentistry, Queen Mary University of London, told attendees at the Congress of the European Academy of Neurology.
On the basis of the results, clinicians should consider testing cognitive processing speed in patients with MS to identify those who are at increased risk for disease progression, Dr. Giovannoni noted. “I urge anybody who runs an MS service to think about putting in place mechanisms in their clinic” to measure cognition of patients over time, he said.
Expand data
Cognitive impairment occurs very early in the course of MS and is part of the disease, although to a greater or lesser degree depending on the patient, Dr. Giovannoni noted. Such impairment has a significant impact on quality of life for patients dealing with this disease, he added.
EXPAND was a phase 3 study of siponimod. Results showed the now-approved oral selective sphingosine 1–phosphate receptor modulator significantly reduced the risk for disability progression in patients with SPMS.
Using the EXPAND clinical trial database, the current researchers assessed 1,628 participants for an association between cognitive processing speed, as measured with the Symbol Digit Modality Test (SDMT), and physical disability progression, as measured with the Expanded Disability Status Scale (EDSS). A score of 7 or more on the EDSS indicates wheelchair dependence.
Dr. Giovannoni noted that cognitive processing speed is considered an indirect measure of thalamic network efficiency and functional brain reserve.
Investigators looked at both the core study, in which all patients continued on treatment or placebo for up to 37 months, and the core plus extension part, in which patients received treatment for up to 5 years.
They separated SDMT scores into quartiles: from worst (n = 435) to two intermediate quartiles (n = 808) to the best quartile (n = 385).
Wheelchair dependence
In addition, the researchers examined the predictive value by baseline SDMT, adjusting for treatment, age, gender, baseline EDSS score, baseline SCMT quartile, and treatment-by-baseline SCMT quartile interaction. On-study SDMT change (month 0-24) was also assessed after adjusting for treatment, age, gender, baseline EDS, baseline SCMT, and on-study change in SCMT quartile.
In the core study, those in the worst SDMT quartile at baseline were numerically more likely to reach deterioration to EDSS 7 or greater (wheelchair dependent), compared with patients in the best SDMT quartile (hazard ratio, 1.31; 95% confidence interval, .72-2.38; P = .371).
The short-term predictive value of baseline SDMT for reaching sustained EDSS of at least 7 was more obvious in the placebo arm than in the treatment arm.
Dr. Giovannoni said this is likely due to the treatment effect of siponimod preventing relatively more events in the worse quartile, and so reducing the risk for wheelchair dependency.
In the core plus extension part, there was an almost twofold increased risk for wheelchair dependence in the worse versus best SDMT groups (HR, 1.81; 95% CI, 1.17-2.78; P = .007).
Both baseline SDMT (HR, 1.81; P = .007) and on-study change in SDMT (HR, 1.73; P = .046) predicted wheelchair dependence in the long-term.
‘More important than a walking stick’
Measuring cognitive change over time “may be a more important predictor than a walking stick in terms of quality of life and outcomes, and it affects clinical decisionmaking,” said Dr. Giovannoni.
The findings are not novel, as post hoc analyses of other studies showed similar results. However, this new analysis adds more evidence to the importance of cognition in MS, Dr. Giovannoni noted.
“I have patients with EDSS of 0 or 1 who are profoundly disabled because of cognition. You shouldn’t just assume someone is not disabled because they don’t have physical disability,” he said.
However, Dr. Giovannoni noted that the study found an association and does not necessarily indicate a cause.
‘Valuable’ insights
Antonia Lefter, MD, of NeuroHope, Monza Oncologic Hospital, Bucharest, Romania, cochaired the session highlighting the research. Commenting on the study, she called this analysis from the “renowned” EXPAND study “valuable.”
In addition, it “underscores” the importance of assessing cognitive processing speed, as it may predict long-term disability progression in patients with SPMS, Dr. Lefter said.
The study was funded by Novartis Pharma AG, Basel, Switzerland. Dr. Giovannoni, a steering committee member of the EXPAND trial, reported receiving consulting fees from AbbVie, Actelion, Atara Bio, Biogen, Celgene, Sanofi-Genzyme, Genentech, GlaxoSmithKline, Merck-Serono, Novartis, Roche, and Reva. He has also received compensation for research from Biogen, Roche, Merck-Serono, Novartis, Sanofi-Genzyme, and Takeda. Dr. Lefter has reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
, new research suggests. In an analysis of more than 1,600 patients with secondary-progressive MS (SPMS), the likelihood of needing a wheelchair was almost doubled in those who had the worst scores on cognitive testing measures, compared with their counterparts who had the best scores.
“These findings should change our world view of MS,” study investigator Gavin Giovannoni, PhD, professor of neurology, Blizard Institute, Faculty of Medicine and Dentistry, Queen Mary University of London, told attendees at the Congress of the European Academy of Neurology.
On the basis of the results, clinicians should consider testing cognitive processing speed in patients with MS to identify those who are at increased risk for disease progression, Dr. Giovannoni noted. “I urge anybody who runs an MS service to think about putting in place mechanisms in their clinic” to measure cognition of patients over time, he said.
Expand data
Cognitive impairment occurs very early in the course of MS and is part of the disease, although to a greater or lesser degree depending on the patient, Dr. Giovannoni noted. Such impairment has a significant impact on quality of life for patients dealing with this disease, he added.
EXPAND was a phase 3 study of siponimod. Results showed the now-approved oral selective sphingosine 1–phosphate receptor modulator significantly reduced the risk for disability progression in patients with SPMS.
Using the EXPAND clinical trial database, the current researchers assessed 1,628 participants for an association between cognitive processing speed, as measured with the Symbol Digit Modality Test (SDMT), and physical disability progression, as measured with the Expanded Disability Status Scale (EDSS). A score of 7 or more on the EDSS indicates wheelchair dependence.
Dr. Giovannoni noted that cognitive processing speed is considered an indirect measure of thalamic network efficiency and functional brain reserve.
Investigators looked at both the core study, in which all patients continued on treatment or placebo for up to 37 months, and the core plus extension part, in which patients received treatment for up to 5 years.
They separated SDMT scores into quartiles: from worst (n = 435) to two intermediate quartiles (n = 808) to the best quartile (n = 385).
Wheelchair dependence
In addition, the researchers examined the predictive value by baseline SDMT, adjusting for treatment, age, gender, baseline EDSS score, baseline SCMT quartile, and treatment-by-baseline SCMT quartile interaction. On-study SDMT change (month 0-24) was also assessed after adjusting for treatment, age, gender, baseline EDS, baseline SCMT, and on-study change in SCMT quartile.
In the core study, those in the worst SDMT quartile at baseline were numerically more likely to reach deterioration to EDSS 7 or greater (wheelchair dependent), compared with patients in the best SDMT quartile (hazard ratio, 1.31; 95% confidence interval, .72-2.38; P = .371).
The short-term predictive value of baseline SDMT for reaching sustained EDSS of at least 7 was more obvious in the placebo arm than in the treatment arm.
Dr. Giovannoni said this is likely due to the treatment effect of siponimod preventing relatively more events in the worse quartile, and so reducing the risk for wheelchair dependency.
In the core plus extension part, there was an almost twofold increased risk for wheelchair dependence in the worse versus best SDMT groups (HR, 1.81; 95% CI, 1.17-2.78; P = .007).
Both baseline SDMT (HR, 1.81; P = .007) and on-study change in SDMT (HR, 1.73; P = .046) predicted wheelchair dependence in the long-term.
‘More important than a walking stick’
Measuring cognitive change over time “may be a more important predictor than a walking stick in terms of quality of life and outcomes, and it affects clinical decisionmaking,” said Dr. Giovannoni.
The findings are not novel, as post hoc analyses of other studies showed similar results. However, this new analysis adds more evidence to the importance of cognition in MS, Dr. Giovannoni noted.
“I have patients with EDSS of 0 or 1 who are profoundly disabled because of cognition. You shouldn’t just assume someone is not disabled because they don’t have physical disability,” he said.
However, Dr. Giovannoni noted that the study found an association and does not necessarily indicate a cause.
‘Valuable’ insights
Antonia Lefter, MD, of NeuroHope, Monza Oncologic Hospital, Bucharest, Romania, cochaired the session highlighting the research. Commenting on the study, she called this analysis from the “renowned” EXPAND study “valuable.”
In addition, it “underscores” the importance of assessing cognitive processing speed, as it may predict long-term disability progression in patients with SPMS, Dr. Lefter said.
The study was funded by Novartis Pharma AG, Basel, Switzerland. Dr. Giovannoni, a steering committee member of the EXPAND trial, reported receiving consulting fees from AbbVie, Actelion, Atara Bio, Biogen, Celgene, Sanofi-Genzyme, Genentech, GlaxoSmithKline, Merck-Serono, Novartis, Roche, and Reva. He has also received compensation for research from Biogen, Roche, Merck-Serono, Novartis, Sanofi-Genzyme, and Takeda. Dr. Lefter has reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
, new research suggests. In an analysis of more than 1,600 patients with secondary-progressive MS (SPMS), the likelihood of needing a wheelchair was almost doubled in those who had the worst scores on cognitive testing measures, compared with their counterparts who had the best scores.
“These findings should change our world view of MS,” study investigator Gavin Giovannoni, PhD, professor of neurology, Blizard Institute, Faculty of Medicine and Dentistry, Queen Mary University of London, told attendees at the Congress of the European Academy of Neurology.
On the basis of the results, clinicians should consider testing cognitive processing speed in patients with MS to identify those who are at increased risk for disease progression, Dr. Giovannoni noted. “I urge anybody who runs an MS service to think about putting in place mechanisms in their clinic” to measure cognition of patients over time, he said.
Expand data
Cognitive impairment occurs very early in the course of MS and is part of the disease, although to a greater or lesser degree depending on the patient, Dr. Giovannoni noted. Such impairment has a significant impact on quality of life for patients dealing with this disease, he added.
EXPAND was a phase 3 study of siponimod. Results showed the now-approved oral selective sphingosine 1–phosphate receptor modulator significantly reduced the risk for disability progression in patients with SPMS.
Using the EXPAND clinical trial database, the current researchers assessed 1,628 participants for an association between cognitive processing speed, as measured with the Symbol Digit Modality Test (SDMT), and physical disability progression, as measured with the Expanded Disability Status Scale (EDSS). A score of 7 or more on the EDSS indicates wheelchair dependence.
Dr. Giovannoni noted that cognitive processing speed is considered an indirect measure of thalamic network efficiency and functional brain reserve.
Investigators looked at both the core study, in which all patients continued on treatment or placebo for up to 37 months, and the core plus extension part, in which patients received treatment for up to 5 years.
They separated SDMT scores into quartiles: from worst (n = 435) to two intermediate quartiles (n = 808) to the best quartile (n = 385).
Wheelchair dependence
In addition, the researchers examined the predictive value by baseline SDMT, adjusting for treatment, age, gender, baseline EDSS score, baseline SCMT quartile, and treatment-by-baseline SCMT quartile interaction. On-study SDMT change (month 0-24) was also assessed after adjusting for treatment, age, gender, baseline EDS, baseline SCMT, and on-study change in SCMT quartile.
In the core study, those in the worst SDMT quartile at baseline were numerically more likely to reach deterioration to EDSS 7 or greater (wheelchair dependent), compared with patients in the best SDMT quartile (hazard ratio, 1.31; 95% confidence interval, .72-2.38; P = .371).
The short-term predictive value of baseline SDMT for reaching sustained EDSS of at least 7 was more obvious in the placebo arm than in the treatment arm.
Dr. Giovannoni said this is likely due to the treatment effect of siponimod preventing relatively more events in the worse quartile, and so reducing the risk for wheelchair dependency.
In the core plus extension part, there was an almost twofold increased risk for wheelchair dependence in the worse versus best SDMT groups (HR, 1.81; 95% CI, 1.17-2.78; P = .007).
Both baseline SDMT (HR, 1.81; P = .007) and on-study change in SDMT (HR, 1.73; P = .046) predicted wheelchair dependence in the long-term.
‘More important than a walking stick’
Measuring cognitive change over time “may be a more important predictor than a walking stick in terms of quality of life and outcomes, and it affects clinical decisionmaking,” said Dr. Giovannoni.
The findings are not novel, as post hoc analyses of other studies showed similar results. However, this new analysis adds more evidence to the importance of cognition in MS, Dr. Giovannoni noted.
“I have patients with EDSS of 0 or 1 who are profoundly disabled because of cognition. You shouldn’t just assume someone is not disabled because they don’t have physical disability,” he said.
However, Dr. Giovannoni noted that the study found an association and does not necessarily indicate a cause.
‘Valuable’ insights
Antonia Lefter, MD, of NeuroHope, Monza Oncologic Hospital, Bucharest, Romania, cochaired the session highlighting the research. Commenting on the study, she called this analysis from the “renowned” EXPAND study “valuable.”
In addition, it “underscores” the importance of assessing cognitive processing speed, as it may predict long-term disability progression in patients with SPMS, Dr. Lefter said.
The study was funded by Novartis Pharma AG, Basel, Switzerland. Dr. Giovannoni, a steering committee member of the EXPAND trial, reported receiving consulting fees from AbbVie, Actelion, Atara Bio, Biogen, Celgene, Sanofi-Genzyme, Genentech, GlaxoSmithKline, Merck-Serono, Novartis, Roche, and Reva. He has also received compensation for research from Biogen, Roche, Merck-Serono, Novartis, Sanofi-Genzyme, and Takeda. Dr. Lefter has reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
From EAN 2022
PTSD may accelerate cognitive decline over time
, new research suggests.
In an analysis of more than 12,000 middle-aged women who had experienced at least one trauma in their lives, those with PTSD symptoms showed an approximately twofold faster decline in cognition during follow-up compared with those who did not have PTSD symptoms.
These associations were not fully explained by other known cognition-related factors such as depression, the researchers noted.
“PTSD may increase the risk of dementia by accelerating cognitive decline at midlife,” coinvestigator Jiaxuan Liu, a doctoral candidate at Harvard TH Chan School of Public Health, Boston, said in an interview.
“Our findings may suggest the value of earlier cognitive screening among individuals with PTSD and the importance of PTSD prevention and treatment across the lifespan,” she added.
The results were published online in JAMA Network Open.
Vital public health issue
“Cognitive decline at midlife and older is of vital public health interest,” Ms. Liu said. “It is a risk factor for a variety of poor health outcomes and strongly predicts Alzheimer’s disease and other dementias.
Although PTSD has been linked to lower cognitive function and dementia incidence, it has not been known whether it is associated with decline in cognitive function, she added.
“In addition, both PTSD and dementia are more common in women than men, so it’s important to understand a possible link,” Ms. Liu said.
Because no large-scale study had examined whether PTSD is associated with cognitive decline in women, the current researchers examined PTSD symptoms and their association with repeated measures of cognitive function among a large civilian trauma-exposed cohort of women aged 50-70 years at study baseline.
Participants were drawn from the Nurses’ Health Study II, a longitudinal study of a cohort of 116,429 U.S. female nurses who were between 25 and 42 years old at enrollment in 1989. Participants completed biennial questionnaires, with follow-up on an ongoing basis.
The current analysis included 12,270 trauma-exposed women (mean age at baseline, 61.1 years) who completed assessments every 1 or 12 months for up to 24 months after baseline. The mean follow-up time was 0.9 years.
In the study population, 95.9% were non-Hispanic White, 1.3% were Hispanic, 1% were Asian, 0.6% were Black, and 1.2% were classified as “other.”
Higher depression scores
Lifetime trauma exposure and PTSD symptoms were assessed from March 1, 2008, to Feb. 28, 2010, using the Short Screening Scale for DSM-IV PTSD.
In total, 67% of the participants reported experiencing PTSD symptoms. The women were divided into four groups, on the basis of symptom number: no PTSD symptoms (n = 4,052), one to three PTSD symptoms (n = 5,058), four to five PTSD symptoms (n = 2,018), and six to seven PTSD symptoms (n = 1,052).
The Cogstate Brief Battery, a validated and self-administered online cognitive assessment, was completed by participants between Oct. 3, 2014, and July 30, 2019. The researchers measured cognitive function with two composite scores: psychomotor speed and attention, and learning and working memory.
Covariates potentially associated with cognitive decline included demographic, educational, and behavior-related health factors such as body mass index, physical activity, cigarette smoking, diet quality, and alcohol consumption.
The researchers conducted secondary analyses that adjusted for symptoms and history of depression as well as the consequences of potential practice effects of taking the test multiple times.
Behavior-related health factors “did not substantially differ by PTSD symptom level,” the investigators noted. However, compared with women who did not have PTSD symptoms, those who had such symptoms had higher depressive symptom scores and higher rates of clinician-diagnosed depression.
Both cognitive composite scores improved through the follow-up period, “likely because of practice effects,” the researchers wrote. But after adjusting for practice effects, they found a decline over time in both composite scores.
Dose-related trajectories
Results showed that having more PTSD symptoms was associated with dose-related poorer cognitive trajectories.
After adjustment for demographic characteristics, women with the highest symptom level (six to seven symptoms) had a significantly worse rate of change in both composite domains of learning and working memory (beta = −0.08 SD/y; 95% confidence interval [CI], −0.11 to −0.04 SD/y; P < .001) and of psychomotor speed and attention (beta = −0.05 SD/y; 95% CI, −0.09 to −0.01 SD/y; P = .02) compared with women with no PTSD symptoms.
Women with four to five PTSD symptoms showed a worse rate of change in learning and working memory compared with those who had no symptoms, but not in psychomotor speed and attention. Women with one to three PTSD symptoms had cognitive scores similar to those of women without PTSD symptoms.
Notably, the associations of PTSD with cognitive change remained evident after additional adjustment for behavioral factors and health conditions – and were only “partially attenuated but still evident” after further adjustment for practice effects and comorbid depression, the investigators wrote.
“We thought PTSD might be associated with worse cognitive decline through health behaviors like smoking and alcohol drinking and higher risk of other health conditions like hypertension and depression,” Ms. Liu said.
However, those factors did not account for the current study’s findings, she noted.
“We could not determine why women with PTSD had faster cognitive decline than those without PTSD,” she said.
Ms. Liu suggested that PTSD “may have effects on the brain, such as altering brain structures and affecting brain immune function.” However, more research is needed “to investigate these mechanisms that might underlie the association we found between PTSD and cognitive decline,” she said.
Neurotoxic effect
In a comment, Howard Fillit, MD, cofounder and chief science officer of the Alzheimer’s Drug Discovery Foundation, said, “It is well known that stress is neurotoxic, and PTSD is a particularly serious form of stress.”
Dr. Fillit, clinical professor of geriatric medicine and palliative care, medicine, and neuroscience at Mount Sinai Hospital, New York, was not involved with the study.
“We tend to think of PTSD in postacute settings, such as soldiers returning from war,” he said. “This study contributes to our understanding of the long-term effects of PTSD on cognitive decline, measured objectively over time”
Dr. Fillit noted that an important implication is that, by increasing the risk for cognitive decline, PTSD also increases risk for Alzheimer’s disease. This leads to the “main take-home, which is that PTSD is a risk factor not only for cognitive decline but also for Alzheimer’s and related dementias,” he said.
However, this opens a potential therapeutic approach, Dr. Fillit added.
Because cortisol and other stress hormones drive the stress response, finding ways to block the neurotoxic effects of these hormones “might be a target to prevent cognitive decline and decrease Alzheimer’s disease risk,” he said.
The study was supported by grants from the National Institute of Mental Health and the National Institutes of Health. Ms. Liu and Dr. Fillit report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
, new research suggests.
In an analysis of more than 12,000 middle-aged women who had experienced at least one trauma in their lives, those with PTSD symptoms showed an approximately twofold faster decline in cognition during follow-up compared with those who did not have PTSD symptoms.
These associations were not fully explained by other known cognition-related factors such as depression, the researchers noted.
“PTSD may increase the risk of dementia by accelerating cognitive decline at midlife,” coinvestigator Jiaxuan Liu, a doctoral candidate at Harvard TH Chan School of Public Health, Boston, said in an interview.
“Our findings may suggest the value of earlier cognitive screening among individuals with PTSD and the importance of PTSD prevention and treatment across the lifespan,” she added.
The results were published online in JAMA Network Open.
Vital public health issue
“Cognitive decline at midlife and older is of vital public health interest,” Ms. Liu said. “It is a risk factor for a variety of poor health outcomes and strongly predicts Alzheimer’s disease and other dementias.
Although PTSD has been linked to lower cognitive function and dementia incidence, it has not been known whether it is associated with decline in cognitive function, she added.
“In addition, both PTSD and dementia are more common in women than men, so it’s important to understand a possible link,” Ms. Liu said.
Because no large-scale study had examined whether PTSD is associated with cognitive decline in women, the current researchers examined PTSD symptoms and their association with repeated measures of cognitive function among a large civilian trauma-exposed cohort of women aged 50-70 years at study baseline.
Participants were drawn from the Nurses’ Health Study II, a longitudinal study of a cohort of 116,429 U.S. female nurses who were between 25 and 42 years old at enrollment in 1989. Participants completed biennial questionnaires, with follow-up on an ongoing basis.
The current analysis included 12,270 trauma-exposed women (mean age at baseline, 61.1 years) who completed assessments every 1 or 12 months for up to 24 months after baseline. The mean follow-up time was 0.9 years.
In the study population, 95.9% were non-Hispanic White, 1.3% were Hispanic, 1% were Asian, 0.6% were Black, and 1.2% were classified as “other.”
Higher depression scores
Lifetime trauma exposure and PTSD symptoms were assessed from March 1, 2008, to Feb. 28, 2010, using the Short Screening Scale for DSM-IV PTSD.
In total, 67% of the participants reported experiencing PTSD symptoms. The women were divided into four groups, on the basis of symptom number: no PTSD symptoms (n = 4,052), one to three PTSD symptoms (n = 5,058), four to five PTSD symptoms (n = 2,018), and six to seven PTSD symptoms (n = 1,052).
The Cogstate Brief Battery, a validated and self-administered online cognitive assessment, was completed by participants between Oct. 3, 2014, and July 30, 2019. The researchers measured cognitive function with two composite scores: psychomotor speed and attention, and learning and working memory.
Covariates potentially associated with cognitive decline included demographic, educational, and behavior-related health factors such as body mass index, physical activity, cigarette smoking, diet quality, and alcohol consumption.
The researchers conducted secondary analyses that adjusted for symptoms and history of depression as well as the consequences of potential practice effects of taking the test multiple times.
Behavior-related health factors “did not substantially differ by PTSD symptom level,” the investigators noted. However, compared with women who did not have PTSD symptoms, those who had such symptoms had higher depressive symptom scores and higher rates of clinician-diagnosed depression.
Both cognitive composite scores improved through the follow-up period, “likely because of practice effects,” the researchers wrote. But after adjusting for practice effects, they found a decline over time in both composite scores.
Dose-related trajectories
Results showed that having more PTSD symptoms was associated with dose-related poorer cognitive trajectories.
After adjustment for demographic characteristics, women with the highest symptom level (six to seven symptoms) had a significantly worse rate of change in both composite domains of learning and working memory (beta = −0.08 SD/y; 95% confidence interval [CI], −0.11 to −0.04 SD/y; P < .001) and of psychomotor speed and attention (beta = −0.05 SD/y; 95% CI, −0.09 to −0.01 SD/y; P = .02) compared with women with no PTSD symptoms.
Women with four to five PTSD symptoms showed a worse rate of change in learning and working memory compared with those who had no symptoms, but not in psychomotor speed and attention. Women with one to three PTSD symptoms had cognitive scores similar to those of women without PTSD symptoms.
Notably, the associations of PTSD with cognitive change remained evident after additional adjustment for behavioral factors and health conditions – and were only “partially attenuated but still evident” after further adjustment for practice effects and comorbid depression, the investigators wrote.
“We thought PTSD might be associated with worse cognitive decline through health behaviors like smoking and alcohol drinking and higher risk of other health conditions like hypertension and depression,” Ms. Liu said.
However, those factors did not account for the current study’s findings, she noted.
“We could not determine why women with PTSD had faster cognitive decline than those without PTSD,” she said.
Ms. Liu suggested that PTSD “may have effects on the brain, such as altering brain structures and affecting brain immune function.” However, more research is needed “to investigate these mechanisms that might underlie the association we found between PTSD and cognitive decline,” she said.
Neurotoxic effect
In a comment, Howard Fillit, MD, cofounder and chief science officer of the Alzheimer’s Drug Discovery Foundation, said, “It is well known that stress is neurotoxic, and PTSD is a particularly serious form of stress.”
Dr. Fillit, clinical professor of geriatric medicine and palliative care, medicine, and neuroscience at Mount Sinai Hospital, New York, was not involved with the study.
“We tend to think of PTSD in postacute settings, such as soldiers returning from war,” he said. “This study contributes to our understanding of the long-term effects of PTSD on cognitive decline, measured objectively over time”
Dr. Fillit noted that an important implication is that, by increasing the risk for cognitive decline, PTSD also increases risk for Alzheimer’s disease. This leads to the “main take-home, which is that PTSD is a risk factor not only for cognitive decline but also for Alzheimer’s and related dementias,” he said.
However, this opens a potential therapeutic approach, Dr. Fillit added.
Because cortisol and other stress hormones drive the stress response, finding ways to block the neurotoxic effects of these hormones “might be a target to prevent cognitive decline and decrease Alzheimer’s disease risk,” he said.
The study was supported by grants from the National Institute of Mental Health and the National Institutes of Health. Ms. Liu and Dr. Fillit report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
, new research suggests.
In an analysis of more than 12,000 middle-aged women who had experienced at least one trauma in their lives, those with PTSD symptoms showed an approximately twofold faster decline in cognition during follow-up compared with those who did not have PTSD symptoms.
These associations were not fully explained by other known cognition-related factors such as depression, the researchers noted.
“PTSD may increase the risk of dementia by accelerating cognitive decline at midlife,” coinvestigator Jiaxuan Liu, a doctoral candidate at Harvard TH Chan School of Public Health, Boston, said in an interview.
“Our findings may suggest the value of earlier cognitive screening among individuals with PTSD and the importance of PTSD prevention and treatment across the lifespan,” she added.
The results were published online in JAMA Network Open.
Vital public health issue
“Cognitive decline at midlife and older is of vital public health interest,” Ms. Liu said. “It is a risk factor for a variety of poor health outcomes and strongly predicts Alzheimer’s disease and other dementias.
Although PTSD has been linked to lower cognitive function and dementia incidence, it has not been known whether it is associated with decline in cognitive function, she added.
“In addition, both PTSD and dementia are more common in women than men, so it’s important to understand a possible link,” Ms. Liu said.
Because no large-scale study had examined whether PTSD is associated with cognitive decline in women, the current researchers examined PTSD symptoms and their association with repeated measures of cognitive function among a large civilian trauma-exposed cohort of women aged 50-70 years at study baseline.
Participants were drawn from the Nurses’ Health Study II, a longitudinal study of a cohort of 116,429 U.S. female nurses who were between 25 and 42 years old at enrollment in 1989. Participants completed biennial questionnaires, with follow-up on an ongoing basis.
The current analysis included 12,270 trauma-exposed women (mean age at baseline, 61.1 years) who completed assessments every 1 or 12 months for up to 24 months after baseline. The mean follow-up time was 0.9 years.
In the study population, 95.9% were non-Hispanic White, 1.3% were Hispanic, 1% were Asian, 0.6% were Black, and 1.2% were classified as “other.”
Higher depression scores
Lifetime trauma exposure and PTSD symptoms were assessed from March 1, 2008, to Feb. 28, 2010, using the Short Screening Scale for DSM-IV PTSD.
In total, 67% of the participants reported experiencing PTSD symptoms. The women were divided into four groups, on the basis of symptom number: no PTSD symptoms (n = 4,052), one to three PTSD symptoms (n = 5,058), four to five PTSD symptoms (n = 2,018), and six to seven PTSD symptoms (n = 1,052).
The Cogstate Brief Battery, a validated and self-administered online cognitive assessment, was completed by participants between Oct. 3, 2014, and July 30, 2019. The researchers measured cognitive function with two composite scores: psychomotor speed and attention, and learning and working memory.
Covariates potentially associated with cognitive decline included demographic, educational, and behavior-related health factors such as body mass index, physical activity, cigarette smoking, diet quality, and alcohol consumption.
The researchers conducted secondary analyses that adjusted for symptoms and history of depression as well as the consequences of potential practice effects of taking the test multiple times.
Behavior-related health factors “did not substantially differ by PTSD symptom level,” the investigators noted. However, compared with women who did not have PTSD symptoms, those who had such symptoms had higher depressive symptom scores and higher rates of clinician-diagnosed depression.
Both cognitive composite scores improved through the follow-up period, “likely because of practice effects,” the researchers wrote. But after adjusting for practice effects, they found a decline over time in both composite scores.
Dose-related trajectories
Results showed that having more PTSD symptoms was associated with dose-related poorer cognitive trajectories.
After adjustment for demographic characteristics, women with the highest symptom level (six to seven symptoms) had a significantly worse rate of change in both composite domains of learning and working memory (beta = −0.08 SD/y; 95% confidence interval [CI], −0.11 to −0.04 SD/y; P < .001) and of psychomotor speed and attention (beta = −0.05 SD/y; 95% CI, −0.09 to −0.01 SD/y; P = .02) compared with women with no PTSD symptoms.
Women with four to five PTSD symptoms showed a worse rate of change in learning and working memory compared with those who had no symptoms, but not in psychomotor speed and attention. Women with one to three PTSD symptoms had cognitive scores similar to those of women without PTSD symptoms.
Notably, the associations of PTSD with cognitive change remained evident after additional adjustment for behavioral factors and health conditions – and were only “partially attenuated but still evident” after further adjustment for practice effects and comorbid depression, the investigators wrote.
“We thought PTSD might be associated with worse cognitive decline through health behaviors like smoking and alcohol drinking and higher risk of other health conditions like hypertension and depression,” Ms. Liu said.
However, those factors did not account for the current study’s findings, she noted.
“We could not determine why women with PTSD had faster cognitive decline than those without PTSD,” she said.
Ms. Liu suggested that PTSD “may have effects on the brain, such as altering brain structures and affecting brain immune function.” However, more research is needed “to investigate these mechanisms that might underlie the association we found between PTSD and cognitive decline,” she said.
Neurotoxic effect
In a comment, Howard Fillit, MD, cofounder and chief science officer of the Alzheimer’s Drug Discovery Foundation, said, “It is well known that stress is neurotoxic, and PTSD is a particularly serious form of stress.”
Dr. Fillit, clinical professor of geriatric medicine and palliative care, medicine, and neuroscience at Mount Sinai Hospital, New York, was not involved with the study.
“We tend to think of PTSD in postacute settings, such as soldiers returning from war,” he said. “This study contributes to our understanding of the long-term effects of PTSD on cognitive decline, measured objectively over time”
Dr. Fillit noted that an important implication is that, by increasing the risk for cognitive decline, PTSD also increases risk for Alzheimer’s disease. This leads to the “main take-home, which is that PTSD is a risk factor not only for cognitive decline but also for Alzheimer’s and related dementias,” he said.
However, this opens a potential therapeutic approach, Dr. Fillit added.
Because cortisol and other stress hormones drive the stress response, finding ways to block the neurotoxic effects of these hormones “might be a target to prevent cognitive decline and decrease Alzheimer’s disease risk,” he said.
The study was supported by grants from the National Institute of Mental Health and the National Institutes of Health. Ms. Liu and Dr. Fillit report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM JAMA NETWORK OPEN
Scientists find brain mechanism behind age-related memory loss
Scientists at Johns Hopkins University have identified a mechanism in the brain behind age-related memory loss, expanding our knowledge of the inner workings of the aging brain and possibly opening the door to new Alzheimer’s treatments.
The researchers looked at the hippocampus, a part of the brain thought to store long-term memories.
Neurons there are responsible for a pair of memory functions – called pattern separation and pattern completion – that work together in young, healthy brains. These functions can swing out of balance with age, impacting memory.
The Johns Hopkins team may have discovered what causes this imbalance. Their findings – reported in a paper in the journal Current Biology – may not only help us improve dementia treatments, but even prevent or delay a loss of thinking skills in the first place, the researchers say.
Pattern separation vs. pattern completion
To understand how the hippocampus changes with age, the researchers looked at rats’ brains. In rats and in humans, pattern separation and pattern completion are present, controlled by neurons in the hippocampus.
As the name suggests, pattern completion is when you take a few details or fragments of information – a few notes of music, or the start of a famous movie quote – and your brain retrieves the full memory. Pattern separation, on the other hand, is being able to tell similar observations or experiences apart (like two visits to the same restaurant) to be stored as separate memories.
These functions occur along a gradient across a tiny region called CA3. That gradient, the study found, disappears with aging, said lead study author Hey-Kyoung Lee, PhD, an assistant research scientist at the university’s Zanvyl Krieger Mind/Brain Institute. “The main consequence of the loss,” Dr. Lee said, “is that pattern completion becomes more dominant in rats as they age.”
What’s happening in the brain
Neurons responsible for pattern completion occupy the “distal” end of CA3, while those in charge of pattern separation reside at the “proximal” end. Dr. Lee said prior studies had not examined the proximal and distal regions separately, as she and her team did in this study.
What was surprising, said Dr. Lee, “was that hyperactivity in aging was observed toward the proximal CA3 region, not the expected distal region.” Contrary to their expectations, that hyperactivity did not enhance function in that area but rather dampened it. Hence: “There is diminished pattern separation and augmented pattern completion,” she said.
– they may recall a certain restaurant they’d been to but not be able to separate what happened during one visit versus another.
Why do some older adults stay sharp?
That memory impairment does not happen to everyone, and it doesn’t happen to all rats either. In fact, the researchers found that some older rats performed spatial-learning tasks as well as young rats did – even though their brains were already beginning to favor pattern completion.
If we can better understand why this happens, we may uncover new therapies for age-related memory loss, Dr. Lee said.
Coauthor Michela Gallagher’s team previously demonstrated that the anti-epilepsy drug levetiracetam improves memory performance by reducing hyperactivity in the hippocampus.
The extra detail this study adds may allow scientists to better aim such drugs in the future, Dr. Lee speculated. “It would give us better control of where we could possibly target the deficits we see.”
A version of this article first appeared on WebMD.com.
Scientists at Johns Hopkins University have identified a mechanism in the brain behind age-related memory loss, expanding our knowledge of the inner workings of the aging brain and possibly opening the door to new Alzheimer’s treatments.
The researchers looked at the hippocampus, a part of the brain thought to store long-term memories.
Neurons there are responsible for a pair of memory functions – called pattern separation and pattern completion – that work together in young, healthy brains. These functions can swing out of balance with age, impacting memory.
The Johns Hopkins team may have discovered what causes this imbalance. Their findings – reported in a paper in the journal Current Biology – may not only help us improve dementia treatments, but even prevent or delay a loss of thinking skills in the first place, the researchers say.
Pattern separation vs. pattern completion
To understand how the hippocampus changes with age, the researchers looked at rats’ brains. In rats and in humans, pattern separation and pattern completion are present, controlled by neurons in the hippocampus.
As the name suggests, pattern completion is when you take a few details or fragments of information – a few notes of music, or the start of a famous movie quote – and your brain retrieves the full memory. Pattern separation, on the other hand, is being able to tell similar observations or experiences apart (like two visits to the same restaurant) to be stored as separate memories.
These functions occur along a gradient across a tiny region called CA3. That gradient, the study found, disappears with aging, said lead study author Hey-Kyoung Lee, PhD, an assistant research scientist at the university’s Zanvyl Krieger Mind/Brain Institute. “The main consequence of the loss,” Dr. Lee said, “is that pattern completion becomes more dominant in rats as they age.”
What’s happening in the brain
Neurons responsible for pattern completion occupy the “distal” end of CA3, while those in charge of pattern separation reside at the “proximal” end. Dr. Lee said prior studies had not examined the proximal and distal regions separately, as she and her team did in this study.
What was surprising, said Dr. Lee, “was that hyperactivity in aging was observed toward the proximal CA3 region, not the expected distal region.” Contrary to their expectations, that hyperactivity did not enhance function in that area but rather dampened it. Hence: “There is diminished pattern separation and augmented pattern completion,” she said.
– they may recall a certain restaurant they’d been to but not be able to separate what happened during one visit versus another.
Why do some older adults stay sharp?
That memory impairment does not happen to everyone, and it doesn’t happen to all rats either. In fact, the researchers found that some older rats performed spatial-learning tasks as well as young rats did – even though their brains were already beginning to favor pattern completion.
If we can better understand why this happens, we may uncover new therapies for age-related memory loss, Dr. Lee said.
Coauthor Michela Gallagher’s team previously demonstrated that the anti-epilepsy drug levetiracetam improves memory performance by reducing hyperactivity in the hippocampus.
The extra detail this study adds may allow scientists to better aim such drugs in the future, Dr. Lee speculated. “It would give us better control of where we could possibly target the deficits we see.”
A version of this article first appeared on WebMD.com.
Scientists at Johns Hopkins University have identified a mechanism in the brain behind age-related memory loss, expanding our knowledge of the inner workings of the aging brain and possibly opening the door to new Alzheimer’s treatments.
The researchers looked at the hippocampus, a part of the brain thought to store long-term memories.
Neurons there are responsible for a pair of memory functions – called pattern separation and pattern completion – that work together in young, healthy brains. These functions can swing out of balance with age, impacting memory.
The Johns Hopkins team may have discovered what causes this imbalance. Their findings – reported in a paper in the journal Current Biology – may not only help us improve dementia treatments, but even prevent or delay a loss of thinking skills in the first place, the researchers say.
Pattern separation vs. pattern completion
To understand how the hippocampus changes with age, the researchers looked at rats’ brains. In rats and in humans, pattern separation and pattern completion are present, controlled by neurons in the hippocampus.
As the name suggests, pattern completion is when you take a few details or fragments of information – a few notes of music, or the start of a famous movie quote – and your brain retrieves the full memory. Pattern separation, on the other hand, is being able to tell similar observations or experiences apart (like two visits to the same restaurant) to be stored as separate memories.
These functions occur along a gradient across a tiny region called CA3. That gradient, the study found, disappears with aging, said lead study author Hey-Kyoung Lee, PhD, an assistant research scientist at the university’s Zanvyl Krieger Mind/Brain Institute. “The main consequence of the loss,” Dr. Lee said, “is that pattern completion becomes more dominant in rats as they age.”
What’s happening in the brain
Neurons responsible for pattern completion occupy the “distal” end of CA3, while those in charge of pattern separation reside at the “proximal” end. Dr. Lee said prior studies had not examined the proximal and distal regions separately, as she and her team did in this study.
What was surprising, said Dr. Lee, “was that hyperactivity in aging was observed toward the proximal CA3 region, not the expected distal region.” Contrary to their expectations, that hyperactivity did not enhance function in that area but rather dampened it. Hence: “There is diminished pattern separation and augmented pattern completion,” she said.
– they may recall a certain restaurant they’d been to but not be able to separate what happened during one visit versus another.
Why do some older adults stay sharp?
That memory impairment does not happen to everyone, and it doesn’t happen to all rats either. In fact, the researchers found that some older rats performed spatial-learning tasks as well as young rats did – even though their brains were already beginning to favor pattern completion.
If we can better understand why this happens, we may uncover new therapies for age-related memory loss, Dr. Lee said.
Coauthor Michela Gallagher’s team previously demonstrated that the anti-epilepsy drug levetiracetam improves memory performance by reducing hyperactivity in the hippocampus.
The extra detail this study adds may allow scientists to better aim such drugs in the future, Dr. Lee speculated. “It would give us better control of where we could possibly target the deficits we see.”
A version of this article first appeared on WebMD.com.
FROM CURRENT BIOLOGY
Can bone density scans help predict dementia risk?
, new research suggests.
In an analysis of more than 900 study participants, women in their 70s with more advanced abdominal aortic calcification (AAC) seen on lateral spine images during dual-energy x-ray absorptiometry (DXA) had a two- to fourfold higher risk for late-life dementia than those with low AAC.
This finding was independent of cardiovascular risk factors and apolipoprotein E (APOE ) genotype.
“While these results are exciting, we now need to undertake further large screening studies in older men and women using this approach to show that the findings are generalizable to older men and can identify people with greater cognitive decline,” coinvestigator Marc Sim, PhD, Edith Cowan University, Joondalup, Australia, said in an interview.
“This will hopefully open the door to studies of early disease-modifying interventions,” Sim said.
The findings were published online in The Lancet Regional Health – Western Pacific.
AAC and cognition
Late-life dementia occurring after age 80 is increasingly common because of both vascular and nonvascular risk factors.
Two recent studies in middle-aged and older men and women showed that AAC identified on bone densitometry was associated with poorer cognition, suggesting it may be related to cognitive decline and increased dementia risk.
This provided the rationale for the current study, Dr. Sim noted.
The researchers assessed AAC using DXA lateral spine images captured in the late 1990s in a prospective cohort of 958 older women who were participating in an osteoporosis study.
AAC was classified into established low, moderate, and extensive categories. At baseline, all women were aged 70 and older, and 45% had low AAC, 36% had moderate AAC, and 19% had extensive AAC.
Over 14.5 years, 150 women (15.7%) had a late-life hospitalization and/or died.
Improved risk prediction
Results showed that, compared with women who had low AAC, women with moderate and extensive AAC were more likely to experience late-life dementia hospitalization (9.3% low, 15.5% moderate, and 18.3% extensive) and death (2.8%, 8.3%, and 9.4%, respectively).
After multivariable adjustment, women with moderate AAC had a two- and threefold increased relative risk for late-life dementia hospitalization or death, compared with their peers who had low AAC.
Women with extensive AAC had a two- and fourfold increase in the adjusted relative risk for late-life dementia hospitalization or death.
“To our knowledge this is the first time it has been shown that AAC from these scans is related to late-life dementia,” Dr. Sim said.
“We demonstrated that AAC improved risk prediction in addition to cardiovascular risk factors and APOE genotype, a genetic risk factor for Alzheimer’s disease, the major form of dementia,” he added.
Dr. Sim noted “these additional lateral spine images” can be taken at the same time that hip and spine bone density tests are done.
“This provides an opportunity to identify AAC in large numbers of people,” he said.
He cautioned, however, that further studies with detailed dementia-related phenotypes, brain imaging, and measures of cognition are needed to confirm whether AAC will add value to dementia risk prediction.
‘Not surprising’
Commenting on the findings for this article, Claire Sexton, DPhil, senior director of scientific programs and outreach at the Alzheimer’s Association, Chicago, noted that AAC is a marker of atherosclerosis and is associated with vascular health outcomes.
Therefore, it is “not surprising it would be associated with dementia too. There’s been previous research linking atherosclerosis and Alzheimer’s disease,” Dr. Sexton said.
“What’s novel about this research is that it’s looking at AAC specifically, which can be identified through a relatively simple test that is already in widespread use,” she added.
Dr. Sexton noted that “much more research” is now needed in larger, more diverse populations in order to better understand the link between AAC and dementia – and whether bone density testing may be an appropriate dementia-screening tool.
“The good news is vascular conditions like atherosclerosis can be managed through lifestyle changes like eating a healthy diet and getting regular exercise. And research tells us what’s good for the heart is good for the brain,” Dr. Sexton said.
The study was funded by Kidney Health Australia, Healthway Health Promotion Foundation of Western Australia, Sir Charles Gairdner Hospital Research Advisory Committee Grant, and the National Health and Medical Research Council of Australia. Dr. Sim and Dr. Sexton have reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
, new research suggests.
In an analysis of more than 900 study participants, women in their 70s with more advanced abdominal aortic calcification (AAC) seen on lateral spine images during dual-energy x-ray absorptiometry (DXA) had a two- to fourfold higher risk for late-life dementia than those with low AAC.
This finding was independent of cardiovascular risk factors and apolipoprotein E (APOE ) genotype.
“While these results are exciting, we now need to undertake further large screening studies in older men and women using this approach to show that the findings are generalizable to older men and can identify people with greater cognitive decline,” coinvestigator Marc Sim, PhD, Edith Cowan University, Joondalup, Australia, said in an interview.
“This will hopefully open the door to studies of early disease-modifying interventions,” Sim said.
The findings were published online in The Lancet Regional Health – Western Pacific.
AAC and cognition
Late-life dementia occurring after age 80 is increasingly common because of both vascular and nonvascular risk factors.
Two recent studies in middle-aged and older men and women showed that AAC identified on bone densitometry was associated with poorer cognition, suggesting it may be related to cognitive decline and increased dementia risk.
This provided the rationale for the current study, Dr. Sim noted.
The researchers assessed AAC using DXA lateral spine images captured in the late 1990s in a prospective cohort of 958 older women who were participating in an osteoporosis study.
AAC was classified into established low, moderate, and extensive categories. At baseline, all women were aged 70 and older, and 45% had low AAC, 36% had moderate AAC, and 19% had extensive AAC.
Over 14.5 years, 150 women (15.7%) had a late-life hospitalization and/or died.
Improved risk prediction
Results showed that, compared with women who had low AAC, women with moderate and extensive AAC were more likely to experience late-life dementia hospitalization (9.3% low, 15.5% moderate, and 18.3% extensive) and death (2.8%, 8.3%, and 9.4%, respectively).
After multivariable adjustment, women with moderate AAC had a two- and threefold increased relative risk for late-life dementia hospitalization or death, compared with their peers who had low AAC.
Women with extensive AAC had a two- and fourfold increase in the adjusted relative risk for late-life dementia hospitalization or death.
“To our knowledge this is the first time it has been shown that AAC from these scans is related to late-life dementia,” Dr. Sim said.
“We demonstrated that AAC improved risk prediction in addition to cardiovascular risk factors and APOE genotype, a genetic risk factor for Alzheimer’s disease, the major form of dementia,” he added.
Dr. Sim noted “these additional lateral spine images” can be taken at the same time that hip and spine bone density tests are done.
“This provides an opportunity to identify AAC in large numbers of people,” he said.
He cautioned, however, that further studies with detailed dementia-related phenotypes, brain imaging, and measures of cognition are needed to confirm whether AAC will add value to dementia risk prediction.
‘Not surprising’
Commenting on the findings for this article, Claire Sexton, DPhil, senior director of scientific programs and outreach at the Alzheimer’s Association, Chicago, noted that AAC is a marker of atherosclerosis and is associated with vascular health outcomes.
Therefore, it is “not surprising it would be associated with dementia too. There’s been previous research linking atherosclerosis and Alzheimer’s disease,” Dr. Sexton said.
“What’s novel about this research is that it’s looking at AAC specifically, which can be identified through a relatively simple test that is already in widespread use,” she added.
Dr. Sexton noted that “much more research” is now needed in larger, more diverse populations in order to better understand the link between AAC and dementia – and whether bone density testing may be an appropriate dementia-screening tool.
“The good news is vascular conditions like atherosclerosis can be managed through lifestyle changes like eating a healthy diet and getting regular exercise. And research tells us what’s good for the heart is good for the brain,” Dr. Sexton said.
The study was funded by Kidney Health Australia, Healthway Health Promotion Foundation of Western Australia, Sir Charles Gairdner Hospital Research Advisory Committee Grant, and the National Health and Medical Research Council of Australia. Dr. Sim and Dr. Sexton have reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
, new research suggests.
In an analysis of more than 900 study participants, women in their 70s with more advanced abdominal aortic calcification (AAC) seen on lateral spine images during dual-energy x-ray absorptiometry (DXA) had a two- to fourfold higher risk for late-life dementia than those with low AAC.
This finding was independent of cardiovascular risk factors and apolipoprotein E (APOE ) genotype.
“While these results are exciting, we now need to undertake further large screening studies in older men and women using this approach to show that the findings are generalizable to older men and can identify people with greater cognitive decline,” coinvestigator Marc Sim, PhD, Edith Cowan University, Joondalup, Australia, said in an interview.
“This will hopefully open the door to studies of early disease-modifying interventions,” Sim said.
The findings were published online in The Lancet Regional Health – Western Pacific.
AAC and cognition
Late-life dementia occurring after age 80 is increasingly common because of both vascular and nonvascular risk factors.
Two recent studies in middle-aged and older men and women showed that AAC identified on bone densitometry was associated with poorer cognition, suggesting it may be related to cognitive decline and increased dementia risk.
This provided the rationale for the current study, Dr. Sim noted.
The researchers assessed AAC using DXA lateral spine images captured in the late 1990s in a prospective cohort of 958 older women who were participating in an osteoporosis study.
AAC was classified into established low, moderate, and extensive categories. At baseline, all women were aged 70 and older, and 45% had low AAC, 36% had moderate AAC, and 19% had extensive AAC.
Over 14.5 years, 150 women (15.7%) had a late-life hospitalization and/or died.
Improved risk prediction
Results showed that, compared with women who had low AAC, women with moderate and extensive AAC were more likely to experience late-life dementia hospitalization (9.3% low, 15.5% moderate, and 18.3% extensive) and death (2.8%, 8.3%, and 9.4%, respectively).
After multivariable adjustment, women with moderate AAC had a two- and threefold increased relative risk for late-life dementia hospitalization or death, compared with their peers who had low AAC.
Women with extensive AAC had a two- and fourfold increase in the adjusted relative risk for late-life dementia hospitalization or death.
“To our knowledge this is the first time it has been shown that AAC from these scans is related to late-life dementia,” Dr. Sim said.
“We demonstrated that AAC improved risk prediction in addition to cardiovascular risk factors and APOE genotype, a genetic risk factor for Alzheimer’s disease, the major form of dementia,” he added.
Dr. Sim noted “these additional lateral spine images” can be taken at the same time that hip and spine bone density tests are done.
“This provides an opportunity to identify AAC in large numbers of people,” he said.
He cautioned, however, that further studies with detailed dementia-related phenotypes, brain imaging, and measures of cognition are needed to confirm whether AAC will add value to dementia risk prediction.
‘Not surprising’
Commenting on the findings for this article, Claire Sexton, DPhil, senior director of scientific programs and outreach at the Alzheimer’s Association, Chicago, noted that AAC is a marker of atherosclerosis and is associated with vascular health outcomes.
Therefore, it is “not surprising it would be associated with dementia too. There’s been previous research linking atherosclerosis and Alzheimer’s disease,” Dr. Sexton said.
“What’s novel about this research is that it’s looking at AAC specifically, which can be identified through a relatively simple test that is already in widespread use,” she added.
Dr. Sexton noted that “much more research” is now needed in larger, more diverse populations in order to better understand the link between AAC and dementia – and whether bone density testing may be an appropriate dementia-screening tool.
“The good news is vascular conditions like atherosclerosis can be managed through lifestyle changes like eating a healthy diet and getting regular exercise. And research tells us what’s good for the heart is good for the brain,” Dr. Sexton said.
The study was funded by Kidney Health Australia, Healthway Health Promotion Foundation of Western Australia, Sir Charles Gairdner Hospital Research Advisory Committee Grant, and the National Health and Medical Research Council of Australia. Dr. Sim and Dr. Sexton have reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM THE LANCET REGIONAL HEALTH – WESTERN PACIFIC
More evidence the flu vaccine may guard against Alzheimer’s
In a large propensity-matched cohort of older adults, those who had received at least one influenza inoculation were 40% less likely than unvaccinated peers to develop AD over the course of 4 years.
“Influenza infection can cause serious health complications, particularly in adults 65 and older. Our study’s findings – that vaccination against the flu virus may also reduce the risk of Alzheimer’s dementia for at least a few years – adds to the already compelling reasons get the flu vaccine annually,” Avram Bukhbinder, MD, of the University of Texas, Houston, said in an interview.
The new findings support earlier work by the same researchers that also suggested a protective effect of flu vaccination on dementia risk.
The latest study was published online in the Journal of Alzheimer’s Disease.
40% lower risk
Prior studies have found a lower risk of dementia of any etiology following influenza vaccination in selected populations, including veterans and patients with serious chronic health conditions.
However, the effect of influenza vaccination on AD risk in a general cohort of older U.S. adults has not been characterized.
Dr. Bukhbinder and colleagues used claims data to create a propensity-matched cohort of 935,887 influenza-vaccinated adults and a like number of unvaccinated adults aged 65 and older.
The median age of the persons in the matched sample was 73.7 years, and 57% were women. All were free of dementia during the 6-year look-back study period.
During median follow-up of 46 months, 47,889 (5.1%) flu-vaccinated adults and 79,630 (8.5%) unvaccinated adults developed AD.
The risk of AD was 40% lower in the vaccinated group (relative risk, 0.60; 95% confidence interval, 0.59-0.61). The absolute risk reduction was 0.034 (95% CI, 0.033-0.035), corresponding to a number needed to treat of 29.4.
Mechanism unclear
“Our study does not address the mechanism(s) underlying the apparent effect of influenza vaccination on Alzheimer’s risk, but we look forward to future research investigating this important question,” Dr. Bukhbinder said.
“One possible mechanism is that, by helping to prevent or mitigate infection with the flu virus and the systemic inflammation that follows such an infection, the flu vaccine helps to decrease the systemic inflammation that may have otherwise occurred,” he explained.
It’s also possible that influenza vaccination may trigger non–influenza-specific changes in the immune system that help to reduce the damage caused by AD pathology, including amyloid plaques and neurofibrillary tangles, he said.
“For example, the influenza vaccine may alter the brain’s immune cells such that they are better at clearing Alzheimer’s pathologies, an effect that has been seen in mice, or it may reprogram these immune cells to respond to Alzheimer’s pathologies in ways that are less likely to damage nearby healthy brain cells, or it may do both,” Dr. Bukhbinder noted.
Alzheimer’s expert weighs in
Heather M. Snyder, PhD, vice president of medical and scientific relations for the Alzheimer’s Association, said this study “suggests that flu vaccination may be valuable for maintaining cognition and memory as we age. This is even more relevant today in the COVID-19 environment.
“It is too early to tell if getting flu vaccine, on its own, can reduce risk of Alzheimer’s. More research is needed to understand the biological mechanisms behind the results in this study,” Dr. Snyder said in an interview.
“For example, it is possible that people who are getting vaccinated also take better care of their health in other ways, and these things add up to lower risk of Alzheimer’s and other dementias,” she noted.
“It is also possible that there are issues related to unequal access and/or vaccine hesitancy and how this may influence the study population and the research results,” Dr. Snyder said.
The study had no specific funding. Dr. Bukhbinder and Dr. Snyder disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
In a large propensity-matched cohort of older adults, those who had received at least one influenza inoculation were 40% less likely than unvaccinated peers to develop AD over the course of 4 years.
“Influenza infection can cause serious health complications, particularly in adults 65 and older. Our study’s findings – that vaccination against the flu virus may also reduce the risk of Alzheimer’s dementia for at least a few years – adds to the already compelling reasons get the flu vaccine annually,” Avram Bukhbinder, MD, of the University of Texas, Houston, said in an interview.
The new findings support earlier work by the same researchers that also suggested a protective effect of flu vaccination on dementia risk.
The latest study was published online in the Journal of Alzheimer’s Disease.
40% lower risk
Prior studies have found a lower risk of dementia of any etiology following influenza vaccination in selected populations, including veterans and patients with serious chronic health conditions.
However, the effect of influenza vaccination on AD risk in a general cohort of older U.S. adults has not been characterized.
Dr. Bukhbinder and colleagues used claims data to create a propensity-matched cohort of 935,887 influenza-vaccinated adults and a like number of unvaccinated adults aged 65 and older.
The median age of the persons in the matched sample was 73.7 years, and 57% were women. All were free of dementia during the 6-year look-back study period.
During median follow-up of 46 months, 47,889 (5.1%) flu-vaccinated adults and 79,630 (8.5%) unvaccinated adults developed AD.
The risk of AD was 40% lower in the vaccinated group (relative risk, 0.60; 95% confidence interval, 0.59-0.61). The absolute risk reduction was 0.034 (95% CI, 0.033-0.035), corresponding to a number needed to treat of 29.4.
Mechanism unclear
“Our study does not address the mechanism(s) underlying the apparent effect of influenza vaccination on Alzheimer’s risk, but we look forward to future research investigating this important question,” Dr. Bukhbinder said.
“One possible mechanism is that, by helping to prevent or mitigate infection with the flu virus and the systemic inflammation that follows such an infection, the flu vaccine helps to decrease the systemic inflammation that may have otherwise occurred,” he explained.
It’s also possible that influenza vaccination may trigger non–influenza-specific changes in the immune system that help to reduce the damage caused by AD pathology, including amyloid plaques and neurofibrillary tangles, he said.
“For example, the influenza vaccine may alter the brain’s immune cells such that they are better at clearing Alzheimer’s pathologies, an effect that has been seen in mice, or it may reprogram these immune cells to respond to Alzheimer’s pathologies in ways that are less likely to damage nearby healthy brain cells, or it may do both,” Dr. Bukhbinder noted.
Alzheimer’s expert weighs in
Heather M. Snyder, PhD, vice president of medical and scientific relations for the Alzheimer’s Association, said this study “suggests that flu vaccination may be valuable for maintaining cognition and memory as we age. This is even more relevant today in the COVID-19 environment.
“It is too early to tell if getting flu vaccine, on its own, can reduce risk of Alzheimer’s. More research is needed to understand the biological mechanisms behind the results in this study,” Dr. Snyder said in an interview.
“For example, it is possible that people who are getting vaccinated also take better care of their health in other ways, and these things add up to lower risk of Alzheimer’s and other dementias,” she noted.
“It is also possible that there are issues related to unequal access and/or vaccine hesitancy and how this may influence the study population and the research results,” Dr. Snyder said.
The study had no specific funding. Dr. Bukhbinder and Dr. Snyder disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
In a large propensity-matched cohort of older adults, those who had received at least one influenza inoculation were 40% less likely than unvaccinated peers to develop AD over the course of 4 years.
“Influenza infection can cause serious health complications, particularly in adults 65 and older. Our study’s findings – that vaccination against the flu virus may also reduce the risk of Alzheimer’s dementia for at least a few years – adds to the already compelling reasons get the flu vaccine annually,” Avram Bukhbinder, MD, of the University of Texas, Houston, said in an interview.
The new findings support earlier work by the same researchers that also suggested a protective effect of flu vaccination on dementia risk.
The latest study was published online in the Journal of Alzheimer’s Disease.
40% lower risk
Prior studies have found a lower risk of dementia of any etiology following influenza vaccination in selected populations, including veterans and patients with serious chronic health conditions.
However, the effect of influenza vaccination on AD risk in a general cohort of older U.S. adults has not been characterized.
Dr. Bukhbinder and colleagues used claims data to create a propensity-matched cohort of 935,887 influenza-vaccinated adults and a like number of unvaccinated adults aged 65 and older.
The median age of the persons in the matched sample was 73.7 years, and 57% were women. All were free of dementia during the 6-year look-back study period.
During median follow-up of 46 months, 47,889 (5.1%) flu-vaccinated adults and 79,630 (8.5%) unvaccinated adults developed AD.
The risk of AD was 40% lower in the vaccinated group (relative risk, 0.60; 95% confidence interval, 0.59-0.61). The absolute risk reduction was 0.034 (95% CI, 0.033-0.035), corresponding to a number needed to treat of 29.4.
Mechanism unclear
“Our study does not address the mechanism(s) underlying the apparent effect of influenza vaccination on Alzheimer’s risk, but we look forward to future research investigating this important question,” Dr. Bukhbinder said.
“One possible mechanism is that, by helping to prevent or mitigate infection with the flu virus and the systemic inflammation that follows such an infection, the flu vaccine helps to decrease the systemic inflammation that may have otherwise occurred,” he explained.
It’s also possible that influenza vaccination may trigger non–influenza-specific changes in the immune system that help to reduce the damage caused by AD pathology, including amyloid plaques and neurofibrillary tangles, he said.
“For example, the influenza vaccine may alter the brain’s immune cells such that they are better at clearing Alzheimer’s pathologies, an effect that has been seen in mice, or it may reprogram these immune cells to respond to Alzheimer’s pathologies in ways that are less likely to damage nearby healthy brain cells, or it may do both,” Dr. Bukhbinder noted.
Alzheimer’s expert weighs in
Heather M. Snyder, PhD, vice president of medical and scientific relations for the Alzheimer’s Association, said this study “suggests that flu vaccination may be valuable for maintaining cognition and memory as we age. This is even more relevant today in the COVID-19 environment.
“It is too early to tell if getting flu vaccine, on its own, can reduce risk of Alzheimer’s. More research is needed to understand the biological mechanisms behind the results in this study,” Dr. Snyder said in an interview.
“For example, it is possible that people who are getting vaccinated also take better care of their health in other ways, and these things add up to lower risk of Alzheimer’s and other dementias,” she noted.
“It is also possible that there are issues related to unequal access and/or vaccine hesitancy and how this may influence the study population and the research results,” Dr. Snyder said.
The study had no specific funding. Dr. Bukhbinder and Dr. Snyder disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM THE JOURNAL OF ALZHEIMER’S DISEASE
COVID-19 tied to increased risk for Alzheimer’s disease and Parkinson’s disease
a new study suggests. However, the research also showed there was no excess risk of these neurologic disorders following COVID than other respiratory infections such as influenza or community-acquired bacterial pneumonia.
Considering these results, study investigator Pardis Zarifkar, MD, department of neurology, Rigshospitalet, Copenhagen University Hospital, urged doctors to “keep an eye on” COVID patients and use “a critical mindset” if these patients present with neurologic issues.
“They should consider whether the patient’s condition is something new or if there were already signs and symptoms before they had COVID-19,” she said.
The findings were presented at the 2022 congress of the European Academy of Neurology and published online in Frontiers in Neurology.
‘Surprising’ increased risk
Previous research shows more than 80% of patients hospitalized with COVID-19 have neurologic symptoms including anosmia, dysgeusia, headache, dizziness, memory and concentration difficulties, fatigue, and irritability.
However, it’s unclear whether COVID-19 affects the risk for specific neurologic diseases and if so, whether this association differs from other respiratory infections.
From electronic health records covering about half the Danish population, researchers identified adults who were tested for COVID-19 or diagnosed with community-acquired bacterial pneumonia from February 2020 to November 2021. They also flagged individuals with influenza in the corresponding prepandemic period (February 2018–November 2019).
Dr. Zarifkar noted influenza A or B and community-acquired bacterial pneumonia are two of the most common respiratory tract infections.
The investigators tracked neurologic diseases up to 12 months after a positive test. They looked at two neurodegenerative diseases, Alzheimer’s disease and Parkinson’s disease, as well as cerebrovascular disorders including ischemic stroke, intracerebral hemorrhage, and subarachnoid hemorrhage.
The study included 43,262 individuals with a positive COVID test without a history of influenza A/B in the past year and 876,356 without a positive COVID test. It also included 1,474 individuals with community-acquired pneumonia without a history of COVID and 8,102 with influenza A or B.
“We wanted to investigate whether COVID-19 is really that much worse than all these other common respiratory infections that we have had for ages and see every single year,” said Dr. Zarifkar.
After 12 months, the relative risk for Alzheimer’s disease was 3.4 (95% confidence interval, 2.3-5.1) in the COVID-positive group versus the COVID-negative group. The risks were greater among inpatients versus outpatients.
These results were rather unexpected, said Dr. Zarifkar. “I would have expected a small increase, but the extent of the increase was quite surprising.”
However, there was no difference when comparing the COVID-19 group with the influenza or bacterial pneumonia groups, which Dr. Zarifkar said was “very reassuring.”
The findings were similar for Parkinson’s disease, where there was a 2.2-fold increased risk of a Parkinson’s disease diagnosis within the first 12 months in COVID-positive individuals, compared with COVID-negative people (RR, 2.2; 95% CI, 1.5-3.4). Again, there was no excess risk, compared with influenza or bacterial pneumonia.
Potential mechanisms
Dr. Zarifkar believes a “constellation” of factors may explain higher risks of these diagnoses in COVID patients. Part of it could be a result of neuroinflammation, which can lead to a toxic accumulation of beta amyloid in Alzheimer’s disease and alpha-synuclein in Parkinson’s disease.
“It can accelerate a neurodegenerative disease already in the making,” she said. But perhaps the biggest driver of differences between the groups is the “scientific focus” on COVID patients. “In Denmark, almost everyone who has had COVID-19, especially severe COVID-19, is offered some sort of cognitive testing, and if you hand out MoCAs [Montreal Cognitive Assessments] which is the cognitive test we use, to almost everyone you’re meeting, you’re going to catch these disorders earlier than you might have otherwise.”
As for cerebrovascular disorders, the study showed an increased risk of ischemic stroke in COVID-positive versus COVID-negative subjects at 12 months (RR, 2.87; 95% confidence interval, 2.2-3.2).
The relatively strong inflammatory response associated with COVID-19, which may create a hypercoagulable state, may help explain the increased ischemic stroke risk in COVID patients, said Dr. Zarifkar.
The study did not show an increased risk for subarachnoid hemorrhage in COVID-positive, compared with COVID-negative, subjects but did reveal an increased risk of intracerebral hemorrhage after 12 months (RR, 4.8; 95% CI, 1.8-12.9).
This could be explained by COVID-positive subjects having a higher risk for ischemic stroke and receiving thrombolysis that may increase risk for bleeding in the brain. However, an analysis accounting for medication use found differences in thrombolysis rates didn’t change the result, said Dr. Zarifkar.
It’s also possible that extracorporeal membrane oxygenation and mechanical ventilation – interventions more frequently used in COVID-19 patients – may increase the risk for bleeding in brain, she added.
The researchers did not find an increased risk for multiple sclerosis, myasthenia gravis, Guillain-Barré syndrome, or narcolepsy in COVID patients. However, Dr. Zarifkar noted that it can take years to detect an association with autoimmune disorders.
The investigators did not stratify risk by disease severity, although this would be an important step, she said. “The threshold of being admitted to the hospital with COVID-19 has been much lower than for influenza or bacterial pneumonia where you’re typically quite ill before you’re admitted, so this might actually dilute the findings and underestimate our findings.”
A national, registry-based study that includes the entire Danish population and additional information on vaccination status, virus variants, socioeconomic status, and comorbidities is needed, said Dr. Zarifkar.
The study was supported by Lundbeck Foundation and Novo Nordisk. Dr. Zarifkar reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
a new study suggests. However, the research also showed there was no excess risk of these neurologic disorders following COVID than other respiratory infections such as influenza or community-acquired bacterial pneumonia.
Considering these results, study investigator Pardis Zarifkar, MD, department of neurology, Rigshospitalet, Copenhagen University Hospital, urged doctors to “keep an eye on” COVID patients and use “a critical mindset” if these patients present with neurologic issues.
“They should consider whether the patient’s condition is something new or if there were already signs and symptoms before they had COVID-19,” she said.
The findings were presented at the 2022 congress of the European Academy of Neurology and published online in Frontiers in Neurology.
‘Surprising’ increased risk
Previous research shows more than 80% of patients hospitalized with COVID-19 have neurologic symptoms including anosmia, dysgeusia, headache, dizziness, memory and concentration difficulties, fatigue, and irritability.
However, it’s unclear whether COVID-19 affects the risk for specific neurologic diseases and if so, whether this association differs from other respiratory infections.
From electronic health records covering about half the Danish population, researchers identified adults who were tested for COVID-19 or diagnosed with community-acquired bacterial pneumonia from February 2020 to November 2021. They also flagged individuals with influenza in the corresponding prepandemic period (February 2018–November 2019).
Dr. Zarifkar noted influenza A or B and community-acquired bacterial pneumonia are two of the most common respiratory tract infections.
The investigators tracked neurologic diseases up to 12 months after a positive test. They looked at two neurodegenerative diseases, Alzheimer’s disease and Parkinson’s disease, as well as cerebrovascular disorders including ischemic stroke, intracerebral hemorrhage, and subarachnoid hemorrhage.
The study included 43,262 individuals with a positive COVID test without a history of influenza A/B in the past year and 876,356 without a positive COVID test. It also included 1,474 individuals with community-acquired pneumonia without a history of COVID and 8,102 with influenza A or B.
“We wanted to investigate whether COVID-19 is really that much worse than all these other common respiratory infections that we have had for ages and see every single year,” said Dr. Zarifkar.
After 12 months, the relative risk for Alzheimer’s disease was 3.4 (95% confidence interval, 2.3-5.1) in the COVID-positive group versus the COVID-negative group. The risks were greater among inpatients versus outpatients.
These results were rather unexpected, said Dr. Zarifkar. “I would have expected a small increase, but the extent of the increase was quite surprising.”
However, there was no difference when comparing the COVID-19 group with the influenza or bacterial pneumonia groups, which Dr. Zarifkar said was “very reassuring.”
The findings were similar for Parkinson’s disease, where there was a 2.2-fold increased risk of a Parkinson’s disease diagnosis within the first 12 months in COVID-positive individuals, compared with COVID-negative people (RR, 2.2; 95% CI, 1.5-3.4). Again, there was no excess risk, compared with influenza or bacterial pneumonia.
Potential mechanisms
Dr. Zarifkar believes a “constellation” of factors may explain higher risks of these diagnoses in COVID patients. Part of it could be a result of neuroinflammation, which can lead to a toxic accumulation of beta amyloid in Alzheimer’s disease and alpha-synuclein in Parkinson’s disease.
“It can accelerate a neurodegenerative disease already in the making,” she said. But perhaps the biggest driver of differences between the groups is the “scientific focus” on COVID patients. “In Denmark, almost everyone who has had COVID-19, especially severe COVID-19, is offered some sort of cognitive testing, and if you hand out MoCAs [Montreal Cognitive Assessments] which is the cognitive test we use, to almost everyone you’re meeting, you’re going to catch these disorders earlier than you might have otherwise.”
As for cerebrovascular disorders, the study showed an increased risk of ischemic stroke in COVID-positive versus COVID-negative subjects at 12 months (RR, 2.87; 95% confidence interval, 2.2-3.2).
The relatively strong inflammatory response associated with COVID-19, which may create a hypercoagulable state, may help explain the increased ischemic stroke risk in COVID patients, said Dr. Zarifkar.
The study did not show an increased risk for subarachnoid hemorrhage in COVID-positive, compared with COVID-negative, subjects but did reveal an increased risk of intracerebral hemorrhage after 12 months (RR, 4.8; 95% CI, 1.8-12.9).
This could be explained by COVID-positive subjects having a higher risk for ischemic stroke and receiving thrombolysis that may increase risk for bleeding in the brain. However, an analysis accounting for medication use found differences in thrombolysis rates didn’t change the result, said Dr. Zarifkar.
It’s also possible that extracorporeal membrane oxygenation and mechanical ventilation – interventions more frequently used in COVID-19 patients – may increase the risk for bleeding in brain, she added.
The researchers did not find an increased risk for multiple sclerosis, myasthenia gravis, Guillain-Barré syndrome, or narcolepsy in COVID patients. However, Dr. Zarifkar noted that it can take years to detect an association with autoimmune disorders.
The investigators did not stratify risk by disease severity, although this would be an important step, she said. “The threshold of being admitted to the hospital with COVID-19 has been much lower than for influenza or bacterial pneumonia where you’re typically quite ill before you’re admitted, so this might actually dilute the findings and underestimate our findings.”
A national, registry-based study that includes the entire Danish population and additional information on vaccination status, virus variants, socioeconomic status, and comorbidities is needed, said Dr. Zarifkar.
The study was supported by Lundbeck Foundation and Novo Nordisk. Dr. Zarifkar reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
a new study suggests. However, the research also showed there was no excess risk of these neurologic disorders following COVID than other respiratory infections such as influenza or community-acquired bacterial pneumonia.
Considering these results, study investigator Pardis Zarifkar, MD, department of neurology, Rigshospitalet, Copenhagen University Hospital, urged doctors to “keep an eye on” COVID patients and use “a critical mindset” if these patients present with neurologic issues.
“They should consider whether the patient’s condition is something new or if there were already signs and symptoms before they had COVID-19,” she said.
The findings were presented at the 2022 congress of the European Academy of Neurology and published online in Frontiers in Neurology.
‘Surprising’ increased risk
Previous research shows more than 80% of patients hospitalized with COVID-19 have neurologic symptoms including anosmia, dysgeusia, headache, dizziness, memory and concentration difficulties, fatigue, and irritability.
However, it’s unclear whether COVID-19 affects the risk for specific neurologic diseases and if so, whether this association differs from other respiratory infections.
From electronic health records covering about half the Danish population, researchers identified adults who were tested for COVID-19 or diagnosed with community-acquired bacterial pneumonia from February 2020 to November 2021. They also flagged individuals with influenza in the corresponding prepandemic period (February 2018–November 2019).
Dr. Zarifkar noted influenza A or B and community-acquired bacterial pneumonia are two of the most common respiratory tract infections.
The investigators tracked neurologic diseases up to 12 months after a positive test. They looked at two neurodegenerative diseases, Alzheimer’s disease and Parkinson’s disease, as well as cerebrovascular disorders including ischemic stroke, intracerebral hemorrhage, and subarachnoid hemorrhage.
The study included 43,262 individuals with a positive COVID test without a history of influenza A/B in the past year and 876,356 without a positive COVID test. It also included 1,474 individuals with community-acquired pneumonia without a history of COVID and 8,102 with influenza A or B.
“We wanted to investigate whether COVID-19 is really that much worse than all these other common respiratory infections that we have had for ages and see every single year,” said Dr. Zarifkar.
After 12 months, the relative risk for Alzheimer’s disease was 3.4 (95% confidence interval, 2.3-5.1) in the COVID-positive group versus the COVID-negative group. The risks were greater among inpatients versus outpatients.
These results were rather unexpected, said Dr. Zarifkar. “I would have expected a small increase, but the extent of the increase was quite surprising.”
However, there was no difference when comparing the COVID-19 group with the influenza or bacterial pneumonia groups, which Dr. Zarifkar said was “very reassuring.”
The findings were similar for Parkinson’s disease, where there was a 2.2-fold increased risk of a Parkinson’s disease diagnosis within the first 12 months in COVID-positive individuals, compared with COVID-negative people (RR, 2.2; 95% CI, 1.5-3.4). Again, there was no excess risk, compared with influenza or bacterial pneumonia.
Potential mechanisms
Dr. Zarifkar believes a “constellation” of factors may explain higher risks of these diagnoses in COVID patients. Part of it could be a result of neuroinflammation, which can lead to a toxic accumulation of beta amyloid in Alzheimer’s disease and alpha-synuclein in Parkinson’s disease.
“It can accelerate a neurodegenerative disease already in the making,” she said. But perhaps the biggest driver of differences between the groups is the “scientific focus” on COVID patients. “In Denmark, almost everyone who has had COVID-19, especially severe COVID-19, is offered some sort of cognitive testing, and if you hand out MoCAs [Montreal Cognitive Assessments] which is the cognitive test we use, to almost everyone you’re meeting, you’re going to catch these disorders earlier than you might have otherwise.”
As for cerebrovascular disorders, the study showed an increased risk of ischemic stroke in COVID-positive versus COVID-negative subjects at 12 months (RR, 2.87; 95% confidence interval, 2.2-3.2).
The relatively strong inflammatory response associated with COVID-19, which may create a hypercoagulable state, may help explain the increased ischemic stroke risk in COVID patients, said Dr. Zarifkar.
The study did not show an increased risk for subarachnoid hemorrhage in COVID-positive, compared with COVID-negative, subjects but did reveal an increased risk of intracerebral hemorrhage after 12 months (RR, 4.8; 95% CI, 1.8-12.9).
This could be explained by COVID-positive subjects having a higher risk for ischemic stroke and receiving thrombolysis that may increase risk for bleeding in the brain. However, an analysis accounting for medication use found differences in thrombolysis rates didn’t change the result, said Dr. Zarifkar.
It’s also possible that extracorporeal membrane oxygenation and mechanical ventilation – interventions more frequently used in COVID-19 patients – may increase the risk for bleeding in brain, she added.
The researchers did not find an increased risk for multiple sclerosis, myasthenia gravis, Guillain-Barré syndrome, or narcolepsy in COVID patients. However, Dr. Zarifkar noted that it can take years to detect an association with autoimmune disorders.
The investigators did not stratify risk by disease severity, although this would be an important step, she said. “The threshold of being admitted to the hospital with COVID-19 has been much lower than for influenza or bacterial pneumonia where you’re typically quite ill before you’re admitted, so this might actually dilute the findings and underestimate our findings.”
A national, registry-based study that includes the entire Danish population and additional information on vaccination status, virus variants, socioeconomic status, and comorbidities is needed, said Dr. Zarifkar.
The study was supported by Lundbeck Foundation and Novo Nordisk. Dr. Zarifkar reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM FRONTIERS IN NEUROLOGY