Alzheimer's & Cognition

MILAN — Recent research allaying concerns about suicidality linked to glucagon-like peptide 1 (GLP-1) receptor agonists, along with evidence of these agents’ potential psychiatric and cognitive benefits, has prompted the lead investigator of a major analysis to urge researchers to explore the potential of these drugs for mental illness.

“So far, we’ve been talking about the safety from a neuropsychiatric perspective in diabetes, but there is also the safety and benefit in people with mental disorders,” Riccardo De Giorgi, MD, PhD, from the Department of Psychiatry, University of Oxford in England, said in an interview.

The results of the meta-analysis were previously reported by this news organization and reviewed by Dr. De Giorgi at the 37th European College of Neuropsychopharmacology (ECNP) Congress. Dr. De Giorgi broached whether GLP-1 inhibitors such as semaglutide might also offer the same benefits in patients without diabetes as they do in those with diabetes, in terms of cognitive deficits and substance use or mood disorders.

Noting that GLP-1s are not approved for psychiatric disorders, Dr. De Giorgi said it can’t be assumed that the “metabolic or maybe even more general mechanisms that are being modified with these medications in diabetes or even in obesity are the same for people with psychiatric disorders. We’re talking about very different things. From a clinical perspective, you could do real harm,” he told this news organization.

Yet Dr. De Giorgi emphasized the importance of exploring the potential benefits of these medications in psychiatry.

“From a research perspective ... I am very worried about missing an opportunity here. This happened with rimonabant, a cannabis medication that was used for weight loss back in 2012 and was withdrawn quite dramatically in Europe immediately after licensing because it increased suicide risk. Since then, nobody has been touching the cannabinoid system, and that’s a shame because in psychiatry, we don’t have that much we can work on. So we don’t want to miss an opportunity with the GLP-1 system — that’s why we need to be cautious and look at safety first,” he said.
 

Signal of Efficacy?

Dr. De Giorgi’s research suggested several potential neurobiological effects of GLP-1 inhibition in diabetes research.

“There was a bit of a signal specifically for the big three dementias — vascular, Lewy Body, and frontotemporal — although there was not enough power,” he reported. “We also saw a reduced risk in nicotine misuse, especially amongst other substance use disorders ... and finally a more tentative association for reduced depression.”

He noted that GLP-1s for psychiatric illness likely have limitations and may not cure mental disorders but could help specific subsets of patients. Rather than aiming for large-scale studies, the focus should be on small, incremental studies to advance the research.

Asked by the session chair, John Cryan, PhD, from University College Cork in Ireland, and chair of the ECNP Scientific Committee whether improvement in patients’ mood could be attributed to weight loss, Dr. De Giorgi replied no.

“We now have quite a lot of studies that show that if there is an effect or association it is seen quite a bit earlier than any weight loss. Remember, weight loss takes quite a lot of time, and at quite high doses, but more provocatively, even if that’s the case, does it matter? We as psychiatrists do worry that we need to disentangle these things, but they don’t do that in cardiology, for example. If they see a benefit in mortality they don’t really care if it’s specifically an effect on heart failure or ischemic disease,” said Dr. De Giorgi.

Regardless of their neuropsychiatric potential, the cardiometabolic benefits of GLP-1 inhibitors are sorely needed in the psychiatric population, noted two experts in a recent JAMA Psychiatry viewpoint article.

Sri Mahavir Agarwal, MD, PhD, and Margaret Hahn, MD, PhD, from the University of Toronto and the Schizophrenia Division at the Centre for Addiction and Mental Health, in Toronto, Ontario, Canada, pointed out that “individuals with severe mental illness (SMI) have exceedingly high rates of metabolic comorbidity; three of four are overweight or obese, whereas the prevalence of type 2 diabetes (T2D) is several-fold higher than in the general population. Consequently, individuals with SMI die 15-20 years earlier from cardiovascular disease (CVD) than do those in the general population with CVD,” they noted.

“The arrival of semaglutide has infused significant enthusiasm in the field of mental health research. The proximal effects of weight and related CV comorbidities are significant in themselves. It is plausible that semaglutide could act through neurogenesis or secondary benefits of improving metabolic health on other important outcomes, such as cognitive health and quality of life, thereby filling an unmet need in the treatment of SMI,” Dr. Agarwal and Dr. Hahn added.
 

An Exciting Opportunity

Current research investigating GLP-1s in psychiatry and neurology is increasingly focused on neuroinflammation, said Dr. De Giorgi.

Research shows significant evidence that certain medications may help reduce dysfunctional inflammatory processes linked to various cognitive and psychiatric disorders, he added.

Many patients with established psychiatric conditions also have physical health issues, which contribute to increased mortality risk, said Dr. De Giorgi. It’s crucial to understand that, if these treatments improve mortality outcomes for psychiatric patients, the specific mechanisms involved are secondary to the results. Psychiatrists must be equipped to prescribe, manage, and initiate these therapies.

“While trials involving psychosis patients are ongoing, we are making progress and should seize this opportunity” said Dr. De Giorgi.

Dr. Cryan agreed: “I think we’ll get there. What these drugs have shown is that you can, through a single mechanism, have multitude effects related to brain-body interactions, and why not focus that on mood and anxiety and cognitive performance? It’s exciting no matter what. We now need to do longitudinal, cross-sectional, placebo-controlled trials in specific patient populations.”

This study received funding from the National Institute for Health and Care Research Oxford Health Biomedical Research Centre and Medical Research Council. Dr. De Giorgi’s coauthors reported receiving funding for other work from Novo Nordisk, Five Lives, Cognetivity Ltd., Cognex, P1vital, Lundbeck, Servier, UCB, Zogenix, Johnson & Johnson, and Syndesi. Dr. Cryan reported no relevant disclosures.

A version of this article appeared on Medscape.com.

MILAN — Recent research allaying concerns about suicidality linked to glucagon-like peptide 1 (GLP-1) receptor agonists, along with evidence of these agents’ potential psychiatric and cognitive benefits, has prompted the lead investigator of a major analysis to urge researchers to explore the potential of these drugs for mental illness.

“So far, we’ve been talking about the safety from a neuropsychiatric perspective in diabetes, but there is also the safety and benefit in people with mental disorders,” Riccardo De Giorgi, MD, PhD, from the Department of Psychiatry, University of Oxford in England, said in an interview.

The results of the meta-analysis were previously reported by this news organization and reviewed by Dr. De Giorgi at the 37th European College of Neuropsychopharmacology (ECNP) Congress. Dr. De Giorgi broached whether GLP-1 inhibitors such as semaglutide might also offer the same benefits in patients without diabetes as they do in those with diabetes, in terms of cognitive deficits and substance use or mood disorders.

Noting that GLP-1s are not approved for psychiatric disorders, Dr. De Giorgi said it can’t be assumed that the “metabolic or maybe even more general mechanisms that are being modified with these medications in diabetes or even in obesity are the same for people with psychiatric disorders. We’re talking about very different things. From a clinical perspective, you could do real harm,” he told this news organization.

Yet Dr. De Giorgi emphasized the importance of exploring the potential benefits of these medications in psychiatry.

“From a research perspective ... I am very worried about missing an opportunity here. This happened with rimonabant, a cannabis medication that was used for weight loss back in 2012 and was withdrawn quite dramatically in Europe immediately after licensing because it increased suicide risk. Since then, nobody has been touching the cannabinoid system, and that’s a shame because in psychiatry, we don’t have that much we can work on. So we don’t want to miss an opportunity with the GLP-1 system — that’s why we need to be cautious and look at safety first,” he said.
 

Signal of Efficacy?

Dr. De Giorgi’s research suggested several potential neurobiological effects of GLP-1 inhibition in diabetes research.

“There was a bit of a signal specifically for the big three dementias — vascular, Lewy Body, and frontotemporal — although there was not enough power,” he reported. “We also saw a reduced risk in nicotine misuse, especially amongst other substance use disorders ... and finally a more tentative association for reduced depression.”

He noted that GLP-1s for psychiatric illness likely have limitations and may not cure mental disorders but could help specific subsets of patients. Rather than aiming for large-scale studies, the focus should be on small, incremental studies to advance the research.

Asked by the session chair, John Cryan, PhD, from University College Cork in Ireland, and chair of the ECNP Scientific Committee whether improvement in patients’ mood could be attributed to weight loss, Dr. De Giorgi replied no.

“We now have quite a lot of studies that show that if there is an effect or association it is seen quite a bit earlier than any weight loss. Remember, weight loss takes quite a lot of time, and at quite high doses, but more provocatively, even if that’s the case, does it matter? We as psychiatrists do worry that we need to disentangle these things, but they don’t do that in cardiology, for example. If they see a benefit in mortality they don’t really care if it’s specifically an effect on heart failure or ischemic disease,” said Dr. De Giorgi.

Regardless of their neuropsychiatric potential, the cardiometabolic benefits of GLP-1 inhibitors are sorely needed in the psychiatric population, noted two experts in a recent JAMA Psychiatry viewpoint article.

Sri Mahavir Agarwal, MD, PhD, and Margaret Hahn, MD, PhD, from the University of Toronto and the Schizophrenia Division at the Centre for Addiction and Mental Health, in Toronto, Ontario, Canada, pointed out that “individuals with severe mental illness (SMI) have exceedingly high rates of metabolic comorbidity; three of four are overweight or obese, whereas the prevalence of type 2 diabetes (T2D) is several-fold higher than in the general population. Consequently, individuals with SMI die 15-20 years earlier from cardiovascular disease (CVD) than do those in the general population with CVD,” they noted.

“The arrival of semaglutide has infused significant enthusiasm in the field of mental health research. The proximal effects of weight and related CV comorbidities are significant in themselves. It is plausible that semaglutide could act through neurogenesis or secondary benefits of improving metabolic health on other important outcomes, such as cognitive health and quality of life, thereby filling an unmet need in the treatment of SMI,” Dr. Agarwal and Dr. Hahn added.
 

An Exciting Opportunity

Current research investigating GLP-1s in psychiatry and neurology is increasingly focused on neuroinflammation, said Dr. De Giorgi.

Research shows significant evidence that certain medications may help reduce dysfunctional inflammatory processes linked to various cognitive and psychiatric disorders, he added.

Many patients with established psychiatric conditions also have physical health issues, which contribute to increased mortality risk, said Dr. De Giorgi. It’s crucial to understand that, if these treatments improve mortality outcomes for psychiatric patients, the specific mechanisms involved are secondary to the results. Psychiatrists must be equipped to prescribe, manage, and initiate these therapies.

“While trials involving psychosis patients are ongoing, we are making progress and should seize this opportunity” said Dr. De Giorgi.

Dr. Cryan agreed: “I think we’ll get there. What these drugs have shown is that you can, through a single mechanism, have multitude effects related to brain-body interactions, and why not focus that on mood and anxiety and cognitive performance? It’s exciting no matter what. We now need to do longitudinal, cross-sectional, placebo-controlled trials in specific patient populations.”

This study received funding from the National Institute for Health and Care Research Oxford Health Biomedical Research Centre and Medical Research Council. Dr. De Giorgi’s coauthors reported receiving funding for other work from Novo Nordisk, Five Lives, Cognetivity Ltd., Cognex, P1vital, Lundbeck, Servier, UCB, Zogenix, Johnson & Johnson, and Syndesi. Dr. Cryan reported no relevant disclosures.

A version of this article appeared on Medscape.com.

MILAN — Recent research allaying concerns about suicidality linked to glucagon-like peptide 1 (GLP-1) receptor agonists, along with evidence of these agents’ potential psychiatric and cognitive benefits, has prompted the lead investigator of a major analysis to urge researchers to explore the potential of these drugs for mental illness.

“So far, we’ve been talking about the safety from a neuropsychiatric perspective in diabetes, but there is also the safety and benefit in people with mental disorders,” Riccardo De Giorgi, MD, PhD, from the Department of Psychiatry, University of Oxford in England, said in an interview.

The results of the meta-analysis were previously reported by this news organization and reviewed by Dr. De Giorgi at the 37th European College of Neuropsychopharmacology (ECNP) Congress. Dr. De Giorgi broached whether GLP-1 inhibitors such as semaglutide might also offer the same benefits in patients without diabetes as they do in those with diabetes, in terms of cognitive deficits and substance use or mood disorders.

Noting that GLP-1s are not approved for psychiatric disorders, Dr. De Giorgi said it can’t be assumed that the “metabolic or maybe even more general mechanisms that are being modified with these medications in diabetes or even in obesity are the same for people with psychiatric disorders. We’re talking about very different things. From a clinical perspective, you could do real harm,” he told this news organization.

Yet Dr. De Giorgi emphasized the importance of exploring the potential benefits of these medications in psychiatry.

“From a research perspective ... I am very worried about missing an opportunity here. This happened with rimonabant, a cannabis medication that was used for weight loss back in 2012 and was withdrawn quite dramatically in Europe immediately after licensing because it increased suicide risk. Since then, nobody has been touching the cannabinoid system, and that’s a shame because in psychiatry, we don’t have that much we can work on. So we don’t want to miss an opportunity with the GLP-1 system — that’s why we need to be cautious and look at safety first,” he said.
 

Signal of Efficacy?

Dr. De Giorgi’s research suggested several potential neurobiological effects of GLP-1 inhibition in diabetes research.

“There was a bit of a signal specifically for the big three dementias — vascular, Lewy Body, and frontotemporal — although there was not enough power,” he reported. “We also saw a reduced risk in nicotine misuse, especially amongst other substance use disorders ... and finally a more tentative association for reduced depression.”

He noted that GLP-1s for psychiatric illness likely have limitations and may not cure mental disorders but could help specific subsets of patients. Rather than aiming for large-scale studies, the focus should be on small, incremental studies to advance the research.

Asked by the session chair, John Cryan, PhD, from University College Cork in Ireland, and chair of the ECNP Scientific Committee whether improvement in patients’ mood could be attributed to weight loss, Dr. De Giorgi replied no.

“We now have quite a lot of studies that show that if there is an effect or association it is seen quite a bit earlier than any weight loss. Remember, weight loss takes quite a lot of time, and at quite high doses, but more provocatively, even if that’s the case, does it matter? We as psychiatrists do worry that we need to disentangle these things, but they don’t do that in cardiology, for example. If they see a benefit in mortality they don’t really care if it’s specifically an effect on heart failure or ischemic disease,” said Dr. De Giorgi.

Regardless of their neuropsychiatric potential, the cardiometabolic benefits of GLP-1 inhibitors are sorely needed in the psychiatric population, noted two experts in a recent JAMA Psychiatry viewpoint article.

Sri Mahavir Agarwal, MD, PhD, and Margaret Hahn, MD, PhD, from the University of Toronto and the Schizophrenia Division at the Centre for Addiction and Mental Health, in Toronto, Ontario, Canada, pointed out that “individuals with severe mental illness (SMI) have exceedingly high rates of metabolic comorbidity; three of four are overweight or obese, whereas the prevalence of type 2 diabetes (T2D) is several-fold higher than in the general population. Consequently, individuals with SMI die 15-20 years earlier from cardiovascular disease (CVD) than do those in the general population with CVD,” they noted.

“The arrival of semaglutide has infused significant enthusiasm in the field of mental health research. The proximal effects of weight and related CV comorbidities are significant in themselves. It is plausible that semaglutide could act through neurogenesis or secondary benefits of improving metabolic health on other important outcomes, such as cognitive health and quality of life, thereby filling an unmet need in the treatment of SMI,” Dr. Agarwal and Dr. Hahn added.
 

An Exciting Opportunity

Current research investigating GLP-1s in psychiatry and neurology is increasingly focused on neuroinflammation, said Dr. De Giorgi.

Research shows significant evidence that certain medications may help reduce dysfunctional inflammatory processes linked to various cognitive and psychiatric disorders, he added.

Many patients with established psychiatric conditions also have physical health issues, which contribute to increased mortality risk, said Dr. De Giorgi. It’s crucial to understand that, if these treatments improve mortality outcomes for psychiatric patients, the specific mechanisms involved are secondary to the results. Psychiatrists must be equipped to prescribe, manage, and initiate these therapies.

“While trials involving psychosis patients are ongoing, we are making progress and should seize this opportunity” said Dr. De Giorgi.

Dr. Cryan agreed: “I think we’ll get there. What these drugs have shown is that you can, through a single mechanism, have multitude effects related to brain-body interactions, and why not focus that on mood and anxiety and cognitive performance? It’s exciting no matter what. We now need to do longitudinal, cross-sectional, placebo-controlled trials in specific patient populations.”

This study received funding from the National Institute for Health and Care Research Oxford Health Biomedical Research Centre and Medical Research Council. Dr. De Giorgi’s coauthors reported receiving funding for other work from Novo Nordisk, Five Lives, Cognetivity Ltd., Cognex, P1vital, Lundbeck, Servier, UCB, Zogenix, Johnson & Johnson, and Syndesi. Dr. Cryan reported no relevant disclosures.

A version of this article appeared on Medscape.com.

TOPLINE:

Diabetes and prediabetes are associated with accelerated brain aging with brain age gaps of 2.29 and 0.50 years, respectively. This association is more pronounced in men and those with poor cardiometabolic health but may be mitigated by a healthy lifestyle.

METHODOLOGY:

• Diabetes is a known risk factor for cognitive impairment, dementia, and global brain atrophy but conflicting results have been reported for prediabetes, and it’s unknown whether a healthy lifestyle can counteract the negative impact of prediabetes.
• Researchers examined the cross-sectional and longitudinal relationship between hyperglycemia and brain aging, as well as the potential mitigating effect of a healthy lifestyle in 31,229 dementia-free adults (mean age, 54.8 years; 53% women) from the UK Biobank, including 13,518 participants with prediabetes and 1149 with diabetes.
• The glycemic status of the participants was determined by their medical history, medication use, and A1c levels.
• The brain age gap was calculated as a difference between chronologic age and brain age estimated from MRI data from six modalities vs several hundred brain MRI phenotypes that were modeled from a subset of healthy individuals.
• The role of sex, cardiometabolic risk factors, and a healthy lifestyle and their association with brain age was also explored, with a healthy lifestyle defined as never smoking, no or light or moderate alcohol consumption, and high physical activity.

TAKEAWAY:

• Prediabetes and diabetes were associated with a higher brain age gap than normoglycemia (beta-coefficient, 0.22 and 2.01; 95% CI, 0.10-0.34 and 1.70-2.32, respectively), and diabetes was more pronounced in men vs women and those with a higher vs lower burden of cardiometabolic risk factors.
• The brain ages of those with prediabetes and diabetes were 0.50 years and 2.29 years older on average than their respective chronologic ages.
• In an exploratory longitudinal analysis of the 2414 participants with two brain MRI scans, diabetes was linked to a 0.27-year annual increase in the brain age gap, and higher A1c, but not prediabetes, was associated with a significant increase in brain age gap.
• A healthy lifestyle attenuated the association between diabetes and a higher brain age gap (P = .003), reducing it by 1.68 years, also with a significant interaction between glycemic status and lifestyle.

IN PRACTICE:

“Our findings highlight diabetes and prediabetes as ideal targets for lifestyle-based interventions to promote brain health,” the authors wrote.

SOURCE:

This study, led by Abigail Dove, Aging Research Center, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden, was published online in Diabetes Care.

LIMITATIONS:

The generalizability of the findings was limited due to a healthy volunteer bias in the UK Biobank. A high proportion of missing data prevented the inclusion of diet in the healthy lifestyle construct. Reverse causality may be possible as an older brain may contribute to the development of prediabetes by making it more difficult to manage medical conditions and adhere to a healthy lifestyle. A1c levels were measured only at baseline, preventing the assessment of changes in glycemic control over time.

DISCLOSURES:

The authors reported receiving funding from the Swedish Research Council; Swedish Research Council for Health, Working Life and Welfare; Karolinska Institutet Board of Research; Riksbankens Jubileumsfond; Marianne and Marcus Wallenberg Foundation; Alzheimerfonden; and Demensfonden. They declared no relevant conflicts of interest.

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

TOPLINE:

Diabetes and prediabetes are associated with accelerated brain aging with brain age gaps of 2.29 and 0.50 years, respectively. This association is more pronounced in men and those with poor cardiometabolic health but may be mitigated by a healthy lifestyle.

METHODOLOGY:

• Diabetes is a known risk factor for cognitive impairment, dementia, and global brain atrophy but conflicting results have been reported for prediabetes, and it’s unknown whether a healthy lifestyle can counteract the negative impact of prediabetes.
• Researchers examined the cross-sectional and longitudinal relationship between hyperglycemia and brain aging, as well as the potential mitigating effect of a healthy lifestyle in 31,229 dementia-free adults (mean age, 54.8 years; 53% women) from the UK Biobank, including 13,518 participants with prediabetes and 1149 with diabetes.
• The glycemic status of the participants was determined by their medical history, medication use, and A1c levels.
• The brain age gap was calculated as a difference between chronologic age and brain age estimated from MRI data from six modalities vs several hundred brain MRI phenotypes that were modeled from a subset of healthy individuals.
• The role of sex, cardiometabolic risk factors, and a healthy lifestyle and their association with brain age was also explored, with a healthy lifestyle defined as never smoking, no or light or moderate alcohol consumption, and high physical activity.

TAKEAWAY:

• Prediabetes and diabetes were associated with a higher brain age gap than normoglycemia (beta-coefficient, 0.22 and 2.01; 95% CI, 0.10-0.34 and 1.70-2.32, respectively), and diabetes was more pronounced in men vs women and those with a higher vs lower burden of cardiometabolic risk factors.
• The brain ages of those with prediabetes and diabetes were 0.50 years and 2.29 years older on average than their respective chronologic ages.
• In an exploratory longitudinal analysis of the 2414 participants with two brain MRI scans, diabetes was linked to a 0.27-year annual increase in the brain age gap, and higher A1c, but not prediabetes, was associated with a significant increase in brain age gap.
• A healthy lifestyle attenuated the association between diabetes and a higher brain age gap (P = .003), reducing it by 1.68 years, also with a significant interaction between glycemic status and lifestyle.

IN PRACTICE:

“Our findings highlight diabetes and prediabetes as ideal targets for lifestyle-based interventions to promote brain health,” the authors wrote.

SOURCE:

This study, led by Abigail Dove, Aging Research Center, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden, was published online in Diabetes Care.

LIMITATIONS:

The generalizability of the findings was limited due to a healthy volunteer bias in the UK Biobank. A high proportion of missing data prevented the inclusion of diet in the healthy lifestyle construct. Reverse causality may be possible as an older brain may contribute to the development of prediabetes by making it more difficult to manage medical conditions and adhere to a healthy lifestyle. A1c levels were measured only at baseline, preventing the assessment of changes in glycemic control over time.

DISCLOSURES:

The authors reported receiving funding from the Swedish Research Council; Swedish Research Council for Health, Working Life and Welfare; Karolinska Institutet Board of Research; Riksbankens Jubileumsfond; Marianne and Marcus Wallenberg Foundation; Alzheimerfonden; and Demensfonden. They declared no relevant conflicts of interest.

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

TOPLINE:

Diabetes and prediabetes are associated with accelerated brain aging with brain age gaps of 2.29 and 0.50 years, respectively. This association is more pronounced in men and those with poor cardiometabolic health but may be mitigated by a healthy lifestyle.

METHODOLOGY:

• Diabetes is a known risk factor for cognitive impairment, dementia, and global brain atrophy but conflicting results have been reported for prediabetes, and it’s unknown whether a healthy lifestyle can counteract the negative impact of prediabetes.
• Researchers examined the cross-sectional and longitudinal relationship between hyperglycemia and brain aging, as well as the potential mitigating effect of a healthy lifestyle in 31,229 dementia-free adults (mean age, 54.8 years; 53% women) from the UK Biobank, including 13,518 participants with prediabetes and 1149 with diabetes.
• The glycemic status of the participants was determined by their medical history, medication use, and A1c levels.
• The brain age gap was calculated as a difference between chronologic age and brain age estimated from MRI data from six modalities vs several hundred brain MRI phenotypes that were modeled from a subset of healthy individuals.
• The role of sex, cardiometabolic risk factors, and a healthy lifestyle and their association with brain age was also explored, with a healthy lifestyle defined as never smoking, no or light or moderate alcohol consumption, and high physical activity.

TAKEAWAY:

• Prediabetes and diabetes were associated with a higher brain age gap than normoglycemia (beta-coefficient, 0.22 and 2.01; 95% CI, 0.10-0.34 and 1.70-2.32, respectively), and diabetes was more pronounced in men vs women and those with a higher vs lower burden of cardiometabolic risk factors.
• The brain ages of those with prediabetes and diabetes were 0.50 years and 2.29 years older on average than their respective chronologic ages.
• In an exploratory longitudinal analysis of the 2414 participants with two brain MRI scans, diabetes was linked to a 0.27-year annual increase in the brain age gap, and higher A1c, but not prediabetes, was associated with a significant increase in brain age gap.
• A healthy lifestyle attenuated the association between diabetes and a higher brain age gap (P = .003), reducing it by 1.68 years, also with a significant interaction between glycemic status and lifestyle.

IN PRACTICE:

“Our findings highlight diabetes and prediabetes as ideal targets for lifestyle-based interventions to promote brain health,” the authors wrote.

SOURCE:

This study, led by Abigail Dove, Aging Research Center, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden, was published online in Diabetes Care.

LIMITATIONS:

The generalizability of the findings was limited due to a healthy volunteer bias in the UK Biobank. A high proportion of missing data prevented the inclusion of diet in the healthy lifestyle construct. Reverse causality may be possible as an older brain may contribute to the development of prediabetes by making it more difficult to manage medical conditions and adhere to a healthy lifestyle. A1c levels were measured only at baseline, preventing the assessment of changes in glycemic control over time.

DISCLOSURES:

The authors reported receiving funding from the Swedish Research Council; Swedish Research Council for Health, Working Life and Welfare; Karolinska Institutet Board of Research; Riksbankens Jubileumsfond; Marianne and Marcus Wallenberg Foundation; Alzheimerfonden; and Demensfonden. They declared no relevant conflicts of interest.

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

MADRID — Patients with type 2 diabetes treated with sodium-glucose cotransporter 2 inhibitors (SGLT2is) show significant reductions in the risk of developing neurodegenerative disorders including Alzheimer’s disease, vascular dementia, and Parkinson’s disease, compared with those treated with other antidiabetic drugs, results from a large population-based cohort show.

“This was the largest nationwide population-based longitudinal cohort study to investigate the association between the use of SGLT2 inhibitors and the incidence of all-cause dementia and Parkinson’s disease,” said first author Hae Kyung Kim, MD, of the Department of Internal Medicine, Yonsei University College of Medicine, Seoul, South Korea, in presenting the findings at the annual meeting of the European Association for the Study of Diabetes.

Type 2 diabetes is known to increase the risk for neurodegenerative diseases such as dementia or Alzheimer’s disease, said Dr. Kim. Key factors attributed to the risk include shared pathophysiological mechanisms such as central nervous system insulin resistance and reduced cerebral glucose metabolism.

While research is lacking on the role of antidiabetic drugs in the treatment of neurodegenerative diseases, the researcher noted that “SGLT2 inhibitors, which have shown significant cardiorenal benefits and enhanced energy metabolism through ketogenesis, offer promise.”

To further investigate, Dr. Kim and her colleagues conducted the retrospective study, evaluating data on more than 1.3 million enrollees in Korea’s National Health Insurance Service Database who were aged 40 years or older, diagnosed with type 2 diabetes, and had initiated antidiabetic drugs between September 2014 and December 2019.

In the propensity score analysis, 358,862 patients were matched 1:1, in groups of 179,431 participants each, based on whether they were treated with SGLT2is or other oral antidiabetic drugs. Patients with a history of neurodegenerative disease, cancer, or use of glucagon-like peptide 1 receptor agonists were excluded.

The patients had a mean age of 57.8 years, 57.9% were men, and 6837 had incident dementia or Parkinson’s disease events reported.

With a mean follow-up of 2.88 years, after adjustment for key variables, those treated with SGLT2is had a 19% reduced risk of developing Alzheimer’s disease (adjusted hazard ratio [aHR], 0.81), a 31% reduced risk for vascular dementia (aHR, 0.69), and a 20% reduced risk for Parkinson’s disease (aHR, 0.80) compared with the non-SGLT2i group.

Furthermore, those receiving SGLT2i treatment had a 21% reduced risk for all-cause dementia (aHR, 0.79) and a 22% reduced risk for all-cause dementia and Parkinson’s disease compared with the oral antidiabetic drug group (aHR, 0.78) with a 6-month drug use lag period.

The association was observed regardless of SGLT2i exposure duration. Subgroup analyses indicated that the reductions in neurodegenerative disorders among those receiving SGLT2is were not associated with factors including age, sex, body mass index, blood pressure, glucose, lipid profiles, kidney function, health behaviors, comorbidities, diabetic complications, or other medication use.

Dr. Kim speculated that mechanisms underlying the reduced dementia risk could include SGLT2i effects of mitigating the common severe risk factors of type 2 diabetes and neurodegenerative diseases, including hypertension, heart failure, and chronic kidney disease, and improving hyperperfusion in the heart and cerebral vascular insufficiency.

Commenting on the study to this news organization, Erik H. Serné, MD, of the VU University Medical Centre, Amsterdam, the Netherlands, who comoderated the session, noted that “people with type 2 diabetes have a 50%-100% increased risk of developing dementia, particularly Alzheimer’s disease and vascular dementia.”

“The increasing prevalence of both conditions poses significant public health challenges, highlighting the need for effective prevention strategies and interventions.”

Currently, treatments for dementia are limited, with most primarily addressing symptoms and not the underlying cause of the neurodegenerative disease, he said.

He noted that, in addition to the effects mentioned by Dr. Kim, SGLT2is are also speculated to provide potential neuroprotective effects through improved glycemic control and insulin sensitivity, reduced inflammation and oxidative stress, enhanced mitochondrial function and energy metabolism, and reduced beta-amyloid and tau pathology.

“These mechanisms collectively may reduce the risk of cognitive decline, particularly in diabetic patients, and warrant further investigation in clinical trials to solidify the neuroprotective role of SGLT2 inhibitors,” said Dr. Serné.

In addition to their benefits in type 2 diabetes, SGLT2is “now offer hope in the prevention of dementia, a disease that has very limited therapeutic options thus far. The current data [presented by Dr. Kim] seem to corroborate this,” he added.

Dr. Kim and Dr. Serné had no disclosures to report.

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

MADRID — Patients with type 2 diabetes treated with sodium-glucose cotransporter 2 inhibitors (SGLT2is) show significant reductions in the risk of developing neurodegenerative disorders including Alzheimer’s disease, vascular dementia, and Parkinson’s disease, compared with those treated with other antidiabetic drugs, results from a large population-based cohort show.

“This was the largest nationwide population-based longitudinal cohort study to investigate the association between the use of SGLT2 inhibitors and the incidence of all-cause dementia and Parkinson’s disease,” said first author Hae Kyung Kim, MD, of the Department of Internal Medicine, Yonsei University College of Medicine, Seoul, South Korea, in presenting the findings at the annual meeting of the European Association for the Study of Diabetes.

Type 2 diabetes is known to increase the risk for neurodegenerative diseases such as dementia or Alzheimer’s disease, said Dr. Kim. Key factors attributed to the risk include shared pathophysiological mechanisms such as central nervous system insulin resistance and reduced cerebral glucose metabolism.

While research is lacking on the role of antidiabetic drugs in the treatment of neurodegenerative diseases, the researcher noted that “SGLT2 inhibitors, which have shown significant cardiorenal benefits and enhanced energy metabolism through ketogenesis, offer promise.”

To further investigate, Dr. Kim and her colleagues conducted the retrospective study, evaluating data on more than 1.3 million enrollees in Korea’s National Health Insurance Service Database who were aged 40 years or older, diagnosed with type 2 diabetes, and had initiated antidiabetic drugs between September 2014 and December 2019.

In the propensity score analysis, 358,862 patients were matched 1:1, in groups of 179,431 participants each, based on whether they were treated with SGLT2is or other oral antidiabetic drugs. Patients with a history of neurodegenerative disease, cancer, or use of glucagon-like peptide 1 receptor agonists were excluded.

The patients had a mean age of 57.8 years, 57.9% were men, and 6837 had incident dementia or Parkinson’s disease events reported.

With a mean follow-up of 2.88 years, after adjustment for key variables, those treated with SGLT2is had a 19% reduced risk of developing Alzheimer’s disease (adjusted hazard ratio [aHR], 0.81), a 31% reduced risk for vascular dementia (aHR, 0.69), and a 20% reduced risk for Parkinson’s disease (aHR, 0.80) compared with the non-SGLT2i group.

Furthermore, those receiving SGLT2i treatment had a 21% reduced risk for all-cause dementia (aHR, 0.79) and a 22% reduced risk for all-cause dementia and Parkinson’s disease compared with the oral antidiabetic drug group (aHR, 0.78) with a 6-month drug use lag period.

The association was observed regardless of SGLT2i exposure duration. Subgroup analyses indicated that the reductions in neurodegenerative disorders among those receiving SGLT2is were not associated with factors including age, sex, body mass index, blood pressure, glucose, lipid profiles, kidney function, health behaviors, comorbidities, diabetic complications, or other medication use.

Dr. Kim speculated that mechanisms underlying the reduced dementia risk could include SGLT2i effects of mitigating the common severe risk factors of type 2 diabetes and neurodegenerative diseases, including hypertension, heart failure, and chronic kidney disease, and improving hyperperfusion in the heart and cerebral vascular insufficiency.

Commenting on the study to this news organization, Erik H. Serné, MD, of the VU University Medical Centre, Amsterdam, the Netherlands, who comoderated the session, noted that “people with type 2 diabetes have a 50%-100% increased risk of developing dementia, particularly Alzheimer’s disease and vascular dementia.”

“The increasing prevalence of both conditions poses significant public health challenges, highlighting the need for effective prevention strategies and interventions.”

Currently, treatments for dementia are limited, with most primarily addressing symptoms and not the underlying cause of the neurodegenerative disease, he said.

He noted that, in addition to the effects mentioned by Dr. Kim, SGLT2is are also speculated to provide potential neuroprotective effects through improved glycemic control and insulin sensitivity, reduced inflammation and oxidative stress, enhanced mitochondrial function and energy metabolism, and reduced beta-amyloid and tau pathology.

“These mechanisms collectively may reduce the risk of cognitive decline, particularly in diabetic patients, and warrant further investigation in clinical trials to solidify the neuroprotective role of SGLT2 inhibitors,” said Dr. Serné.

In addition to their benefits in type 2 diabetes, SGLT2is “now offer hope in the prevention of dementia, a disease that has very limited therapeutic options thus far. The current data [presented by Dr. Kim] seem to corroborate this,” he added.

Dr. Kim and Dr. Serné had no disclosures to report.

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

MADRID — Patients with type 2 diabetes treated with sodium-glucose cotransporter 2 inhibitors (SGLT2is) show significant reductions in the risk of developing neurodegenerative disorders including Alzheimer’s disease, vascular dementia, and Parkinson’s disease, compared with those treated with other antidiabetic drugs, results from a large population-based cohort show.

“This was the largest nationwide population-based longitudinal cohort study to investigate the association between the use of SGLT2 inhibitors and the incidence of all-cause dementia and Parkinson’s disease,” said first author Hae Kyung Kim, MD, of the Department of Internal Medicine, Yonsei University College of Medicine, Seoul, South Korea, in presenting the findings at the annual meeting of the European Association for the Study of Diabetes.

Type 2 diabetes is known to increase the risk for neurodegenerative diseases such as dementia or Alzheimer’s disease, said Dr. Kim. Key factors attributed to the risk include shared pathophysiological mechanisms such as central nervous system insulin resistance and reduced cerebral glucose metabolism.

While research is lacking on the role of antidiabetic drugs in the treatment of neurodegenerative diseases, the researcher noted that “SGLT2 inhibitors, which have shown significant cardiorenal benefits and enhanced energy metabolism through ketogenesis, offer promise.”

To further investigate, Dr. Kim and her colleagues conducted the retrospective study, evaluating data on more than 1.3 million enrollees in Korea’s National Health Insurance Service Database who were aged 40 years or older, diagnosed with type 2 diabetes, and had initiated antidiabetic drugs between September 2014 and December 2019.

In the propensity score analysis, 358,862 patients were matched 1:1, in groups of 179,431 participants each, based on whether they were treated with SGLT2is or other oral antidiabetic drugs. Patients with a history of neurodegenerative disease, cancer, or use of glucagon-like peptide 1 receptor agonists were excluded.

The patients had a mean age of 57.8 years, 57.9% were men, and 6837 had incident dementia or Parkinson’s disease events reported.

With a mean follow-up of 2.88 years, after adjustment for key variables, those treated with SGLT2is had a 19% reduced risk of developing Alzheimer’s disease (adjusted hazard ratio [aHR], 0.81), a 31% reduced risk for vascular dementia (aHR, 0.69), and a 20% reduced risk for Parkinson’s disease (aHR, 0.80) compared with the non-SGLT2i group.

Furthermore, those receiving SGLT2i treatment had a 21% reduced risk for all-cause dementia (aHR, 0.79) and a 22% reduced risk for all-cause dementia and Parkinson’s disease compared with the oral antidiabetic drug group (aHR, 0.78) with a 6-month drug use lag period.

The association was observed regardless of SGLT2i exposure duration. Subgroup analyses indicated that the reductions in neurodegenerative disorders among those receiving SGLT2is were not associated with factors including age, sex, body mass index, blood pressure, glucose, lipid profiles, kidney function, health behaviors, comorbidities, diabetic complications, or other medication use.

Dr. Kim speculated that mechanisms underlying the reduced dementia risk could include SGLT2i effects of mitigating the common severe risk factors of type 2 diabetes and neurodegenerative diseases, including hypertension, heart failure, and chronic kidney disease, and improving hyperperfusion in the heart and cerebral vascular insufficiency.

Commenting on the study to this news organization, Erik H. Serné, MD, of the VU University Medical Centre, Amsterdam, the Netherlands, who comoderated the session, noted that “people with type 2 diabetes have a 50%-100% increased risk of developing dementia, particularly Alzheimer’s disease and vascular dementia.”

“The increasing prevalence of both conditions poses significant public health challenges, highlighting the need for effective prevention strategies and interventions.”

Currently, treatments for dementia are limited, with most primarily addressing symptoms and not the underlying cause of the neurodegenerative disease, he said.

He noted that, in addition to the effects mentioned by Dr. Kim, SGLT2is are also speculated to provide potential neuroprotective effects through improved glycemic control and insulin sensitivity, reduced inflammation and oxidative stress, enhanced mitochondrial function and energy metabolism, and reduced beta-amyloid and tau pathology.

“These mechanisms collectively may reduce the risk of cognitive decline, particularly in diabetic patients, and warrant further investigation in clinical trials to solidify the neuroprotective role of SGLT2 inhibitors,” said Dr. Serné.

In addition to their benefits in type 2 diabetes, SGLT2is “now offer hope in the prevention of dementia, a disease that has very limited therapeutic options thus far. The current data [presented by Dr. Kim] seem to corroborate this,” he added.

Dr. Kim and Dr. Serné had no disclosures to report.

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

Outside of caffeine, I have very few addictions. One of them is “Midnight Diner.”

“Midnight Diner” is a quirky, sometimes funny, sometimes bittersweet, Japanese series on Netflix. It’s about a small diner in Tokyo, open only in the wee hours of the morning, its enigmatic owner/cook, and the eclectic patrons that come and go. Each is seeking a dish that means something to them.

One episode (spoiler alert, in case you’re planning to watch it) deals with the regulars realizing a fellow who frequently comes in and orders potato salad is secretly Japan’s most famous porn actor, Erect Oki. This revelation garners him the respect, awe, and envy of the other male patrons, though Mr. Oki would rather be left to his potato salad.

The jokes are there ... but as things develop, we learn he has the potato salad because it reminds him of his mother’s potato salad — and that he’s been cut off from his family for more than 20 years because of his career path. The potato salad is all he has left.

While preparing for a shoot, he learns his mother has Alzheimer’s disease, and immediately returns home. As they sit talking on the patio of a care center, she tells him about her son, who lives in Tokyo, and loves her potato salad. The show doesn’t make it clear if she ever remembers who he is.

In the darkening hallways of her mind, she asks his sister for help in making potato salad for her visitor. It’s too salty, though whether this is from the ingredients or his tears is also never stated.

The episode is a poignant reminder of how Alzheimer’s disease is a worldwide human problem. Not American. Not western. Not restricted by race, or ethnicity, or continent. It effects us all as a species, as families, and as individuals. No matter what our jobs or backgrounds are.

For those of us on this side of the desk, it’s a reminder that effective treatments for Alzheimer’s disease are still not available. Yes, we have all kinds of new toys, but from a practical viewpoint it’s hard to say that we’ve made any major advances. I’m sure my drug reps will disagree with me, and I’m not saying any of the treatments of the last 28 years are worthless, but even now we’re still far from a cure, or even something that stops progression.

That’s not from lack of trying, either.

For all the jokes about his job, Mr. Oki is no different from any other children trying to hold onto their parents as the disease slowly takes them away.

I hope we have real answers, soon.
 

Dr. Block has a solo neurology practice in Scottsdale, Arizona.

Outside of caffeine, I have very few addictions. One of them is “Midnight Diner.”

“Midnight Diner” is a quirky, sometimes funny, sometimes bittersweet, Japanese series on Netflix. It’s about a small diner in Tokyo, open only in the wee hours of the morning, its enigmatic owner/cook, and the eclectic patrons that come and go. Each is seeking a dish that means something to them.

One episode (spoiler alert, in case you’re planning to watch it) deals with the regulars realizing a fellow who frequently comes in and orders potato salad is secretly Japan’s most famous porn actor, Erect Oki. This revelation garners him the respect, awe, and envy of the other male patrons, though Mr. Oki would rather be left to his potato salad.

The jokes are there ... but as things develop, we learn he has the potato salad because it reminds him of his mother’s potato salad — and that he’s been cut off from his family for more than 20 years because of his career path. The potato salad is all he has left.

While preparing for a shoot, he learns his mother has Alzheimer’s disease, and immediately returns home. As they sit talking on the patio of a care center, she tells him about her son, who lives in Tokyo, and loves her potato salad. The show doesn’t make it clear if she ever remembers who he is.

In the darkening hallways of her mind, she asks his sister for help in making potato salad for her visitor. It’s too salty, though whether this is from the ingredients or his tears is also never stated.

The episode is a poignant reminder of how Alzheimer’s disease is a worldwide human problem. Not American. Not western. Not restricted by race, or ethnicity, or continent. It effects us all as a species, as families, and as individuals. No matter what our jobs or backgrounds are.

For those of us on this side of the desk, it’s a reminder that effective treatments for Alzheimer’s disease are still not available. Yes, we have all kinds of new toys, but from a practical viewpoint it’s hard to say that we’ve made any major advances. I’m sure my drug reps will disagree with me, and I’m not saying any of the treatments of the last 28 years are worthless, but even now we’re still far from a cure, or even something that stops progression.

That’s not from lack of trying, either.

For all the jokes about his job, Mr. Oki is no different from any other children trying to hold onto their parents as the disease slowly takes them away.

I hope we have real answers, soon.
 

Dr. Block has a solo neurology practice in Scottsdale, Arizona.

Outside of caffeine, I have very few addictions. One of them is “Midnight Diner.”

“Midnight Diner” is a quirky, sometimes funny, sometimes bittersweet, Japanese series on Netflix. It’s about a small diner in Tokyo, open only in the wee hours of the morning, its enigmatic owner/cook, and the eclectic patrons that come and go. Each is seeking a dish that means something to them.

One episode (spoiler alert, in case you’re planning to watch it) deals with the regulars realizing a fellow who frequently comes in and orders potato salad is secretly Japan’s most famous porn actor, Erect Oki. This revelation garners him the respect, awe, and envy of the other male patrons, though Mr. Oki would rather be left to his potato salad.

The jokes are there ... but as things develop, we learn he has the potato salad because it reminds him of his mother’s potato salad — and that he’s been cut off from his family for more than 20 years because of his career path. The potato salad is all he has left.

While preparing for a shoot, he learns his mother has Alzheimer’s disease, and immediately returns home. As they sit talking on the patio of a care center, she tells him about her son, who lives in Tokyo, and loves her potato salad. The show doesn’t make it clear if she ever remembers who he is.

In the darkening hallways of her mind, she asks his sister for help in making potato salad for her visitor. It’s too salty, though whether this is from the ingredients or his tears is also never stated.

The episode is a poignant reminder of how Alzheimer’s disease is a worldwide human problem. Not American. Not western. Not restricted by race, or ethnicity, or continent. It effects us all as a species, as families, and as individuals. No matter what our jobs or backgrounds are.

For those of us on this side of the desk, it’s a reminder that effective treatments for Alzheimer’s disease are still not available. Yes, we have all kinds of new toys, but from a practical viewpoint it’s hard to say that we’ve made any major advances. I’m sure my drug reps will disagree with me, and I’m not saying any of the treatments of the last 28 years are worthless, but even now we’re still far from a cure, or even something that stops progression.

That’s not from lack of trying, either.

For all the jokes about his job, Mr. Oki is no different from any other children trying to hold onto their parents as the disease slowly takes them away.

I hope we have real answers, soon.
 

Dr. Block has a solo neurology practice in Scottsdale, Arizona.

Postoperative cognitive dysfunction (POCD) is a form of cognitive decline that involves a functional deterioration of activities of the nervous system, such as selective attention, vigilance, perception, learning, memory, executive function, verbal and language abilities, emotion, visuospatial and visuomotor skills. It occurs in the absence of cranial trauma or other brain injuries, and prevalence rates range from 36.6% in young adults to 42.4% in older adults, as a consequence of significant invasive procedures such as cardiac, noncardiac, and carotid surgeries that are lengthy and intensive.

Alzheimer’s disease (AD), the most common form of dementia, accounts for about two thirds of all cases of dementia globally. It is estimated that 41 million patients with dementia remain undiagnosed worldwide, and 25% of patients are diagnosed only when they are fully symptomatic. AD is a neurodegenerative disorder defined by neuropathologic changes, including beta-amyloid (Abeta) plaques composed of aggregated Abeta and neurofibrillary tangles containing aggregated tau proteins.

Patients with AD are unaware of their condition. Dementia, especially in its early stages, is often a hidden disease. Even when suspected, patients and families may believe that the symptoms are part of normal aging and may not report them to the doctor. In these patients, surgery may unmask subclinical dementia.

The complex correlation between POCD and AD has sparked debate following numerous anecdotal reports of how older adults undergoing surgical procedures may experience long-term cognitive decline with clinical characteristics such as those of patients with dementia. Despite advances in knowledge, it is still difficult to establish a priori how much surgery and anesthesia can increase the risk or accelerate the progression of a prodromal and asymptomatic AD condition (stages I-II) to clinically evident stage III AD. The current trend of an aging population poses a challenge for anesthesiology surgery because as the age of patients undergoing surgery increases, so does the likelihood of developing POCD.

Recent research in these fields has improved knowledge of the characteristics, epidemiology, risk factors, pathogenesis, and potential prevention strategies associated with POCD. It has improved the perspectives of future prevention and treatment.
 

Definition and Diagnostic Criteria

POCD, according to the cognitive impairment classification in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, is characterized by mild neurologic disturbance resulting from routine surgical procedures, excluding conditions such as deafness, dementia, or amnesia. The definition of POCD involves prolonged cognitive decline that can last for weeks, months, or even years. POCD may be confused with postoperative delirium, an acute and fluctuating disorder of consciousness that typically occurs within 3 days of surgery.

The diagnosis of POCD is based primarily on neurocognitive function scales. Widely used assessments include the Montreal Cognitive Assessment, the Wechsler Memory Scale, and the Mini-Mental State Examination.
 

Epidemiology

POCD is prevalent among patients undergoing cardiac or orthopedic surgery. In patients undergoing aortic-coronary bypass and cardiopulmonary bypass, 50%-70% develop POCD 1 week after surgery. In addition, 10%-30% experience long-term effects on cognitive function at 6 months after the procedure. In patients undergoing hip arthroplasty, 20%-50% exhibit POCD within 1 week of surgery, with 10%-14% still presenting it after 3 months.

Risk Factors

Age

POCD is typically observed in patients older than 65 years. However, after surgery, around 30% of younger patients and about 40% of older patients develop POCD at the time of hospital discharge. Specifically, 12.7% of older patients continue to have POCD 3 months after surgery, compared with 5% of younger patients.

Type of Surgery 

Hip and knee arthroplasty procedures entail a higher risk for POCD than general surgery. The same is true of cardiac surgery, especially aortic-coronary bypass and cardiopulmonary bypass.

Types of Anesthesia 

Initial assessments of postoperative cognitive function in cardiac surgery did not provide significant correlations between observed changes and the type of anesthesia because of the high number of confounding factors involved. A more recent meta-analysis of 28 randomized clinical trials concluded that the incidence of POCD is lower in surgeries using intravenous anesthesia with propofol than in those using inhalation anesthesia with isoflurane or sevoflurane.

Pain

Postoperative pain is a common issue, mainly resulting from substantial surgical trauma or potential wound infection. Patient-controlled postoperative analgesia independently increases the risk for POCD, compared with oral postoperative analgesia. Meta-analyses indicate that persistent pain can lead to a decline in patients’ cognitive abilities, attention, memory, and information processing.

Evolving Scenarios

Current research on POCD has deepened our understanding of its pathogenesis, implicating factors such as central nervous system inflammation, neuronal apoptosis, synaptic plasticity damage, abnormal tau protein modification, chronic pain, and mitochondrial metabolic disorders. Several neuroprotective drugs are currently under study, but none have shown consistent benefits for the prevention and treatment of POCD. The available evidence on the subject does not unambiguously guide the practicing physician. But neither does it exclude the importance of a careful assessment of POCD risk factors and the cognitive status of an older patient before surgery to provide useful information to the patient, family, and doctors when deciding on appropriate and shared procedures.

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

Postoperative cognitive dysfunction (POCD) is a form of cognitive decline that involves a functional deterioration of activities of the nervous system, such as selective attention, vigilance, perception, learning, memory, executive function, verbal and language abilities, emotion, visuospatial and visuomotor skills. It occurs in the absence of cranial trauma or other brain injuries, and prevalence rates range from 36.6% in young adults to 42.4% in older adults, as a consequence of significant invasive procedures such as cardiac, noncardiac, and carotid surgeries that are lengthy and intensive.

Alzheimer’s disease (AD), the most common form of dementia, accounts for about two thirds of all cases of dementia globally. It is estimated that 41 million patients with dementia remain undiagnosed worldwide, and 25% of patients are diagnosed only when they are fully symptomatic. AD is a neurodegenerative disorder defined by neuropathologic changes, including beta-amyloid (Abeta) plaques composed of aggregated Abeta and neurofibrillary tangles containing aggregated tau proteins.

Patients with AD are unaware of their condition. Dementia, especially in its early stages, is often a hidden disease. Even when suspected, patients and families may believe that the symptoms are part of normal aging and may not report them to the doctor. In these patients, surgery may unmask subclinical dementia.

The complex correlation between POCD and AD has sparked debate following numerous anecdotal reports of how older adults undergoing surgical procedures may experience long-term cognitive decline with clinical characteristics such as those of patients with dementia. Despite advances in knowledge, it is still difficult to establish a priori how much surgery and anesthesia can increase the risk or accelerate the progression of a prodromal and asymptomatic AD condition (stages I-II) to clinically evident stage III AD. The current trend of an aging population poses a challenge for anesthesiology surgery because as the age of patients undergoing surgery increases, so does the likelihood of developing POCD.

Recent research in these fields has improved knowledge of the characteristics, epidemiology, risk factors, pathogenesis, and potential prevention strategies associated with POCD. It has improved the perspectives of future prevention and treatment.
 

Definition and Diagnostic Criteria

POCD, according to the cognitive impairment classification in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, is characterized by mild neurologic disturbance resulting from routine surgical procedures, excluding conditions such as deafness, dementia, or amnesia. The definition of POCD involves prolonged cognitive decline that can last for weeks, months, or even years. POCD may be confused with postoperative delirium, an acute and fluctuating disorder of consciousness that typically occurs within 3 days of surgery.

The diagnosis of POCD is based primarily on neurocognitive function scales. Widely used assessments include the Montreal Cognitive Assessment, the Wechsler Memory Scale, and the Mini-Mental State Examination.
 

Epidemiology

POCD is prevalent among patients undergoing cardiac or orthopedic surgery. In patients undergoing aortic-coronary bypass and cardiopulmonary bypass, 50%-70% develop POCD 1 week after surgery. In addition, 10%-30% experience long-term effects on cognitive function at 6 months after the procedure. In patients undergoing hip arthroplasty, 20%-50% exhibit POCD within 1 week of surgery, with 10%-14% still presenting it after 3 months.

Risk Factors

Age

POCD is typically observed in patients older than 65 years. However, after surgery, around 30% of younger patients and about 40% of older patients develop POCD at the time of hospital discharge. Specifically, 12.7% of older patients continue to have POCD 3 months after surgery, compared with 5% of younger patients.

Type of Surgery 

Hip and knee arthroplasty procedures entail a higher risk for POCD than general surgery. The same is true of cardiac surgery, especially aortic-coronary bypass and cardiopulmonary bypass.

Types of Anesthesia 

Initial assessments of postoperative cognitive function in cardiac surgery did not provide significant correlations between observed changes and the type of anesthesia because of the high number of confounding factors involved. A more recent meta-analysis of 28 randomized clinical trials concluded that the incidence of POCD is lower in surgeries using intravenous anesthesia with propofol than in those using inhalation anesthesia with isoflurane or sevoflurane.

Pain

Postoperative pain is a common issue, mainly resulting from substantial surgical trauma or potential wound infection. Patient-controlled postoperative analgesia independently increases the risk for POCD, compared with oral postoperative analgesia. Meta-analyses indicate that persistent pain can lead to a decline in patients’ cognitive abilities, attention, memory, and information processing.

Evolving Scenarios

Current research on POCD has deepened our understanding of its pathogenesis, implicating factors such as central nervous system inflammation, neuronal apoptosis, synaptic plasticity damage, abnormal tau protein modification, chronic pain, and mitochondrial metabolic disorders. Several neuroprotective drugs are currently under study, but none have shown consistent benefits for the prevention and treatment of POCD. The available evidence on the subject does not unambiguously guide the practicing physician. But neither does it exclude the importance of a careful assessment of POCD risk factors and the cognitive status of an older patient before surgery to provide useful information to the patient, family, and doctors when deciding on appropriate and shared procedures.

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

Postoperative cognitive dysfunction (POCD) is a form of cognitive decline that involves a functional deterioration of activities of the nervous system, such as selective attention, vigilance, perception, learning, memory, executive function, verbal and language abilities, emotion, visuospatial and visuomotor skills. It occurs in the absence of cranial trauma or other brain injuries, and prevalence rates range from 36.6% in young adults to 42.4% in older adults, as a consequence of significant invasive procedures such as cardiac, noncardiac, and carotid surgeries that are lengthy and intensive.

Alzheimer’s disease (AD), the most common form of dementia, accounts for about two thirds of all cases of dementia globally. It is estimated that 41 million patients with dementia remain undiagnosed worldwide, and 25% of patients are diagnosed only when they are fully symptomatic. AD is a neurodegenerative disorder defined by neuropathologic changes, including beta-amyloid (Abeta) plaques composed of aggregated Abeta and neurofibrillary tangles containing aggregated tau proteins.

Patients with AD are unaware of their condition. Dementia, especially in its early stages, is often a hidden disease. Even when suspected, patients and families may believe that the symptoms are part of normal aging and may not report them to the doctor. In these patients, surgery may unmask subclinical dementia.

The complex correlation between POCD and AD has sparked debate following numerous anecdotal reports of how older adults undergoing surgical procedures may experience long-term cognitive decline with clinical characteristics such as those of patients with dementia. Despite advances in knowledge, it is still difficult to establish a priori how much surgery and anesthesia can increase the risk or accelerate the progression of a prodromal and asymptomatic AD condition (stages I-II) to clinically evident stage III AD. The current trend of an aging population poses a challenge for anesthesiology surgery because as the age of patients undergoing surgery increases, so does the likelihood of developing POCD.

Recent research in these fields has improved knowledge of the characteristics, epidemiology, risk factors, pathogenesis, and potential prevention strategies associated with POCD. It has improved the perspectives of future prevention and treatment.
 

Definition and Diagnostic Criteria

POCD, according to the cognitive impairment classification in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, is characterized by mild neurologic disturbance resulting from routine surgical procedures, excluding conditions such as deafness, dementia, or amnesia. The definition of POCD involves prolonged cognitive decline that can last for weeks, months, or even years. POCD may be confused with postoperative delirium, an acute and fluctuating disorder of consciousness that typically occurs within 3 days of surgery.

The diagnosis of POCD is based primarily on neurocognitive function scales. Widely used assessments include the Montreal Cognitive Assessment, the Wechsler Memory Scale, and the Mini-Mental State Examination.
 

Epidemiology

POCD is prevalent among patients undergoing cardiac or orthopedic surgery. In patients undergoing aortic-coronary bypass and cardiopulmonary bypass, 50%-70% develop POCD 1 week after surgery. In addition, 10%-30% experience long-term effects on cognitive function at 6 months after the procedure. In patients undergoing hip arthroplasty, 20%-50% exhibit POCD within 1 week of surgery, with 10%-14% still presenting it after 3 months.

Risk Factors

Age

POCD is typically observed in patients older than 65 years. However, after surgery, around 30% of younger patients and about 40% of older patients develop POCD at the time of hospital discharge. Specifically, 12.7% of older patients continue to have POCD 3 months after surgery, compared with 5% of younger patients.

Type of Surgery 

Hip and knee arthroplasty procedures entail a higher risk for POCD than general surgery. The same is true of cardiac surgery, especially aortic-coronary bypass and cardiopulmonary bypass.

Types of Anesthesia 

Initial assessments of postoperative cognitive function in cardiac surgery did not provide significant correlations between observed changes and the type of anesthesia because of the high number of confounding factors involved. A more recent meta-analysis of 28 randomized clinical trials concluded that the incidence of POCD is lower in surgeries using intravenous anesthesia with propofol than in those using inhalation anesthesia with isoflurane or sevoflurane.

Pain

Postoperative pain is a common issue, mainly resulting from substantial surgical trauma or potential wound infection. Patient-controlled postoperative analgesia independently increases the risk for POCD, compared with oral postoperative analgesia. Meta-analyses indicate that persistent pain can lead to a decline in patients’ cognitive abilities, attention, memory, and information processing.

Evolving Scenarios

Current research on POCD has deepened our understanding of its pathogenesis, implicating factors such as central nervous system inflammation, neuronal apoptosis, synaptic plasticity damage, abnormal tau protein modification, chronic pain, and mitochondrial metabolic disorders. Several neuroprotective drugs are currently under study, but none have shown consistent benefits for the prevention and treatment of POCD. The available evidence on the subject does not unambiguously guide the practicing physician. But neither does it exclude the importance of a careful assessment of POCD risk factors and the cognitive status of an older patient before surgery to provide useful information to the patient, family, and doctors when deciding on appropriate and shared procedures.

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

TOPLINE:

The likelihood of receiving a dementia diagnosis in older adults varies significantly by region across the United States, a new study suggests. Rates ranged from 1.7% to 5.4%, with variations more pronounced in those aged 66-74 years and Black or Hispanic individuals.

METHODOLOGY:

• Researchers analyzed newly diagnosed cases of Alzheimer’s disease and related dementias (ADRD) using the 2018-2019 Medicare claims data for 4.8 million older adults across 306 hospital referral regions (HRRs).
• Participants were categorized by age and race or ethnicity to examine variations in diagnosis rates.
• Regional characteristics such as education level and prevalence of obesity, smoking, and diabetes were included to adjust for population risk factors.
• ADRD-specific diagnostic intensity was calculated as the ratio of the observed-to-expected new cases of ADRD in each HRR.

TAKEAWAY:

• Unadjusted analysis for that overall, 3% of older adults received a new ADRD diagnosis in 2019, with rates ranging from 1.7 to 5.4 per 100 individuals across HRRs and varied by age category.
• Regions in the South had the highest unadjusted ADRD case concentration, and the areas in the West/Northwest had the lowest.
• The ADRD-specific diagnosis intensity was 0.69-1.47 and varied the most in Black and Hispanic individuals and those aged 66-74 years.
• Regional differences in ADRD diagnosis rates are not fully explained by population risk factors, indicating potential health system-level differences.

IN PRACTICE:

“From place to place, the likelihood of getting your dementia diagnosed varies, and that may happen because of everything from practice norms for healthcare providers to individual patients’ knowledge and care-seeking behavior. These findings go beyond demographic and population-level differences in risk and indicate that there are health system-level differences that could be targeted and remediated,” lead author Julie P.W. Bynum, MD, MPH, said in a press release.

SOURCE:

The study was led by Dr. Bynum, professor of internal medicine, University of Michigan Medical School, Ann Arbor, Michigan, and published online in Alzheimer’s & Dementia.

LIMITATIONS:

The results may not be generalizable to other groups. The observational design of the study cannot completely negate residual confounding. The measures of population risks are coarser than those used in well-characterized epidemiologic studies, leading to potential imprecision. Finally, the study was not designed to determine whether regional differences in the likelihood of ADRD diagnosis resulted in differences in the population health outcomes.

DISCLOSURES:

The study was supported by a grant from the National Institute on Aging. The authors reported no conflicts of interest.

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

TOPLINE:

The likelihood of receiving a dementia diagnosis in older adults varies significantly by region across the United States, a new study suggests. Rates ranged from 1.7% to 5.4%, with variations more pronounced in those aged 66-74 years and Black or Hispanic individuals.

METHODOLOGY:

• Researchers analyzed newly diagnosed cases of Alzheimer’s disease and related dementias (ADRD) using the 2018-2019 Medicare claims data for 4.8 million older adults across 306 hospital referral regions (HRRs).
• Participants were categorized by age and race or ethnicity to examine variations in diagnosis rates.
• Regional characteristics such as education level and prevalence of obesity, smoking, and diabetes were included to adjust for population risk factors.
• ADRD-specific diagnostic intensity was calculated as the ratio of the observed-to-expected new cases of ADRD in each HRR.

TAKEAWAY:

• Unadjusted analysis for that overall, 3% of older adults received a new ADRD diagnosis in 2019, with rates ranging from 1.7 to 5.4 per 100 individuals across HRRs and varied by age category.
• Regions in the South had the highest unadjusted ADRD case concentration, and the areas in the West/Northwest had the lowest.
• The ADRD-specific diagnosis intensity was 0.69-1.47 and varied the most in Black and Hispanic individuals and those aged 66-74 years.
• Regional differences in ADRD diagnosis rates are not fully explained by population risk factors, indicating potential health system-level differences.

IN PRACTICE:

“From place to place, the likelihood of getting your dementia diagnosed varies, and that may happen because of everything from practice norms for healthcare providers to individual patients’ knowledge and care-seeking behavior. These findings go beyond demographic and population-level differences in risk and indicate that there are health system-level differences that could be targeted and remediated,” lead author Julie P.W. Bynum, MD, MPH, said in a press release.

SOURCE:

The study was led by Dr. Bynum, professor of internal medicine, University of Michigan Medical School, Ann Arbor, Michigan, and published online in Alzheimer’s & Dementia.

LIMITATIONS:

The results may not be generalizable to other groups. The observational design of the study cannot completely negate residual confounding. The measures of population risks are coarser than those used in well-characterized epidemiologic studies, leading to potential imprecision. Finally, the study was not designed to determine whether regional differences in the likelihood of ADRD diagnosis resulted in differences in the population health outcomes.

DISCLOSURES:

The study was supported by a grant from the National Institute on Aging. The authors reported no conflicts of interest.

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

TOPLINE:

The likelihood of receiving a dementia diagnosis in older adults varies significantly by region across the United States, a new study suggests. Rates ranged from 1.7% to 5.4%, with variations more pronounced in those aged 66-74 years and Black or Hispanic individuals.

METHODOLOGY:

• Researchers analyzed newly diagnosed cases of Alzheimer’s disease and related dementias (ADRD) using the 2018-2019 Medicare claims data for 4.8 million older adults across 306 hospital referral regions (HRRs).
• Participants were categorized by age and race or ethnicity to examine variations in diagnosis rates.
• Regional characteristics such as education level and prevalence of obesity, smoking, and diabetes were included to adjust for population risk factors.
• ADRD-specific diagnostic intensity was calculated as the ratio of the observed-to-expected new cases of ADRD in each HRR.

TAKEAWAY:

• Unadjusted analysis for that overall, 3% of older adults received a new ADRD diagnosis in 2019, with rates ranging from 1.7 to 5.4 per 100 individuals across HRRs and varied by age category.
• Regions in the South had the highest unadjusted ADRD case concentration, and the areas in the West/Northwest had the lowest.
• The ADRD-specific diagnosis intensity was 0.69-1.47 and varied the most in Black and Hispanic individuals and those aged 66-74 years.
• Regional differences in ADRD diagnosis rates are not fully explained by population risk factors, indicating potential health system-level differences.

IN PRACTICE:

“From place to place, the likelihood of getting your dementia diagnosed varies, and that may happen because of everything from practice norms for healthcare providers to individual patients’ knowledge and care-seeking behavior. These findings go beyond demographic and population-level differences in risk and indicate that there are health system-level differences that could be targeted and remediated,” lead author Julie P.W. Bynum, MD, MPH, said in a press release.

SOURCE:

The study was led by Dr. Bynum, professor of internal medicine, University of Michigan Medical School, Ann Arbor, Michigan, and published online in Alzheimer’s & Dementia.

LIMITATIONS:

The results may not be generalizable to other groups. The observational design of the study cannot completely negate residual confounding. The measures of population risks are coarser than those used in well-characterized epidemiologic studies, leading to potential imprecision. Finally, the study was not designed to determine whether regional differences in the likelihood of ADRD diagnosis resulted in differences in the population health outcomes.

DISCLOSURES:

The study was supported by a grant from the National Institute on Aging. The authors reported no conflicts of interest.

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

TOPLINE:

Addressing vision impairments could help with dementia prevention, as vision impairment is linked to 19% of dementia cases in older adults.
 

METHODOLOGY:

• Researchers conducted a cross-sectional analysis using data from the National Health and Aging Trends Study (NHATS).
• The analysis included 2767 US adults aged 71 years or older (54.7% female and 45.3% male).
• Vision impairments were defined using 2019 World Health Organization criteria. Near and distance vision impairments were defined as greater than 0.30 logMAR, and contrast sensitivity impairment was identified by scores below 1.55 logCS.
• Dementia was classified using a standardized algorithm developed in NHATS, which incorporated a series of tests measuring cognition, memory and orientation, reports of Alzheimer’s disease, or a dementia diagnosis from the patient or a proxy, and an informant questionnaire (Ascertain Dementia-8 Dementia Screening Interview).
• The study analyzed data from 2021, with the primary outcome being the population attributable fraction (PAF) of dementia from vision impairment.

TAKEAWAY:

• The PAF of dementia associated with at least one vision impairment was 19% (95% CI, 8.2-29.7).
• Impairment in contrast sensitivity had the highest PAF among all other vision issues, at 15% (95% CI, 6.6-23.6). This figure was higher than that for impairment of near acuity, at 9.7% (95% CI, 2.6-17.0), or distance acuity, at 4.9% (95% CI, 0.1-9.9).
• The highest PAFs for dementia due to vision impairment was among participants aged 71-79 years (24.3%; 95% CI, 6.6-41.8), women (26.8%; 95% CI, 12.2-39.9), and non-Hispanic White participants (22.3%; 95% CI, 9.6-34.5).

IN PRACTICE:

“While not proving a cause-and-effect relationship, these findings support inclusion of multiple objective measures of vision impairments, including contrast sensitivity and visual acuity, to capture the total potential impact of addressing vision impairment on dementia,” study authors wrote.

SOURCE:

This study was led by Jason R. Smith, ScM, of the Department of Epidemiology at the Johns Hopkins Bloomberg School of Public Health in Baltimore. It was published online in JAMA Ophthalmology.

LIMITATIONS:

The limited sample sizes for American Indian, Alaska Native, Asian, and Hispanic groups prevented researchers from calculating PAFs for these populations. The cross-sectional design prevented the researchers from examining the timing of vision impairment in relation to a diagnosis of dementia. The study did not explore links between other measures of vision and dementia. Those with early cognitive impairment may not have updated glasses, affecting visual performance. The findings from the study may not apply to institutionalized older adults.

DISCLOSURES:

Jennifer A. Deal, PhD, MHS, reported receiving personal fees from Frontiers in Epidemiology, Velux Stiftung, and Medical Education Speakers Network outside the submitted work. Nicholas S. Reed, AuD, PhD, reported receiving stock options from Neosensory outside the submitted work. No other disclosures were reported.

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

TOPLINE:

Addressing vision impairments could help with dementia prevention, as vision impairment is linked to 19% of dementia cases in older adults.
 

METHODOLOGY:

• Researchers conducted a cross-sectional analysis using data from the National Health and Aging Trends Study (NHATS).
• The analysis included 2767 US adults aged 71 years or older (54.7% female and 45.3% male).
• Vision impairments were defined using 2019 World Health Organization criteria. Near and distance vision impairments were defined as greater than 0.30 logMAR, and contrast sensitivity impairment was identified by scores below 1.55 logCS.
• Dementia was classified using a standardized algorithm developed in NHATS, which incorporated a series of tests measuring cognition, memory and orientation, reports of Alzheimer’s disease, or a dementia diagnosis from the patient or a proxy, and an informant questionnaire (Ascertain Dementia-8 Dementia Screening Interview).
• The study analyzed data from 2021, with the primary outcome being the population attributable fraction (PAF) of dementia from vision impairment.

TAKEAWAY:

• The PAF of dementia associated with at least one vision impairment was 19% (95% CI, 8.2-29.7).
• Impairment in contrast sensitivity had the highest PAF among all other vision issues, at 15% (95% CI, 6.6-23.6). This figure was higher than that for impairment of near acuity, at 9.7% (95% CI, 2.6-17.0), or distance acuity, at 4.9% (95% CI, 0.1-9.9).
• The highest PAFs for dementia due to vision impairment was among participants aged 71-79 years (24.3%; 95% CI, 6.6-41.8), women (26.8%; 95% CI, 12.2-39.9), and non-Hispanic White participants (22.3%; 95% CI, 9.6-34.5).

IN PRACTICE:

“While not proving a cause-and-effect relationship, these findings support inclusion of multiple objective measures of vision impairments, including contrast sensitivity and visual acuity, to capture the total potential impact of addressing vision impairment on dementia,” study authors wrote.

SOURCE:

This study was led by Jason R. Smith, ScM, of the Department of Epidemiology at the Johns Hopkins Bloomberg School of Public Health in Baltimore. It was published online in JAMA Ophthalmology.

LIMITATIONS:

The limited sample sizes for American Indian, Alaska Native, Asian, and Hispanic groups prevented researchers from calculating PAFs for these populations. The cross-sectional design prevented the researchers from examining the timing of vision impairment in relation to a diagnosis of dementia. The study did not explore links between other measures of vision and dementia. Those with early cognitive impairment may not have updated glasses, affecting visual performance. The findings from the study may not apply to institutionalized older adults.

DISCLOSURES:

Jennifer A. Deal, PhD, MHS, reported receiving personal fees from Frontiers in Epidemiology, Velux Stiftung, and Medical Education Speakers Network outside the submitted work. Nicholas S. Reed, AuD, PhD, reported receiving stock options from Neosensory outside the submitted work. No other disclosures were reported.

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

TOPLINE:

Addressing vision impairments could help with dementia prevention, as vision impairment is linked to 19% of dementia cases in older adults.
 

METHODOLOGY:

• Researchers conducted a cross-sectional analysis using data from the National Health and Aging Trends Study (NHATS).
• The analysis included 2767 US adults aged 71 years or older (54.7% female and 45.3% male).
• Vision impairments were defined using 2019 World Health Organization criteria. Near and distance vision impairments were defined as greater than 0.30 logMAR, and contrast sensitivity impairment was identified by scores below 1.55 logCS.
• Dementia was classified using a standardized algorithm developed in NHATS, which incorporated a series of tests measuring cognition, memory and orientation, reports of Alzheimer’s disease, or a dementia diagnosis from the patient or a proxy, and an informant questionnaire (Ascertain Dementia-8 Dementia Screening Interview).
• The study analyzed data from 2021, with the primary outcome being the population attributable fraction (PAF) of dementia from vision impairment.

TAKEAWAY:

• The PAF of dementia associated with at least one vision impairment was 19% (95% CI, 8.2-29.7).
• Impairment in contrast sensitivity had the highest PAF among all other vision issues, at 15% (95% CI, 6.6-23.6). This figure was higher than that for impairment of near acuity, at 9.7% (95% CI, 2.6-17.0), or distance acuity, at 4.9% (95% CI, 0.1-9.9).
• The highest PAFs for dementia due to vision impairment was among participants aged 71-79 years (24.3%; 95% CI, 6.6-41.8), women (26.8%; 95% CI, 12.2-39.9), and non-Hispanic White participants (22.3%; 95% CI, 9.6-34.5).

IN PRACTICE:

“While not proving a cause-and-effect relationship, these findings support inclusion of multiple objective measures of vision impairments, including contrast sensitivity and visual acuity, to capture the total potential impact of addressing vision impairment on dementia,” study authors wrote.

SOURCE:

This study was led by Jason R. Smith, ScM, of the Department of Epidemiology at the Johns Hopkins Bloomberg School of Public Health in Baltimore. It was published online in JAMA Ophthalmology.

LIMITATIONS:

The limited sample sizes for American Indian, Alaska Native, Asian, and Hispanic groups prevented researchers from calculating PAFs for these populations. The cross-sectional design prevented the researchers from examining the timing of vision impairment in relation to a diagnosis of dementia. The study did not explore links between other measures of vision and dementia. Those with early cognitive impairment may not have updated glasses, affecting visual performance. The findings from the study may not apply to institutionalized older adults.

DISCLOSURES:

Jennifer A. Deal, PhD, MHS, reported receiving personal fees from Frontiers in Epidemiology, Velux Stiftung, and Medical Education Speakers Network outside the submitted work. Nicholas S. Reed, AuD, PhD, reported receiving stock options from Neosensory outside the submitted work. No other disclosures were reported.

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

In a recent study, patients with multiple sclerosis (MS) had half the rate of amyloid beta pathology versus matched controls without MS, supporting authors’ suspicion that MS may protect against Alzheimer’s disease. Understanding how MS does this may drive new treatment strategies, said the authors of the study, which was published online in Annals of Neurology. Regarding current treatments, they added, the availability of new disease-modifying Alzheimer’s disease therapies increases the importance of early diagnosis in cognitively impaired people including those with MS.

Confirmatory Studies Needed

“Replication and confirmation of these findings, including in studies representative of the real-world Alzheimer’s population in race/ethnicity and sex/gender, are needed before any clinical implications can be drawn,” said Claire Sexton, DPhil, Alzheimer’s Association senior director of scientific programs and outreach. She was not involved with the study but was asked to comment.

The study’s most important immediate implication, said Dr. Sexton, is that it “opens the door to questions about why MS may be associated with Alzheimer’s risk.”

Alzheimer's Association

Anecdotal Observation

Although life expectancy for people with MS is increasing, the authors, led by Matthew R. Brier, MD, PhD, an assistant professor at Washington University in St. Louis, Missouri, said they have seen no concomitant rise in Alzheimer’s disease dementia among their patients with MS. This anecdotal observation fueled their hypothesis that Alzheimer’s disease pathology occurs less frequently in this population.

To test their hypothesis, the investigators sequentially enrolled 100 patients with MS (age 60 years or older), along with 300 non-MS controls matched for age, sex, apolipoprotein E (apoE) proteotype, and cognitive status. All participants underwent the Mini-Mental State Examination (MMSE) and PrecivityAD2 (C2N Diagnostics) blood testing.

Washngton University

Possible Explanations

The authors hypothesized that the lower rate of amyloid pathology observed in their patients with MS may stem from the following possibly overlapping mechanisms:

• MS components, such as persistent perilesional immune activity, may inhibit amyloid beta deposition or facilitate its clearance.
• Exposure to MS drugs may impact Alzheimer’s disease pathology. Most study patients with MS were exposed to beta interferons or glatiramer acetate, the authors noted, and 39 had switched to high-efficacy medications such as B-cell depleting therapies and natalizumab.
• MS’s genetic signature may protect against AD.

“Investigating these ideas would advance our understanding of the relationship between MS and Alzheimer’s, and potentially inform avenues for treatment,” said Dr. Sexton. In this regard, the Alzheimer’s Association has funded an ongoing study examining a drug currently used to promote myelin formation in individuals with MS in genetically engineered Alzheimer’s-like mice. Additional Association-funded studies that examine inflammation also may improve understanding of the mechanisms that may link these diseases, said Dr. Sexton. 

The study authors added that unusual cases, such as a study patient who had high amyloid burden by PET but negative APS2 and tau PET, also may shed light on interactions between MS, amyloid pathology, and tau pathology.

Limitations of the present study include the fact that plasma Alzheimer’s disease biomarkers are potentially affected by other conditions as well, according to a study published in Nature Medicine. Additional shortcomings include the MS cohort’s relatively small size and lack of diagnostic confirmation by cerebrospinal fluid. Although MMSE scores among patients with MS were slightly lower, the authors added, this disparity would lead one to expect more, not less, amyloid pathology among these patients if their cognitive impairment resulted from Alzheimer’s disease.

Dr. Sexton reported no relevant financial interests.

The study was supported by the Hope Center for Neurological Disorders at Washington University in St. Louis and by C2N Diagnostics. Washington University in St. Louis holds equity in C2N Diagnostics and may receive royalties resulting from use of PrecivityAD2.

In a recent study, patients with multiple sclerosis (MS) had half the rate of amyloid beta pathology versus matched controls without MS, supporting authors’ suspicion that MS may protect against Alzheimer’s disease. Understanding how MS does this may drive new treatment strategies, said the authors of the study, which was published online in Annals of Neurology. Regarding current treatments, they added, the availability of new disease-modifying Alzheimer’s disease therapies increases the importance of early diagnosis in cognitively impaired people including those with MS.

Confirmatory Studies Needed

“Replication and confirmation of these findings, including in studies representative of the real-world Alzheimer’s population in race/ethnicity and sex/gender, are needed before any clinical implications can be drawn,” said Claire Sexton, DPhil, Alzheimer’s Association senior director of scientific programs and outreach. She was not involved with the study but was asked to comment.

The study’s most important immediate implication, said Dr. Sexton, is that it “opens the door to questions about why MS may be associated with Alzheimer’s risk.”

Alzheimer's Association

Anecdotal Observation

Although life expectancy for people with MS is increasing, the authors, led by Matthew R. Brier, MD, PhD, an assistant professor at Washington University in St. Louis, Missouri, said they have seen no concomitant rise in Alzheimer’s disease dementia among their patients with MS. This anecdotal observation fueled their hypothesis that Alzheimer’s disease pathology occurs less frequently in this population.

To test their hypothesis, the investigators sequentially enrolled 100 patients with MS (age 60 years or older), along with 300 non-MS controls matched for age, sex, apolipoprotein E (apoE) proteotype, and cognitive status. All participants underwent the Mini-Mental State Examination (MMSE) and PrecivityAD2 (C2N Diagnostics) blood testing.

Washngton University

Possible Explanations

The authors hypothesized that the lower rate of amyloid pathology observed in their patients with MS may stem from the following possibly overlapping mechanisms:

• MS components, such as persistent perilesional immune activity, may inhibit amyloid beta deposition or facilitate its clearance.
• Exposure to MS drugs may impact Alzheimer’s disease pathology. Most study patients with MS were exposed to beta interferons or glatiramer acetate, the authors noted, and 39 had switched to high-efficacy medications such as B-cell depleting therapies and natalizumab.
• MS’s genetic signature may protect against AD.

“Investigating these ideas would advance our understanding of the relationship between MS and Alzheimer’s, and potentially inform avenues for treatment,” said Dr. Sexton. In this regard, the Alzheimer’s Association has funded an ongoing study examining a drug currently used to promote myelin formation in individuals with MS in genetically engineered Alzheimer’s-like mice. Additional Association-funded studies that examine inflammation also may improve understanding of the mechanisms that may link these diseases, said Dr. Sexton. 

The study authors added that unusual cases, such as a study patient who had high amyloid burden by PET but negative APS2 and tau PET, also may shed light on interactions between MS, amyloid pathology, and tau pathology.

Limitations of the present study include the fact that plasma Alzheimer’s disease biomarkers are potentially affected by other conditions as well, according to a study published in Nature Medicine. Additional shortcomings include the MS cohort’s relatively small size and lack of diagnostic confirmation by cerebrospinal fluid. Although MMSE scores among patients with MS were slightly lower, the authors added, this disparity would lead one to expect more, not less, amyloid pathology among these patients if their cognitive impairment resulted from Alzheimer’s disease.

Dr. Sexton reported no relevant financial interests.

The study was supported by the Hope Center for Neurological Disorders at Washington University in St. Louis and by C2N Diagnostics. Washington University in St. Louis holds equity in C2N Diagnostics and may receive royalties resulting from use of PrecivityAD2.

In a recent study, patients with multiple sclerosis (MS) had half the rate of amyloid beta pathology versus matched controls without MS, supporting authors’ suspicion that MS may protect against Alzheimer’s disease. Understanding how MS does this may drive new treatment strategies, said the authors of the study, which was published online in Annals of Neurology. Regarding current treatments, they added, the availability of new disease-modifying Alzheimer’s disease therapies increases the importance of early diagnosis in cognitively impaired people including those with MS.

Confirmatory Studies Needed

“Replication and confirmation of these findings, including in studies representative of the real-world Alzheimer’s population in race/ethnicity and sex/gender, are needed before any clinical implications can be drawn,” said Claire Sexton, DPhil, Alzheimer’s Association senior director of scientific programs and outreach. She was not involved with the study but was asked to comment.

The study’s most important immediate implication, said Dr. Sexton, is that it “opens the door to questions about why MS may be associated with Alzheimer’s risk.”

Alzheimer's Association

Anecdotal Observation

Although life expectancy for people with MS is increasing, the authors, led by Matthew R. Brier, MD, PhD, an assistant professor at Washington University in St. Louis, Missouri, said they have seen no concomitant rise in Alzheimer’s disease dementia among their patients with MS. This anecdotal observation fueled their hypothesis that Alzheimer’s disease pathology occurs less frequently in this population.

To test their hypothesis, the investigators sequentially enrolled 100 patients with MS (age 60 years or older), along with 300 non-MS controls matched for age, sex, apolipoprotein E (apoE) proteotype, and cognitive status. All participants underwent the Mini-Mental State Examination (MMSE) and PrecivityAD2 (C2N Diagnostics) blood testing.

Washngton University

Possible Explanations

The authors hypothesized that the lower rate of amyloid pathology observed in their patients with MS may stem from the following possibly overlapping mechanisms:

• MS components, such as persistent perilesional immune activity, may inhibit amyloid beta deposition or facilitate its clearance.
• Exposure to MS drugs may impact Alzheimer’s disease pathology. Most study patients with MS were exposed to beta interferons or glatiramer acetate, the authors noted, and 39 had switched to high-efficacy medications such as B-cell depleting therapies and natalizumab.
• MS’s genetic signature may protect against AD.

“Investigating these ideas would advance our understanding of the relationship between MS and Alzheimer’s, and potentially inform avenues for treatment,” said Dr. Sexton. In this regard, the Alzheimer’s Association has funded an ongoing study examining a drug currently used to promote myelin formation in individuals with MS in genetically engineered Alzheimer’s-like mice. Additional Association-funded studies that examine inflammation also may improve understanding of the mechanisms that may link these diseases, said Dr. Sexton. 

The study authors added that unusual cases, such as a study patient who had high amyloid burden by PET but negative APS2 and tau PET, also may shed light on interactions between MS, amyloid pathology, and tau pathology.

Limitations of the present study include the fact that plasma Alzheimer’s disease biomarkers are potentially affected by other conditions as well, according to a study published in Nature Medicine. Additional shortcomings include the MS cohort’s relatively small size and lack of diagnostic confirmation by cerebrospinal fluid. Although MMSE scores among patients with MS were slightly lower, the authors added, this disparity would lead one to expect more, not less, amyloid pathology among these patients if their cognitive impairment resulted from Alzheimer’s disease.

Dr. Sexton reported no relevant financial interests.

The study was supported by the Hope Center for Neurological Disorders at Washington University in St. Louis and by C2N Diagnostics. Washington University in St. Louis holds equity in C2N Diagnostics and may receive royalties resulting from use of PrecivityAD2.

Researchers have discovered that a brain network involved in reward processing and attention to stimuli is markedly bigger in people with depression, remains stable over time, is unaffected by mood changes, and can be detected in children before onset of depression symptoms.

Using a novel brain-mapping technique, researchers found that the frontostriatal salience network was expanded nearly twofold in the brains of most individuals studied with depression compared with controls.

“This expansion in cortex was trait-like, meaning it was stable over time and did not change as symptoms changed over time,” said lead author Charles Lynch, PhD, assistant professor of neuroscience, Department of Psychiatry, Weill Cornell Medicine in New York.

It could also be detected in children who later developed depression, suggesting it may serve as a biomarker of depression risk. Investigators said the findings could aid in prevention and early detection of depression, as well as the development of more personalized treatment.

The study was published online in Nature.
 

Prewired for Depression?

Precision functional mapping is a relatively new approach to brain mapping in individuals that uses large amounts of fMRI data from hours of scans per person. The technique has been used to show differences in brain networks between and in healthy individuals but had not been used to study brain networks in people with depression.

“We leveraged our large longitudinal datasets — with many hours of functional MRI scanning per subject — to construct individual-specific maps of functional brain networks in each patient using precision functional mapping, instead of relying on group average,” Dr. Lynch said.

In the primary analysis of 141 adults with major depression and 37 healthy controls, the frontostriatal salience network — which is involved in reward processing and attention to internal and external stimuli — was markedly larger in these individuals with depression.

“This is one of the first times these kinds of personalized maps have been created in individuals with depression, and this is how we first observed of the salience network being larger in individuals with depression,” Dr. Lynch said.

In four of the six individuals, the salience network was expanded more than twofold, outside the range observed in all 37 healthy controls. On average, the salience network occupied 73% more of the cortical surface relative to the average in healthy controls.

The findings were replicated using independent samples of repeatedly sampled individuals with depression and in large-scale group average data.

The expansion of the salience network did not change over time and was unaffected by changes in mood state.

“These observations led us to propose that instead of driving changes in depressive symptoms over time, salience network expansion may be a stable marker of risk for developing depression,” the study team wrote.

An analysis of brain scans from 57 children who went on to develop depressive symptoms during adolescence and an equal number of children who did not develop depressive symptoms supports this theory.

On average, the salience network occupied roughly 36% more of cortex in the children with no current or previous symptoms of depression at the time of their fMRI scans but who subsequently developed clinically significant symptoms of depression, relative to children with no depressive symptoms at any study time point, the researchers found.
 

Immediate Clinical Impact?

Reached for comment, Shaheen Lakhan, MD, PhD, neurologist and researcher based in Miami, said this research “exemplifies the promising intersection of neurology and digital health, where advanced neuroimaging and data-driven approaches can transform mental health care into a more precise and individualized practice,” Dr. Lakhan said. “By identifying this brain network expansion, we’re unlocking new possibilities for precision medicine in mental health.”

Dr. Lakhan, who wasn’t involved in this research, said identifying the expansion of the frontostriatal salience network in individuals with depression opens new avenues for developing novel therapeutics.

“By targeting this network through neuromodulation techniques like deep brain stimulation, transcranial magnetic stimulation, and prescription digital therapeutics, treatments can be more precisely tailored to individual neurobiological profiles,” Dr. Lakhan said. “Additionally, this network expansion could serve as a biomarker for early detection, allowing for preventive strategies or personalized treatment plans, particularly for those at risk of developing depression.”

In addition, a greater understanding of the mechanisms driving salience network expansion offers potential for discovering new pharmacological targets, Dr. Lakhan noted.

“Drugs that modulate synaptic plasticity or network connectivity might be developed to reverse or mitigate these neural changes. The findings also support the use of longitudinal monitoring to predict and preempt symptom emergence, improving outcomes through timely intervention. This research paves the way for more personalized, precise, and proactive approaches in treating depression,” Dr. Lakhan concluded.

Also weighing in, Teddy Akiki, MD, with the Department of Psychiatry and Behavioral Sciences at Stanford Medicine in California, noted that the effect size of the frontostriatal salience network difference in depression is “remarkably larger than typically seen in neuroimaging studies of depression, which often describe subtle differences. The consistency across multiple datasets and across time at the individual level adds significant weight to these findings, suggesting that it is a trait marker rather than a state-dependent marker.”

“The observation that this expansion is present even before the onset of depressive symptoms in adolescence suggests its potential as a biomarker for depression risk,” Dr. Akiki said. “This approach could lead to earlier identification of at-risk individuals and potentially inform the development of targeted preventive interventions.”

He cautioned that it remains to be seen whether interventions targeting the salience network can effectively prevent or treat depression.

This research was supported in part by the National Institute of Mental Health, the National Institute on Drug Addiction, the Hope for Depression Research Foundation, and the Foundation for OCD Research. Dr. Lynch and a coauthor are listed as inventors for Cornell University patent applications on neuroimaging biomarkers for depression which are pending or in preparation. Dr. Liston has served as a scientific advisor or consultant to Compass Pathways PLC, Delix Therapeutics, and Brainify.AI. Dr. Lakhan and Dr. Akiki had no relevant disclosures.

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

Researchers have discovered that a brain network involved in reward processing and attention to stimuli is markedly bigger in people with depression, remains stable over time, is unaffected by mood changes, and can be detected in children before onset of depression symptoms.

Using a novel brain-mapping technique, researchers found that the frontostriatal salience network was expanded nearly twofold in the brains of most individuals studied with depression compared with controls.

“This expansion in cortex was trait-like, meaning it was stable over time and did not change as symptoms changed over time,” said lead author Charles Lynch, PhD, assistant professor of neuroscience, Department of Psychiatry, Weill Cornell Medicine in New York.

It could also be detected in children who later developed depression, suggesting it may serve as a biomarker of depression risk. Investigators said the findings could aid in prevention and early detection of depression, as well as the development of more personalized treatment.

The study was published online in Nature.
 

Prewired for Depression?

Precision functional mapping is a relatively new approach to brain mapping in individuals that uses large amounts of fMRI data from hours of scans per person. The technique has been used to show differences in brain networks between and in healthy individuals but had not been used to study brain networks in people with depression.

“We leveraged our large longitudinal datasets — with many hours of functional MRI scanning per subject — to construct individual-specific maps of functional brain networks in each patient using precision functional mapping, instead of relying on group average,” Dr. Lynch said.

In the primary analysis of 141 adults with major depression and 37 healthy controls, the frontostriatal salience network — which is involved in reward processing and attention to internal and external stimuli — was markedly larger in these individuals with depression.

“This is one of the first times these kinds of personalized maps have been created in individuals with depression, and this is how we first observed of the salience network being larger in individuals with depression,” Dr. Lynch said.

In four of the six individuals, the salience network was expanded more than twofold, outside the range observed in all 37 healthy controls. On average, the salience network occupied 73% more of the cortical surface relative to the average in healthy controls.

The findings were replicated using independent samples of repeatedly sampled individuals with depression and in large-scale group average data.

The expansion of the salience network did not change over time and was unaffected by changes in mood state.

“These observations led us to propose that instead of driving changes in depressive symptoms over time, salience network expansion may be a stable marker of risk for developing depression,” the study team wrote.

An analysis of brain scans from 57 children who went on to develop depressive symptoms during adolescence and an equal number of children who did not develop depressive symptoms supports this theory.

On average, the salience network occupied roughly 36% more of cortex in the children with no current or previous symptoms of depression at the time of their fMRI scans but who subsequently developed clinically significant symptoms of depression, relative to children with no depressive symptoms at any study time point, the researchers found.
 

Immediate Clinical Impact?

Reached for comment, Shaheen Lakhan, MD, PhD, neurologist and researcher based in Miami, said this research “exemplifies the promising intersection of neurology and digital health, where advanced neuroimaging and data-driven approaches can transform mental health care into a more precise and individualized practice,” Dr. Lakhan said. “By identifying this brain network expansion, we’re unlocking new possibilities for precision medicine in mental health.”

Dr. Lakhan, who wasn’t involved in this research, said identifying the expansion of the frontostriatal salience network in individuals with depression opens new avenues for developing novel therapeutics.

“By targeting this network through neuromodulation techniques like deep brain stimulation, transcranial magnetic stimulation, and prescription digital therapeutics, treatments can be more precisely tailored to individual neurobiological profiles,” Dr. Lakhan said. “Additionally, this network expansion could serve as a biomarker for early detection, allowing for preventive strategies or personalized treatment plans, particularly for those at risk of developing depression.”

In addition, a greater understanding of the mechanisms driving salience network expansion offers potential for discovering new pharmacological targets, Dr. Lakhan noted.

“Drugs that modulate synaptic plasticity or network connectivity might be developed to reverse or mitigate these neural changes. The findings also support the use of longitudinal monitoring to predict and preempt symptom emergence, improving outcomes through timely intervention. This research paves the way for more personalized, precise, and proactive approaches in treating depression,” Dr. Lakhan concluded.

Also weighing in, Teddy Akiki, MD, with the Department of Psychiatry and Behavioral Sciences at Stanford Medicine in California, noted that the effect size of the frontostriatal salience network difference in depression is “remarkably larger than typically seen in neuroimaging studies of depression, which often describe subtle differences. The consistency across multiple datasets and across time at the individual level adds significant weight to these findings, suggesting that it is a trait marker rather than a state-dependent marker.”

“The observation that this expansion is present even before the onset of depressive symptoms in adolescence suggests its potential as a biomarker for depression risk,” Dr. Akiki said. “This approach could lead to earlier identification of at-risk individuals and potentially inform the development of targeted preventive interventions.”

He cautioned that it remains to be seen whether interventions targeting the salience network can effectively prevent or treat depression.

This research was supported in part by the National Institute of Mental Health, the National Institute on Drug Addiction, the Hope for Depression Research Foundation, and the Foundation for OCD Research. Dr. Lynch and a coauthor are listed as inventors for Cornell University patent applications on neuroimaging biomarkers for depression which are pending or in preparation. Dr. Liston has served as a scientific advisor or consultant to Compass Pathways PLC, Delix Therapeutics, and Brainify.AI. Dr. Lakhan and Dr. Akiki had no relevant disclosures.

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

Researchers have discovered that a brain network involved in reward processing and attention to stimuli is markedly bigger in people with depression, remains stable over time, is unaffected by mood changes, and can be detected in children before onset of depression symptoms.

Using a novel brain-mapping technique, researchers found that the frontostriatal salience network was expanded nearly twofold in the brains of most individuals studied with depression compared with controls.

“This expansion in cortex was trait-like, meaning it was stable over time and did not change as symptoms changed over time,” said lead author Charles Lynch, PhD, assistant professor of neuroscience, Department of Psychiatry, Weill Cornell Medicine in New York.

It could also be detected in children who later developed depression, suggesting it may serve as a biomarker of depression risk. Investigators said the findings could aid in prevention and early detection of depression, as well as the development of more personalized treatment.

The study was published online in Nature.
 

Prewired for Depression?

Precision functional mapping is a relatively new approach to brain mapping in individuals that uses large amounts of fMRI data from hours of scans per person. The technique has been used to show differences in brain networks between and in healthy individuals but had not been used to study brain networks in people with depression.

“We leveraged our large longitudinal datasets — with many hours of functional MRI scanning per subject — to construct individual-specific maps of functional brain networks in each patient using precision functional mapping, instead of relying on group average,” Dr. Lynch said.

In the primary analysis of 141 adults with major depression and 37 healthy controls, the frontostriatal salience network — which is involved in reward processing and attention to internal and external stimuli — was markedly larger in these individuals with depression.

“This is one of the first times these kinds of personalized maps have been created in individuals with depression, and this is how we first observed of the salience network being larger in individuals with depression,” Dr. Lynch said.

In four of the six individuals, the salience network was expanded more than twofold, outside the range observed in all 37 healthy controls. On average, the salience network occupied 73% more of the cortical surface relative to the average in healthy controls.

The findings were replicated using independent samples of repeatedly sampled individuals with depression and in large-scale group average data.

The expansion of the salience network did not change over time and was unaffected by changes in mood state.

“These observations led us to propose that instead of driving changes in depressive symptoms over time, salience network expansion may be a stable marker of risk for developing depression,” the study team wrote.

An analysis of brain scans from 57 children who went on to develop depressive symptoms during adolescence and an equal number of children who did not develop depressive symptoms supports this theory.

On average, the salience network occupied roughly 36% more of cortex in the children with no current or previous symptoms of depression at the time of their fMRI scans but who subsequently developed clinically significant symptoms of depression, relative to children with no depressive symptoms at any study time point, the researchers found.
 

Immediate Clinical Impact?

Reached for comment, Shaheen Lakhan, MD, PhD, neurologist and researcher based in Miami, said this research “exemplifies the promising intersection of neurology and digital health, where advanced neuroimaging and data-driven approaches can transform mental health care into a more precise and individualized practice,” Dr. Lakhan said. “By identifying this brain network expansion, we’re unlocking new possibilities for precision medicine in mental health.”

Dr. Lakhan, who wasn’t involved in this research, said identifying the expansion of the frontostriatal salience network in individuals with depression opens new avenues for developing novel therapeutics.

“By targeting this network through neuromodulation techniques like deep brain stimulation, transcranial magnetic stimulation, and prescription digital therapeutics, treatments can be more precisely tailored to individual neurobiological profiles,” Dr. Lakhan said. “Additionally, this network expansion could serve as a biomarker for early detection, allowing for preventive strategies or personalized treatment plans, particularly for those at risk of developing depression.”

In addition, a greater understanding of the mechanisms driving salience network expansion offers potential for discovering new pharmacological targets, Dr. Lakhan noted.

“Drugs that modulate synaptic plasticity or network connectivity might be developed to reverse or mitigate these neural changes. The findings also support the use of longitudinal monitoring to predict and preempt symptom emergence, improving outcomes through timely intervention. This research paves the way for more personalized, precise, and proactive approaches in treating depression,” Dr. Lakhan concluded.

Also weighing in, Teddy Akiki, MD, with the Department of Psychiatry and Behavioral Sciences at Stanford Medicine in California, noted that the effect size of the frontostriatal salience network difference in depression is “remarkably larger than typically seen in neuroimaging studies of depression, which often describe subtle differences. The consistency across multiple datasets and across time at the individual level adds significant weight to these findings, suggesting that it is a trait marker rather than a state-dependent marker.”

“The observation that this expansion is present even before the onset of depressive symptoms in adolescence suggests its potential as a biomarker for depression risk,” Dr. Akiki said. “This approach could lead to earlier identification of at-risk individuals and potentially inform the development of targeted preventive interventions.”

He cautioned that it remains to be seen whether interventions targeting the salience network can effectively prevent or treat depression.

This research was supported in part by the National Institute of Mental Health, the National Institute on Drug Addiction, the Hope for Depression Research Foundation, and the Foundation for OCD Research. Dr. Lynch and a coauthor are listed as inventors for Cornell University patent applications on neuroimaging biomarkers for depression which are pending or in preparation. Dr. Liston has served as a scientific advisor or consultant to Compass Pathways PLC, Delix Therapeutics, and Brainify.AI. Dr. Lakhan and Dr. Akiki had no relevant disclosures.

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

Living in areas saturated with artificial outdoor light at night is associated with an increased risk for Alzheimer’s disease, a new national study suggested.

Analyses of state and county light pollution data and Medicare claims showed that areas with higher average nighttime light intensity had a greater prevalence of Alzheimer’s disease.

Among people aged 65 years or older, Alzheimer’s disease prevalence was more strongly associated with nightly light pollution exposure than with alcohol misuse, chronic kidney disease, depression, or obesity.

In those younger than 65 years, greater nighttime light intensity had a stronger association with Alzheimer’s disease prevalence than any other risk factor included in the study.

“The results are pretty striking when you do these comparisons and it’s true for people of all ages,” said Robin Voigt-Zuwala, PhD, lead author and director, Circadian Rhythm Research Laboratory, Rush University, Chicago, Illinois.

The study was published online in Frontiers of Neuroscience.
 

Shining a Light

Exposure to artificial outdoor light at night has been associated with adverse health effects such as sleep disruption, obesity, atherosclerosis, and cancer, but this is the first study to look specifically at Alzheimer’s disease, investigators noted.

Two recent studies reported higher risks for mild cognitive impairment among Chinese veterans and late-onset dementia among Italian residents living in areas with brighter outdoor light at night.

For this study, Dr. Voigt-Zuwala and colleagues examined the relationship between Alzheimer’s disease prevalence and average nighttime light intensity in the lower 48 states using data from Medicare Part A and B, the Centers for Disease Control and Prevention, and NASA satellite–acquired radiance data.

The data were averaged for the years 2012-2018 and states divided into five groups based on average nighttime light intensity.

The darkest states were Montana, Wyoming, South Dakota, Idaho, Maine, New Mexico, Vermont, Oregon, Utah, and Nevada. The brightest states were Indiana, Illinois, Florida, Ohio, Massachusetts, Connecticut, Maryland, Delaware, Rhode Island, and New Jersey.

Analysis of variance revealed a significant difference in Alzheimer’s disease prevalence between state groups (P < .0001). Multiple comparisons testing also showed that states with the lowest average nighttime light had significantly different Alzheimer’s disease prevalence than those with higher intensity.

The same positive relationship was observed when each year was assessed individually and at the county level, using data from 45 counties and the District of Columbia.
 

Strong Association

The investigators also found that state average nighttime light intensity is significantly associated with Alzheimer’s disease prevalence (P = .006). This effect was seen across all ages, sexes, and races except Asian Pacific Island, the latter possibly related to statistical power, the authors said.

When known or proposed risk factors for Alzheimer’s disease were added to the model, atrial fibrillation, diabetes, hyperlipidemia, hypertension, and stroke had a stronger association with Alzheimer’s disease than average nighttime light intensity.

Nighttime light intensity, however, was more strongly associated with Alzheimer’s disease prevalence than alcohol abuse, chronic kidney disease, depression, heart failure, and obesity.

Moreover, in people younger than 65 years, nighttime light pollution had a stronger association with Alzheimer’s disease prevalence than all other risk factors (P = .007).

The mechanism behind this increased vulnerability is unclear, but there may be an interplay between genetic susceptibility of an individual and how they respond to light, Dr. Voigt-Zuwala suggested.

“APOE4 is the genotype most highly associated with Alzheimer’s disease risk, and maybe the people who have that genotype are just more sensitive to the effects of light exposure at night, more sensitive to circadian rhythm disruption,” she said.

The authors noted that additional research is needed but suggested light pollution may also influence Alzheimer’s disease through sleep disruption, which can promote inflammation, activate microglia and astrocytes, and negatively alter the clearance of amyloid beta, and by decreasing the levels of brain-derived neurotrophic factor.
 

Are We Measuring the Right Light?

“It’s a good article and it’s got a good message, but I have some caveats to that,” said George C. Brainard, PhD, director, Light Research Program, Thomas Jefferson University in Philadelphia, Pennsylvania, and a pioneer in the study of how light affects biology including breast cancer in night-shift workers.

The biggest caveat, and one acknowledged by the authors, is that the study didn’t measure indoor light exposure and relied instead on satellite imaging.

“They’re very striking images, but they may not be particularly relevant. And here’s why: People don’t live outdoors all night,” Dr. Brainard said.

Instead, people spend much of their time at night indoors where they’re exposed to lighting in the home and from smartphones, laptops, and television screens.

“It doesn’t invalidate their work. It’s an important advancement, an important observation,” Dr. Brainard said. “But the important thing really is to find out what is the population exposed to that triggers this response, and it’s probably indoor lighting related to the amount and physical characteristics of indoor lighting. It doesn’t mean outdoor lighting can’t play a role. It certainly can.”

Reached for comment, Erik Musiek, MD, PhD, a professor of neurology whose lab at Washington University School of Medicine in St. Louis, Missouri, has extensively studied circadian clock disruption and Alzheimer’s disease pathology in the brain, said the study provides a 10,000-foot view of the issue.

For example, the study was not designed to detect whether people living in high light pollution areas are actually experiencing more outdoor light at night and if risk factors such as air pollution and low socioeconomic status may correlate with these areas.

“Most of what we worry about is do people have lights on in the house, do they have their TV on, their screens up to their face late at night? This can’t tell us about that,” Dr. Musiek said. “But on the other hand, this kind of light exposure is something that public policy can affect.”

“It’s hard to control people’s personal habits nor should we probably, but we can control what types of bulbs you put into streetlights, how bright they are, and where you put lighting in a public place,” he added. “So I do think there’s value there.”

At least 19 states, the District of Columbia, and Puerto Rico have laws in place to reduce light pollution, with the majority doing so to promote energy conservation, public safety, aesthetic interests, or astronomical research, according to the National Conference of State Legislatures.

To respond to some of the limitations in this study, Dr. Voigt-Zuwala is writing a grant application for a new project to look at both indoor and outdoor light exposure on an individual level.

“This is what I’ve been wanting to study for a long time, and this study is just sort of the stepping stone, the proof of concept that this is something we need to be investigating,” she said.

Dr. Voigt-Zuwala reported RO1 and R24 grants from the National Institutes of Health (NIH), one coauthor reported an NIH R24 grant; another reported having no conflicts of interest. Dr. Brainard reported having no relevant conflicts of interest. Dr. Musiek reported research funding from Eisai Pharmaceuticals.

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

Living in areas saturated with artificial outdoor light at night is associated with an increased risk for Alzheimer’s disease, a new national study suggested.

Analyses of state and county light pollution data and Medicare claims showed that areas with higher average nighttime light intensity had a greater prevalence of Alzheimer’s disease.

Among people aged 65 years or older, Alzheimer’s disease prevalence was more strongly associated with nightly light pollution exposure than with alcohol misuse, chronic kidney disease, depression, or obesity.

In those younger than 65 years, greater nighttime light intensity had a stronger association with Alzheimer’s disease prevalence than any other risk factor included in the study.

“The results are pretty striking when you do these comparisons and it’s true for people of all ages,” said Robin Voigt-Zuwala, PhD, lead author and director, Circadian Rhythm Research Laboratory, Rush University, Chicago, Illinois.

The study was published online in Frontiers of Neuroscience.
 

Shining a Light

Exposure to artificial outdoor light at night has been associated with adverse health effects such as sleep disruption, obesity, atherosclerosis, and cancer, but this is the first study to look specifically at Alzheimer’s disease, investigators noted.

Two recent studies reported higher risks for mild cognitive impairment among Chinese veterans and late-onset dementia among Italian residents living in areas with brighter outdoor light at night.

For this study, Dr. Voigt-Zuwala and colleagues examined the relationship between Alzheimer’s disease prevalence and average nighttime light intensity in the lower 48 states using data from Medicare Part A and B, the Centers for Disease Control and Prevention, and NASA satellite–acquired radiance data.

The data were averaged for the years 2012-2018 and states divided into five groups based on average nighttime light intensity.

The darkest states were Montana, Wyoming, South Dakota, Idaho, Maine, New Mexico, Vermont, Oregon, Utah, and Nevada. The brightest states were Indiana, Illinois, Florida, Ohio, Massachusetts, Connecticut, Maryland, Delaware, Rhode Island, and New Jersey.

Analysis of variance revealed a significant difference in Alzheimer’s disease prevalence between state groups (P < .0001). Multiple comparisons testing also showed that states with the lowest average nighttime light had significantly different Alzheimer’s disease prevalence than those with higher intensity.

The same positive relationship was observed when each year was assessed individually and at the county level, using data from 45 counties and the District of Columbia.
 

Strong Association

The investigators also found that state average nighttime light intensity is significantly associated with Alzheimer’s disease prevalence (P = .006). This effect was seen across all ages, sexes, and races except Asian Pacific Island, the latter possibly related to statistical power, the authors said.

When known or proposed risk factors for Alzheimer’s disease were added to the model, atrial fibrillation, diabetes, hyperlipidemia, hypertension, and stroke had a stronger association with Alzheimer’s disease than average nighttime light intensity.

Nighttime light intensity, however, was more strongly associated with Alzheimer’s disease prevalence than alcohol abuse, chronic kidney disease, depression, heart failure, and obesity.

Moreover, in people younger than 65 years, nighttime light pollution had a stronger association with Alzheimer’s disease prevalence than all other risk factors (P = .007).

The mechanism behind this increased vulnerability is unclear, but there may be an interplay between genetic susceptibility of an individual and how they respond to light, Dr. Voigt-Zuwala suggested.

“APOE4 is the genotype most highly associated with Alzheimer’s disease risk, and maybe the people who have that genotype are just more sensitive to the effects of light exposure at night, more sensitive to circadian rhythm disruption,” she said.

The authors noted that additional research is needed but suggested light pollution may also influence Alzheimer’s disease through sleep disruption, which can promote inflammation, activate microglia and astrocytes, and negatively alter the clearance of amyloid beta, and by decreasing the levels of brain-derived neurotrophic factor.
 

Are We Measuring the Right Light?

“It’s a good article and it’s got a good message, but I have some caveats to that,” said George C. Brainard, PhD, director, Light Research Program, Thomas Jefferson University in Philadelphia, Pennsylvania, and a pioneer in the study of how light affects biology including breast cancer in night-shift workers.

The biggest caveat, and one acknowledged by the authors, is that the study didn’t measure indoor light exposure and relied instead on satellite imaging.

“They’re very striking images, but they may not be particularly relevant. And here’s why: People don’t live outdoors all night,” Dr. Brainard said.

Instead, people spend much of their time at night indoors where they’re exposed to lighting in the home and from smartphones, laptops, and television screens.

“It doesn’t invalidate their work. It’s an important advancement, an important observation,” Dr. Brainard said. “But the important thing really is to find out what is the population exposed to that triggers this response, and it’s probably indoor lighting related to the amount and physical characteristics of indoor lighting. It doesn’t mean outdoor lighting can’t play a role. It certainly can.”

Reached for comment, Erik Musiek, MD, PhD, a professor of neurology whose lab at Washington University School of Medicine in St. Louis, Missouri, has extensively studied circadian clock disruption and Alzheimer’s disease pathology in the brain, said the study provides a 10,000-foot view of the issue.

For example, the study was not designed to detect whether people living in high light pollution areas are actually experiencing more outdoor light at night and if risk factors such as air pollution and low socioeconomic status may correlate with these areas.

“Most of what we worry about is do people have lights on in the house, do they have their TV on, their screens up to their face late at night? This can’t tell us about that,” Dr. Musiek said. “But on the other hand, this kind of light exposure is something that public policy can affect.”

“It’s hard to control people’s personal habits nor should we probably, but we can control what types of bulbs you put into streetlights, how bright they are, and where you put lighting in a public place,” he added. “So I do think there’s value there.”

At least 19 states, the District of Columbia, and Puerto Rico have laws in place to reduce light pollution, with the majority doing so to promote energy conservation, public safety, aesthetic interests, or astronomical research, according to the National Conference of State Legislatures.

To respond to some of the limitations in this study, Dr. Voigt-Zuwala is writing a grant application for a new project to look at both indoor and outdoor light exposure on an individual level.

“This is what I’ve been wanting to study for a long time, and this study is just sort of the stepping stone, the proof of concept that this is something we need to be investigating,” she said.

Dr. Voigt-Zuwala reported RO1 and R24 grants from the National Institutes of Health (NIH), one coauthor reported an NIH R24 grant; another reported having no conflicts of interest. Dr. Brainard reported having no relevant conflicts of interest. Dr. Musiek reported research funding from Eisai Pharmaceuticals.

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

Living in areas saturated with artificial outdoor light at night is associated with an increased risk for Alzheimer’s disease, a new national study suggested.

Analyses of state and county light pollution data and Medicare claims showed that areas with higher average nighttime light intensity had a greater prevalence of Alzheimer’s disease.

Among people aged 65 years or older, Alzheimer’s disease prevalence was more strongly associated with nightly light pollution exposure than with alcohol misuse, chronic kidney disease, depression, or obesity.

In those younger than 65 years, greater nighttime light intensity had a stronger association with Alzheimer’s disease prevalence than any other risk factor included in the study.

“The results are pretty striking when you do these comparisons and it’s true for people of all ages,” said Robin Voigt-Zuwala, PhD, lead author and director, Circadian Rhythm Research Laboratory, Rush University, Chicago, Illinois.

The study was published online in Frontiers of Neuroscience.
 

Shining a Light

Exposure to artificial outdoor light at night has been associated with adverse health effects such as sleep disruption, obesity, atherosclerosis, and cancer, but this is the first study to look specifically at Alzheimer’s disease, investigators noted.

Two recent studies reported higher risks for mild cognitive impairment among Chinese veterans and late-onset dementia among Italian residents living in areas with brighter outdoor light at night.

For this study, Dr. Voigt-Zuwala and colleagues examined the relationship between Alzheimer’s disease prevalence and average nighttime light intensity in the lower 48 states using data from Medicare Part A and B, the Centers for Disease Control and Prevention, and NASA satellite–acquired radiance data.

The data were averaged for the years 2012-2018 and states divided into five groups based on average nighttime light intensity.

The darkest states were Montana, Wyoming, South Dakota, Idaho, Maine, New Mexico, Vermont, Oregon, Utah, and Nevada. The brightest states were Indiana, Illinois, Florida, Ohio, Massachusetts, Connecticut, Maryland, Delaware, Rhode Island, and New Jersey.

Analysis of variance revealed a significant difference in Alzheimer’s disease prevalence between state groups (P < .0001). Multiple comparisons testing also showed that states with the lowest average nighttime light had significantly different Alzheimer’s disease prevalence than those with higher intensity.

The same positive relationship was observed when each year was assessed individually and at the county level, using data from 45 counties and the District of Columbia.
 

Strong Association

The investigators also found that state average nighttime light intensity is significantly associated with Alzheimer’s disease prevalence (P = .006). This effect was seen across all ages, sexes, and races except Asian Pacific Island, the latter possibly related to statistical power, the authors said.

When known or proposed risk factors for Alzheimer’s disease were added to the model, atrial fibrillation, diabetes, hyperlipidemia, hypertension, and stroke had a stronger association with Alzheimer’s disease than average nighttime light intensity.

Nighttime light intensity, however, was more strongly associated with Alzheimer’s disease prevalence than alcohol abuse, chronic kidney disease, depression, heart failure, and obesity.

Moreover, in people younger than 65 years, nighttime light pollution had a stronger association with Alzheimer’s disease prevalence than all other risk factors (P = .007).

The mechanism behind this increased vulnerability is unclear, but there may be an interplay between genetic susceptibility of an individual and how they respond to light, Dr. Voigt-Zuwala suggested.

“APOE4 is the genotype most highly associated with Alzheimer’s disease risk, and maybe the people who have that genotype are just more sensitive to the effects of light exposure at night, more sensitive to circadian rhythm disruption,” she said.

The authors noted that additional research is needed but suggested light pollution may also influence Alzheimer’s disease through sleep disruption, which can promote inflammation, activate microglia and astrocytes, and negatively alter the clearance of amyloid beta, and by decreasing the levels of brain-derived neurotrophic factor.
 

Are We Measuring the Right Light?

“It’s a good article and it’s got a good message, but I have some caveats to that,” said George C. Brainard, PhD, director, Light Research Program, Thomas Jefferson University in Philadelphia, Pennsylvania, and a pioneer in the study of how light affects biology including breast cancer in night-shift workers.

The biggest caveat, and one acknowledged by the authors, is that the study didn’t measure indoor light exposure and relied instead on satellite imaging.

“They’re very striking images, but they may not be particularly relevant. And here’s why: People don’t live outdoors all night,” Dr. Brainard said.

Instead, people spend much of their time at night indoors where they’re exposed to lighting in the home and from smartphones, laptops, and television screens.

“It doesn’t invalidate their work. It’s an important advancement, an important observation,” Dr. Brainard said. “But the important thing really is to find out what is the population exposed to that triggers this response, and it’s probably indoor lighting related to the amount and physical characteristics of indoor lighting. It doesn’t mean outdoor lighting can’t play a role. It certainly can.”

Reached for comment, Erik Musiek, MD, PhD, a professor of neurology whose lab at Washington University School of Medicine in St. Louis, Missouri, has extensively studied circadian clock disruption and Alzheimer’s disease pathology in the brain, said the study provides a 10,000-foot view of the issue.

For example, the study was not designed to detect whether people living in high light pollution areas are actually experiencing more outdoor light at night and if risk factors such as air pollution and low socioeconomic status may correlate with these areas.

“Most of what we worry about is do people have lights on in the house, do they have their TV on, their screens up to their face late at night? This can’t tell us about that,” Dr. Musiek said. “But on the other hand, this kind of light exposure is something that public policy can affect.”

“It’s hard to control people’s personal habits nor should we probably, but we can control what types of bulbs you put into streetlights, how bright they are, and where you put lighting in a public place,” he added. “So I do think there’s value there.”

At least 19 states, the District of Columbia, and Puerto Rico have laws in place to reduce light pollution, with the majority doing so to promote energy conservation, public safety, aesthetic interests, or astronomical research, according to the National Conference of State Legislatures.

To respond to some of the limitations in this study, Dr. Voigt-Zuwala is writing a grant application for a new project to look at both indoor and outdoor light exposure on an individual level.

“This is what I’ve been wanting to study for a long time, and this study is just sort of the stepping stone, the proof of concept that this is something we need to be investigating,” she said.

Dr. Voigt-Zuwala reported RO1 and R24 grants from the National Institutes of Health (NIH), one coauthor reported an NIH R24 grant; another reported having no conflicts of interest. Dr. Brainard reported having no relevant conflicts of interest. Dr. Musiek reported research funding from Eisai Pharmaceuticals.

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