Alzheimer's & Cognition

Patients with psychotic disorders such as schizophrenia are more than twice as likely as those without a psychotic disorder to eventually develop dementia, new research suggests.

Results from a review and meta-analysis of almost 13 million total participants from nine countries showed that, across multiple different psychotic disorders, there was a 2.5-fold higher risk of developing dementia later in life compared with individuals who did not have a disorder. This was regardless of the age at which the patients first developed the mental illness.

Moreover, participants with a psychotic disorder tended to be younger than average when diagnosed with dementia. Two studies showed that those with psychotic disorders were more likely to be diagnosed with dementia as early as in their 60s.

“The findings add to a growing body of evidence linking psychiatric disorders with later cognitive decline and dementia,” senior investigator Jean Stafford, PhD, a research fellow at MRC Unit for Lifelong Health and Ageing, University College London, told this news organization.

Dr. Stafford noted that the results highlight the importance of being aware of and watchful for symptoms of cognitive decline in patients with psychotic disorders in mid- and late life.

“In addition, given that people with psychotic disorders are at higher risk of experiencing multiple health conditions, including dementia, managing overall physical and mental health in this group is crucial,” she said.

The findings were published online in Psychological Medicine.
 

Bringing the evidence together

There is increasing evidence that multiple psychiatric symptoms and diagnoses are associated with cognitive decline and dementia, with particularly strong evidence for late-life depression, Dr. Stafford said.

“However, the relationship between psychotic disorders and dementia is less well-established,” she added.

Last year, her team published a study showing a strong association between very late onset psychotic disorders, defined as first diagnosed after age 60 years, and increased risk for dementia in Swedish population register data.

“We also became aware of several other large studies on the topic published in the last few years and realized that an up-to-date systematic review and meta-analysis was needed to bring together the evidence, specifically focusing on longitudinal studies,” Dr. Stafford said.

The researchers searched four databases of prospective and retrospective longitudinal studies published through March 2022. Studies were required to focus on adults aged 18 years or older with a clinical diagnosis of a nonaffective psychotic disorder and a comparison group consisting of adults without a nonaffective psychotic disorder.

Of 9,496 papers, the investigators selected 11 published from 2003 to 2022 that met criteria for inclusion in their meta-analysis (12,997,101 participants), with follow-up periods ranging from 1.57 to 33 years.

The studies hailed from Denmark, Finland, Sweden, the United Kingdom, the United States, Australia, Taiwan, New Zealand, and Israel.

Random-effects meta-analyses were used to pool estimates across studies. The researchers assessed the risk of bias for each study. They also included two additional studies in the review, but not the meta-analysis, that focused specifically on late-onset acute and transient psychosis and late-onset delusional disorder.

The other studies focused on late-onset schizophrenia and/or very late onset schizophrenia-like psychoses, schizophrenia, psychotic disorders, and schizophrenia in older people.

Most studies investigated the incidence of all-cause dementia, although one study focused on the incidence of Alzheimer’s disease.
 

Potential mechanisms

The narrative review showed that most studies (n = 10) were of high methodological quality, although two were rated as fair and one as poor.

Almost all studies accounted for basic sociodemographic confounders. Several also adjusted for comorbidities, alcohol/substance use disorders, medications, smoking status, and income/education level.

Pooled estimates from the meta-analyzed studies showed that only one showed no significant association between psychotic disorders and dementia, whereas 10 reported increased risk (pooled risk ratio, 2.52; 95% confidence interval, 1.67-3.80; I², 99.7%).

Subgroup analyses showed higher risk in participants with typical and late-onset psychotic disorders (pooled RR, 2.10; 95% CI, 2.33-4.14; I², 77.5%; P = .004) vs. those with very late onset schizophrenia-like psychoses (pooled RR, 2.77; 95% CI, 1.74-4.40 I², 98.9%; P < .001).

The effect was larger in studies with a follow-up of less than 10 years vs. those with a follow-up of 10 years or more, and it was also greater in studies conducted in non-European vs. European countries (all P < .001).

Studies with more female participants (≥ 60%) showed higher risk compared with those that had a lower percentage of female participants. Studies published during or after 2020 showed a stronger association than those published before 2020 (all P < .001).

There was also a higher risk for dementia in studies investigating broader nonaffective psychotic disorders compared with studies investigating only schizophrenia, in prospective vs. retrospective studies, and in studies with a minimum age of less than 60 years at baseline vs. a minimum age of 60 or older (all P < .001).

“Several possible mechanisms could underlie these findings, although we were not able to directly test these in our review,” Dr. Stafford said. She noted that psychotic disorders and other psychiatric diagnoses may cause dementia.

“People with psychotic disorders such as schizophrenia are also at higher risk of health conditions including cardiovascular disease and diabetes, which are known risk factors for dementia and could underpin these associations,” said Dr. Stafford.

It is also possible “that psychotic symptoms could be early markers of dementia for some people, rather than causes,” she added.
 

Neuroimaging evidence lacking

Commenting on the study, Dilip V. Jeste, MD, former senior associate dean for healthy aging and senior care and distinguished professor of psychiatry and neurosciences at the University of California, San Diego, complimented the investigators for “an excellent article on an important but difficult topic.”

Limitations “pertain not to the meta-analysis but to the original studies,” said Dr. Jeste, who was not involved with the review. Diagnosing dementia in individuals with psychotic disorders is “challenging because cognitive deficits and behavioral symptoms in psychotic disorders may be misdiagnosed as dementia in some individuals – and vice versa,” he added.

Moreover, the studies did not specify the type of dementia, such as Alzheimer’s disease, vascular, Lewy body, frontotemporal, or mixed. Together, “they account for 90% of the dementias, and most patients with these dementias have brain abnormalities that can clearly be seen on MRI,” Dr. Jeste said.

However, patients with schizophrenia who are diagnosed with dementia “rarely show severe brain atrophy, even in specific regions commonly observed in nonpsychotic people with these dementias,” Dr. Jeste noted.

Thus, objective neuroimaging-based evidence for dementia and its subtype “is lacking in most of the published studies of persons with psychotic disorders diagnosed as having dementia,” he said.

There is a “clear need for comprehensive studies of dementia in people with psychotic disorders to understand the significance of the results,” Dr. Jeste concluded.

The review did not receive any funding. Dr. Stafford was supported by an NIHR-UCLH BRC Postdoctoral Bridging Fellowship and the National Institute for Health Research Biomedical Research Centre at University College London Hospitals NHS Foundation Trust. Dr. Stafford was also the principal investigator in one of the studies meeting the inclusion criteria of the review. The other investigators and Dr. Jeste reported no relevant financial relationships.

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

Patients with psychotic disorders such as schizophrenia are more than twice as likely as those without a psychotic disorder to eventually develop dementia, new research suggests.

Results from a review and meta-analysis of almost 13 million total participants from nine countries showed that, across multiple different psychotic disorders, there was a 2.5-fold higher risk of developing dementia later in life compared with individuals who did not have a disorder. This was regardless of the age at which the patients first developed the mental illness.

Moreover, participants with a psychotic disorder tended to be younger than average when diagnosed with dementia. Two studies showed that those with psychotic disorders were more likely to be diagnosed with dementia as early as in their 60s.

“The findings add to a growing body of evidence linking psychiatric disorders with later cognitive decline and dementia,” senior investigator Jean Stafford, PhD, a research fellow at MRC Unit for Lifelong Health and Ageing, University College London, told this news organization.

Dr. Stafford noted that the results highlight the importance of being aware of and watchful for symptoms of cognitive decline in patients with psychotic disorders in mid- and late life.

“In addition, given that people with psychotic disorders are at higher risk of experiencing multiple health conditions, including dementia, managing overall physical and mental health in this group is crucial,” she said.

The findings were published online in Psychological Medicine.
 

Bringing the evidence together

There is increasing evidence that multiple psychiatric symptoms and diagnoses are associated with cognitive decline and dementia, with particularly strong evidence for late-life depression, Dr. Stafford said.

“However, the relationship between psychotic disorders and dementia is less well-established,” she added.

Last year, her team published a study showing a strong association between very late onset psychotic disorders, defined as first diagnosed after age 60 years, and increased risk for dementia in Swedish population register data.

“We also became aware of several other large studies on the topic published in the last few years and realized that an up-to-date systematic review and meta-analysis was needed to bring together the evidence, specifically focusing on longitudinal studies,” Dr. Stafford said.

The researchers searched four databases of prospective and retrospective longitudinal studies published through March 2022. Studies were required to focus on adults aged 18 years or older with a clinical diagnosis of a nonaffective psychotic disorder and a comparison group consisting of adults without a nonaffective psychotic disorder.

Of 9,496 papers, the investigators selected 11 published from 2003 to 2022 that met criteria for inclusion in their meta-analysis (12,997,101 participants), with follow-up periods ranging from 1.57 to 33 years.

The studies hailed from Denmark, Finland, Sweden, the United Kingdom, the United States, Australia, Taiwan, New Zealand, and Israel.

Random-effects meta-analyses were used to pool estimates across studies. The researchers assessed the risk of bias for each study. They also included two additional studies in the review, but not the meta-analysis, that focused specifically on late-onset acute and transient psychosis and late-onset delusional disorder.

The other studies focused on late-onset schizophrenia and/or very late onset schizophrenia-like psychoses, schizophrenia, psychotic disorders, and schizophrenia in older people.

Most studies investigated the incidence of all-cause dementia, although one study focused on the incidence of Alzheimer’s disease.
 

Potential mechanisms

The narrative review showed that most studies (n = 10) were of high methodological quality, although two were rated as fair and one as poor.

Almost all studies accounted for basic sociodemographic confounders. Several also adjusted for comorbidities, alcohol/substance use disorders, medications, smoking status, and income/education level.

Pooled estimates from the meta-analyzed studies showed that only one showed no significant association between psychotic disorders and dementia, whereas 10 reported increased risk (pooled risk ratio, 2.52; 95% confidence interval, 1.67-3.80; I², 99.7%).

Subgroup analyses showed higher risk in participants with typical and late-onset psychotic disorders (pooled RR, 2.10; 95% CI, 2.33-4.14; I², 77.5%; P = .004) vs. those with very late onset schizophrenia-like psychoses (pooled RR, 2.77; 95% CI, 1.74-4.40 I², 98.9%; P < .001).

The effect was larger in studies with a follow-up of less than 10 years vs. those with a follow-up of 10 years or more, and it was also greater in studies conducted in non-European vs. European countries (all P < .001).

Studies with more female participants (≥ 60%) showed higher risk compared with those that had a lower percentage of female participants. Studies published during or after 2020 showed a stronger association than those published before 2020 (all P < .001).

There was also a higher risk for dementia in studies investigating broader nonaffective psychotic disorders compared with studies investigating only schizophrenia, in prospective vs. retrospective studies, and in studies with a minimum age of less than 60 years at baseline vs. a minimum age of 60 or older (all P < .001).

“Several possible mechanisms could underlie these findings, although we were not able to directly test these in our review,” Dr. Stafford said. She noted that psychotic disorders and other psychiatric diagnoses may cause dementia.

“People with psychotic disorders such as schizophrenia are also at higher risk of health conditions including cardiovascular disease and diabetes, which are known risk factors for dementia and could underpin these associations,” said Dr. Stafford.

It is also possible “that psychotic symptoms could be early markers of dementia for some people, rather than causes,” she added.
 

Neuroimaging evidence lacking

Commenting on the study, Dilip V. Jeste, MD, former senior associate dean for healthy aging and senior care and distinguished professor of psychiatry and neurosciences at the University of California, San Diego, complimented the investigators for “an excellent article on an important but difficult topic.”

Limitations “pertain not to the meta-analysis but to the original studies,” said Dr. Jeste, who was not involved with the review. Diagnosing dementia in individuals with psychotic disorders is “challenging because cognitive deficits and behavioral symptoms in psychotic disorders may be misdiagnosed as dementia in some individuals – and vice versa,” he added.

Moreover, the studies did not specify the type of dementia, such as Alzheimer’s disease, vascular, Lewy body, frontotemporal, or mixed. Together, “they account for 90% of the dementias, and most patients with these dementias have brain abnormalities that can clearly be seen on MRI,” Dr. Jeste said.

However, patients with schizophrenia who are diagnosed with dementia “rarely show severe brain atrophy, even in specific regions commonly observed in nonpsychotic people with these dementias,” Dr. Jeste noted.

Thus, objective neuroimaging-based evidence for dementia and its subtype “is lacking in most of the published studies of persons with psychotic disorders diagnosed as having dementia,” he said.

There is a “clear need for comprehensive studies of dementia in people with psychotic disorders to understand the significance of the results,” Dr. Jeste concluded.

The review did not receive any funding. Dr. Stafford was supported by an NIHR-UCLH BRC Postdoctoral Bridging Fellowship and the National Institute for Health Research Biomedical Research Centre at University College London Hospitals NHS Foundation Trust. Dr. Stafford was also the principal investigator in one of the studies meeting the inclusion criteria of the review. The other investigators and Dr. Jeste reported no relevant financial relationships.

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

Patients with psychotic disorders such as schizophrenia are more than twice as likely as those without a psychotic disorder to eventually develop dementia, new research suggests.

Results from a review and meta-analysis of almost 13 million total participants from nine countries showed that, across multiple different psychotic disorders, there was a 2.5-fold higher risk of developing dementia later in life compared with individuals who did not have a disorder. This was regardless of the age at which the patients first developed the mental illness.

Moreover, participants with a psychotic disorder tended to be younger than average when diagnosed with dementia. Two studies showed that those with psychotic disorders were more likely to be diagnosed with dementia as early as in their 60s.

“The findings add to a growing body of evidence linking psychiatric disorders with later cognitive decline and dementia,” senior investigator Jean Stafford, PhD, a research fellow at MRC Unit for Lifelong Health and Ageing, University College London, told this news organization.

Dr. Stafford noted that the results highlight the importance of being aware of and watchful for symptoms of cognitive decline in patients with psychotic disorders in mid- and late life.

“In addition, given that people with psychotic disorders are at higher risk of experiencing multiple health conditions, including dementia, managing overall physical and mental health in this group is crucial,” she said.

The findings were published online in Psychological Medicine.
 

Bringing the evidence together

There is increasing evidence that multiple psychiatric symptoms and diagnoses are associated with cognitive decline and dementia, with particularly strong evidence for late-life depression, Dr. Stafford said.

“However, the relationship between psychotic disorders and dementia is less well-established,” she added.

Last year, her team published a study showing a strong association between very late onset psychotic disorders, defined as first diagnosed after age 60 years, and increased risk for dementia in Swedish population register data.

“We also became aware of several other large studies on the topic published in the last few years and realized that an up-to-date systematic review and meta-analysis was needed to bring together the evidence, specifically focusing on longitudinal studies,” Dr. Stafford said.

The researchers searched four databases of prospective and retrospective longitudinal studies published through March 2022. Studies were required to focus on adults aged 18 years or older with a clinical diagnosis of a nonaffective psychotic disorder and a comparison group consisting of adults without a nonaffective psychotic disorder.

Of 9,496 papers, the investigators selected 11 published from 2003 to 2022 that met criteria for inclusion in their meta-analysis (12,997,101 participants), with follow-up periods ranging from 1.57 to 33 years.

The studies hailed from Denmark, Finland, Sweden, the United Kingdom, the United States, Australia, Taiwan, New Zealand, and Israel.

Random-effects meta-analyses were used to pool estimates across studies. The researchers assessed the risk of bias for each study. They also included two additional studies in the review, but not the meta-analysis, that focused specifically on late-onset acute and transient psychosis and late-onset delusional disorder.

The other studies focused on late-onset schizophrenia and/or very late onset schizophrenia-like psychoses, schizophrenia, psychotic disorders, and schizophrenia in older people.

Most studies investigated the incidence of all-cause dementia, although one study focused on the incidence of Alzheimer’s disease.
 

Potential mechanisms

The narrative review showed that most studies (n = 10) were of high methodological quality, although two were rated as fair and one as poor.

Almost all studies accounted for basic sociodemographic confounders. Several also adjusted for comorbidities, alcohol/substance use disorders, medications, smoking status, and income/education level.

Pooled estimates from the meta-analyzed studies showed that only one showed no significant association between psychotic disorders and dementia, whereas 10 reported increased risk (pooled risk ratio, 2.52; 95% confidence interval, 1.67-3.80; I², 99.7%).

Subgroup analyses showed higher risk in participants with typical and late-onset psychotic disorders (pooled RR, 2.10; 95% CI, 2.33-4.14; I², 77.5%; P = .004) vs. those with very late onset schizophrenia-like psychoses (pooled RR, 2.77; 95% CI, 1.74-4.40 I², 98.9%; P < .001).

The effect was larger in studies with a follow-up of less than 10 years vs. those with a follow-up of 10 years or more, and it was also greater in studies conducted in non-European vs. European countries (all P < .001).

Studies with more female participants (≥ 60%) showed higher risk compared with those that had a lower percentage of female participants. Studies published during or after 2020 showed a stronger association than those published before 2020 (all P < .001).

There was also a higher risk for dementia in studies investigating broader nonaffective psychotic disorders compared with studies investigating only schizophrenia, in prospective vs. retrospective studies, and in studies with a minimum age of less than 60 years at baseline vs. a minimum age of 60 or older (all P < .001).

“Several possible mechanisms could underlie these findings, although we were not able to directly test these in our review,” Dr. Stafford said. She noted that psychotic disorders and other psychiatric diagnoses may cause dementia.

“People with psychotic disorders such as schizophrenia are also at higher risk of health conditions including cardiovascular disease and diabetes, which are known risk factors for dementia and could underpin these associations,” said Dr. Stafford.

It is also possible “that psychotic symptoms could be early markers of dementia for some people, rather than causes,” she added.
 

Neuroimaging evidence lacking

Commenting on the study, Dilip V. Jeste, MD, former senior associate dean for healthy aging and senior care and distinguished professor of psychiatry and neurosciences at the University of California, San Diego, complimented the investigators for “an excellent article on an important but difficult topic.”

Limitations “pertain not to the meta-analysis but to the original studies,” said Dr. Jeste, who was not involved with the review. Diagnosing dementia in individuals with psychotic disorders is “challenging because cognitive deficits and behavioral symptoms in psychotic disorders may be misdiagnosed as dementia in some individuals – and vice versa,” he added.

Moreover, the studies did not specify the type of dementia, such as Alzheimer’s disease, vascular, Lewy body, frontotemporal, or mixed. Together, “they account for 90% of the dementias, and most patients with these dementias have brain abnormalities that can clearly be seen on MRI,” Dr. Jeste said.

However, patients with schizophrenia who are diagnosed with dementia “rarely show severe brain atrophy, even in specific regions commonly observed in nonpsychotic people with these dementias,” Dr. Jeste noted.

Thus, objective neuroimaging-based evidence for dementia and its subtype “is lacking in most of the published studies of persons with psychotic disorders diagnosed as having dementia,” he said.

There is a “clear need for comprehensive studies of dementia in people with psychotic disorders to understand the significance of the results,” Dr. Jeste concluded.

The review did not receive any funding. Dr. Stafford was supported by an NIHR-UCLH BRC Postdoctoral Bridging Fellowship and the National Institute for Health Research Biomedical Research Centre at University College London Hospitals NHS Foundation Trust. Dr. Stafford was also the principal investigator in one of the studies meeting the inclusion criteria of the review. The other investigators and Dr. Jeste reported no relevant financial relationships.

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

Drugs commonly used to treat erectile dysfunction (ED) are not associated with a decreased risk of Alzheimer’s disease and related dementias (ADRD), new research shows.

The findings contradict results from a previous study that suggested that individuals who take sildenafil (Viagra) were significantly less likely to develop Alzheimer’s.

The new research, part of a larger effort to identify existing medications that could be repurposed to treat ADRD, employed a study design that reduced the risk for potential bias that may have influenced the earlier findings, the investigators note.

“That study came out last fall and was widely covered in the media, and we thought there were some methodological shortcomings that might have explained the results,” lead investigator Rishi Desai, PhD, assistant professor of medicine at Harvard Medical School and an associate epidemiologist at Brigham and Women’s Hospital, both in Boston, said in an interview.

The new study was published online in Brain Communications.


 

Not the final word?

Animal studies suggest that phosphodiesterase-5 (PDE5) inhibitors, a drug class that includes the ED drugs sildenafil and tadalafil (Cialis), improve memory and cognitive function and reduce amyloid burden. But studies in humans have yielded conflicting results.*

Although the new research and the work published last year both drew on Medicare data, they examined different patient populations.

The first study compared those who took sildenafil for any reason to those who did not take it. That design likely resulted in an analysis of a comparison of individuals with ED – the most common indication for sildenafil – to generally older individuals with diabetes or hypertension, Dr. Desai said.

In contrast, the current study included only those with pulmonary arterial hypertension (PAH), which is also an indication for PDE5 inhibitors. The researchers compared ADRD incidence in those who took PDE5 inhibitors with the incidence among those who took a different medication to treat their PAH. They used propensity matching to create two groups with similar characteristics and examined the data using four analytic strategies.

The investigators found no significant difference between groups in the incidence of ADRD, regardless of the strategy they used. Cell culture studies also revealed no protective effect from PDE5 inhibitors.

“No study of this kind should claim the final word,” Dr. Desai said. “It is extremely difficult to nail down causality from these types of data sources.”
 

Impressive study design

Commenting on the findings, David Knopman, MD, professor of neurology at Mayo Clinic, Rochester, Minn., described the study design as “impressive” for its efforts to minimize bias, a key limitation in the previous study.

“It was always the case that the claims about sildenafil needed further developmental work prior to testing the drug in randomized controlled trials,” Dr. Knopman said. “The evidence for the use of the drug was never sufficient for clinicians to use it in their patients.”

The study was funded by National Institute on Aging. Dr. Desai is an investigator who receives research grants from Bayer, Vertex, and Novartis that were given to the Brigham and Women’s Hospital for unrelated projects. Dr. Knopman has disclosed no relevant financial relationships.

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

Correction, 11/3/22: An earlier version of this article misstated the abbreviation for phosphodiesterase-5. It is PDE-5.

Drugs commonly used to treat erectile dysfunction (ED) are not associated with a decreased risk of Alzheimer’s disease and related dementias (ADRD), new research shows.

The findings contradict results from a previous study that suggested that individuals who take sildenafil (Viagra) were significantly less likely to develop Alzheimer’s.

The new research, part of a larger effort to identify existing medications that could be repurposed to treat ADRD, employed a study design that reduced the risk for potential bias that may have influenced the earlier findings, the investigators note.

“That study came out last fall and was widely covered in the media, and we thought there were some methodological shortcomings that might have explained the results,” lead investigator Rishi Desai, PhD, assistant professor of medicine at Harvard Medical School and an associate epidemiologist at Brigham and Women’s Hospital, both in Boston, said in an interview.

The new study was published online in Brain Communications.


 

Not the final word?

Animal studies suggest that phosphodiesterase-5 (PDE5) inhibitors, a drug class that includes the ED drugs sildenafil and tadalafil (Cialis), improve memory and cognitive function and reduce amyloid burden. But studies in humans have yielded conflicting results.*

Although the new research and the work published last year both drew on Medicare data, they examined different patient populations.

The first study compared those who took sildenafil for any reason to those who did not take it. That design likely resulted in an analysis of a comparison of individuals with ED – the most common indication for sildenafil – to generally older individuals with diabetes or hypertension, Dr. Desai said.

In contrast, the current study included only those with pulmonary arterial hypertension (PAH), which is also an indication for PDE5 inhibitors. The researchers compared ADRD incidence in those who took PDE5 inhibitors with the incidence among those who took a different medication to treat their PAH. They used propensity matching to create two groups with similar characteristics and examined the data using four analytic strategies.

The investigators found no significant difference between groups in the incidence of ADRD, regardless of the strategy they used. Cell culture studies also revealed no protective effect from PDE5 inhibitors.

“No study of this kind should claim the final word,” Dr. Desai said. “It is extremely difficult to nail down causality from these types of data sources.”
 

Impressive study design

Commenting on the findings, David Knopman, MD, professor of neurology at Mayo Clinic, Rochester, Minn., described the study design as “impressive” for its efforts to minimize bias, a key limitation in the previous study.

“It was always the case that the claims about sildenafil needed further developmental work prior to testing the drug in randomized controlled trials,” Dr. Knopman said. “The evidence for the use of the drug was never sufficient for clinicians to use it in their patients.”

The study was funded by National Institute on Aging. Dr. Desai is an investigator who receives research grants from Bayer, Vertex, and Novartis that were given to the Brigham and Women’s Hospital for unrelated projects. Dr. Knopman has disclosed no relevant financial relationships.

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

Correction, 11/3/22: An earlier version of this article misstated the abbreviation for phosphodiesterase-5. It is PDE-5.

Drugs commonly used to treat erectile dysfunction (ED) are not associated with a decreased risk of Alzheimer’s disease and related dementias (ADRD), new research shows.

The findings contradict results from a previous study that suggested that individuals who take sildenafil (Viagra) were significantly less likely to develop Alzheimer’s.

The new research, part of a larger effort to identify existing medications that could be repurposed to treat ADRD, employed a study design that reduced the risk for potential bias that may have influenced the earlier findings, the investigators note.

“That study came out last fall and was widely covered in the media, and we thought there were some methodological shortcomings that might have explained the results,” lead investigator Rishi Desai, PhD, assistant professor of medicine at Harvard Medical School and an associate epidemiologist at Brigham and Women’s Hospital, both in Boston, said in an interview.

The new study was published online in Brain Communications.


 

Not the final word?

Animal studies suggest that phosphodiesterase-5 (PDE5) inhibitors, a drug class that includes the ED drugs sildenafil and tadalafil (Cialis), improve memory and cognitive function and reduce amyloid burden. But studies in humans have yielded conflicting results.*

Although the new research and the work published last year both drew on Medicare data, they examined different patient populations.

The first study compared those who took sildenafil for any reason to those who did not take it. That design likely resulted in an analysis of a comparison of individuals with ED – the most common indication for sildenafil – to generally older individuals with diabetes or hypertension, Dr. Desai said.

In contrast, the current study included only those with pulmonary arterial hypertension (PAH), which is also an indication for PDE5 inhibitors. The researchers compared ADRD incidence in those who took PDE5 inhibitors with the incidence among those who took a different medication to treat their PAH. They used propensity matching to create two groups with similar characteristics and examined the data using four analytic strategies.

The investigators found no significant difference between groups in the incidence of ADRD, regardless of the strategy they used. Cell culture studies also revealed no protective effect from PDE5 inhibitors.

“No study of this kind should claim the final word,” Dr. Desai said. “It is extremely difficult to nail down causality from these types of data sources.”
 

Impressive study design

Commenting on the findings, David Knopman, MD, professor of neurology at Mayo Clinic, Rochester, Minn., described the study design as “impressive” for its efforts to minimize bias, a key limitation in the previous study.

“It was always the case that the claims about sildenafil needed further developmental work prior to testing the drug in randomized controlled trials,” Dr. Knopman said. “The evidence for the use of the drug was never sufficient for clinicians to use it in their patients.”

The study was funded by National Institute on Aging. Dr. Desai is an investigator who receives research grants from Bayer, Vertex, and Novartis that were given to the Brigham and Women’s Hospital for unrelated projects. Dr. Knopman has disclosed no relevant financial relationships.

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

Correction, 11/3/22: An earlier version of this article misstated the abbreviation for phosphodiesterase-5. It is PDE-5.

A 67-year-old man asks about what he can do to prevent dementia. He reports his mother had dementia, and he wants to do everything he can to prevent it. Which of the following has evidence of benefit?

A) Thiamine

B) Vitamin E

C) Multivitamin (MV)

D) Keto diet

E) Red wine
 

FDA-approved therapies for dementia

To date the actual therapies for dementia have been disappointing. Donepezil, the most prescribed medication for the treatment of dementia has a number-needed-to treat (NNT) over 17, and causes frequent side effects. Aducanumab was recently approved by the Food and Drug Administration for the treatment of Alzheimer’s disease (AD), but controversy has arisen, as the clinical results were modest, and the price tag will be large – estimated at $30,000-$50,000/year.

Preventive options that may decrease the likelihood of dementia

Patients often ask the question stated above. Regarding how to respond to that question, choice C, MV, has some recent evidence of benefit. Baker and colleagues studied the effect of cocoa extract and multivitamins on cognitive function in the COSMOS-Mind trial.¹ A total of 2,262 people were enrolled, and over 90% completed baseline and at least one annual cognitive assessment. Cocoa extract had no impact on global cognition (confidence interval [CI], –.02-.08, P = .28), but MV supplementation did have a statistically significant impact on global cognition (CI, .02-.12, P less than .007).

Vitamin E has been enthusiastically endorsed in the past as a treatment to prevent cognitive decline. The most recent Cochrane review on vitamin E concluded there was no evidence that the alpha-tocopherol form of vitamin E given to people with MCI prevents progression to dementia, or that it improves cognitive function in people with MCI or dementia due to AD.²

Exercise has long been a mainstay of our advice to patients as something they can do to help prevent dementia. Yu and colleagues did a meta-analysis of almost 400 randomized controlled trials and observational studies to grade the evidence on different interventions.³ They gave exercise a grade B for evidence of benefit.

A recent study addressed this issue, and I think it is helpful on quantifying how much exercise is needed. Del Pozo Cruz and colleagues did a prospective population-based cohort study of 78,000 adults aged 40-79, with an average of 6.9 years of follow up.⁴ The optimal step count was 9,826 steps (hazard ratio [HR], 0.49; 95% CI, 0.39-0.62) and the minimal step count for benefit was 3,826 steps (HR, 0.75; 95% CI, 0.67-0.83).
 

Modifiable factors

The other major modifiable factors to consider are problems with special senses. Both vision loss and hearing loss have been associated with cognitive impairment.

Shang and colleagues published a meta-analysis of 14 cohort studies addressing vision impairment and cognitive function involving more than 6 million individuals.⁵ They concluded that vision impairment is associated with an increased risk of both dementia and cognitive impairment in older adults.

Loughrey and colleagues performed a meta-analysis of 36 studies addressing hearing loss and cognitive decline.⁶ They reported that, among cross-sectional studies, a significant association was found for cognitive impairment (odds ratio [OR], 2.00; 95% CI, 1.39-2.89) and dementia (OR, 2.42; 95% CI, 1.24-4.72). A similar finding was present in prospective cohort studies with a significant association being found for cognitive impairment (OR, 1.22; 95% CI, 1.09-1.36) and dementia (OR, 1.28; 95% CI, 1.02-1.59).

A 25-year prospective, population-based study of patients with hearing loss revealed a difference in the rate of change in MMSE score over the 25-year follow-up between participants with hearing loss not using hearing aids matched with controls who didn’t have hearing loss. Those with untreated hearing loss had more cognitive decline than that of patients without hearing loss.⁷ The subjects with hearing loss using a hearing aid had no difference in cognitive decline from controls.
 

Pearl

Several simple and safe interventions may protect our patients from cognitive decline. These include taking a daily multivitamin, walking more than 4,000 steps a day, and optimizing vision and hearing.

Dr. Paauw is professor of medicine in the division of general internal medicine at the University of Washington, Seattle, and he serves as third-year medical student clerkship director at the University of Washington. Contact Dr. Paauw at [email protected].

References

1. Baker LD et al. Effects of cocoa extract and a multivitamin on cognitive function: A randomized clinical trial. Alzheimer’s Dement. 2022 Sep 14. doi: 10.1002/alz.12767.

2. Farina N et al. Vitamin E for Alzheimer’s dementia and mild cognitive impairment. Cochrane Database Syst Rev. 2017 Apr 18;4(4):CD002854. doi: 10.1002/14651858.CD002854.pub5.

3. Yu JT et al. Evidence-based prevention of Alzheimer’s disease: Systematic review and meta-analysis of 243 observational prospective studies and 153 randomised controlled trials. J Neurol Neurosurg Psychiatry. 2020 Nov;91(11):1201-9.

4. Del Pozo Cruz B et al. Association of daily step count and intensity with incident dementia in 78,430 adults living in the UK. JAMA Neurol. 2022 Oct 1;79(10):1059-63.

5. Shang X et al. The association between vision impairment and incidence of dementia and cognitive impairment: A systematic review and meta-analysis. Ophthalmology. 2021 Aug;128(8):1135-49.

6. Loughrey DG et al. Association of age-related hearing loss with cognitive function, cognitive impairment, and dementia: A systematic review and meta-analysis. JAMA Otolaryngol Head Neck Surg. 2018 Feb 1;144(2):115-26.

7. Amieva H et al. Self-reported hearing loss, hearing aids, and cognitive decline in elderly adults: A 25-year study. J Am Geriatr Soc. 2015 Oct;63(10):2099-104.

A 67-year-old man asks about what he can do to prevent dementia. He reports his mother had dementia, and he wants to do everything he can to prevent it. Which of the following has evidence of benefit?

A) Thiamine

B) Vitamin E

C) Multivitamin (MV)

D) Keto diet

E) Red wine
 

FDA-approved therapies for dementia

To date the actual therapies for dementia have been disappointing. Donepezil, the most prescribed medication for the treatment of dementia has a number-needed-to treat (NNT) over 17, and causes frequent side effects. Aducanumab was recently approved by the Food and Drug Administration for the treatment of Alzheimer’s disease (AD), but controversy has arisen, as the clinical results were modest, and the price tag will be large – estimated at $30,000-$50,000/year.

Preventive options that may decrease the likelihood of dementia

Patients often ask the question stated above. Regarding how to respond to that question, choice C, MV, has some recent evidence of benefit. Baker and colleagues studied the effect of cocoa extract and multivitamins on cognitive function in the COSMOS-Mind trial.¹ A total of 2,262 people were enrolled, and over 90% completed baseline and at least one annual cognitive assessment. Cocoa extract had no impact on global cognition (confidence interval [CI], –.02-.08, P = .28), but MV supplementation did have a statistically significant impact on global cognition (CI, .02-.12, P less than .007).

Vitamin E has been enthusiastically endorsed in the past as a treatment to prevent cognitive decline. The most recent Cochrane review on vitamin E concluded there was no evidence that the alpha-tocopherol form of vitamin E given to people with MCI prevents progression to dementia, or that it improves cognitive function in people with MCI or dementia due to AD.²

Exercise has long been a mainstay of our advice to patients as something they can do to help prevent dementia. Yu and colleagues did a meta-analysis of almost 400 randomized controlled trials and observational studies to grade the evidence on different interventions.³ They gave exercise a grade B for evidence of benefit.

A recent study addressed this issue, and I think it is helpful on quantifying how much exercise is needed. Del Pozo Cruz and colleagues did a prospective population-based cohort study of 78,000 adults aged 40-79, with an average of 6.9 years of follow up.⁴ The optimal step count was 9,826 steps (hazard ratio [HR], 0.49; 95% CI, 0.39-0.62) and the minimal step count for benefit was 3,826 steps (HR, 0.75; 95% CI, 0.67-0.83).
 

Modifiable factors

The other major modifiable factors to consider are problems with special senses. Both vision loss and hearing loss have been associated with cognitive impairment.

Shang and colleagues published a meta-analysis of 14 cohort studies addressing vision impairment and cognitive function involving more than 6 million individuals.⁵ They concluded that vision impairment is associated with an increased risk of both dementia and cognitive impairment in older adults.

Loughrey and colleagues performed a meta-analysis of 36 studies addressing hearing loss and cognitive decline.⁶ They reported that, among cross-sectional studies, a significant association was found for cognitive impairment (odds ratio [OR], 2.00; 95% CI, 1.39-2.89) and dementia (OR, 2.42; 95% CI, 1.24-4.72). A similar finding was present in prospective cohort studies with a significant association being found for cognitive impairment (OR, 1.22; 95% CI, 1.09-1.36) and dementia (OR, 1.28; 95% CI, 1.02-1.59).

A 25-year prospective, population-based study of patients with hearing loss revealed a difference in the rate of change in MMSE score over the 25-year follow-up between participants with hearing loss not using hearing aids matched with controls who didn’t have hearing loss. Those with untreated hearing loss had more cognitive decline than that of patients without hearing loss.⁷ The subjects with hearing loss using a hearing aid had no difference in cognitive decline from controls.
 

Pearl

Several simple and safe interventions may protect our patients from cognitive decline. These include taking a daily multivitamin, walking more than 4,000 steps a day, and optimizing vision and hearing.

Dr. Paauw is professor of medicine in the division of general internal medicine at the University of Washington, Seattle, and he serves as third-year medical student clerkship director at the University of Washington. Contact Dr. Paauw at [email protected].

References

1. Baker LD et al. Effects of cocoa extract and a multivitamin on cognitive function: A randomized clinical trial. Alzheimer’s Dement. 2022 Sep 14. doi: 10.1002/alz.12767.

2. Farina N et al. Vitamin E for Alzheimer’s dementia and mild cognitive impairment. Cochrane Database Syst Rev. 2017 Apr 18;4(4):CD002854. doi: 10.1002/14651858.CD002854.pub5.

3. Yu JT et al. Evidence-based prevention of Alzheimer’s disease: Systematic review and meta-analysis of 243 observational prospective studies and 153 randomised controlled trials. J Neurol Neurosurg Psychiatry. 2020 Nov;91(11):1201-9.

4. Del Pozo Cruz B et al. Association of daily step count and intensity with incident dementia in 78,430 adults living in the UK. JAMA Neurol. 2022 Oct 1;79(10):1059-63.

5. Shang X et al. The association between vision impairment and incidence of dementia and cognitive impairment: A systematic review and meta-analysis. Ophthalmology. 2021 Aug;128(8):1135-49.

6. Loughrey DG et al. Association of age-related hearing loss with cognitive function, cognitive impairment, and dementia: A systematic review and meta-analysis. JAMA Otolaryngol Head Neck Surg. 2018 Feb 1;144(2):115-26.

7. Amieva H et al. Self-reported hearing loss, hearing aids, and cognitive decline in elderly adults: A 25-year study. J Am Geriatr Soc. 2015 Oct;63(10):2099-104.

A 67-year-old man asks about what he can do to prevent dementia. He reports his mother had dementia, and he wants to do everything he can to prevent it. Which of the following has evidence of benefit?

A) Thiamine

B) Vitamin E

C) Multivitamin (MV)

D) Keto diet

E) Red wine
 

FDA-approved therapies for dementia

To date the actual therapies for dementia have been disappointing. Donepezil, the most prescribed medication for the treatment of dementia has a number-needed-to treat (NNT) over 17, and causes frequent side effects. Aducanumab was recently approved by the Food and Drug Administration for the treatment of Alzheimer’s disease (AD), but controversy has arisen, as the clinical results were modest, and the price tag will be large – estimated at $30,000-$50,000/year.

Preventive options that may decrease the likelihood of dementia

Patients often ask the question stated above. Regarding how to respond to that question, choice C, MV, has some recent evidence of benefit. Baker and colleagues studied the effect of cocoa extract and multivitamins on cognitive function in the COSMOS-Mind trial.¹ A total of 2,262 people were enrolled, and over 90% completed baseline and at least one annual cognitive assessment. Cocoa extract had no impact on global cognition (confidence interval [CI], –.02-.08, P = .28), but MV supplementation did have a statistically significant impact on global cognition (CI, .02-.12, P less than .007).

Vitamin E has been enthusiastically endorsed in the past as a treatment to prevent cognitive decline. The most recent Cochrane review on vitamin E concluded there was no evidence that the alpha-tocopherol form of vitamin E given to people with MCI prevents progression to dementia, or that it improves cognitive function in people with MCI or dementia due to AD.²

Exercise has long been a mainstay of our advice to patients as something they can do to help prevent dementia. Yu and colleagues did a meta-analysis of almost 400 randomized controlled trials and observational studies to grade the evidence on different interventions.³ They gave exercise a grade B for evidence of benefit.

A recent study addressed this issue, and I think it is helpful on quantifying how much exercise is needed. Del Pozo Cruz and colleagues did a prospective population-based cohort study of 78,000 adults aged 40-79, with an average of 6.9 years of follow up.⁴ The optimal step count was 9,826 steps (hazard ratio [HR], 0.49; 95% CI, 0.39-0.62) and the minimal step count for benefit was 3,826 steps (HR, 0.75; 95% CI, 0.67-0.83).
 

Modifiable factors

The other major modifiable factors to consider are problems with special senses. Both vision loss and hearing loss have been associated with cognitive impairment.

Shang and colleagues published a meta-analysis of 14 cohort studies addressing vision impairment and cognitive function involving more than 6 million individuals.⁵ They concluded that vision impairment is associated with an increased risk of both dementia and cognitive impairment in older adults.

Loughrey and colleagues performed a meta-analysis of 36 studies addressing hearing loss and cognitive decline.⁶ They reported that, among cross-sectional studies, a significant association was found for cognitive impairment (odds ratio [OR], 2.00; 95% CI, 1.39-2.89) and dementia (OR, 2.42; 95% CI, 1.24-4.72). A similar finding was present in prospective cohort studies with a significant association being found for cognitive impairment (OR, 1.22; 95% CI, 1.09-1.36) and dementia (OR, 1.28; 95% CI, 1.02-1.59).

A 25-year prospective, population-based study of patients with hearing loss revealed a difference in the rate of change in MMSE score over the 25-year follow-up between participants with hearing loss not using hearing aids matched with controls who didn’t have hearing loss. Those with untreated hearing loss had more cognitive decline than that of patients without hearing loss.⁷ The subjects with hearing loss using a hearing aid had no difference in cognitive decline from controls.
 

Pearl

Several simple and safe interventions may protect our patients from cognitive decline. These include taking a daily multivitamin, walking more than 4,000 steps a day, and optimizing vision and hearing.

Dr. Paauw is professor of medicine in the division of general internal medicine at the University of Washington, Seattle, and he serves as third-year medical student clerkship director at the University of Washington. Contact Dr. Paauw at [email protected].

References

1. Baker LD et al. Effects of cocoa extract and a multivitamin on cognitive function: A randomized clinical trial. Alzheimer’s Dement. 2022 Sep 14. doi: 10.1002/alz.12767.

2. Farina N et al. Vitamin E for Alzheimer’s dementia and mild cognitive impairment. Cochrane Database Syst Rev. 2017 Apr 18;4(4):CD002854. doi: 10.1002/14651858.CD002854.pub5.

3. Yu JT et al. Evidence-based prevention of Alzheimer’s disease: Systematic review and meta-analysis of 243 observational prospective studies and 153 randomised controlled trials. J Neurol Neurosurg Psychiatry. 2020 Nov;91(11):1201-9.

4. Del Pozo Cruz B et al. Association of daily step count and intensity with incident dementia in 78,430 adults living in the UK. JAMA Neurol. 2022 Oct 1;79(10):1059-63.

5. Shang X et al. The association between vision impairment and incidence of dementia and cognitive impairment: A systematic review and meta-analysis. Ophthalmology. 2021 Aug;128(8):1135-49.

6. Loughrey DG et al. Association of age-related hearing loss with cognitive function, cognitive impairment, and dementia: A systematic review and meta-analysis. JAMA Otolaryngol Head Neck Surg. 2018 Feb 1;144(2):115-26.

7. Amieva H et al. Self-reported hearing loss, hearing aids, and cognitive decline in elderly adults: A 25-year study. J Am Geriatr Soc. 2015 Oct;63(10):2099-104.

Contrary to some prior studies, new research suggests that a healthy diet, including the Mediterranean diet, does not reduce dementia risk.

After adjusting for relevant demographic and other lifestyle measures, there was no association between adherence to healthy dietary advice or the Mediterranean diet on the future risk of dementia or amyloid-beta (Abeta) accumulation.

OksanaKiian/Getty Images

“While our study does not rule out a possible association between diet and dementia, we did not find a link in our study, which had a long follow-up period, included younger participants than some other studies and did not require people to remember what foods they had eaten regularly years before,” study investigator Isabelle Glans, MD, of Lund (Sweden) University, said in a news release.

The findings were published online in Neurology.
 

No risk reduction

Several studies have investigated how dietary habits affect dementia risk, with inconsistent results.

The new findings are based on 28,025 adults (61% women; mean age, 58 years at baseline) who were free of dementia at baseline and were followed over a 20-year period as part of the Swedish Malmö Diet and Cancer Study. Dietary habits were assessed with a 7-day food diary, detailed food frequency questionnaire, and in-person interview.

During follow-up, 1,943 individuals (6.9%) developed dementia.

Compared with those who did not develop dementia, those who did develop dementia during follow-up were older and had a lower level of education and more cardiovascular risk factors and comorbidities at baseline.

Individuals who adhered to conventional healthy dietary recommendations did not have a lower risk of developing all-cause dementia (hazard ratio comparing worst with best adherence, 0.93; 95% confidence interval, 0.81-1.08), Alzheimer’s disease (HR, 1.03; 95% CI, 0.85-1.23) or vascular dementia (HR, 0.93; 95% CI, 0.69-1.26).

Adherence to the modified Mediterranean diet also did not appear to lower the risk of all-cause dementia (HR, 0.93; 95% CI, 0.75-1.15), Alzheimer’s disease (HR, 0.90; 95% CI, 0.68-1.19), or vascular dementia (HR, 1.00; 95% CI, 0.65-1.55).

There was also no significant association between diet and Alzheimer’s disease–related pathology, as measured by cerebrospinal fluid analysis of Abeta42 in a subgroup of 738 participants. Various sensitivity analyses yielded similar results.
 

Diet still matters

The authors of an accompanying editorial noted that diet as a “singular factor may not have a strong enough effect on cognition, but is more likely to be considered as one factor embedded with various others, the sum of which may influence the course of cognitive function (diet, regular exercise, vascular risk factor control, avoiding cigarette smoking, drinking alcohol in moderation, etc).

“Diet should not be forgotten and it still matters” but should be regarded as “one part of a multidomain intervention with respect to cognitive performance,” wrote Nils Peters, MD, with the University of Basel (Switzerland), and Benedetta Nacmias, PhD, with the University of Florence (Italy)).

“Key questions that remain include how to provide evidence for promoting the implications of dietary habits on cognition? Overall, dietary strategies will most likely be implicated either in order to reduce the increasing number of older subjects with dementia, or to extend healthy life expectancy, or both,” Dr. Peters and Dr. Nacmias said.

The study had no commercial funding. Dr. Glans, Dr. Peters, and Dr. Nacmias disclosed no relevant financial relationships.

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

Contrary to some prior studies, new research suggests that a healthy diet, including the Mediterranean diet, does not reduce dementia risk.

After adjusting for relevant demographic and other lifestyle measures, there was no association between adherence to healthy dietary advice or the Mediterranean diet on the future risk of dementia or amyloid-beta (Abeta) accumulation.

OksanaKiian/Getty Images

“While our study does not rule out a possible association between diet and dementia, we did not find a link in our study, which had a long follow-up period, included younger participants than some other studies and did not require people to remember what foods they had eaten regularly years before,” study investigator Isabelle Glans, MD, of Lund (Sweden) University, said in a news release.

The findings were published online in Neurology.
 

No risk reduction

Several studies have investigated how dietary habits affect dementia risk, with inconsistent results.

The new findings are based on 28,025 adults (61% women; mean age, 58 years at baseline) who were free of dementia at baseline and were followed over a 20-year period as part of the Swedish Malmö Diet and Cancer Study. Dietary habits were assessed with a 7-day food diary, detailed food frequency questionnaire, and in-person interview.

During follow-up, 1,943 individuals (6.9%) developed dementia.

Compared with those who did not develop dementia, those who did develop dementia during follow-up were older and had a lower level of education and more cardiovascular risk factors and comorbidities at baseline.

Individuals who adhered to conventional healthy dietary recommendations did not have a lower risk of developing all-cause dementia (hazard ratio comparing worst with best adherence, 0.93; 95% confidence interval, 0.81-1.08), Alzheimer’s disease (HR, 1.03; 95% CI, 0.85-1.23) or vascular dementia (HR, 0.93; 95% CI, 0.69-1.26).

Adherence to the modified Mediterranean diet also did not appear to lower the risk of all-cause dementia (HR, 0.93; 95% CI, 0.75-1.15), Alzheimer’s disease (HR, 0.90; 95% CI, 0.68-1.19), or vascular dementia (HR, 1.00; 95% CI, 0.65-1.55).

There was also no significant association between diet and Alzheimer’s disease–related pathology, as measured by cerebrospinal fluid analysis of Abeta42 in a subgroup of 738 participants. Various sensitivity analyses yielded similar results.
 

Diet still matters

The authors of an accompanying editorial noted that diet as a “singular factor may not have a strong enough effect on cognition, but is more likely to be considered as one factor embedded with various others, the sum of which may influence the course of cognitive function (diet, regular exercise, vascular risk factor control, avoiding cigarette smoking, drinking alcohol in moderation, etc).

“Diet should not be forgotten and it still matters” but should be regarded as “one part of a multidomain intervention with respect to cognitive performance,” wrote Nils Peters, MD, with the University of Basel (Switzerland), and Benedetta Nacmias, PhD, with the University of Florence (Italy)).

“Key questions that remain include how to provide evidence for promoting the implications of dietary habits on cognition? Overall, dietary strategies will most likely be implicated either in order to reduce the increasing number of older subjects with dementia, or to extend healthy life expectancy, or both,” Dr. Peters and Dr. Nacmias said.

The study had no commercial funding. Dr. Glans, Dr. Peters, and Dr. Nacmias disclosed no relevant financial relationships.

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

Contrary to some prior studies, new research suggests that a healthy diet, including the Mediterranean diet, does not reduce dementia risk.

After adjusting for relevant demographic and other lifestyle measures, there was no association between adherence to healthy dietary advice or the Mediterranean diet on the future risk of dementia or amyloid-beta (Abeta) accumulation.

OksanaKiian/Getty Images

“While our study does not rule out a possible association between diet and dementia, we did not find a link in our study, which had a long follow-up period, included younger participants than some other studies and did not require people to remember what foods they had eaten regularly years before,” study investigator Isabelle Glans, MD, of Lund (Sweden) University, said in a news release.

The findings were published online in Neurology.
 

No risk reduction

Several studies have investigated how dietary habits affect dementia risk, with inconsistent results.

The new findings are based on 28,025 adults (61% women; mean age, 58 years at baseline) who were free of dementia at baseline and were followed over a 20-year period as part of the Swedish Malmö Diet and Cancer Study. Dietary habits were assessed with a 7-day food diary, detailed food frequency questionnaire, and in-person interview.

During follow-up, 1,943 individuals (6.9%) developed dementia.

Compared with those who did not develop dementia, those who did develop dementia during follow-up were older and had a lower level of education and more cardiovascular risk factors and comorbidities at baseline.

Individuals who adhered to conventional healthy dietary recommendations did not have a lower risk of developing all-cause dementia (hazard ratio comparing worst with best adherence, 0.93; 95% confidence interval, 0.81-1.08), Alzheimer’s disease (HR, 1.03; 95% CI, 0.85-1.23) or vascular dementia (HR, 0.93; 95% CI, 0.69-1.26).

Adherence to the modified Mediterranean diet also did not appear to lower the risk of all-cause dementia (HR, 0.93; 95% CI, 0.75-1.15), Alzheimer’s disease (HR, 0.90; 95% CI, 0.68-1.19), or vascular dementia (HR, 1.00; 95% CI, 0.65-1.55).

There was also no significant association between diet and Alzheimer’s disease–related pathology, as measured by cerebrospinal fluid analysis of Abeta42 in a subgroup of 738 participants. Various sensitivity analyses yielded similar results.
 

Diet still matters

The authors of an accompanying editorial noted that diet as a “singular factor may not have a strong enough effect on cognition, but is more likely to be considered as one factor embedded with various others, the sum of which may influence the course of cognitive function (diet, regular exercise, vascular risk factor control, avoiding cigarette smoking, drinking alcohol in moderation, etc).

“Diet should not be forgotten and it still matters” but should be regarded as “one part of a multidomain intervention with respect to cognitive performance,” wrote Nils Peters, MD, with the University of Basel (Switzerland), and Benedetta Nacmias, PhD, with the University of Florence (Italy)).

“Key questions that remain include how to provide evidence for promoting the implications of dietary habits on cognition? Overall, dietary strategies will most likely be implicated either in order to reduce the increasing number of older subjects with dementia, or to extend healthy life expectancy, or both,” Dr. Peters and Dr. Nacmias said.

The study had no commercial funding. Dr. Glans, Dr. Peters, and Dr. Nacmias disclosed no relevant financial relationships.

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

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.