Alzheimer's & Cognition

U.K. scientists show it is possible to spot signs of brain impairment in patients as early as 9 years before they receive a diagnosis of dementia, offering hope for interventions to reduce the risk of the disease developing.

To date it has been unclear whether it might be possible to detect changes in brain function before the onset of symptoms, so researchers at the University of Cambridge and Cambridge University Hospitals NHS Foundation Trust set out to determine whether people who developed a range of neurodegenerative diagnoses demonstrated reduced cognitive function at their baseline assessment.

The authors explained: “The pathophysiological processes of neurodegenerative diseases begin years before diagnosis. However, prediagnostic changes in cognition and physical function are poorly understood, especially in sporadic neurodegenerative disease.”
 

Prediagnostic cognitive and functional impairment identified

The researchers analyzed data from the UK Biobank and compared cognitive and functional measures, including problem solving, memory, reaction times and grip strength, as well as data on weight loss and gain and on the number of falls, in individuals who subsequently developed a number of dementia-related diseases (Alzheimer’s disease, Parkinson’s disease, frontotemporal dementia, progressive supranuclear palsy, dementia with Lewy bodies, and multiple system atrophy), with those who did not have a neurodegenerative diagnosis. After adjustment for the effects of age, the same measures were regressed against time to diagnosis. The study was published in Alzheimer’s & Dementia: The Journal of the Alzheimer’s Association.

The researchers found evidence of prediagnostic cognitive impairment and decline with time, particularly in Alzheimer’s disease where those who went on to develop the disease scored more poorly compared with healthy individuals when it came to problem solving tasks, reaction times, remembering lists of numbers, prospective memory, and pair matching. This was also the case for people who developed frontotemporal dementia, the authors said.

Nol Swaddiwudhipong, MB, of the University of Cambridge, and first author, said: “When we looked back at patients’ histories, it became clear that they were showing some cognitive impairment several years before their symptoms became obvious enough to prompt a diagnosis. The impairments were often subtle, but across a number of aspects of cognition.”

Prediagnostic functional impairment and decline was also observed in multiple diseases, the authors said. People who went on to develop Alzheimer’s disease were more likely than were healthy adults to have had a fall in the previous 12 months, with those patients who went on to develop progressive supranuclear palsy (PSP) being more than twice as likely as healthy individuals to have had a fall.

The time between baseline assessment and diagnosis varied between 4.7 years for dementia with Lewy bodies and 8.3 years for Alzheimer’s disease.

“For every condition studied – including Parkinson’s disease and dementia with Lewy bodies – patients reported poorer overall health at baseline,” said the authors.
 

Potential for new treatments

The study findings that cognitive and functional decline occurs “years before symptoms become obvious” in multiple neurodegenerative diseases, raises the possibility that in the future at-risk patients could be screened to help select those who would benefit from interventions to reduce their risk of developing one of the conditions, or to help identify patients suitable for recruitment to clinical trials for new treatments.

Dr Swaddiwudhipong emphasized: “This is a step towards us being able to screen people who are at greatest risk – for example, people over 50 or those who have high blood pressure or do not do enough exercise – and intervene at an earlier stage to help them reduce their risk.”

There are currently very few effective treatments for dementia or other forms of neurodegeneration, the authors pointed out, in part because these conditions are often only diagnosed once symptoms appear, whereas the underlying neurodegeneration may have “begun years, even decades, earlier.” This means that by the time patients take part in clinical trials, it may already be too late in the disease process to alter its course, they explained.

Timothy Rittman, BMBS, PhD, department of clinical neurosciences, University of Cambridge, and senior author, explained that the findings could also help identify people who can participate in clinical trials for potential new treatments. “The problem with clinical trials is that by necessity they often recruit patients with a diagnosis, but we know that by this point they are already some way down the road and their condition cannot be stopped. If we can find these individuals early enough, we’ll have a better chance of seeing if the drugs are effective,” he emphasized.

Commenting on the new research, Richard Oakley, PhD, associate director of research at Alzheimer’s Society, said: “Studies like this show the importance in continued investment in dementia research to revolutionize diagnosis and drive new treatments, so one day we will beat dementia.”

The research was funded by the Medical Research Council with support from the NIHR Cambridge Biomedical Research Centre. The authors reported no conflicts of interest.

A version of this article first appeared on Medscape UK.

U.K. scientists show it is possible to spot signs of brain impairment in patients as early as 9 years before they receive a diagnosis of dementia, offering hope for interventions to reduce the risk of the disease developing.

To date it has been unclear whether it might be possible to detect changes in brain function before the onset of symptoms, so researchers at the University of Cambridge and Cambridge University Hospitals NHS Foundation Trust set out to determine whether people who developed a range of neurodegenerative diagnoses demonstrated reduced cognitive function at their baseline assessment.

The authors explained: “The pathophysiological processes of neurodegenerative diseases begin years before diagnosis. However, prediagnostic changes in cognition and physical function are poorly understood, especially in sporadic neurodegenerative disease.”
 

Prediagnostic cognitive and functional impairment identified

The researchers analyzed data from the UK Biobank and compared cognitive and functional measures, including problem solving, memory, reaction times and grip strength, as well as data on weight loss and gain and on the number of falls, in individuals who subsequently developed a number of dementia-related diseases (Alzheimer’s disease, Parkinson’s disease, frontotemporal dementia, progressive supranuclear palsy, dementia with Lewy bodies, and multiple system atrophy), with those who did not have a neurodegenerative diagnosis. After adjustment for the effects of age, the same measures were regressed against time to diagnosis. The study was published in Alzheimer’s & Dementia: The Journal of the Alzheimer’s Association.

The researchers found evidence of prediagnostic cognitive impairment and decline with time, particularly in Alzheimer’s disease where those who went on to develop the disease scored more poorly compared with healthy individuals when it came to problem solving tasks, reaction times, remembering lists of numbers, prospective memory, and pair matching. This was also the case for people who developed frontotemporal dementia, the authors said.

Nol Swaddiwudhipong, MB, of the University of Cambridge, and first author, said: “When we looked back at patients’ histories, it became clear that they were showing some cognitive impairment several years before their symptoms became obvious enough to prompt a diagnosis. The impairments were often subtle, but across a number of aspects of cognition.”

Prediagnostic functional impairment and decline was also observed in multiple diseases, the authors said. People who went on to develop Alzheimer’s disease were more likely than were healthy adults to have had a fall in the previous 12 months, with those patients who went on to develop progressive supranuclear palsy (PSP) being more than twice as likely as healthy individuals to have had a fall.

The time between baseline assessment and diagnosis varied between 4.7 years for dementia with Lewy bodies and 8.3 years for Alzheimer’s disease.

“For every condition studied – including Parkinson’s disease and dementia with Lewy bodies – patients reported poorer overall health at baseline,” said the authors.
 

Potential for new treatments

The study findings that cognitive and functional decline occurs “years before symptoms become obvious” in multiple neurodegenerative diseases, raises the possibility that in the future at-risk patients could be screened to help select those who would benefit from interventions to reduce their risk of developing one of the conditions, or to help identify patients suitable for recruitment to clinical trials for new treatments.

Dr Swaddiwudhipong emphasized: “This is a step towards us being able to screen people who are at greatest risk – for example, people over 50 or those who have high blood pressure or do not do enough exercise – and intervene at an earlier stage to help them reduce their risk.”

There are currently very few effective treatments for dementia or other forms of neurodegeneration, the authors pointed out, in part because these conditions are often only diagnosed once symptoms appear, whereas the underlying neurodegeneration may have “begun years, even decades, earlier.” This means that by the time patients take part in clinical trials, it may already be too late in the disease process to alter its course, they explained.

Timothy Rittman, BMBS, PhD, department of clinical neurosciences, University of Cambridge, and senior author, explained that the findings could also help identify people who can participate in clinical trials for potential new treatments. “The problem with clinical trials is that by necessity they often recruit patients with a diagnosis, but we know that by this point they are already some way down the road and their condition cannot be stopped. If we can find these individuals early enough, we’ll have a better chance of seeing if the drugs are effective,” he emphasized.

Commenting on the new research, Richard Oakley, PhD, associate director of research at Alzheimer’s Society, said: “Studies like this show the importance in continued investment in dementia research to revolutionize diagnosis and drive new treatments, so one day we will beat dementia.”

The research was funded by the Medical Research Council with support from the NIHR Cambridge Biomedical Research Centre. The authors reported no conflicts of interest.

A version of this article first appeared on Medscape UK.

U.K. scientists show it is possible to spot signs of brain impairment in patients as early as 9 years before they receive a diagnosis of dementia, offering hope for interventions to reduce the risk of the disease developing.

To date it has been unclear whether it might be possible to detect changes in brain function before the onset of symptoms, so researchers at the University of Cambridge and Cambridge University Hospitals NHS Foundation Trust set out to determine whether people who developed a range of neurodegenerative diagnoses demonstrated reduced cognitive function at their baseline assessment.

The authors explained: “The pathophysiological processes of neurodegenerative diseases begin years before diagnosis. However, prediagnostic changes in cognition and physical function are poorly understood, especially in sporadic neurodegenerative disease.”
 

Prediagnostic cognitive and functional impairment identified

The researchers analyzed data from the UK Biobank and compared cognitive and functional measures, including problem solving, memory, reaction times and grip strength, as well as data on weight loss and gain and on the number of falls, in individuals who subsequently developed a number of dementia-related diseases (Alzheimer’s disease, Parkinson’s disease, frontotemporal dementia, progressive supranuclear palsy, dementia with Lewy bodies, and multiple system atrophy), with those who did not have a neurodegenerative diagnosis. After adjustment for the effects of age, the same measures were regressed against time to diagnosis. The study was published in Alzheimer’s & Dementia: The Journal of the Alzheimer’s Association.

The researchers found evidence of prediagnostic cognitive impairment and decline with time, particularly in Alzheimer’s disease where those who went on to develop the disease scored more poorly compared with healthy individuals when it came to problem solving tasks, reaction times, remembering lists of numbers, prospective memory, and pair matching. This was also the case for people who developed frontotemporal dementia, the authors said.

Nol Swaddiwudhipong, MB, of the University of Cambridge, and first author, said: “When we looked back at patients’ histories, it became clear that they were showing some cognitive impairment several years before their symptoms became obvious enough to prompt a diagnosis. The impairments were often subtle, but across a number of aspects of cognition.”

Prediagnostic functional impairment and decline was also observed in multiple diseases, the authors said. People who went on to develop Alzheimer’s disease were more likely than were healthy adults to have had a fall in the previous 12 months, with those patients who went on to develop progressive supranuclear palsy (PSP) being more than twice as likely as healthy individuals to have had a fall.

The time between baseline assessment and diagnosis varied between 4.7 years for dementia with Lewy bodies and 8.3 years for Alzheimer’s disease.

“For every condition studied – including Parkinson’s disease and dementia with Lewy bodies – patients reported poorer overall health at baseline,” said the authors.
 

Potential for new treatments

The study findings that cognitive and functional decline occurs “years before symptoms become obvious” in multiple neurodegenerative diseases, raises the possibility that in the future at-risk patients could be screened to help select those who would benefit from interventions to reduce their risk of developing one of the conditions, or to help identify patients suitable for recruitment to clinical trials for new treatments.

Dr Swaddiwudhipong emphasized: “This is a step towards us being able to screen people who are at greatest risk – for example, people over 50 or those who have high blood pressure or do not do enough exercise – and intervene at an earlier stage to help them reduce their risk.”

There are currently very few effective treatments for dementia or other forms of neurodegeneration, the authors pointed out, in part because these conditions are often only diagnosed once symptoms appear, whereas the underlying neurodegeneration may have “begun years, even decades, earlier.” This means that by the time patients take part in clinical trials, it may already be too late in the disease process to alter its course, they explained.

Timothy Rittman, BMBS, PhD, department of clinical neurosciences, University of Cambridge, and senior author, explained that the findings could also help identify people who can participate in clinical trials for potential new treatments. “The problem with clinical trials is that by necessity they often recruit patients with a diagnosis, but we know that by this point they are already some way down the road and their condition cannot be stopped. If we can find these individuals early enough, we’ll have a better chance of seeing if the drugs are effective,” he emphasized.

Commenting on the new research, Richard Oakley, PhD, associate director of research at Alzheimer’s Society, said: “Studies like this show the importance in continued investment in dementia research to revolutionize diagnosis and drive new treatments, so one day we will beat dementia.”

The research was funded by the Medical Research Council with support from the NIHR Cambridge Biomedical Research Centre. The authors reported no conflicts of interest.

A version of this article first appeared on Medscape UK.

Thiazolidinediones (TZDs), such as pioglitazone, appear to be protective against dementia whereas sulfonylureas appear to increase the risk, a new observational study in patients with type 2 diabetes suggests.

The data, obtained from nationwide electronic medical records from the Department of Veterans Affairs, yielded a 22% lower risk of dementia with TZD monotherapy and a 12% elevated risk with sulfonylurea monotherapy, compared with metformin monotherapy. The apparent protective effects of TZDs were greater among individuals with overweight or obesity.

“Our findings provide additional information to aid clinicians’ selection of [glucose-lowering medications] for patients with mild or moderate type 2 diabetes and [who] are at high risk of dementia,” Xin Tang and colleagues wrote in their article, published online in BMJ Open Diabetes Research & Care.

The results “add substantially to the literature concerning the effects of [glucose-lowering medications] on dementia where previous findings have been inconsistent. Studies with a follow-up time of less than 3 years have mainly reported null associations, while studies with longer a follow-up time typically yielded protective findings. With a mean follow-up time of 6.8 years, we had a sufficient duration to detect treatment differences,” the investigators wrote.

“Supplementing [a] sulfonylurea with either metformin or [a] TZD may partially offset its prodementia effects. These findings may help inform medication selection for elderly patients with T2D at high risk of dementia,” they added.
 

Randomized trials needed to determine cause and effect

Ivan Koychev, PhD, a senior clinical researcher in the department of psychiatry at the University of Oxford (England), told the UK Science Media Centre: “This is a large, well-conducted real-world data study that highlights the importance of checking whether already prescribed medications may be useful for preventing dementia.”

The findings regarding TZDs, also known as glitazones, are in line with existing literature suggesting dementia protection with other drugs prescribed for type 2 diabetes that weren’t examined in the current study, such as newer agents like glucagonlike peptide–1 (GLP-1) agonists and sodium-glucose cotransporter 2 (SGLT2) inhibitors, Dr. Koychev said.

“The main limitations of this study is that following the initial 2-year period the authors were interested in, the participants may have been prescribed one of the other type 2 diabetes drugs [GLP-1 agonists or SGLT2 inhibitors] that have been found to reduce dementia risk, thus potentially making the direct glitazone [TZD] effect more difficult to discern,” Dr. Koychev noted.

And, he pointed out that the study design limits attribution of causality. “It is also important to note that people with type 2 diabetes do run a higher risk of both dementia and cognitive deficits and that these medications are only prescribed in these patients, so all this data is from this patient group rather than the general population.”

James Connell, PhD, head of translational science at Alzheimer’s Research UK, agreed. “While this observational study found that those with type 2 diabetes taking thiazolidinedione had a lower dementia risk than those on the most common medication for type 2 diabetes, it only shows an association between taking the drug and dementia risk and not a causal relationship.

“Double-blind and placebo-controlled clinical trials are needed to see whether the drug [TDZ] could help lower dementia risk in people with and without diabetes. Anyone with any questions about what treatments they are receiving should speak to their doctor,” he told the UK Science Media Centre.
 

Opposite effects of sulfonylureas, TZDs versus metformin

The study authors analyzed 559,106 VA patients with type 2 diabetes who initiated glucose-lowering medication during 2001-2017 and took it for at least a year. They were aged 60 years or older and did not have dementia at baseline. Most were White (76.8%) and male (96.9%), two-thirds (63.1%) had obesity, and mean hemoglobin A1c was 6.8%.

Overall, 31,125 developed all-cause dementia. The incidence rate was 8.2 cases per 1,000 person-years, ranging from 6.2 cases per 1,000 person-years among those taking metformin monotherapy to 13.4 cases per 1,000 person-years in those taking both sulfonylurea and a TZD.

Compared with metformin monotherapy, the hazard ratio for all-cause dementia for sulfonylurea monotherapy was a significant 1.12. The increased risk was also seen for vascular dementia, with an HR of 1.14.

In contrast, TZD monotherapy was associated with a significantly lower risk for all-cause dementia (HR, 0.78), as well as for Alzheimer’s disease (HR, 0.89) and vascular dementia (HR, 0.43), compared with metformin monotherapy.

The combination of metformin and TZD also lowered the risk of all-cause dementia, while regimens including sulfonylureas raised the risks for all-cause and vascular dementia.

Most of the results didn’t change significantly when the drug exposure window was extended to 2 years.
 

Effects more pronounced in those with obesity

The protective 1-year effects of TZD monotherapy and of metformin plus TZD, compared with metformin alone, were more significant among participants aged 75 or younger and with a body mass index above 25 kg/m², compared with those who were older than 75 years and with normal BMIs, respectively.

On the other hand, the greater risk for dementia incurred with sulfonylureas was further increased among those with higher BMI.

This research was partially funded by grants from the National Human Genome Research Institute, the National Science Foundation, the National Institute of Diabetes and Digestive and Kidney Disease, and the National Heart, Lung, and Blood Institute. Dr. Koychev is chief investigator for a trial, sponsored by Oxford University and funded by Novo Nordisk, testing whether the GLP-1 agonist semaglutide reduces the risk for dementia in aging adults.

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

Thiazolidinediones (TZDs), such as pioglitazone, appear to be protective against dementia whereas sulfonylureas appear to increase the risk, a new observational study in patients with type 2 diabetes suggests.

The data, obtained from nationwide electronic medical records from the Department of Veterans Affairs, yielded a 22% lower risk of dementia with TZD monotherapy and a 12% elevated risk with sulfonylurea monotherapy, compared with metformin monotherapy. The apparent protective effects of TZDs were greater among individuals with overweight or obesity.

“Our findings provide additional information to aid clinicians’ selection of [glucose-lowering medications] for patients with mild or moderate type 2 diabetes and [who] are at high risk of dementia,” Xin Tang and colleagues wrote in their article, published online in BMJ Open Diabetes Research & Care.

The results “add substantially to the literature concerning the effects of [glucose-lowering medications] on dementia where previous findings have been inconsistent. Studies with a follow-up time of less than 3 years have mainly reported null associations, while studies with longer a follow-up time typically yielded protective findings. With a mean follow-up time of 6.8 years, we had a sufficient duration to detect treatment differences,” the investigators wrote.

“Supplementing [a] sulfonylurea with either metformin or [a] TZD may partially offset its prodementia effects. These findings may help inform medication selection for elderly patients with T2D at high risk of dementia,” they added.
 

Randomized trials needed to determine cause and effect

Ivan Koychev, PhD, a senior clinical researcher in the department of psychiatry at the University of Oxford (England), told the UK Science Media Centre: “This is a large, well-conducted real-world data study that highlights the importance of checking whether already prescribed medications may be useful for preventing dementia.”

The findings regarding TZDs, also known as glitazones, are in line with existing literature suggesting dementia protection with other drugs prescribed for type 2 diabetes that weren’t examined in the current study, such as newer agents like glucagonlike peptide–1 (GLP-1) agonists and sodium-glucose cotransporter 2 (SGLT2) inhibitors, Dr. Koychev said.

“The main limitations of this study is that following the initial 2-year period the authors were interested in, the participants may have been prescribed one of the other type 2 diabetes drugs [GLP-1 agonists or SGLT2 inhibitors] that have been found to reduce dementia risk, thus potentially making the direct glitazone [TZD] effect more difficult to discern,” Dr. Koychev noted.

And, he pointed out that the study design limits attribution of causality. “It is also important to note that people with type 2 diabetes do run a higher risk of both dementia and cognitive deficits and that these medications are only prescribed in these patients, so all this data is from this patient group rather than the general population.”

James Connell, PhD, head of translational science at Alzheimer’s Research UK, agreed. “While this observational study found that those with type 2 diabetes taking thiazolidinedione had a lower dementia risk than those on the most common medication for type 2 diabetes, it only shows an association between taking the drug and dementia risk and not a causal relationship.

“Double-blind and placebo-controlled clinical trials are needed to see whether the drug [TDZ] could help lower dementia risk in people with and without diabetes. Anyone with any questions about what treatments they are receiving should speak to their doctor,” he told the UK Science Media Centre.
 

Opposite effects of sulfonylureas, TZDs versus metformin

The study authors analyzed 559,106 VA patients with type 2 diabetes who initiated glucose-lowering medication during 2001-2017 and took it for at least a year. They were aged 60 years or older and did not have dementia at baseline. Most were White (76.8%) and male (96.9%), two-thirds (63.1%) had obesity, and mean hemoglobin A1c was 6.8%.

Overall, 31,125 developed all-cause dementia. The incidence rate was 8.2 cases per 1,000 person-years, ranging from 6.2 cases per 1,000 person-years among those taking metformin monotherapy to 13.4 cases per 1,000 person-years in those taking both sulfonylurea and a TZD.

Compared with metformin monotherapy, the hazard ratio for all-cause dementia for sulfonylurea monotherapy was a significant 1.12. The increased risk was also seen for vascular dementia, with an HR of 1.14.

In contrast, TZD monotherapy was associated with a significantly lower risk for all-cause dementia (HR, 0.78), as well as for Alzheimer’s disease (HR, 0.89) and vascular dementia (HR, 0.43), compared with metformin monotherapy.

The combination of metformin and TZD also lowered the risk of all-cause dementia, while regimens including sulfonylureas raised the risks for all-cause and vascular dementia.

Most of the results didn’t change significantly when the drug exposure window was extended to 2 years.
 

Effects more pronounced in those with obesity

The protective 1-year effects of TZD monotherapy and of metformin plus TZD, compared with metformin alone, were more significant among participants aged 75 or younger and with a body mass index above 25 kg/m², compared with those who were older than 75 years and with normal BMIs, respectively.

On the other hand, the greater risk for dementia incurred with sulfonylureas was further increased among those with higher BMI.

This research was partially funded by grants from the National Human Genome Research Institute, the National Science Foundation, the National Institute of Diabetes and Digestive and Kidney Disease, and the National Heart, Lung, and Blood Institute. Dr. Koychev is chief investigator for a trial, sponsored by Oxford University and funded by Novo Nordisk, testing whether the GLP-1 agonist semaglutide reduces the risk for dementia in aging adults.

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

Thiazolidinediones (TZDs), such as pioglitazone, appear to be protective against dementia whereas sulfonylureas appear to increase the risk, a new observational study in patients with type 2 diabetes suggests.

The data, obtained from nationwide electronic medical records from the Department of Veterans Affairs, yielded a 22% lower risk of dementia with TZD monotherapy and a 12% elevated risk with sulfonylurea monotherapy, compared with metformin monotherapy. The apparent protective effects of TZDs were greater among individuals with overweight or obesity.

“Our findings provide additional information to aid clinicians’ selection of [glucose-lowering medications] for patients with mild or moderate type 2 diabetes and [who] are at high risk of dementia,” Xin Tang and colleagues wrote in their article, published online in BMJ Open Diabetes Research & Care.

The results “add substantially to the literature concerning the effects of [glucose-lowering medications] on dementia where previous findings have been inconsistent. Studies with a follow-up time of less than 3 years have mainly reported null associations, while studies with longer a follow-up time typically yielded protective findings. With a mean follow-up time of 6.8 years, we had a sufficient duration to detect treatment differences,” the investigators wrote.

“Supplementing [a] sulfonylurea with either metformin or [a] TZD may partially offset its prodementia effects. These findings may help inform medication selection for elderly patients with T2D at high risk of dementia,” they added.
 

Randomized trials needed to determine cause and effect

Ivan Koychev, PhD, a senior clinical researcher in the department of psychiatry at the University of Oxford (England), told the UK Science Media Centre: “This is a large, well-conducted real-world data study that highlights the importance of checking whether already prescribed medications may be useful for preventing dementia.”

The findings regarding TZDs, also known as glitazones, are in line with existing literature suggesting dementia protection with other drugs prescribed for type 2 diabetes that weren’t examined in the current study, such as newer agents like glucagonlike peptide–1 (GLP-1) agonists and sodium-glucose cotransporter 2 (SGLT2) inhibitors, Dr. Koychev said.

“The main limitations of this study is that following the initial 2-year period the authors were interested in, the participants may have been prescribed one of the other type 2 diabetes drugs [GLP-1 agonists or SGLT2 inhibitors] that have been found to reduce dementia risk, thus potentially making the direct glitazone [TZD] effect more difficult to discern,” Dr. Koychev noted.

And, he pointed out that the study design limits attribution of causality. “It is also important to note that people with type 2 diabetes do run a higher risk of both dementia and cognitive deficits and that these medications are only prescribed in these patients, so all this data is from this patient group rather than the general population.”

James Connell, PhD, head of translational science at Alzheimer’s Research UK, agreed. “While this observational study found that those with type 2 diabetes taking thiazolidinedione had a lower dementia risk than those on the most common medication for type 2 diabetes, it only shows an association between taking the drug and dementia risk and not a causal relationship.

“Double-blind and placebo-controlled clinical trials are needed to see whether the drug [TDZ] could help lower dementia risk in people with and without diabetes. Anyone with any questions about what treatments they are receiving should speak to their doctor,” he told the UK Science Media Centre.
 

Opposite effects of sulfonylureas, TZDs versus metformin

The study authors analyzed 559,106 VA patients with type 2 diabetes who initiated glucose-lowering medication during 2001-2017 and took it for at least a year. They were aged 60 years or older and did not have dementia at baseline. Most were White (76.8%) and male (96.9%), two-thirds (63.1%) had obesity, and mean hemoglobin A1c was 6.8%.

Overall, 31,125 developed all-cause dementia. The incidence rate was 8.2 cases per 1,000 person-years, ranging from 6.2 cases per 1,000 person-years among those taking metformin monotherapy to 13.4 cases per 1,000 person-years in those taking both sulfonylurea and a TZD.

Compared with metformin monotherapy, the hazard ratio for all-cause dementia for sulfonylurea monotherapy was a significant 1.12. The increased risk was also seen for vascular dementia, with an HR of 1.14.

In contrast, TZD monotherapy was associated with a significantly lower risk for all-cause dementia (HR, 0.78), as well as for Alzheimer’s disease (HR, 0.89) and vascular dementia (HR, 0.43), compared with metformin monotherapy.

The combination of metformin and TZD also lowered the risk of all-cause dementia, while regimens including sulfonylureas raised the risks for all-cause and vascular dementia.

Most of the results didn’t change significantly when the drug exposure window was extended to 2 years.
 

Effects more pronounced in those with obesity

The protective 1-year effects of TZD monotherapy and of metformin plus TZD, compared with metformin alone, were more significant among participants aged 75 or younger and with a body mass index above 25 kg/m², compared with those who were older than 75 years and with normal BMIs, respectively.

On the other hand, the greater risk for dementia incurred with sulfonylureas was further increased among those with higher BMI.

This research was partially funded by grants from the National Human Genome Research Institute, the National Science Foundation, the National Institute of Diabetes and Digestive and Kidney Disease, and the National Heart, Lung, and Blood Institute. Dr. Koychev is chief investigator for a trial, sponsored by Oxford University and funded by Novo Nordisk, testing whether the GLP-1 agonist semaglutide reduces the risk for dementia in aging adults.

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

Revised ICD-10-CM codes for neurocognitive disorders are now in effect, the American Psychiatric Association has announced

The coding changes for major and mild neurocognitive disorders represent “the most consequential” coding changes for DSM-5 disorders since the Oct. 1, 2015, changeover from ICD-9-CM to ICD-10-CM,” Michael First, MD, professor of clinical psychiatry at Columbia University, in New York, wrote in a statement published in Psychiatric News.

The updated codes for neurocognitive disorders are “much more specific and indicate all the different types of behavioral problems that could occur with dementia,” First, who served as editor of the DSM-5-TR, added in an interview.

This year, coding changes that affect psychiatry are largely confined to major and mild neurocognitive disorders, but they represent “a big switch-over,” Dr. First said.
 

What’s new

The first three characters that make up the ICD-10-CM code for major neurocognitive disorder depend on the type of etiologic medical condition and are unchanged:

• F01 for major neurocognitive disorder caused by vascular disease
• F02 for major neurocognitive disorder caused by other medical conditions in which the specific etiologic medical condition is indicated by also listing the ICD-10-CM code for the medical condition
• F03 for major neurocognitive disorder when the medical etiology is unknown

However, DSM-5-TR diagnostic criteria for major neurocognitive disorder include severity specifiers (mild, moderate, severe), but there is no provision for indicating this “clinically important” information in the current ICD-10-CM code for major neurocognitive disorder, Dr. First explained.

The 2022 coding changes for major neurocognitive disorder include the provision of a fourth character code to indicate the severity of the major neurocognitive disorder – “A” indicates mild (difficulties with instrumental activities of daily living, such as housework and managing money); “B,” moderate (difficulties with basic activities of daily living, such as feeding and dressing); and “C,” severe (fully dependent) impairment.

The coding changes for major neurocognitive disorder also now include fifth and sixth characters to indicate the presence of an accompanying behavioral or psychological disturbance, such as agitation, psychotic disturbance, mood symptoms, and anxiety.

The update, which went into effect Oct. 1, also adds to ICD-10-CM two new mental disorder codes, F06.71 and F06.70 for mild neurocognitive disorder caused by a medical condition with or without a behavioral disturbance, respectively.

The coding changes affecting psychiatry are outlined in the APA’s 2022 DSM-5-TR Update: Supplement to the Diagnostic and Statistical Manual of Mental Disorders and DSM-5-TR Neurocognitive Disorders Supplement.
 

Annual event

Every Oct. 1, ICD-10-CM codes for all of medicine are updated, with new codes being added and others revised or deleted. Only a small fraction of the 68,000 codes is affected. Last year, 159 new codes were added, 25 codes were deleted, and 27 existing codes were revised.

All HIPAA-compliant health care entities are required to use the most up-to-date ICD-10-CM codes.

“I think there’s a grace period where you can still use the old codes, but there will be a point where if you use the old code, it’ll get rejected because it won’t be considered a valid code,” said Dr. First.

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

Revised ICD-10-CM codes for neurocognitive disorders are now in effect, the American Psychiatric Association has announced

The coding changes for major and mild neurocognitive disorders represent “the most consequential” coding changes for DSM-5 disorders since the Oct. 1, 2015, changeover from ICD-9-CM to ICD-10-CM,” Michael First, MD, professor of clinical psychiatry at Columbia University, in New York, wrote in a statement published in Psychiatric News.

The updated codes for neurocognitive disorders are “much more specific and indicate all the different types of behavioral problems that could occur with dementia,” First, who served as editor of the DSM-5-TR, added in an interview.

This year, coding changes that affect psychiatry are largely confined to major and mild neurocognitive disorders, but they represent “a big switch-over,” Dr. First said.
 

What’s new

The first three characters that make up the ICD-10-CM code for major neurocognitive disorder depend on the type of etiologic medical condition and are unchanged:

• F01 for major neurocognitive disorder caused by vascular disease
• F02 for major neurocognitive disorder caused by other medical conditions in which the specific etiologic medical condition is indicated by also listing the ICD-10-CM code for the medical condition
• F03 for major neurocognitive disorder when the medical etiology is unknown

However, DSM-5-TR diagnostic criteria for major neurocognitive disorder include severity specifiers (mild, moderate, severe), but there is no provision for indicating this “clinically important” information in the current ICD-10-CM code for major neurocognitive disorder, Dr. First explained.

The 2022 coding changes for major neurocognitive disorder include the provision of a fourth character code to indicate the severity of the major neurocognitive disorder – “A” indicates mild (difficulties with instrumental activities of daily living, such as housework and managing money); “B,” moderate (difficulties with basic activities of daily living, such as feeding and dressing); and “C,” severe (fully dependent) impairment.

The coding changes for major neurocognitive disorder also now include fifth and sixth characters to indicate the presence of an accompanying behavioral or psychological disturbance, such as agitation, psychotic disturbance, mood symptoms, and anxiety.

The update, which went into effect Oct. 1, also adds to ICD-10-CM two new mental disorder codes, F06.71 and F06.70 for mild neurocognitive disorder caused by a medical condition with or without a behavioral disturbance, respectively.

The coding changes affecting psychiatry are outlined in the APA’s 2022 DSM-5-TR Update: Supplement to the Diagnostic and Statistical Manual of Mental Disorders and DSM-5-TR Neurocognitive Disorders Supplement.
 

Annual event

Every Oct. 1, ICD-10-CM codes for all of medicine are updated, with new codes being added and others revised or deleted. Only a small fraction of the 68,000 codes is affected. Last year, 159 new codes were added, 25 codes were deleted, and 27 existing codes were revised.

All HIPAA-compliant health care entities are required to use the most up-to-date ICD-10-CM codes.

“I think there’s a grace period where you can still use the old codes, but there will be a point where if you use the old code, it’ll get rejected because it won’t be considered a valid code,” said Dr. First.

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

Revised ICD-10-CM codes for neurocognitive disorders are now in effect, the American Psychiatric Association has announced

The coding changes for major and mild neurocognitive disorders represent “the most consequential” coding changes for DSM-5 disorders since the Oct. 1, 2015, changeover from ICD-9-CM to ICD-10-CM,” Michael First, MD, professor of clinical psychiatry at Columbia University, in New York, wrote in a statement published in Psychiatric News.

The updated codes for neurocognitive disorders are “much more specific and indicate all the different types of behavioral problems that could occur with dementia,” First, who served as editor of the DSM-5-TR, added in an interview.

This year, coding changes that affect psychiatry are largely confined to major and mild neurocognitive disorders, but they represent “a big switch-over,” Dr. First said.
 

What’s new

The first three characters that make up the ICD-10-CM code for major neurocognitive disorder depend on the type of etiologic medical condition and are unchanged:

• F01 for major neurocognitive disorder caused by vascular disease
• F02 for major neurocognitive disorder caused by other medical conditions in which the specific etiologic medical condition is indicated by also listing the ICD-10-CM code for the medical condition
• F03 for major neurocognitive disorder when the medical etiology is unknown

However, DSM-5-TR diagnostic criteria for major neurocognitive disorder include severity specifiers (mild, moderate, severe), but there is no provision for indicating this “clinically important” information in the current ICD-10-CM code for major neurocognitive disorder, Dr. First explained.

The 2022 coding changes for major neurocognitive disorder include the provision of a fourth character code to indicate the severity of the major neurocognitive disorder – “A” indicates mild (difficulties with instrumental activities of daily living, such as housework and managing money); “B,” moderate (difficulties with basic activities of daily living, such as feeding and dressing); and “C,” severe (fully dependent) impairment.

The coding changes for major neurocognitive disorder also now include fifth and sixth characters to indicate the presence of an accompanying behavioral or psychological disturbance, such as agitation, psychotic disturbance, mood symptoms, and anxiety.

The update, which went into effect Oct. 1, also adds to ICD-10-CM two new mental disorder codes, F06.71 and F06.70 for mild neurocognitive disorder caused by a medical condition with or without a behavioral disturbance, respectively.

The coding changes affecting psychiatry are outlined in the APA’s 2022 DSM-5-TR Update: Supplement to the Diagnostic and Statistical Manual of Mental Disorders and DSM-5-TR Neurocognitive Disorders Supplement.
 

Annual event

Every Oct. 1, ICD-10-CM codes for all of medicine are updated, with new codes being added and others revised or deleted. Only a small fraction of the 68,000 codes is affected. Last year, 159 new codes were added, 25 codes were deleted, and 27 existing codes were revised.

All HIPAA-compliant health care entities are required to use the most up-to-date ICD-10-CM codes.

“I think there’s a grace period where you can still use the old codes, but there will be a point where if you use the old code, it’ll get rejected because it won’t be considered a valid code,” said Dr. First.

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

Lecanemab (Eisai/Biogen), an investigational amyloid-clearing monoclonal antibody, reduced cognitive decline by 27%, compared with placebo and decreased amyloid levels in the brain of adults enrolled in a phase 3 trial.

The Clarity AD trial included 1,795 adults with early AD and confirmed amyloid pathology in the brain. Treatment consisted of lecanemab 10 mg/kg biweekly or matching placebo.

Treatment with lecanemab met the primary endpoint, reducing clinical decline on the global cognitive and functional scale, the Clinical Dementia Rating–Sum of Boxes (CDR-SB), at 18 months by 27%, compared with placebo, with a treatment difference in the score change of –0.45 (P = .00005), the companies reported.

Starting as early as 6 months, across all time points, treatment with lecanemab yielded highly statistically significant changes in CDR-SB from baseline, compared with placebo (all P < .01).

The study also met all key secondary endpoints with highly statistically significant results, compared with placebo (P < .01).

Key secondary endpoints, in comparison with placebo, were change from baseline at 18 months in amyloid levels in the brain measured by amyloid PET, the AD Assessment Scale–cognitive subscale14 (ADAS-cog14), the AD Composite Score (ADCOMS), and the AD Cooperative Study–Activities of Daily Living Scale for Mild Cognitive Impairment (ADCS MCI-ADL).
 

Imaging abnormalities within expectations

Overall, rates of amyloid-related imaging abnormalities (ARIA) related to lecanemab were “within expectations,” the companies said.

The incidence of ARIA related to edema (ARIA-E) was 12.5% in the lecanemab group and 1.7% in the placebo group.

The incidence of symptomatic ARIA-E was 2.8% and 0.0%, respectively, and the rate of cerebral hemorrhage (ARIA-H) was 17.0% and 8.7%. The total incidence of ARIA (ARIA-E and/or ARIA-H) was 21.3% in the lecanemab group and 9.3% in the placebo group.

Full results of the Clarity AD trial will be presented in November at the Clinical Trials on Alzheimer’s Congress.
 

Incremental benefit

Responding to the findings, the Alzheimer’s Association said in a statement that it “enthusiastically welcomes” the positive findings. It noted that these are “the most encouraging results in clinical trials treating the underlying causes of Alzheimer’s to date.

“For people in the earliest stages of Alzheimer’s, this treatment has the potential to change the course of the disease in a clinically meaningful way. These results indicate lecanemab may give people more time at or near their full abilities to participate in daily life, remain independent and make future health care decisions,” the Alzheimer’s Association added.

Also weighing in, Howard Fillit, MD, cofounder and chief science officer at the Alzheimer’s Drug Discovery Foundation, said in a release that “the combination of the biomarker change – reduced amyloid – plus slowing of cognitive decline in this study is encouraging news for the 57 million patients around the world living with Alzheimer’s.

“However, amyloid-clearing drugs will provide an incremental benefit at best, and there is still a pressing need for the next generation of drugs focused on other targets based on our knowledge of the biology of aging,” Dr. Fillit cautioned.

“We are optimistic about the future as many of these drugs are in development, with 75% of drugs in the pipeline now targeting nonamyloid pathways of neurodegeneration,” he added.

In July 2022, the Food and Drug Administration accepted Eisai’s biologics license application for lecanemab under the accelerated approval pathway and granted priority review. Lecanemab has a prescription Drugs User Fee Act action date of Jan. 6, 2023.

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

Lecanemab (Eisai/Biogen), an investigational amyloid-clearing monoclonal antibody, reduced cognitive decline by 27%, compared with placebo and decreased amyloid levels in the brain of adults enrolled in a phase 3 trial.

The Clarity AD trial included 1,795 adults with early AD and confirmed amyloid pathology in the brain. Treatment consisted of lecanemab 10 mg/kg biweekly or matching placebo.

Treatment with lecanemab met the primary endpoint, reducing clinical decline on the global cognitive and functional scale, the Clinical Dementia Rating–Sum of Boxes (CDR-SB), at 18 months by 27%, compared with placebo, with a treatment difference in the score change of –0.45 (P = .00005), the companies reported.

Starting as early as 6 months, across all time points, treatment with lecanemab yielded highly statistically significant changes in CDR-SB from baseline, compared with placebo (all P < .01).

The study also met all key secondary endpoints with highly statistically significant results, compared with placebo (P < .01).

Key secondary endpoints, in comparison with placebo, were change from baseline at 18 months in amyloid levels in the brain measured by amyloid PET, the AD Assessment Scale–cognitive subscale14 (ADAS-cog14), the AD Composite Score (ADCOMS), and the AD Cooperative Study–Activities of Daily Living Scale for Mild Cognitive Impairment (ADCS MCI-ADL).
 

Imaging abnormalities within expectations

Overall, rates of amyloid-related imaging abnormalities (ARIA) related to lecanemab were “within expectations,” the companies said.

The incidence of ARIA related to edema (ARIA-E) was 12.5% in the lecanemab group and 1.7% in the placebo group.

The incidence of symptomatic ARIA-E was 2.8% and 0.0%, respectively, and the rate of cerebral hemorrhage (ARIA-H) was 17.0% and 8.7%. The total incidence of ARIA (ARIA-E and/or ARIA-H) was 21.3% in the lecanemab group and 9.3% in the placebo group.

Full results of the Clarity AD trial will be presented in November at the Clinical Trials on Alzheimer’s Congress.
 

Incremental benefit

Responding to the findings, the Alzheimer’s Association said in a statement that it “enthusiastically welcomes” the positive findings. It noted that these are “the most encouraging results in clinical trials treating the underlying causes of Alzheimer’s to date.

“For people in the earliest stages of Alzheimer’s, this treatment has the potential to change the course of the disease in a clinically meaningful way. These results indicate lecanemab may give people more time at or near their full abilities to participate in daily life, remain independent and make future health care decisions,” the Alzheimer’s Association added.

Also weighing in, Howard Fillit, MD, cofounder and chief science officer at the Alzheimer’s Drug Discovery Foundation, said in a release that “the combination of the biomarker change – reduced amyloid – plus slowing of cognitive decline in this study is encouraging news for the 57 million patients around the world living with Alzheimer’s.

“However, amyloid-clearing drugs will provide an incremental benefit at best, and there is still a pressing need for the next generation of drugs focused on other targets based on our knowledge of the biology of aging,” Dr. Fillit cautioned.

“We are optimistic about the future as many of these drugs are in development, with 75% of drugs in the pipeline now targeting nonamyloid pathways of neurodegeneration,” he added.

In July 2022, the Food and Drug Administration accepted Eisai’s biologics license application for lecanemab under the accelerated approval pathway and granted priority review. Lecanemab has a prescription Drugs User Fee Act action date of Jan. 6, 2023.

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

Lecanemab (Eisai/Biogen), an investigational amyloid-clearing monoclonal antibody, reduced cognitive decline by 27%, compared with placebo and decreased amyloid levels in the brain of adults enrolled in a phase 3 trial.

The Clarity AD trial included 1,795 adults with early AD and confirmed amyloid pathology in the brain. Treatment consisted of lecanemab 10 mg/kg biweekly or matching placebo.

Treatment with lecanemab met the primary endpoint, reducing clinical decline on the global cognitive and functional scale, the Clinical Dementia Rating–Sum of Boxes (CDR-SB), at 18 months by 27%, compared with placebo, with a treatment difference in the score change of –0.45 (P = .00005), the companies reported.

Starting as early as 6 months, across all time points, treatment with lecanemab yielded highly statistically significant changes in CDR-SB from baseline, compared with placebo (all P < .01).

The study also met all key secondary endpoints with highly statistically significant results, compared with placebo (P < .01).

Key secondary endpoints, in comparison with placebo, were change from baseline at 18 months in amyloid levels in the brain measured by amyloid PET, the AD Assessment Scale–cognitive subscale14 (ADAS-cog14), the AD Composite Score (ADCOMS), and the AD Cooperative Study–Activities of Daily Living Scale for Mild Cognitive Impairment (ADCS MCI-ADL).
 

Imaging abnormalities within expectations

Overall, rates of amyloid-related imaging abnormalities (ARIA) related to lecanemab were “within expectations,” the companies said.

The incidence of ARIA related to edema (ARIA-E) was 12.5% in the lecanemab group and 1.7% in the placebo group.

The incidence of symptomatic ARIA-E was 2.8% and 0.0%, respectively, and the rate of cerebral hemorrhage (ARIA-H) was 17.0% and 8.7%. The total incidence of ARIA (ARIA-E and/or ARIA-H) was 21.3% in the lecanemab group and 9.3% in the placebo group.

Full results of the Clarity AD trial will be presented in November at the Clinical Trials on Alzheimer’s Congress.
 

Incremental benefit

Responding to the findings, the Alzheimer’s Association said in a statement that it “enthusiastically welcomes” the positive findings. It noted that these are “the most encouraging results in clinical trials treating the underlying causes of Alzheimer’s to date.

“For people in the earliest stages of Alzheimer’s, this treatment has the potential to change the course of the disease in a clinically meaningful way. These results indicate lecanemab may give people more time at or near their full abilities to participate in daily life, remain independent and make future health care decisions,” the Alzheimer’s Association added.

Also weighing in, Howard Fillit, MD, cofounder and chief science officer at the Alzheimer’s Drug Discovery Foundation, said in a release that “the combination of the biomarker change – reduced amyloid – plus slowing of cognitive decline in this study is encouraging news for the 57 million patients around the world living with Alzheimer’s.

“However, amyloid-clearing drugs will provide an incremental benefit at best, and there is still a pressing need for the next generation of drugs focused on other targets based on our knowledge of the biology of aging,” Dr. Fillit cautioned.

“We are optimistic about the future as many of these drugs are in development, with 75% of drugs in the pipeline now targeting nonamyloid pathways of neurodegeneration,” he added.

In July 2022, the Food and Drug Administration accepted Eisai’s biologics license application for lecanemab under the accelerated approval pathway and granted priority review. Lecanemab has a prescription Drugs User Fee Act action date of Jan. 6, 2023.

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

Nightmares in healthy middle-aged and older adults may be an independent risk factor for cognitive decline and dementia, particularly in men, new research suggests.

Results from a large cohort study showed that healthy middle-aged adults who had bad dreams at least once a week were four times more likely to experience cognitive decline over the following decade, and older adults were twice as likely to be diagnosed with dementia, compared with peers who never had bad dreams.

Frequent nightmares may “identify people who are at high risk of developing dementia in the future, several years or decades before the characteristic memory and thinking problems emerge,” study investigator Abidemi Otaiku, BMBS, University of Birmingham, England, said in an interview.

“This would be the optimum time for doctors to intervene to try and slow down or prevent dementia from developing,” Dr. Otaiku said.

The findings were published online in The Lancet journal eClinicalMedicine).
 

Distressing dreams

Distressing dreams have been previously associated with faster cognitive decline and increased dementia risk in patients with Parkinson’s disease (PD), but whether the same holds for individuals from the general population without PD is unknown.

To investigate, Dr. Otaiku examined data from three community-based cohorts in the United States. This included 605 middle-aged adults (aged 35-64 years) who were followed for up to 13 years and 2,600 adults aged 79 and older who were followed for up to 7 years. All were considered cognitively normal at baseline.

The prevalence of frequent distressing dreams, defined as occurring “once a week or more,” was higher in the older cohort compared with the middle-aged cohort (6.9% vs. 6.0%, respectively).

This is in line with other research that showed distressing dreams remain relatively stable throughout early adulthood and then progressively increase in prevalence from middle to older adulthood. 

After adjustment for all covariates, a higher frequency of distressing dreams was linearly and statistically significantly associated with a higher risk for cognitive decline in middle-aged adults (P = .016) and a higher risk for dementia in older adults (P = .001).

In the fully adjusted model, compared with middle-aged adults who never had bad dreams, those who reported having one or more bad dreams weekly had a fourfold risk for cognitive decline (adjusted odds ratio [aOR], 3.99; 95% confidence interval [CI], 1.07-14.85).

Older adults who had one or more bad dreams weekly had a greater than twofold increased risk for developing dementia (aOR, 2.21; 95% CI, 1.35-3.62).
 

Early days

In sex-stratified analyses, distressing dreams were strongly and statistically significantly associated with cognitive decline and dementia in men, but were only weakly and nonsignificantly associated with cognitive decline and dementia in women.

Dr. Otaiku said he suspects some individuals in the preclinical phase of dementia have “subtle neurodegeneration occurring over time in the right frontal lobe: the area of the brain that helps to downregulate negative emotions whilst we are awake, and also whilst we are dreaming.”

This could result in “depression and anxiety in the day, and nightmares and bad dreams during the night,” he said.

It is possible that treatment for frequent nightmares may help to slow cognitive decline and delay or prevent dementia, Dr. Otaiku added.

He noted that prazosin is used to treat nightmares and has been shown to prevent memory decline and reduce amyloid B generation in preclinical studies of Alzheimer’s disease.

“This is an exciting prospect [but] it is still early days and we will need research to see whether treating nightmares might help to reduce dementia risk down the line,” Dr. Otaiku said.
 

Credible research

In an interview regarding these findings, Maria C. Carrillo, PhD, chief science officer for the Alzheimer’s Association, said: “This is credible research consistent with the idea that sleep disturbances may be a risk factor or warning sign of cognitive decline.”

She added that “what’s novel here” is the researchers examined distressing dreams – not more physical sleep disturbances and disorders such as insomnia or apnea.

“However, nightmares can disturb sleep in the same way these disorders do by waking people up in the middle of the night,” said Dr. Carrillo, who was not involved with the study.

“Previous research has pointed to nightmares being indicative of potential changes in the brain that can precede other dementias like Parkinson’s disease. More research is needed to tease out what exactly is happening in the brain during nightmares that may be contributing to this increased risk,” she said.

Dr. Carrillo noted that “getting good sleep” is important for overall health, which includes brain health.

“The good news is there are treatments – both drug and nondrug – that can help address sleep disturbances,” she added.

This study received no external funding. Dr. Otaiku and Dr. Carrillo have reported no relevant financial relationships.

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

Nightmares in healthy middle-aged and older adults may be an independent risk factor for cognitive decline and dementia, particularly in men, new research suggests.

Results from a large cohort study showed that healthy middle-aged adults who had bad dreams at least once a week were four times more likely to experience cognitive decline over the following decade, and older adults were twice as likely to be diagnosed with dementia, compared with peers who never had bad dreams.

Frequent nightmares may “identify people who are at high risk of developing dementia in the future, several years or decades before the characteristic memory and thinking problems emerge,” study investigator Abidemi Otaiku, BMBS, University of Birmingham, England, said in an interview.

“This would be the optimum time for doctors to intervene to try and slow down or prevent dementia from developing,” Dr. Otaiku said.

The findings were published online in The Lancet journal eClinicalMedicine).
 

Distressing dreams

Distressing dreams have been previously associated with faster cognitive decline and increased dementia risk in patients with Parkinson’s disease (PD), but whether the same holds for individuals from the general population without PD is unknown.

To investigate, Dr. Otaiku examined data from three community-based cohorts in the United States. This included 605 middle-aged adults (aged 35-64 years) who were followed for up to 13 years and 2,600 adults aged 79 and older who were followed for up to 7 years. All were considered cognitively normal at baseline.

The prevalence of frequent distressing dreams, defined as occurring “once a week or more,” was higher in the older cohort compared with the middle-aged cohort (6.9% vs. 6.0%, respectively).

This is in line with other research that showed distressing dreams remain relatively stable throughout early adulthood and then progressively increase in prevalence from middle to older adulthood. 

After adjustment for all covariates, a higher frequency of distressing dreams was linearly and statistically significantly associated with a higher risk for cognitive decline in middle-aged adults (P = .016) and a higher risk for dementia in older adults (P = .001).

In the fully adjusted model, compared with middle-aged adults who never had bad dreams, those who reported having one or more bad dreams weekly had a fourfold risk for cognitive decline (adjusted odds ratio [aOR], 3.99; 95% confidence interval [CI], 1.07-14.85).

Older adults who had one or more bad dreams weekly had a greater than twofold increased risk for developing dementia (aOR, 2.21; 95% CI, 1.35-3.62).
 

Early days

In sex-stratified analyses, distressing dreams were strongly and statistically significantly associated with cognitive decline and dementia in men, but were only weakly and nonsignificantly associated with cognitive decline and dementia in women.

Dr. Otaiku said he suspects some individuals in the preclinical phase of dementia have “subtle neurodegeneration occurring over time in the right frontal lobe: the area of the brain that helps to downregulate negative emotions whilst we are awake, and also whilst we are dreaming.”

This could result in “depression and anxiety in the day, and nightmares and bad dreams during the night,” he said.

It is possible that treatment for frequent nightmares may help to slow cognitive decline and delay or prevent dementia, Dr. Otaiku added.

He noted that prazosin is used to treat nightmares and has been shown to prevent memory decline and reduce amyloid B generation in preclinical studies of Alzheimer’s disease.

“This is an exciting prospect [but] it is still early days and we will need research to see whether treating nightmares might help to reduce dementia risk down the line,” Dr. Otaiku said.
 

Credible research

In an interview regarding these findings, Maria C. Carrillo, PhD, chief science officer for the Alzheimer’s Association, said: “This is credible research consistent with the idea that sleep disturbances may be a risk factor or warning sign of cognitive decline.”

She added that “what’s novel here” is the researchers examined distressing dreams – not more physical sleep disturbances and disorders such as insomnia or apnea.

“However, nightmares can disturb sleep in the same way these disorders do by waking people up in the middle of the night,” said Dr. Carrillo, who was not involved with the study.

“Previous research has pointed to nightmares being indicative of potential changes in the brain that can precede other dementias like Parkinson’s disease. More research is needed to tease out what exactly is happening in the brain during nightmares that may be contributing to this increased risk,” she said.

Dr. Carrillo noted that “getting good sleep” is important for overall health, which includes brain health.

“The good news is there are treatments – both drug and nondrug – that can help address sleep disturbances,” she added.

This study received no external funding. Dr. Otaiku and Dr. Carrillo have reported no relevant financial relationships.

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

Nightmares in healthy middle-aged and older adults may be an independent risk factor for cognitive decline and dementia, particularly in men, new research suggests.

Results from a large cohort study showed that healthy middle-aged adults who had bad dreams at least once a week were four times more likely to experience cognitive decline over the following decade, and older adults were twice as likely to be diagnosed with dementia, compared with peers who never had bad dreams.

Frequent nightmares may “identify people who are at high risk of developing dementia in the future, several years or decades before the characteristic memory and thinking problems emerge,” study investigator Abidemi Otaiku, BMBS, University of Birmingham, England, said in an interview.

“This would be the optimum time for doctors to intervene to try and slow down or prevent dementia from developing,” Dr. Otaiku said.

The findings were published online in The Lancet journal eClinicalMedicine).
 

Distressing dreams

Distressing dreams have been previously associated with faster cognitive decline and increased dementia risk in patients with Parkinson’s disease (PD), but whether the same holds for individuals from the general population without PD is unknown.

To investigate, Dr. Otaiku examined data from three community-based cohorts in the United States. This included 605 middle-aged adults (aged 35-64 years) who were followed for up to 13 years and 2,600 adults aged 79 and older who were followed for up to 7 years. All were considered cognitively normal at baseline.

The prevalence of frequent distressing dreams, defined as occurring “once a week or more,” was higher in the older cohort compared with the middle-aged cohort (6.9% vs. 6.0%, respectively).

This is in line with other research that showed distressing dreams remain relatively stable throughout early adulthood and then progressively increase in prevalence from middle to older adulthood. 

After adjustment for all covariates, a higher frequency of distressing dreams was linearly and statistically significantly associated with a higher risk for cognitive decline in middle-aged adults (P = .016) and a higher risk for dementia in older adults (P = .001).

In the fully adjusted model, compared with middle-aged adults who never had bad dreams, those who reported having one or more bad dreams weekly had a fourfold risk for cognitive decline (adjusted odds ratio [aOR], 3.99; 95% confidence interval [CI], 1.07-14.85).

Older adults who had one or more bad dreams weekly had a greater than twofold increased risk for developing dementia (aOR, 2.21; 95% CI, 1.35-3.62).
 

Early days

In sex-stratified analyses, distressing dreams were strongly and statistically significantly associated with cognitive decline and dementia in men, but were only weakly and nonsignificantly associated with cognitive decline and dementia in women.

Dr. Otaiku said he suspects some individuals in the preclinical phase of dementia have “subtle neurodegeneration occurring over time in the right frontal lobe: the area of the brain that helps to downregulate negative emotions whilst we are awake, and also whilst we are dreaming.”

This could result in “depression and anxiety in the day, and nightmares and bad dreams during the night,” he said.

It is possible that treatment for frequent nightmares may help to slow cognitive decline and delay or prevent dementia, Dr. Otaiku added.

He noted that prazosin is used to treat nightmares and has been shown to prevent memory decline and reduce amyloid B generation in preclinical studies of Alzheimer’s disease.

“This is an exciting prospect [but] it is still early days and we will need research to see whether treating nightmares might help to reduce dementia risk down the line,” Dr. Otaiku said.
 

Credible research

In an interview regarding these findings, Maria C. Carrillo, PhD, chief science officer for the Alzheimer’s Association, said: “This is credible research consistent with the idea that sleep disturbances may be a risk factor or warning sign of cognitive decline.”

She added that “what’s novel here” is the researchers examined distressing dreams – not more physical sleep disturbances and disorders such as insomnia or apnea.

“However, nightmares can disturb sleep in the same way these disorders do by waking people up in the middle of the night,” said Dr. Carrillo, who was not involved with the study.

“Previous research has pointed to nightmares being indicative of potential changes in the brain that can precede other dementias like Parkinson’s disease. More research is needed to tease out what exactly is happening in the brain during nightmares that may be contributing to this increased risk,” she said.

Dr. Carrillo noted that “getting good sleep” is important for overall health, which includes brain health.

“The good news is there are treatments – both drug and nondrug – that can help address sleep disturbances,” she added.

This study received no external funding. Dr. Otaiku and Dr. Carrillo have reported no relevant financial relationships.

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

COVID-19 has been linked to a significantly increased risk for new-onset Alzheimer’s disease (AD), a new study suggests.

The study of more than 6 million people aged 65 years or older found a 50%-80% increased risk for AD in the year after COVID-19; the risk was especially high for women older than 85 years.

However, the investigators were quick to point out that the observational retrospective study offers no evidence that COVID-19 causes AD. There could be a viral etiology at play, or the connection could be related to inflammation in neural tissue from the SARS-CoV-2 infection. Or it could simply be that exposure to the health care system for COVID-19 increased the odds of detection of existing undiagnosed AD cases.

Whatever the case, these findings point to a potential spike in AD cases, which is a cause for concern, study investigator Pamela Davis, MD, PhD, a professor in the Center for Community Health Integration at Case Western Reserve University, Cleveland, said in an interview.

“COVID may be giving us a legacy of ongoing medical difficulties,” Dr. Davis said. “We were already concerned about having a very large care burden and cost burden from Alzheimer’s disease. If this is another burden that’s increased by COVID, this is something we’re really going to have to prepare for.”

The findings were published online in Journal of Alzheimer’s Disease.
 

Increased risk

Earlier research points to a potential link between COVID-19 and increased risk for AD and Parkinson’s disease.

For the current study, researchers analyzed anonymous electronic health records of 6.2 million adults aged 65 years or older who received medical treatment between February 2020 and May 2021 and had no prior diagnosis of AD. The database includes information on almost 30% of the entire U.S. population.

Overall, there were 410,748 cases of COVID-19 during the study period.

The overall risk for new diagnosis of AD in the COVID-19 cohort was close to double that of those who did not have COVID-19 (0.68% vs. 0.35%, respectively).

After propensity-score matching, those who have had COVID-19 had a significantly higher risk for an AD diagnosis compared with those who were not infected (hazard ratio [HR], 1.69; 95% confidence interval [CI],1.53-1.72).

Risk for AD was elevated in all age groups, regardless of gender or ethnicity. Researchers did not collect data on COVID-19 severity, and the medical codes for long COVID were not published until after the study had ended.

Those with the highest risk were individuals older than 85 years (HR, 1.89; 95% CI, 1.73-2.07) and women (HR, 1.82; 95% CI, 1.69-1.97).

“We expected to see some impact, but I was surprised that it was as potent as it was,” Dr. Davis said.
 

Association, not causation

Heather Snyder, PhD, Alzheimer’s Association vice president of medical and scientific relations, who commented on the findings for this article, called the study interesting but emphasized caution in interpreting the results.

“Because this study only showed an association through medical records, we cannot know what the underlying mechanisms driving this association are without more research,” Dr. Snyder said. “If you have had COVID-19, it doesn’t mean you’re going to get dementia. But if you have had COVID-19 and are experiencing long-term symptoms including cognitive difficulties, talk to your doctor.”

Dr. Davis agreed, noting that this type of study offers information on association, but not causation. “I do think that this makes it imperative that we continue to follow the population for what’s going on in various neurodegenerative diseases,” Dr. Davis said.

The study was funded by the National Institute of Aging, National Institute on Alcohol Abuse and Alcoholism, the Clinical and Translational Science Collaborative of Cleveland, and the National Cancer Institute. Dr. Synder reports no relevant financial conflicts.

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

COVID-19 has been linked to a significantly increased risk for new-onset Alzheimer’s disease (AD), a new study suggests.

The study of more than 6 million people aged 65 years or older found a 50%-80% increased risk for AD in the year after COVID-19; the risk was especially high for women older than 85 years.

However, the investigators were quick to point out that the observational retrospective study offers no evidence that COVID-19 causes AD. There could be a viral etiology at play, or the connection could be related to inflammation in neural tissue from the SARS-CoV-2 infection. Or it could simply be that exposure to the health care system for COVID-19 increased the odds of detection of existing undiagnosed AD cases.

Whatever the case, these findings point to a potential spike in AD cases, which is a cause for concern, study investigator Pamela Davis, MD, PhD, a professor in the Center for Community Health Integration at Case Western Reserve University, Cleveland, said in an interview.

“COVID may be giving us a legacy of ongoing medical difficulties,” Dr. Davis said. “We were already concerned about having a very large care burden and cost burden from Alzheimer’s disease. If this is another burden that’s increased by COVID, this is something we’re really going to have to prepare for.”

The findings were published online in Journal of Alzheimer’s Disease.
 

Increased risk

Earlier research points to a potential link between COVID-19 and increased risk for AD and Parkinson’s disease.

For the current study, researchers analyzed anonymous electronic health records of 6.2 million adults aged 65 years or older who received medical treatment between February 2020 and May 2021 and had no prior diagnosis of AD. The database includes information on almost 30% of the entire U.S. population.

Overall, there were 410,748 cases of COVID-19 during the study period.

The overall risk for new diagnosis of AD in the COVID-19 cohort was close to double that of those who did not have COVID-19 (0.68% vs. 0.35%, respectively).

After propensity-score matching, those who have had COVID-19 had a significantly higher risk for an AD diagnosis compared with those who were not infected (hazard ratio [HR], 1.69; 95% confidence interval [CI],1.53-1.72).

Risk for AD was elevated in all age groups, regardless of gender or ethnicity. Researchers did not collect data on COVID-19 severity, and the medical codes for long COVID were not published until after the study had ended.

Those with the highest risk were individuals older than 85 years (HR, 1.89; 95% CI, 1.73-2.07) and women (HR, 1.82; 95% CI, 1.69-1.97).

“We expected to see some impact, but I was surprised that it was as potent as it was,” Dr. Davis said.
 

Association, not causation

Heather Snyder, PhD, Alzheimer’s Association vice president of medical and scientific relations, who commented on the findings for this article, called the study interesting but emphasized caution in interpreting the results.

“Because this study only showed an association through medical records, we cannot know what the underlying mechanisms driving this association are without more research,” Dr. Snyder said. “If you have had COVID-19, it doesn’t mean you’re going to get dementia. But if you have had COVID-19 and are experiencing long-term symptoms including cognitive difficulties, talk to your doctor.”

Dr. Davis agreed, noting that this type of study offers information on association, but not causation. “I do think that this makes it imperative that we continue to follow the population for what’s going on in various neurodegenerative diseases,” Dr. Davis said.

The study was funded by the National Institute of Aging, National Institute on Alcohol Abuse and Alcoholism, the Clinical and Translational Science Collaborative of Cleveland, and the National Cancer Institute. Dr. Synder reports no relevant financial conflicts.

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

COVID-19 has been linked to a significantly increased risk for new-onset Alzheimer’s disease (AD), a new study suggests.

The study of more than 6 million people aged 65 years or older found a 50%-80% increased risk for AD in the year after COVID-19; the risk was especially high for women older than 85 years.

However, the investigators were quick to point out that the observational retrospective study offers no evidence that COVID-19 causes AD. There could be a viral etiology at play, or the connection could be related to inflammation in neural tissue from the SARS-CoV-2 infection. Or it could simply be that exposure to the health care system for COVID-19 increased the odds of detection of existing undiagnosed AD cases.

Whatever the case, these findings point to a potential spike in AD cases, which is a cause for concern, study investigator Pamela Davis, MD, PhD, a professor in the Center for Community Health Integration at Case Western Reserve University, Cleveland, said in an interview.

“COVID may be giving us a legacy of ongoing medical difficulties,” Dr. Davis said. “We were already concerned about having a very large care burden and cost burden from Alzheimer’s disease. If this is another burden that’s increased by COVID, this is something we’re really going to have to prepare for.”

The findings were published online in Journal of Alzheimer’s Disease.
 

Increased risk

Earlier research points to a potential link between COVID-19 and increased risk for AD and Parkinson’s disease.

For the current study, researchers analyzed anonymous electronic health records of 6.2 million adults aged 65 years or older who received medical treatment between February 2020 and May 2021 and had no prior diagnosis of AD. The database includes information on almost 30% of the entire U.S. population.

Overall, there were 410,748 cases of COVID-19 during the study period.

The overall risk for new diagnosis of AD in the COVID-19 cohort was close to double that of those who did not have COVID-19 (0.68% vs. 0.35%, respectively).

After propensity-score matching, those who have had COVID-19 had a significantly higher risk for an AD diagnosis compared with those who were not infected (hazard ratio [HR], 1.69; 95% confidence interval [CI],1.53-1.72).

Risk for AD was elevated in all age groups, regardless of gender or ethnicity. Researchers did not collect data on COVID-19 severity, and the medical codes for long COVID were not published until after the study had ended.

Those with the highest risk were individuals older than 85 years (HR, 1.89; 95% CI, 1.73-2.07) and women (HR, 1.82; 95% CI, 1.69-1.97).

“We expected to see some impact, but I was surprised that it was as potent as it was,” Dr. Davis said.
 

Association, not causation

Heather Snyder, PhD, Alzheimer’s Association vice president of medical and scientific relations, who commented on the findings for this article, called the study interesting but emphasized caution in interpreting the results.

“Because this study only showed an association through medical records, we cannot know what the underlying mechanisms driving this association are without more research,” Dr. Snyder said. “If you have had COVID-19, it doesn’t mean you’re going to get dementia. But if you have had COVID-19 and are experiencing long-term symptoms including cognitive difficulties, talk to your doctor.”

Dr. Davis agreed, noting that this type of study offers information on association, but not causation. “I do think that this makes it imperative that we continue to follow the population for what’s going on in various neurodegenerative diseases,” Dr. Davis said.

The study was funded by the National Institute of Aging, National Institute on Alcohol Abuse and Alcoholism, the Clinical and Translational Science Collaborative of Cleveland, and the National Cancer Institute. Dr. Synder reports no relevant financial conflicts.

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

Unexpected results from a phase 3 trial exploring the effect of multivitamins and cognition have now been published.

Findings from a phase 3 study show daily multivitamin use, but not cocoa, is linked to a significantly slower rate of age-related cognitive decline.

Originally presented last November at the 14th Clinical Trials on Alzheimer’s Disease (CTAD) conference, this is the first large-scale, long-term randomized controlled trial to examine the effects of cocoa extract and multivitamins on global cognition. The trial’s primary focus was on cocoa extract, which earlier studies suggest may preserve cognitive function. Analyzing the effect of multivitamins was a secondary outcome.

Showing vitamins, but not cocoa, were beneficial is the exact opposite of what researchers expected. Still, the results offer an interesting new direction for future study, lead investigator Laura D. Baker, PhD, professor of gerontology and geriatric medicine at Wake Forest University, Winston-Salem, N.C., said in an interview.

“This study made us take notice of a pathway for possible cognitive protection,” Dr. Baker said. “Without this study, we would never have looked down that road.”

The full results were published online in Alzheimer’s and Dementia.
 

Unexpected effect

The COSMOS-Mind study is a substudy to a larger parent trial called COSMOS. It investigated the effects of cocoa extract and a standard multivitamin-mineral on cardiovascular and cancer outcomes in more than 21,000 older participants.

In COSMOS-Mind, researchers tested whether daily intake of cocoa extract vs. placebo and a multivitamin-mineral vs. placebo improved cognition in older adults.

More than 2,200 participants aged 65 and older were enrolled and followed for 3 years. They completed tests over the telephone at baseline and annually to evaluate memory and other cognitive abilities.

Results showed cocoa extract had no effect on global cognition compared with placebo (mean z-score, 0.03; P = .28). Daily multivitamin use, however, did show significant benefits on global cognition vs. placebo (mean z, 0.07, P = .007).

The beneficial effect was most pronounced in participants with a history of cardiovascular disease (no history 0.06 vs. history 0.14; P = .01).

Researchers found similar protective effects for memory and executive function. 

Dr. Baker suggested one possible explanation for the positive effects of multivitamins may be the boost in micronutrients and essential minerals they provided.

“With nutrient-deficient diets plus a high prevalence of cardiovascular disease, diabetes, and other medical comorbidities that we know impact the bioavailability of these nutrients, we are possibly dealing with older adults who are at below optimum in terms of their essential micronutrients and minerals,” she said.

“Even suboptimum levels of micronutrients and essential minerals can have significant consequences for brain health,” she added.
 

More research needed

Intriguing as the results may be, more work is needed before the findings could affect nutritional guidance, according to Maria C. Carrillo, PhD, chief science officer for the Alzheimer’s Association.

“While the Alzheimer’s Association is encouraged by these results, we are not ready to recommend widespread use of a multivitamin supplement to reduce risk of cognitive decline in older adults,” Dr. Carrillo said in a statement.

“For now, and until there is more data, people should talk with their health care providers about the benefits and risks of all dietary supplements, including multivitamins,” she added.

Dr. Baker agreed, noting that the study was not designed to measure multivitamin use as a primary outcome. In addition, nearly 90% of the participants were non-Hispanic White, which is not representative of the overall population demographics.

The investigators are now designing another, larger trial that would include a more diverse participant pool. It will be aimed specifically at learning more about how and why multivitamins seem to offer a protective effect on cognition, Dr. Baker noted.

The study was funded by the National Institute on Aging of the National Institutes of Health. Dr. Baker and Dr. Carrillo report no relevant financial relationships.

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

Unexpected results from a phase 3 trial exploring the effect of multivitamins and cognition have now been published.

Findings from a phase 3 study show daily multivitamin use, but not cocoa, is linked to a significantly slower rate of age-related cognitive decline.

Originally presented last November at the 14th Clinical Trials on Alzheimer’s Disease (CTAD) conference, this is the first large-scale, long-term randomized controlled trial to examine the effects of cocoa extract and multivitamins on global cognition. The trial’s primary focus was on cocoa extract, which earlier studies suggest may preserve cognitive function. Analyzing the effect of multivitamins was a secondary outcome.

Showing vitamins, but not cocoa, were beneficial is the exact opposite of what researchers expected. Still, the results offer an interesting new direction for future study, lead investigator Laura D. Baker, PhD, professor of gerontology and geriatric medicine at Wake Forest University, Winston-Salem, N.C., said in an interview.

“This study made us take notice of a pathway for possible cognitive protection,” Dr. Baker said. “Without this study, we would never have looked down that road.”

The full results were published online in Alzheimer’s and Dementia.
 

Unexpected effect

The COSMOS-Mind study is a substudy to a larger parent trial called COSMOS. It investigated the effects of cocoa extract and a standard multivitamin-mineral on cardiovascular and cancer outcomes in more than 21,000 older participants.

In COSMOS-Mind, researchers tested whether daily intake of cocoa extract vs. placebo and a multivitamin-mineral vs. placebo improved cognition in older adults.

More than 2,200 participants aged 65 and older were enrolled and followed for 3 years. They completed tests over the telephone at baseline and annually to evaluate memory and other cognitive abilities.

Results showed cocoa extract had no effect on global cognition compared with placebo (mean z-score, 0.03; P = .28). Daily multivitamin use, however, did show significant benefits on global cognition vs. placebo (mean z, 0.07, P = .007).

The beneficial effect was most pronounced in participants with a history of cardiovascular disease (no history 0.06 vs. history 0.14; P = .01).

Researchers found similar protective effects for memory and executive function. 

Dr. Baker suggested one possible explanation for the positive effects of multivitamins may be the boost in micronutrients and essential minerals they provided.

“With nutrient-deficient diets plus a high prevalence of cardiovascular disease, diabetes, and other medical comorbidities that we know impact the bioavailability of these nutrients, we are possibly dealing with older adults who are at below optimum in terms of their essential micronutrients and minerals,” she said.

“Even suboptimum levels of micronutrients and essential minerals can have significant consequences for brain health,” she added.
 

More research needed

Intriguing as the results may be, more work is needed before the findings could affect nutritional guidance, according to Maria C. Carrillo, PhD, chief science officer for the Alzheimer’s Association.

“While the Alzheimer’s Association is encouraged by these results, we are not ready to recommend widespread use of a multivitamin supplement to reduce risk of cognitive decline in older adults,” Dr. Carrillo said in a statement.

“For now, and until there is more data, people should talk with their health care providers about the benefits and risks of all dietary supplements, including multivitamins,” she added.

Dr. Baker agreed, noting that the study was not designed to measure multivitamin use as a primary outcome. In addition, nearly 90% of the participants were non-Hispanic White, which is not representative of the overall population demographics.

The investigators are now designing another, larger trial that would include a more diverse participant pool. It will be aimed specifically at learning more about how and why multivitamins seem to offer a protective effect on cognition, Dr. Baker noted.

The study was funded by the National Institute on Aging of the National Institutes of Health. Dr. Baker and Dr. Carrillo report no relevant financial relationships.

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

Unexpected results from a phase 3 trial exploring the effect of multivitamins and cognition have now been published.

Findings from a phase 3 study show daily multivitamin use, but not cocoa, is linked to a significantly slower rate of age-related cognitive decline.

Originally presented last November at the 14th Clinical Trials on Alzheimer’s Disease (CTAD) conference, this is the first large-scale, long-term randomized controlled trial to examine the effects of cocoa extract and multivitamins on global cognition. The trial’s primary focus was on cocoa extract, which earlier studies suggest may preserve cognitive function. Analyzing the effect of multivitamins was a secondary outcome.

Showing vitamins, but not cocoa, were beneficial is the exact opposite of what researchers expected. Still, the results offer an interesting new direction for future study, lead investigator Laura D. Baker, PhD, professor of gerontology and geriatric medicine at Wake Forest University, Winston-Salem, N.C., said in an interview.

“This study made us take notice of a pathway for possible cognitive protection,” Dr. Baker said. “Without this study, we would never have looked down that road.”

The full results were published online in Alzheimer’s and Dementia.
 

Unexpected effect

The COSMOS-Mind study is a substudy to a larger parent trial called COSMOS. It investigated the effects of cocoa extract and a standard multivitamin-mineral on cardiovascular and cancer outcomes in more than 21,000 older participants.

In COSMOS-Mind, researchers tested whether daily intake of cocoa extract vs. placebo and a multivitamin-mineral vs. placebo improved cognition in older adults.

More than 2,200 participants aged 65 and older were enrolled and followed for 3 years. They completed tests over the telephone at baseline and annually to evaluate memory and other cognitive abilities.

Results showed cocoa extract had no effect on global cognition compared with placebo (mean z-score, 0.03; P = .28). Daily multivitamin use, however, did show significant benefits on global cognition vs. placebo (mean z, 0.07, P = .007).

The beneficial effect was most pronounced in participants with a history of cardiovascular disease (no history 0.06 vs. history 0.14; P = .01).

Researchers found similar protective effects for memory and executive function. 

Dr. Baker suggested one possible explanation for the positive effects of multivitamins may be the boost in micronutrients and essential minerals they provided.

“With nutrient-deficient diets plus a high prevalence of cardiovascular disease, diabetes, and other medical comorbidities that we know impact the bioavailability of these nutrients, we are possibly dealing with older adults who are at below optimum in terms of their essential micronutrients and minerals,” she said.

“Even suboptimum levels of micronutrients and essential minerals can have significant consequences for brain health,” she added.
 

More research needed

Intriguing as the results may be, more work is needed before the findings could affect nutritional guidance, according to Maria C. Carrillo, PhD, chief science officer for the Alzheimer’s Association.

“While the Alzheimer’s Association is encouraged by these results, we are not ready to recommend widespread use of a multivitamin supplement to reduce risk of cognitive decline in older adults,” Dr. Carrillo said in a statement.

“For now, and until there is more data, people should talk with their health care providers about the benefits and risks of all dietary supplements, including multivitamins,” she added.

Dr. Baker agreed, noting that the study was not designed to measure multivitamin use as a primary outcome. In addition, nearly 90% of the participants were non-Hispanic White, which is not representative of the overall population demographics.

The investigators are now designing another, larger trial that would include a more diverse participant pool. It will be aimed specifically at learning more about how and why multivitamins seem to offer a protective effect on cognition, Dr. Baker noted.

The study was funded by the National Institute on Aging of the National Institutes of Health. Dr. Baker and Dr. Carrillo report no relevant financial relationships.

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

BARCELONA – Treatment of patients with chronic heart failure with sacubitril/valsartan (Entresto), a mainstay agent for people with this disorder, produced no hint of incremental adverse cognitive effects during 3 years of treatment in a prospective, controlled, multicenter study with nearly 600 patients, although some experts note that possible adverse cognitive effects of sacubitril were not an issue for many heart failure clinicians, even before the study ran.

The potential for an adverse effect of sacubitril on cognition had arisen as a hypothetical concern because sacubitril inhibits the human enzyme neprilysin. This activity results in beneficial effects for patients with heart failure by increasing levels of several endogenous vasoactive peptides. But neprilysin also degrades amyloid beta peptides and so inhibition of this enzyme could possibly result in accumulation of amyloid peptides in the brain with potential neurotoxic effects, which raised concern among some cardiologists and patients that sacubitril/valsartan could hasten cognitive decline.

Catherine Hackett/MDedge News

Results from the new study, PERSPECTIVE, showed “no evidence that neprilysin inhibition increased the risk of cognitive impairment due to the accumulation of beta amyloid” in patients with heart failure with either mid-range or preserved ejection fraction,” John McMurray, MD, said at the annual congress of the European Society of Cardiology.

Dr. McMurray, professor of medical cardiology at the University of Glasgow, highlighted that the study enrolled only patients with heart failure with a left ventricular ejection fraction of greater than 40% because the study designers considered it “unethical” to withhold treatment with sacubitril/valsartan from patients with an ejection fraction of 40% or less (heart failure with reduced ejection fraction, HFrEF), whereas “no mandate” exists in current treatment guidelines for using sacubitril/valsartan in patients with heart failure and higher ejection fractions. He added that he could see no reason why the results seen in patients with higher ejection fractions would not also apply to those with HFrEF.
 

Reassuring results, but cost still a drag on uptake

“This was a well-designed trial” with results that are “very reassuring” for a lack of harm from sacubitril/valsartan, commented Biykem Bozkurt, MD, PhD, the study’s designated discussant and professor of medicine at Baylor College of Medicine, Houston. The findings “solidify the lack of risk and are very exciting for the heart failure community because the question has bothered a large number of people, especially older patients” with heart failure.

Catherine Hackett/MDedge News

Following these results, “hopefully more patients with heart failure will receive” sacubitril/valsartan, agreed Dr. McMurray, but he added the caveat that the relatively high cost of the agent (which has a U.S. list price of roughly $6,000/year) has been the primary barrier to wider uptake of the drug for patients with heart failure. Treatment with sacubitril/valsartan is recommended in several society guidelines as a core intervention for patients with HFrEF and as a treatment option for patients with heart failure and higher ejection fractions.

“Cost remains the single biggest deterrent for use” of sacubitril/valsartan, agreed Dipti N. Itchhaporia, MD, director of disease management at the Hoag Heart and Vascular Institute in Newport Beach, Calif. “Concerns about cognitive impairment has not been why people have not been using sacubitril/valsartan,” Dr. Itchhaporia commented in an interview.

PERSPECTIVE enrolled patients with heart failure with an ejection fraction greater than 40% and at least 60 years old at any of 137 sites in 20 countries, with about a third of enrolled patients coming from U.S. centers. The study, which ran enrollment during January 2017–May 2019, excluded people with clinically discernible cognitive impairment at the time of entry.

Researchers randomized patients to either a standard regimen of sacubitril/valsartan (295) or valsartan (297) on top of their background treatment, with most patients also receiving a beta-blocker, a diuretic, and a statin. The enrolled patients averaged about 72 years of age, and more than one-third were at least 75 years old.

The study’s primary endpoint was the performance of these patients in seven different tests of cognitive function using a proprietary metric, the CogState Global Cognitive Composite Score, measured at baseline and then every 6 months during follow-up designed to run for 3 years on treatment (the researchers collected data for at least 30 months of follow-up from 71%-73% of enrolled patients). Average changes in these scores over time tracked nearly the same in both treatment arms and met the study’s prespecified criteria for noninferiority of the sacubitril valsartan treatment, Dr. McMurray reported. The results also showed that roughly 60% of patients in both arms had “some degree of cognitive impairment” during follow-up.

A secondary outcome measure used PET imaging to quantify cerebral accumulation of beta amyloid, and again the results met the study’s prespecified threshold for noninferiority for the patients treated with sacubitril/valsartan, said Dr. McMurray.

Another concern raised by some experts was the relatively brief follow-up of 3 years, and the complexity of heart failure patients who could face several other causes of cognitive decline. The findings “help reassure, but 3 years is not long enough, and I’m not sure the study eliminated all the other possible variables,” commented Dr. Itchhaporia.

But Dr. McMurray contended that 3 years represents robust follow-up in patients with heart failure who notoriously have limited life expectancy following their diagnosis. “Three years is a long time for patients with heart failure.”

The findings also raise the prospect of developing sacubitril/valsartan as an antihypertensive treatment, an indication that has been avoided until now because of the uncertain cognitive effects of the agent and the need for prolonged use when the treated disorder is hypertension instead of heart failure.

PERSPECTIVE was funded by Novartis, the company that markets sacubitril/valsartan (Entresto). Dr. McMurray has received consulting and lecture fees from Novartis and he and his institution have received research funding from Novartis. Dr. Bozkurt has been a consultant to numerous companies but has no relationship with Novartis. Dr. Itchhaporia had no disclosures.

BARCELONA – Treatment of patients with chronic heart failure with sacubitril/valsartan (Entresto), a mainstay agent for people with this disorder, produced no hint of incremental adverse cognitive effects during 3 years of treatment in a prospective, controlled, multicenter study with nearly 600 patients, although some experts note that possible adverse cognitive effects of sacubitril were not an issue for many heart failure clinicians, even before the study ran.

The potential for an adverse effect of sacubitril on cognition had arisen as a hypothetical concern because sacubitril inhibits the human enzyme neprilysin. This activity results in beneficial effects for patients with heart failure by increasing levels of several endogenous vasoactive peptides. But neprilysin also degrades amyloid beta peptides and so inhibition of this enzyme could possibly result in accumulation of amyloid peptides in the brain with potential neurotoxic effects, which raised concern among some cardiologists and patients that sacubitril/valsartan could hasten cognitive decline.

Catherine Hackett/MDedge News

Results from the new study, PERSPECTIVE, showed “no evidence that neprilysin inhibition increased the risk of cognitive impairment due to the accumulation of beta amyloid” in patients with heart failure with either mid-range or preserved ejection fraction,” John McMurray, MD, said at the annual congress of the European Society of Cardiology.

Dr. McMurray, professor of medical cardiology at the University of Glasgow, highlighted that the study enrolled only patients with heart failure with a left ventricular ejection fraction of greater than 40% because the study designers considered it “unethical” to withhold treatment with sacubitril/valsartan from patients with an ejection fraction of 40% or less (heart failure with reduced ejection fraction, HFrEF), whereas “no mandate” exists in current treatment guidelines for using sacubitril/valsartan in patients with heart failure and higher ejection fractions. He added that he could see no reason why the results seen in patients with higher ejection fractions would not also apply to those with HFrEF.
 

Reassuring results, but cost still a drag on uptake

“This was a well-designed trial” with results that are “very reassuring” for a lack of harm from sacubitril/valsartan, commented Biykem Bozkurt, MD, PhD, the study’s designated discussant and professor of medicine at Baylor College of Medicine, Houston. The findings “solidify the lack of risk and are very exciting for the heart failure community because the question has bothered a large number of people, especially older patients” with heart failure.

Catherine Hackett/MDedge News

Following these results, “hopefully more patients with heart failure will receive” sacubitril/valsartan, agreed Dr. McMurray, but he added the caveat that the relatively high cost of the agent (which has a U.S. list price of roughly $6,000/year) has been the primary barrier to wider uptake of the drug for patients with heart failure. Treatment with sacubitril/valsartan is recommended in several society guidelines as a core intervention for patients with HFrEF and as a treatment option for patients with heart failure and higher ejection fractions.

“Cost remains the single biggest deterrent for use” of sacubitril/valsartan, agreed Dipti N. Itchhaporia, MD, director of disease management at the Hoag Heart and Vascular Institute in Newport Beach, Calif. “Concerns about cognitive impairment has not been why people have not been using sacubitril/valsartan,” Dr. Itchhaporia commented in an interview.

PERSPECTIVE enrolled patients with heart failure with an ejection fraction greater than 40% and at least 60 years old at any of 137 sites in 20 countries, with about a third of enrolled patients coming from U.S. centers. The study, which ran enrollment during January 2017–May 2019, excluded people with clinically discernible cognitive impairment at the time of entry.

Researchers randomized patients to either a standard regimen of sacubitril/valsartan (295) or valsartan (297) on top of their background treatment, with most patients also receiving a beta-blocker, a diuretic, and a statin. The enrolled patients averaged about 72 years of age, and more than one-third were at least 75 years old.

The study’s primary endpoint was the performance of these patients in seven different tests of cognitive function using a proprietary metric, the CogState Global Cognitive Composite Score, measured at baseline and then every 6 months during follow-up designed to run for 3 years on treatment (the researchers collected data for at least 30 months of follow-up from 71%-73% of enrolled patients). Average changes in these scores over time tracked nearly the same in both treatment arms and met the study’s prespecified criteria for noninferiority of the sacubitril valsartan treatment, Dr. McMurray reported. The results also showed that roughly 60% of patients in both arms had “some degree of cognitive impairment” during follow-up.

A secondary outcome measure used PET imaging to quantify cerebral accumulation of beta amyloid, and again the results met the study’s prespecified threshold for noninferiority for the patients treated with sacubitril/valsartan, said Dr. McMurray.

Another concern raised by some experts was the relatively brief follow-up of 3 years, and the complexity of heart failure patients who could face several other causes of cognitive decline. The findings “help reassure, but 3 years is not long enough, and I’m not sure the study eliminated all the other possible variables,” commented Dr. Itchhaporia.

But Dr. McMurray contended that 3 years represents robust follow-up in patients with heart failure who notoriously have limited life expectancy following their diagnosis. “Three years is a long time for patients with heart failure.”

The findings also raise the prospect of developing sacubitril/valsartan as an antihypertensive treatment, an indication that has been avoided until now because of the uncertain cognitive effects of the agent and the need for prolonged use when the treated disorder is hypertension instead of heart failure.

PERSPECTIVE was funded by Novartis, the company that markets sacubitril/valsartan (Entresto). Dr. McMurray has received consulting and lecture fees from Novartis and he and his institution have received research funding from Novartis. Dr. Bozkurt has been a consultant to numerous companies but has no relationship with Novartis. Dr. Itchhaporia had no disclosures.

BARCELONA – Treatment of patients with chronic heart failure with sacubitril/valsartan (Entresto), a mainstay agent for people with this disorder, produced no hint of incremental adverse cognitive effects during 3 years of treatment in a prospective, controlled, multicenter study with nearly 600 patients, although some experts note that possible adverse cognitive effects of sacubitril were not an issue for many heart failure clinicians, even before the study ran.

The potential for an adverse effect of sacubitril on cognition had arisen as a hypothetical concern because sacubitril inhibits the human enzyme neprilysin. This activity results in beneficial effects for patients with heart failure by increasing levels of several endogenous vasoactive peptides. But neprilysin also degrades amyloid beta peptides and so inhibition of this enzyme could possibly result in accumulation of amyloid peptides in the brain with potential neurotoxic effects, which raised concern among some cardiologists and patients that sacubitril/valsartan could hasten cognitive decline.

Catherine Hackett/MDedge News

Results from the new study, PERSPECTIVE, showed “no evidence that neprilysin inhibition increased the risk of cognitive impairment due to the accumulation of beta amyloid” in patients with heart failure with either mid-range or preserved ejection fraction,” John McMurray, MD, said at the annual congress of the European Society of Cardiology.

Dr. McMurray, professor of medical cardiology at the University of Glasgow, highlighted that the study enrolled only patients with heart failure with a left ventricular ejection fraction of greater than 40% because the study designers considered it “unethical” to withhold treatment with sacubitril/valsartan from patients with an ejection fraction of 40% or less (heart failure with reduced ejection fraction, HFrEF), whereas “no mandate” exists in current treatment guidelines for using sacubitril/valsartan in patients with heart failure and higher ejection fractions. He added that he could see no reason why the results seen in patients with higher ejection fractions would not also apply to those with HFrEF.
 

Reassuring results, but cost still a drag on uptake

“This was a well-designed trial” with results that are “very reassuring” for a lack of harm from sacubitril/valsartan, commented Biykem Bozkurt, MD, PhD, the study’s designated discussant and professor of medicine at Baylor College of Medicine, Houston. The findings “solidify the lack of risk and are very exciting for the heart failure community because the question has bothered a large number of people, especially older patients” with heart failure.

Catherine Hackett/MDedge News

Following these results, “hopefully more patients with heart failure will receive” sacubitril/valsartan, agreed Dr. McMurray, but he added the caveat that the relatively high cost of the agent (which has a U.S. list price of roughly $6,000/year) has been the primary barrier to wider uptake of the drug for patients with heart failure. Treatment with sacubitril/valsartan is recommended in several society guidelines as a core intervention for patients with HFrEF and as a treatment option for patients with heart failure and higher ejection fractions.

“Cost remains the single biggest deterrent for use” of sacubitril/valsartan, agreed Dipti N. Itchhaporia, MD, director of disease management at the Hoag Heart and Vascular Institute in Newport Beach, Calif. “Concerns about cognitive impairment has not been why people have not been using sacubitril/valsartan,” Dr. Itchhaporia commented in an interview.

PERSPECTIVE enrolled patients with heart failure with an ejection fraction greater than 40% and at least 60 years old at any of 137 sites in 20 countries, with about a third of enrolled patients coming from U.S. centers. The study, which ran enrollment during January 2017–May 2019, excluded people with clinically discernible cognitive impairment at the time of entry.

Researchers randomized patients to either a standard regimen of sacubitril/valsartan (295) or valsartan (297) on top of their background treatment, with most patients also receiving a beta-blocker, a diuretic, and a statin. The enrolled patients averaged about 72 years of age, and more than one-third were at least 75 years old.

The study’s primary endpoint was the performance of these patients in seven different tests of cognitive function using a proprietary metric, the CogState Global Cognitive Composite Score, measured at baseline and then every 6 months during follow-up designed to run for 3 years on treatment (the researchers collected data for at least 30 months of follow-up from 71%-73% of enrolled patients). Average changes in these scores over time tracked nearly the same in both treatment arms and met the study’s prespecified criteria for noninferiority of the sacubitril valsartan treatment, Dr. McMurray reported. The results also showed that roughly 60% of patients in both arms had “some degree of cognitive impairment” during follow-up.

A secondary outcome measure used PET imaging to quantify cerebral accumulation of beta amyloid, and again the results met the study’s prespecified threshold for noninferiority for the patients treated with sacubitril/valsartan, said Dr. McMurray.

Another concern raised by some experts was the relatively brief follow-up of 3 years, and the complexity of heart failure patients who could face several other causes of cognitive decline. The findings “help reassure, but 3 years is not long enough, and I’m not sure the study eliminated all the other possible variables,” commented Dr. Itchhaporia.

But Dr. McMurray contended that 3 years represents robust follow-up in patients with heart failure who notoriously have limited life expectancy following their diagnosis. “Three years is a long time for patients with heart failure.”

The findings also raise the prospect of developing sacubitril/valsartan as an antihypertensive treatment, an indication that has been avoided until now because of the uncertain cognitive effects of the agent and the need for prolonged use when the treated disorder is hypertension instead of heart failure.

PERSPECTIVE was funded by Novartis, the company that markets sacubitril/valsartan (Entresto). Dr. McMurray has received consulting and lecture fees from Novartis and he and his institution have received research funding from Novartis. Dr. Bozkurt has been a consultant to numerous companies but has no relationship with Novartis. Dr. Itchhaporia had no disclosures.

Watching TV may increase your risk of dementia, while using a computer may lower it, new research suggests.

The relationship to dementia with these activities remained strong no matter how much physical activity a person did, the authors wrote in Proceedings of the National Academy of Sciences.

Both watching TV and using a computer have been linked to increased risk of chronic disease and mortality, while exercise and physical activity (PA) have shown benefit in reducing cognitive decline, structural brain atrophy, and dementia risk in older adults, the authors wrote.

The authors said they wanted to try to understand the effects of watching TV and using computers on dementia risk, because people in the United States and Europe have been engaging in both of these activities more often.

They concluded that it’s not the sitting part of sedentary behavior (SB) that potentially has the effect on dementia but what people are doing while sitting.

Some of the results were surprising, lead author David Raichlen, PhD, professor of Human and Evolutionary Biology at University of Southern California, Los Angeles, said in an interview.

Previous literature on sedentary behaviors have documented their negative effects on a wide range of health outcomes, rather than finding positive associations, he explained.
 

More than 140,000 included in study

The researchers conducted their prospective cohort study using data from the United Kingdom Biobank. After excluding people younger than 60, those with prevalent dementia at the start of follow-up, and those without complete data, 146,651 participants were included.

The participants were followed from their baseline visit until they received a dementia diagnosis, died, were lost to follow-up, or were last admitted to the hospital.

TV-watching time was linked with an increased risk of incident dementia (HR [95% confidence interval] = 1.31 [1.23-1.40]), and computer use was linked with a reduced risk of incident dementia HR [95% CI] = 0.80 [0.76-0.85]).

TV’s link with higher dementia risk increased in those who had the highest use, compared with those who had the lowest use (HR [95% CI] = 1.28 [1.18-1.39].

Similarly, the link with risk reduction for dementia with computer use increased with more use.

Both medium and high computer time were associated with reduced risk of incident dementia (HR [95% CI] = 0.70 [0.64-0.76] and HR [95% CI] = 0.76 [0.70-0.83] respectively).

Dr. Raichlen pointed out that the high use of TV in this study was 4 or more hours a day and computer use – which included leisure use, not work use – had benefits on dementia risk after just half an hour.

These results remained significant after researchers adjusted for demographic, health, and lifestyle variables, including time spent on physical activity, sleeping, obesity, alcohol consumption, smoking status, diet scores, education level, body mass index, and employment type.
 

Physical is still better than sedentary activity

One potential reason for the different effects on dementia risk in the two activities studied, the authors write, is that sitting down to watch TV is associated with “uniquely low levels of muscle activity and energy expenditure, compared with sitting to use a computer.”

Andrew Budson, MD, chief of Cognitive & Behavioral Neurology and Associate Chief of Staff for Education for the VA Boston Healthcare System, Mass., who was not part of the study, said he thinks a more likely explanation for the study findings lies in the active versus passive tasks required in the two kinds of viewing that the authors reference.

“When we’re doing cognitive activity involving using the computer, we’re using large parts of our cortex to carry out that activity, whereas when we’re watching TV, there are probably relatively small amounts of our brain that are actually active,” Dr. Budson, author of Seven Steps to Managing Your Memory, explained in an interview.

“This is one of the first times I’ve been convinced that even when the computer activity isn’t completely new and novel, it may be beneficial,” Dr. Budson said.

It would be much better to do physical activity, but if the choice is sedentary activity, active cognitive activities, such as computer use, are better than TV watching, he continued.

The results of the current study are consistent with previous work showing that the type of sedentary behavior matters, according to the authors.

“Several studies have shown that TV time is associated with mortality and poor cardiometabolic biomarkers, whereas computer time is not,” they wrote.

A limitation of the study is that sedentary behaviors were self-reported via questionnaires, and there may be errors in recall.

“The use of objective methods for measuring both SB and PA are needed in future studies,” they write.

The authors receive support from the National Institutes of Health, the State of Arizona, the Arizona Department of Health Services, and the McKnight Brain Research Foundation. Neither the authors nor Dr. Budson declared relevant financial relationships.

Watching TV may increase your risk of dementia, while using a computer may lower it, new research suggests.

The relationship to dementia with these activities remained strong no matter how much physical activity a person did, the authors wrote in Proceedings of the National Academy of Sciences.

Both watching TV and using a computer have been linked to increased risk of chronic disease and mortality, while exercise and physical activity (PA) have shown benefit in reducing cognitive decline, structural brain atrophy, and dementia risk in older adults, the authors wrote.

The authors said they wanted to try to understand the effects of watching TV and using computers on dementia risk, because people in the United States and Europe have been engaging in both of these activities more often.

They concluded that it’s not the sitting part of sedentary behavior (SB) that potentially has the effect on dementia but what people are doing while sitting.

Some of the results were surprising, lead author David Raichlen, PhD, professor of Human and Evolutionary Biology at University of Southern California, Los Angeles, said in an interview.

Previous literature on sedentary behaviors have documented their negative effects on a wide range of health outcomes, rather than finding positive associations, he explained.
 

More than 140,000 included in study

The researchers conducted their prospective cohort study using data from the United Kingdom Biobank. After excluding people younger than 60, those with prevalent dementia at the start of follow-up, and those without complete data, 146,651 participants were included.

The participants were followed from their baseline visit until they received a dementia diagnosis, died, were lost to follow-up, or were last admitted to the hospital.

TV-watching time was linked with an increased risk of incident dementia (HR [95% confidence interval] = 1.31 [1.23-1.40]), and computer use was linked with a reduced risk of incident dementia HR [95% CI] = 0.80 [0.76-0.85]).

TV’s link with higher dementia risk increased in those who had the highest use, compared with those who had the lowest use (HR [95% CI] = 1.28 [1.18-1.39].

Similarly, the link with risk reduction for dementia with computer use increased with more use.

Both medium and high computer time were associated with reduced risk of incident dementia (HR [95% CI] = 0.70 [0.64-0.76] and HR [95% CI] = 0.76 [0.70-0.83] respectively).

Dr. Raichlen pointed out that the high use of TV in this study was 4 or more hours a day and computer use – which included leisure use, not work use – had benefits on dementia risk after just half an hour.

These results remained significant after researchers adjusted for demographic, health, and lifestyle variables, including time spent on physical activity, sleeping, obesity, alcohol consumption, smoking status, diet scores, education level, body mass index, and employment type.
 

Physical is still better than sedentary activity

One potential reason for the different effects on dementia risk in the two activities studied, the authors write, is that sitting down to watch TV is associated with “uniquely low levels of muscle activity and energy expenditure, compared with sitting to use a computer.”

Andrew Budson, MD, chief of Cognitive & Behavioral Neurology and Associate Chief of Staff for Education for the VA Boston Healthcare System, Mass., who was not part of the study, said he thinks a more likely explanation for the study findings lies in the active versus passive tasks required in the two kinds of viewing that the authors reference.

“When we’re doing cognitive activity involving using the computer, we’re using large parts of our cortex to carry out that activity, whereas when we’re watching TV, there are probably relatively small amounts of our brain that are actually active,” Dr. Budson, author of Seven Steps to Managing Your Memory, explained in an interview.

“This is one of the first times I’ve been convinced that even when the computer activity isn’t completely new and novel, it may be beneficial,” Dr. Budson said.

It would be much better to do physical activity, but if the choice is sedentary activity, active cognitive activities, such as computer use, are better than TV watching, he continued.

The results of the current study are consistent with previous work showing that the type of sedentary behavior matters, according to the authors.

“Several studies have shown that TV time is associated with mortality and poor cardiometabolic biomarkers, whereas computer time is not,” they wrote.

A limitation of the study is that sedentary behaviors were self-reported via questionnaires, and there may be errors in recall.

“The use of objective methods for measuring both SB and PA are needed in future studies,” they write.

The authors receive support from the National Institutes of Health, the State of Arizona, the Arizona Department of Health Services, and the McKnight Brain Research Foundation. Neither the authors nor Dr. Budson declared relevant financial relationships.

Watching TV may increase your risk of dementia, while using a computer may lower it, new research suggests.

The relationship to dementia with these activities remained strong no matter how much physical activity a person did, the authors wrote in Proceedings of the National Academy of Sciences.

Both watching TV and using a computer have been linked to increased risk of chronic disease and mortality, while exercise and physical activity (PA) have shown benefit in reducing cognitive decline, structural brain atrophy, and dementia risk in older adults, the authors wrote.

The authors said they wanted to try to understand the effects of watching TV and using computers on dementia risk, because people in the United States and Europe have been engaging in both of these activities more often.

They concluded that it’s not the sitting part of sedentary behavior (SB) that potentially has the effect on dementia but what people are doing while sitting.

Some of the results were surprising, lead author David Raichlen, PhD, professor of Human and Evolutionary Biology at University of Southern California, Los Angeles, said in an interview.

Previous literature on sedentary behaviors have documented their negative effects on a wide range of health outcomes, rather than finding positive associations, he explained.
 

More than 140,000 included in study

The researchers conducted their prospective cohort study using data from the United Kingdom Biobank. After excluding people younger than 60, those with prevalent dementia at the start of follow-up, and those without complete data, 146,651 participants were included.

The participants were followed from their baseline visit until they received a dementia diagnosis, died, were lost to follow-up, or were last admitted to the hospital.

TV-watching time was linked with an increased risk of incident dementia (HR [95% confidence interval] = 1.31 [1.23-1.40]), and computer use was linked with a reduced risk of incident dementia HR [95% CI] = 0.80 [0.76-0.85]).

TV’s link with higher dementia risk increased in those who had the highest use, compared with those who had the lowest use (HR [95% CI] = 1.28 [1.18-1.39].

Similarly, the link with risk reduction for dementia with computer use increased with more use.

Both medium and high computer time were associated with reduced risk of incident dementia (HR [95% CI] = 0.70 [0.64-0.76] and HR [95% CI] = 0.76 [0.70-0.83] respectively).

Dr. Raichlen pointed out that the high use of TV in this study was 4 or more hours a day and computer use – which included leisure use, not work use – had benefits on dementia risk after just half an hour.

These results remained significant after researchers adjusted for demographic, health, and lifestyle variables, including time spent on physical activity, sleeping, obesity, alcohol consumption, smoking status, diet scores, education level, body mass index, and employment type.
 

Physical is still better than sedentary activity

One potential reason for the different effects on dementia risk in the two activities studied, the authors write, is that sitting down to watch TV is associated with “uniquely low levels of muscle activity and energy expenditure, compared with sitting to use a computer.”

Andrew Budson, MD, chief of Cognitive & Behavioral Neurology and Associate Chief of Staff for Education for the VA Boston Healthcare System, Mass., who was not part of the study, said he thinks a more likely explanation for the study findings lies in the active versus passive tasks required in the two kinds of viewing that the authors reference.

“When we’re doing cognitive activity involving using the computer, we’re using large parts of our cortex to carry out that activity, whereas when we’re watching TV, there are probably relatively small amounts of our brain that are actually active,” Dr. Budson, author of Seven Steps to Managing Your Memory, explained in an interview.

“This is one of the first times I’ve been convinced that even when the computer activity isn’t completely new and novel, it may be beneficial,” Dr. Budson said.

It would be much better to do physical activity, but if the choice is sedentary activity, active cognitive activities, such as computer use, are better than TV watching, he continued.

The results of the current study are consistent with previous work showing that the type of sedentary behavior matters, according to the authors.

“Several studies have shown that TV time is associated with mortality and poor cardiometabolic biomarkers, whereas computer time is not,” they wrote.

A limitation of the study is that sedentary behaviors were self-reported via questionnaires, and there may be errors in recall.

“The use of objective methods for measuring both SB and PA are needed in future studies,” they write.

The authors receive support from the National Institutes of Health, the State of Arizona, the Arizona Department of Health Services, and the McKnight Brain Research Foundation. Neither the authors nor Dr. Budson declared relevant financial relationships.

Older adults with atrial cardiopathy may have up to 35% higher risk for dementia even before symptoms develop, new research suggests.

“We cautiously suggest that an understanding of this relationship might provide a basis for new interventional strategies to help thwart the development of dementia,” the authors write.

The research, led by Michelle C. Johansen, MD, department of neurology, Johns Hopkins University, Baltimore, was published online in the Journal of the American Heart Association.

Atrial cardiopathy, characterized by abnormal size and function of the left atrium, has been associated with an increased risk of stroke and atrial fibrillation (AFib), and because both stroke and AFib are associated with an increased dementia risk, the authors write, it was important to investigate whether atrial cardiopathy is linked to dementia.

If that’s the case, they reasoned, the next question was whether that link is independent of AFib and stroke, and their new research suggests that it is.

For this analysis, the researchers conducted a prospective cohort analysis of participants in the Atherosclerosis Risk in Communities (ARIC) study who were attending visit 5 (2011-2013). During their fifth, sixth, and seventh clinical visits, the ARIC participants were evaluated for cognitive decline indicating dementia.

They studied a diverse population of 5,078 older adults living in four U.S. communities: Washington County, Md.; Forsyth County, N.C.; the northwestern suburbs of Minneapolis; and Jackson, Miss.

Just more than a third (34%) had atrial cardiopathy (average age, 75 years; 59% female; 21% Black) and 763 participants developed dementia.

Investigators found that atrial cardiopathy was significantly associated with dementia (adjusted hazard ratio, 1.35 [95% confidence interval, 1.16-1.58]).

They considered ARIC participants to have atrial cardiopathy if they had at least one of the following: P-wave terminal force greater than 5,000 mV·ms in ECG lead V1; NTproBNP greater than 250 pg/mL; or left atrial volume index greater than or equal to 34 mL/m² by transthoracic echocardiography.

The risk of dementia was even stronger when the researchers defined cardiopathy by at least two biomarkers instead of one (aHR, 1.54 [95% CI, 1.25-1.89]).

The authors point out, however, that this study is observational and cannot make a causal link.

Clifford Kavinsky, MD, PhD, head of the Comprehensive Stroke and Cardiology Clinic at Rush University Medical Center, Chicago, told this news organization that much more research would need to be done to show convincingly that atrial cardiopathy causes dementia.

He called the findings “provocative in trying to understand in a general sense how cardiac dysfunction leads to dementia.”

“We all know heart failure leads to dementia, but now we see there may be a relationship with just dysfunction of the upper chambers,” he said.
 

Unresolved questions

But it still not clear is what is mediating the connection, who is at risk, and how the increased risk can be prevented, he said.

He said he also wonders whether the results eliminated all patients with atrial fibrillation, a point the authors acknowledge as well.

Researchers list in the limitations that “asymptomatic AFib or silent cerebral infarction may have been missed by the ARIC adjudication process.”

There is broad understanding that preventing heart disease is important for a wide array of reasons, Dr. Kavinsky noted, and one of the reasons is cognitive deterioration.

He said this study helps identify that “even dysfunction of the upper chambers of the heart contributes to the evolution of dementia.”

The study amplifies the need to shift to prevention with heart disease in general, and more specifically in atrial dysfunction, Dr. Kavinsky said, noting a lot of atrial dysfunction is mediated by underlying hypertension and coronary disease.

Researchers evaluated cognitive decline in all participants with a comprehensive array of neuropsychological tests and interviewed some of the patients.

“A diagnosis of dementia was generated based on testing results by a computer diagnostic algorithm and then decided upon by an expert based on the Diagnostic and Statistical Manual of Mental Disorders and the criteria outlined by the National Institutes of Health and the National Institutes of Health,” they write.

Dr. Johansen reported funding from National Institute of Neurological Disorders and Stroke. Study coauthor disclosures are listed in the paper. Dr. Kavinsky has disclosed no relevant financial relationships.

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

Older adults with atrial cardiopathy may have up to 35% higher risk for dementia even before symptoms develop, new research suggests.

“We cautiously suggest that an understanding of this relationship might provide a basis for new interventional strategies to help thwart the development of dementia,” the authors write.

The research, led by Michelle C. Johansen, MD, department of neurology, Johns Hopkins University, Baltimore, was published online in the Journal of the American Heart Association.

Atrial cardiopathy, characterized by abnormal size and function of the left atrium, has been associated with an increased risk of stroke and atrial fibrillation (AFib), and because both stroke and AFib are associated with an increased dementia risk, the authors write, it was important to investigate whether atrial cardiopathy is linked to dementia.

If that’s the case, they reasoned, the next question was whether that link is independent of AFib and stroke, and their new research suggests that it is.

For this analysis, the researchers conducted a prospective cohort analysis of participants in the Atherosclerosis Risk in Communities (ARIC) study who were attending visit 5 (2011-2013). During their fifth, sixth, and seventh clinical visits, the ARIC participants were evaluated for cognitive decline indicating dementia.

They studied a diverse population of 5,078 older adults living in four U.S. communities: Washington County, Md.; Forsyth County, N.C.; the northwestern suburbs of Minneapolis; and Jackson, Miss.

Just more than a third (34%) had atrial cardiopathy (average age, 75 years; 59% female; 21% Black) and 763 participants developed dementia.

Investigators found that atrial cardiopathy was significantly associated with dementia (adjusted hazard ratio, 1.35 [95% confidence interval, 1.16-1.58]).

They considered ARIC participants to have atrial cardiopathy if they had at least one of the following: P-wave terminal force greater than 5,000 mV·ms in ECG lead V1; NTproBNP greater than 250 pg/mL; or left atrial volume index greater than or equal to 34 mL/m² by transthoracic echocardiography.

The risk of dementia was even stronger when the researchers defined cardiopathy by at least two biomarkers instead of one (aHR, 1.54 [95% CI, 1.25-1.89]).

The authors point out, however, that this study is observational and cannot make a causal link.

Clifford Kavinsky, MD, PhD, head of the Comprehensive Stroke and Cardiology Clinic at Rush University Medical Center, Chicago, told this news organization that much more research would need to be done to show convincingly that atrial cardiopathy causes dementia.

He called the findings “provocative in trying to understand in a general sense how cardiac dysfunction leads to dementia.”

“We all know heart failure leads to dementia, but now we see there may be a relationship with just dysfunction of the upper chambers,” he said.
 

Unresolved questions

But it still not clear is what is mediating the connection, who is at risk, and how the increased risk can be prevented, he said.

He said he also wonders whether the results eliminated all patients with atrial fibrillation, a point the authors acknowledge as well.

Researchers list in the limitations that “asymptomatic AFib or silent cerebral infarction may have been missed by the ARIC adjudication process.”

There is broad understanding that preventing heart disease is important for a wide array of reasons, Dr. Kavinsky noted, and one of the reasons is cognitive deterioration.

He said this study helps identify that “even dysfunction of the upper chambers of the heart contributes to the evolution of dementia.”

The study amplifies the need to shift to prevention with heart disease in general, and more specifically in atrial dysfunction, Dr. Kavinsky said, noting a lot of atrial dysfunction is mediated by underlying hypertension and coronary disease.

Researchers evaluated cognitive decline in all participants with a comprehensive array of neuropsychological tests and interviewed some of the patients.

“A diagnosis of dementia was generated based on testing results by a computer diagnostic algorithm and then decided upon by an expert based on the Diagnostic and Statistical Manual of Mental Disorders and the criteria outlined by the National Institutes of Health and the National Institutes of Health,” they write.

Dr. Johansen reported funding from National Institute of Neurological Disorders and Stroke. Study coauthor disclosures are listed in the paper. Dr. Kavinsky has disclosed no relevant financial relationships.

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

Older adults with atrial cardiopathy may have up to 35% higher risk for dementia even before symptoms develop, new research suggests.

“We cautiously suggest that an understanding of this relationship might provide a basis for new interventional strategies to help thwart the development of dementia,” the authors write.

The research, led by Michelle C. Johansen, MD, department of neurology, Johns Hopkins University, Baltimore, was published online in the Journal of the American Heart Association.

Atrial cardiopathy, characterized by abnormal size and function of the left atrium, has been associated with an increased risk of stroke and atrial fibrillation (AFib), and because both stroke and AFib are associated with an increased dementia risk, the authors write, it was important to investigate whether atrial cardiopathy is linked to dementia.

If that’s the case, they reasoned, the next question was whether that link is independent of AFib and stroke, and their new research suggests that it is.

For this analysis, the researchers conducted a prospective cohort analysis of participants in the Atherosclerosis Risk in Communities (ARIC) study who were attending visit 5 (2011-2013). During their fifth, sixth, and seventh clinical visits, the ARIC participants were evaluated for cognitive decline indicating dementia.

They studied a diverse population of 5,078 older adults living in four U.S. communities: Washington County, Md.; Forsyth County, N.C.; the northwestern suburbs of Minneapolis; and Jackson, Miss.

Just more than a third (34%) had atrial cardiopathy (average age, 75 years; 59% female; 21% Black) and 763 participants developed dementia.

Investigators found that atrial cardiopathy was significantly associated with dementia (adjusted hazard ratio, 1.35 [95% confidence interval, 1.16-1.58]).

They considered ARIC participants to have atrial cardiopathy if they had at least one of the following: P-wave terminal force greater than 5,000 mV·ms in ECG lead V1; NTproBNP greater than 250 pg/mL; or left atrial volume index greater than or equal to 34 mL/m² by transthoracic echocardiography.

The risk of dementia was even stronger when the researchers defined cardiopathy by at least two biomarkers instead of one (aHR, 1.54 [95% CI, 1.25-1.89]).

The authors point out, however, that this study is observational and cannot make a causal link.

Clifford Kavinsky, MD, PhD, head of the Comprehensive Stroke and Cardiology Clinic at Rush University Medical Center, Chicago, told this news organization that much more research would need to be done to show convincingly that atrial cardiopathy causes dementia.

He called the findings “provocative in trying to understand in a general sense how cardiac dysfunction leads to dementia.”

“We all know heart failure leads to dementia, but now we see there may be a relationship with just dysfunction of the upper chambers,” he said.
 

Unresolved questions

But it still not clear is what is mediating the connection, who is at risk, and how the increased risk can be prevented, he said.

He said he also wonders whether the results eliminated all patients with atrial fibrillation, a point the authors acknowledge as well.

Researchers list in the limitations that “asymptomatic AFib or silent cerebral infarction may have been missed by the ARIC adjudication process.”

There is broad understanding that preventing heart disease is important for a wide array of reasons, Dr. Kavinsky noted, and one of the reasons is cognitive deterioration.

He said this study helps identify that “even dysfunction of the upper chambers of the heart contributes to the evolution of dementia.”

The study amplifies the need to shift to prevention with heart disease in general, and more specifically in atrial dysfunction, Dr. Kavinsky said, noting a lot of atrial dysfunction is mediated by underlying hypertension and coronary disease.

Researchers evaluated cognitive decline in all participants with a comprehensive array of neuropsychological tests and interviewed some of the patients.

“A diagnosis of dementia was generated based on testing results by a computer diagnostic algorithm and then decided upon by an expert based on the Diagnostic and Statistical Manual of Mental Disorders and the criteria outlined by the National Institutes of Health and the National Institutes of Health,” they write.

Dr. Johansen reported funding from National Institute of Neurological Disorders and Stroke. Study coauthor disclosures are listed in the paper. Dr. Kavinsky has disclosed no relevant financial relationships.

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