Alzheimer's & Cognition

PHOENIX – Artificial intelligence (AI) is poised to dramatically alter health care, and it presents opportunities for increased production and automation of some tasks. However, it is prone to error and ‘hallucinations’ despite an authoritative tone, so its conclusions must be verified.

Those were some of the messages from a talk by John Morren, MD, an associate professor of neurology at Case Western Reserve University, Cleveland, who spoke about AI at the 2023 annual meeting of the American Association for Neuromuscular and Electrodiagnostic Medicine (AANEM).

He encouraged attendees to get involved in the conversation of AI, because it is here to stay and will have a big impact on health care. “If we’re not around the table making decisions, decisions will be made for us in our absence and won’t be in our favor,” said Dr. Morren.

He started out his talk by asking if anyone in the room had used AI. After about half raised their hands, he countered that nearly everyone likely had. Voice assistants like SIRI and Alexa, social media with curated feeds, online shopping tools that provide product suggestions, and content recommendations from streaming services like Netflix all rely on AI technology.

Within medicine, AI is already playing a role in various fields, including medical imaging, disease diagnosis, drug discovery and development, predictive analytics, personalized medicine, telemedicine, and health care management.

It also has potential to be used on the job. For example, ChatGPT can generate and refine conversations towards a specific length, format, style, and level of detail. Alternatives include Bing AI from Microsoft, Bard AI from Google, Writesonic, Copy.ai, SpinBot, HIX.AI, and Chatsonic.

Specific to medicine, Consensus is a search engine that uses AI to search for, summarize, and synthesize studies from peer-reviewed literature.
 

Trust, but verify

Dr. Morren presented some specific use cases, including patient education and responses to patient inquiries, as well as generating letters to insurance companies appealing denial of coverage claims. He also showed an example where he asked Bing AI to explain to a patient, at a sixth- to seventh-grade reading level, the red-flag symptoms of myasthenic crisis.

AI can generate summaries of clinical evidence of previous studies. Asked by this reporter how to trust the accuracies of the summaries if the user hasn’t thoroughly read the papers, he acknowledged the imperfection of AI. “I would say that if you’re going to make a decision that you would not have made normally based on the summary that it’s giving, if you can find the fact that you’re anchoring the decision on, go into the article yourself and make sure that it’s well vetted. The AI is just good to tap you on your shoulder and say, ‘hey, just consider this.’ That’s all it is. You should always trust, but verify. If the AI is forcing you to say something new that you would not say, maybe don’t do it – or at least research it to know that it’s the truth and then you elevate yourself and get yourself to the next level.”
 

Limitations

The need to verify can create its own burden, according to one attendee. “I often find I end up spending more time verifying [what ChatGPT has provided]. This seems to take more time than a traditional way of going to PubMed or UpToDate or any of the other human generated consensus way,” he said.

Dr. Morren replied that he wouldn’t recommend using ChatGPT to query medical literature. Instead he recommended Consensus, which only searches the peer-reviewed medical literature.

Another key limitation is that most AI programs are date limited: For example, ChatGPT doesn’t include information after September 2021, though this may change with paid subscriptions. He also starkly warned the audience to never enter sensitive information, including patient identifiers.

There are legal and ethical considerations to AI. Dr. Morren warned against overreliance on AI, as this could undermine compassion and lead to erosion of trust, which makes it important to disclose any use of AI-generated content.

Another attendee raised concerns that AI may be generating research content, including slides for presentations, abstracts, titles, or article text. Dr. Morren said that some organizations, such as the International Committee of Medical Journal Editors, have incorporated AI in their recommendations, stating that authors should disclose any contributions of AI to their publications. However, there is little that can be done to identify AI-generated content, leaving it up to the honor code.

Asked to make predictions about how AI will evolve in the clinic over the next 2-3 years, Dr. Morren suggested that it will likely be embedded in electronic medical records. He anticipated that it will save physicians time so that they can spend more time interacting directly with patients. He quoted Eric Topol, MD, professor of medicine at Scripps Research Translational Institute, La Jolla, Calif., as saying that AI could save 20% of a physician’s time, which could be spent with patients. Dr. Morren saw it differently. “I know where that 20% of time liberated is going to go. I’m going to see 20% more patients. I’m a realist,” he said, to audience laughter.

He also predicted that AI will be found in wearables and devices, allowing health care to expand into the patient’s home in real time. “A lot of what we’re wearing is going to be an extension of the doctor’s office,” he said.

For those hoping for more guidance, Dr. Morren noted that he is the chairman of the professional practice committee of AANEM, and the group will be putting out a position statement within the next couple of months. “It will be a little bit of a blueprint for the path going forward. There are specific things that need to be done. In research, for example, you have to ensure that datasets are diverse enough. To do that we need to have inter-institutional collaboration. We have to ensure patient privacy. Consent for this needs to be a little more explicit because this is a novel area. Those are things that need to be stipulated and ratified through a task force.”

Dr. Morren has no relevant financial disclosures.

PHOENIX – Artificial intelligence (AI) is poised to dramatically alter health care, and it presents opportunities for increased production and automation of some tasks. However, it is prone to error and ‘hallucinations’ despite an authoritative tone, so its conclusions must be verified.

Those were some of the messages from a talk by John Morren, MD, an associate professor of neurology at Case Western Reserve University, Cleveland, who spoke about AI at the 2023 annual meeting of the American Association for Neuromuscular and Electrodiagnostic Medicine (AANEM).

He encouraged attendees to get involved in the conversation of AI, because it is here to stay and will have a big impact on health care. “If we’re not around the table making decisions, decisions will be made for us in our absence and won’t be in our favor,” said Dr. Morren.

He started out his talk by asking if anyone in the room had used AI. After about half raised their hands, he countered that nearly everyone likely had. Voice assistants like SIRI and Alexa, social media with curated feeds, online shopping tools that provide product suggestions, and content recommendations from streaming services like Netflix all rely on AI technology.

Within medicine, AI is already playing a role in various fields, including medical imaging, disease diagnosis, drug discovery and development, predictive analytics, personalized medicine, telemedicine, and health care management.

It also has potential to be used on the job. For example, ChatGPT can generate and refine conversations towards a specific length, format, style, and level of detail. Alternatives include Bing AI from Microsoft, Bard AI from Google, Writesonic, Copy.ai, SpinBot, HIX.AI, and Chatsonic.

Specific to medicine, Consensus is a search engine that uses AI to search for, summarize, and synthesize studies from peer-reviewed literature.
 

Trust, but verify

Dr. Morren presented some specific use cases, including patient education and responses to patient inquiries, as well as generating letters to insurance companies appealing denial of coverage claims. He also showed an example where he asked Bing AI to explain to a patient, at a sixth- to seventh-grade reading level, the red-flag symptoms of myasthenic crisis.

AI can generate summaries of clinical evidence of previous studies. Asked by this reporter how to trust the accuracies of the summaries if the user hasn’t thoroughly read the papers, he acknowledged the imperfection of AI. “I would say that if you’re going to make a decision that you would not have made normally based on the summary that it’s giving, if you can find the fact that you’re anchoring the decision on, go into the article yourself and make sure that it’s well vetted. The AI is just good to tap you on your shoulder and say, ‘hey, just consider this.’ That’s all it is. You should always trust, but verify. If the AI is forcing you to say something new that you would not say, maybe don’t do it – or at least research it to know that it’s the truth and then you elevate yourself and get yourself to the next level.”
 

Limitations

The need to verify can create its own burden, according to one attendee. “I often find I end up spending more time verifying [what ChatGPT has provided]. This seems to take more time than a traditional way of going to PubMed or UpToDate or any of the other human generated consensus way,” he said.

Dr. Morren replied that he wouldn’t recommend using ChatGPT to query medical literature. Instead he recommended Consensus, which only searches the peer-reviewed medical literature.

Another key limitation is that most AI programs are date limited: For example, ChatGPT doesn’t include information after September 2021, though this may change with paid subscriptions. He also starkly warned the audience to never enter sensitive information, including patient identifiers.

There are legal and ethical considerations to AI. Dr. Morren warned against overreliance on AI, as this could undermine compassion and lead to erosion of trust, which makes it important to disclose any use of AI-generated content.

Another attendee raised concerns that AI may be generating research content, including slides for presentations, abstracts, titles, or article text. Dr. Morren said that some organizations, such as the International Committee of Medical Journal Editors, have incorporated AI in their recommendations, stating that authors should disclose any contributions of AI to their publications. However, there is little that can be done to identify AI-generated content, leaving it up to the honor code.

Asked to make predictions about how AI will evolve in the clinic over the next 2-3 years, Dr. Morren suggested that it will likely be embedded in electronic medical records. He anticipated that it will save physicians time so that they can spend more time interacting directly with patients. He quoted Eric Topol, MD, professor of medicine at Scripps Research Translational Institute, La Jolla, Calif., as saying that AI could save 20% of a physician’s time, which could be spent with patients. Dr. Morren saw it differently. “I know where that 20% of time liberated is going to go. I’m going to see 20% more patients. I’m a realist,” he said, to audience laughter.

He also predicted that AI will be found in wearables and devices, allowing health care to expand into the patient’s home in real time. “A lot of what we’re wearing is going to be an extension of the doctor’s office,” he said.

For those hoping for more guidance, Dr. Morren noted that he is the chairman of the professional practice committee of AANEM, and the group will be putting out a position statement within the next couple of months. “It will be a little bit of a blueprint for the path going forward. There are specific things that need to be done. In research, for example, you have to ensure that datasets are diverse enough. To do that we need to have inter-institutional collaboration. We have to ensure patient privacy. Consent for this needs to be a little more explicit because this is a novel area. Those are things that need to be stipulated and ratified through a task force.”

Dr. Morren has no relevant financial disclosures.

PHOENIX – Artificial intelligence (AI) is poised to dramatically alter health care, and it presents opportunities for increased production and automation of some tasks. However, it is prone to error and ‘hallucinations’ despite an authoritative tone, so its conclusions must be verified.

Those were some of the messages from a talk by John Morren, MD, an associate professor of neurology at Case Western Reserve University, Cleveland, who spoke about AI at the 2023 annual meeting of the American Association for Neuromuscular and Electrodiagnostic Medicine (AANEM).

He encouraged attendees to get involved in the conversation of AI, because it is here to stay and will have a big impact on health care. “If we’re not around the table making decisions, decisions will be made for us in our absence and won’t be in our favor,” said Dr. Morren.

He started out his talk by asking if anyone in the room had used AI. After about half raised their hands, he countered that nearly everyone likely had. Voice assistants like SIRI and Alexa, social media with curated feeds, online shopping tools that provide product suggestions, and content recommendations from streaming services like Netflix all rely on AI technology.

Within medicine, AI is already playing a role in various fields, including medical imaging, disease diagnosis, drug discovery and development, predictive analytics, personalized medicine, telemedicine, and health care management.

It also has potential to be used on the job. For example, ChatGPT can generate and refine conversations towards a specific length, format, style, and level of detail. Alternatives include Bing AI from Microsoft, Bard AI from Google, Writesonic, Copy.ai, SpinBot, HIX.AI, and Chatsonic.

Specific to medicine, Consensus is a search engine that uses AI to search for, summarize, and synthesize studies from peer-reviewed literature.
 

Trust, but verify

Dr. Morren presented some specific use cases, including patient education and responses to patient inquiries, as well as generating letters to insurance companies appealing denial of coverage claims. He also showed an example where he asked Bing AI to explain to a patient, at a sixth- to seventh-grade reading level, the red-flag symptoms of myasthenic crisis.

AI can generate summaries of clinical evidence of previous studies. Asked by this reporter how to trust the accuracies of the summaries if the user hasn’t thoroughly read the papers, he acknowledged the imperfection of AI. “I would say that if you’re going to make a decision that you would not have made normally based on the summary that it’s giving, if you can find the fact that you’re anchoring the decision on, go into the article yourself and make sure that it’s well vetted. The AI is just good to tap you on your shoulder and say, ‘hey, just consider this.’ That’s all it is. You should always trust, but verify. If the AI is forcing you to say something new that you would not say, maybe don’t do it – or at least research it to know that it’s the truth and then you elevate yourself and get yourself to the next level.”
 

Limitations

The need to verify can create its own burden, according to one attendee. “I often find I end up spending more time verifying [what ChatGPT has provided]. This seems to take more time than a traditional way of going to PubMed or UpToDate or any of the other human generated consensus way,” he said.

Dr. Morren replied that he wouldn’t recommend using ChatGPT to query medical literature. Instead he recommended Consensus, which only searches the peer-reviewed medical literature.

Another key limitation is that most AI programs are date limited: For example, ChatGPT doesn’t include information after September 2021, though this may change with paid subscriptions. He also starkly warned the audience to never enter sensitive information, including patient identifiers.

There are legal and ethical considerations to AI. Dr. Morren warned against overreliance on AI, as this could undermine compassion and lead to erosion of trust, which makes it important to disclose any use of AI-generated content.

Another attendee raised concerns that AI may be generating research content, including slides for presentations, abstracts, titles, or article text. Dr. Morren said that some organizations, such as the International Committee of Medical Journal Editors, have incorporated AI in their recommendations, stating that authors should disclose any contributions of AI to their publications. However, there is little that can be done to identify AI-generated content, leaving it up to the honor code.

Asked to make predictions about how AI will evolve in the clinic over the next 2-3 years, Dr. Morren suggested that it will likely be embedded in electronic medical records. He anticipated that it will save physicians time so that they can spend more time interacting directly with patients. He quoted Eric Topol, MD, professor of medicine at Scripps Research Translational Institute, La Jolla, Calif., as saying that AI could save 20% of a physician’s time, which could be spent with patients. Dr. Morren saw it differently. “I know where that 20% of time liberated is going to go. I’m going to see 20% more patients. I’m a realist,” he said, to audience laughter.

He also predicted that AI will be found in wearables and devices, allowing health care to expand into the patient’s home in real time. “A lot of what we’re wearing is going to be an extension of the doctor’s office,” he said.

For those hoping for more guidance, Dr. Morren noted that he is the chairman of the professional practice committee of AANEM, and the group will be putting out a position statement within the next couple of months. “It will be a little bit of a blueprint for the path going forward. There are specific things that need to be done. In research, for example, you have to ensure that datasets are diverse enough. To do that we need to have inter-institutional collaboration. We have to ensure patient privacy. Consent for this needs to be a little more explicit because this is a novel area. Those are things that need to be stipulated and ratified through a task force.”

Dr. Morren has no relevant financial disclosures.

Results of a trial using an intensive, 4-year program aimed at blood pressure lowering showed that intervention reduced not only blood pressure, but also significantly reduced the risk of total dementia over that period.

All-cause dementia, the primary outcome, was significantly reduced by 15% in the intervention group, compared with usual care, and cognitive impairment no dementia (CIND), a secondary outcome, was also significantly reduced by 16%.

“Blood pressure reduction is effective in reducing the risk of dementia in patients with hypertension,” concluded Jiang He, MD, PhD, professor of epidemiology and medicine and director of Tulane University’s Translational Science Institute, New Orleans. “This proven, effective intervention should be widely scaled up to reduce the global burden of dementia.”

He presented these results from the China Rural Hypertension Control Project (CRHCP) at the annual scientific sessions of the American Heart Association.

Target organ damage

Keith Ferdinand, MD, also from Tulane University, commented on the findings during a press conference at the meeting, noting that the result “opens our opportunity to recognize that the target organ damage of hypertension also now includes dementia.”

The researchers were able to “rigorously lower blood pressure from 157 to 127.6 in the intervention, 155 to 147 in the controls – 22 mg Hg – and if you look at the P values for all the various outcomes, they were very robust,” Dr. Ferdinand said.

Another interesting feature about the strategy used in this trial is that “this was true team-based care,” he pointed out. The trained interventionists in the study, called village doctors, collaborated with primary care physicians and initiated medications. “They stayed on a simple treatment protocol, and they were able to assist patients to ensure they had free medications, health coaching for lifestyle, home blood pressure measurement, and ensuring adherence.”

So, Dr. Ferdinand added, “one of the questions is whether this is a model we can use in other places around the globe, in places with low resources, and in the United States in disadvantaged populations.”

Public health priority

It’s estimated that the global number of those living with dementia will increase from 57.4 million in 2019 to 152.8 million by 2050, Dr. He said. “In the absence of curative treatment, the primary prevention of dementia through risk factor reduction, such as blood pressure lowering, becomes a public health priority.”

Previous randomized trials have lacked sample size and duration but have reported a nonsignificant reduction in dementia associated with antihypertensive treatment in patients with hypertension or a history of stroke, Dr. He noted.

This new trial aimed to test the effectiveness of intensive BP intervention to reduce the risk of all-cause dementia and cognitive impairment over a 48-month intervention period versus usual care.

It was an open-label, blinded-endpoint, cluster-randomized trial, and included 33,995 individual patients from 325 villages in China, aged 40 years and older, with untreated hypertension. The villages were randomly assigned to an intervention group or usual care, stratified by province, county, and township.

Patients were eligible if they had mean untreated systolic BP greater than 140 mm Hg and/or diastolic BP greater than 90 mm Hg or mean treated systolic BP of greater than 130 and/or diastolic greater than 80 mm Hg. Patients with a history of cardiovascular disease, chronic kidney disease, or diabetes and a mean systolic BP greater than 130 mm Hg and/or diastolic BP greater than 80 mm Hg from six measures on two different days were also eligible.

All were enrolled in the China New Rural Cooperative Medical Scheme, which covers 99% of rural residents for health care services, Dr. He noted.

The intervention was a simple stepped-care protocol for hypertension treatment, aimed at achieving a target systolic BP of less than 130 mm Hg and diastolic of less than 80 mm Hg.

Village doctors started and titrated antihypertensive treatment based on a protocol and were able to deliver discounted and free medications to patients. They also did health coaching on lifestyle modification and adherence to medication, and instructed patients on home BP monitoring.

Patients were provided training, supervision, and consultation by primary care physicians and hypertension specialists.

At the month 48 follow-up visit, the participants were assessed by neurologists who were blinded to randomization assignments. Neurologists did a variety of tests and assessments including collecting data on the patient’s medical and psychiatric history and risk factors for dementia, as well as neurologic assessment using the Mini-Mental State Examination, the Functional Activities Questionnaire, and the Quick Dementia Rating System.

The primary outcome was all-cause dementia, defined according to recommendations from the National Institute on Aging–Alzheimer’s Association work groups on diagnostic guidelines for Alzheimer’s disease.

Secondary outcomes included CIND, a composite outcome of dementia or CIND, and a composite of dementia or deaths.

The final diagnosis of all-cause dementia or CIND was made by an expert adjudication panel blinded to the intervention assignment.

At 48 months, 91.3% of patients completed the follow-up for clinical outcomes. Participants were an average of 63 years of age, 61% were female, and 23% had less than a primary school education, Dr. He noted.

The net group differences in systolic and diastolic BP reduction were 22 and 9.3 mm Hg, respectively (P < .0001).

Significant differences were also seen between the groups in the primary outcome of all-cause dementia, as well as secondary outcomes of CIND, dementia or cognitive impairment, or dementia or deaths.

Serious adverse events were more common in the usual care group, and there was no difference between groups in the occurrence of falls or syncope.

The effect was consistent across subgroups, Dr. He said, including age, sex, education, cigarette smoking, body mass index, systolic BP, and fasting plasma glucose at baseline.

First definitive evidence

Invited discussant for the trial, Daniel W. Jones, MD, University of Mississippi Medical Center, Jackson, and past president of the AHA, pointed out that previous results from CRHCP on cardiovascular outcomes, reported earlier in 2023 in The Lancet, showed that, similar to results of the large SPRINT trial, lowering systolic BP to a goal of less than 130 mm Hg reduced a composite endpoint of MI, stroke, heart failure requiring hospitalization, and cardiovascular disease death over the 36-month follow-up.

The SPRINT findings also suggested a possible reduction in dementia, Dr. Jones said.

Now, in these new CRHCP results, “there was a clear benefit for intensive BP control in reducing risk for dementia and cognitive dysfunction,” he said. “This is, importantly, the first definitive evidence of dementia risk reduction demonstrated in a randomized controlled clinical trial. This outcome supports observational data that shows a strong relationship between BP and dementia.”

Since it is the first of its kind though, replication of the results will be important, he noted.

The study also showed that the intervention, using minimally trained village doctors, sustained BP control for 48 months. “This model could be used in any setting with modifications, including in the United States,” Dr. Jones said.

The study was supported by the Ministry of Science and Technology of China; U.S. investigators did not receive financial support from this study. The researchers and Dr. Jones disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

Results of a trial using an intensive, 4-year program aimed at blood pressure lowering showed that intervention reduced not only blood pressure, but also significantly reduced the risk of total dementia over that period.

All-cause dementia, the primary outcome, was significantly reduced by 15% in the intervention group, compared with usual care, and cognitive impairment no dementia (CIND), a secondary outcome, was also significantly reduced by 16%.

“Blood pressure reduction is effective in reducing the risk of dementia in patients with hypertension,” concluded Jiang He, MD, PhD, professor of epidemiology and medicine and director of Tulane University’s Translational Science Institute, New Orleans. “This proven, effective intervention should be widely scaled up to reduce the global burden of dementia.”

He presented these results from the China Rural Hypertension Control Project (CRHCP) at the annual scientific sessions of the American Heart Association.

Target organ damage

Keith Ferdinand, MD, also from Tulane University, commented on the findings during a press conference at the meeting, noting that the result “opens our opportunity to recognize that the target organ damage of hypertension also now includes dementia.”

The researchers were able to “rigorously lower blood pressure from 157 to 127.6 in the intervention, 155 to 147 in the controls – 22 mg Hg – and if you look at the P values for all the various outcomes, they were very robust,” Dr. Ferdinand said.

Another interesting feature about the strategy used in this trial is that “this was true team-based care,” he pointed out. The trained interventionists in the study, called village doctors, collaborated with primary care physicians and initiated medications. “They stayed on a simple treatment protocol, and they were able to assist patients to ensure they had free medications, health coaching for lifestyle, home blood pressure measurement, and ensuring adherence.”

So, Dr. Ferdinand added, “one of the questions is whether this is a model we can use in other places around the globe, in places with low resources, and in the United States in disadvantaged populations.”

Public health priority

It’s estimated that the global number of those living with dementia will increase from 57.4 million in 2019 to 152.8 million by 2050, Dr. He said. “In the absence of curative treatment, the primary prevention of dementia through risk factor reduction, such as blood pressure lowering, becomes a public health priority.”

Previous randomized trials have lacked sample size and duration but have reported a nonsignificant reduction in dementia associated with antihypertensive treatment in patients with hypertension or a history of stroke, Dr. He noted.

This new trial aimed to test the effectiveness of intensive BP intervention to reduce the risk of all-cause dementia and cognitive impairment over a 48-month intervention period versus usual care.

It was an open-label, blinded-endpoint, cluster-randomized trial, and included 33,995 individual patients from 325 villages in China, aged 40 years and older, with untreated hypertension. The villages were randomly assigned to an intervention group or usual care, stratified by province, county, and township.

Patients were eligible if they had mean untreated systolic BP greater than 140 mm Hg and/or diastolic BP greater than 90 mm Hg or mean treated systolic BP of greater than 130 and/or diastolic greater than 80 mm Hg. Patients with a history of cardiovascular disease, chronic kidney disease, or diabetes and a mean systolic BP greater than 130 mm Hg and/or diastolic BP greater than 80 mm Hg from six measures on two different days were also eligible.

All were enrolled in the China New Rural Cooperative Medical Scheme, which covers 99% of rural residents for health care services, Dr. He noted.

The intervention was a simple stepped-care protocol for hypertension treatment, aimed at achieving a target systolic BP of less than 130 mm Hg and diastolic of less than 80 mm Hg.

Village doctors started and titrated antihypertensive treatment based on a protocol and were able to deliver discounted and free medications to patients. They also did health coaching on lifestyle modification and adherence to medication, and instructed patients on home BP monitoring.

Patients were provided training, supervision, and consultation by primary care physicians and hypertension specialists.

At the month 48 follow-up visit, the participants were assessed by neurologists who were blinded to randomization assignments. Neurologists did a variety of tests and assessments including collecting data on the patient’s medical and psychiatric history and risk factors for dementia, as well as neurologic assessment using the Mini-Mental State Examination, the Functional Activities Questionnaire, and the Quick Dementia Rating System.

The primary outcome was all-cause dementia, defined according to recommendations from the National Institute on Aging–Alzheimer’s Association work groups on diagnostic guidelines for Alzheimer’s disease.

Secondary outcomes included CIND, a composite outcome of dementia or CIND, and a composite of dementia or deaths.

The final diagnosis of all-cause dementia or CIND was made by an expert adjudication panel blinded to the intervention assignment.

At 48 months, 91.3% of patients completed the follow-up for clinical outcomes. Participants were an average of 63 years of age, 61% were female, and 23% had less than a primary school education, Dr. He noted.

The net group differences in systolic and diastolic BP reduction were 22 and 9.3 mm Hg, respectively (P < .0001).

Significant differences were also seen between the groups in the primary outcome of all-cause dementia, as well as secondary outcomes of CIND, dementia or cognitive impairment, or dementia or deaths.

Serious adverse events were more common in the usual care group, and there was no difference between groups in the occurrence of falls or syncope.

The effect was consistent across subgroups, Dr. He said, including age, sex, education, cigarette smoking, body mass index, systolic BP, and fasting plasma glucose at baseline.

First definitive evidence

Invited discussant for the trial, Daniel W. Jones, MD, University of Mississippi Medical Center, Jackson, and past president of the AHA, pointed out that previous results from CRHCP on cardiovascular outcomes, reported earlier in 2023 in The Lancet, showed that, similar to results of the large SPRINT trial, lowering systolic BP to a goal of less than 130 mm Hg reduced a composite endpoint of MI, stroke, heart failure requiring hospitalization, and cardiovascular disease death over the 36-month follow-up.

The SPRINT findings also suggested a possible reduction in dementia, Dr. Jones said.

Now, in these new CRHCP results, “there was a clear benefit for intensive BP control in reducing risk for dementia and cognitive dysfunction,” he said. “This is, importantly, the first definitive evidence of dementia risk reduction demonstrated in a randomized controlled clinical trial. This outcome supports observational data that shows a strong relationship between BP and dementia.”

Since it is the first of its kind though, replication of the results will be important, he noted.

The study also showed that the intervention, using minimally trained village doctors, sustained BP control for 48 months. “This model could be used in any setting with modifications, including in the United States,” Dr. Jones said.

The study was supported by the Ministry of Science and Technology of China; U.S. investigators did not receive financial support from this study. The researchers and Dr. Jones disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

Results of a trial using an intensive, 4-year program aimed at blood pressure lowering showed that intervention reduced not only blood pressure, but also significantly reduced the risk of total dementia over that period.

All-cause dementia, the primary outcome, was significantly reduced by 15% in the intervention group, compared with usual care, and cognitive impairment no dementia (CIND), a secondary outcome, was also significantly reduced by 16%.

“Blood pressure reduction is effective in reducing the risk of dementia in patients with hypertension,” concluded Jiang He, MD, PhD, professor of epidemiology and medicine and director of Tulane University’s Translational Science Institute, New Orleans. “This proven, effective intervention should be widely scaled up to reduce the global burden of dementia.”

He presented these results from the China Rural Hypertension Control Project (CRHCP) at the annual scientific sessions of the American Heart Association.

Target organ damage

Keith Ferdinand, MD, also from Tulane University, commented on the findings during a press conference at the meeting, noting that the result “opens our opportunity to recognize that the target organ damage of hypertension also now includes dementia.”

The researchers were able to “rigorously lower blood pressure from 157 to 127.6 in the intervention, 155 to 147 in the controls – 22 mg Hg – and if you look at the P values for all the various outcomes, they were very robust,” Dr. Ferdinand said.

Another interesting feature about the strategy used in this trial is that “this was true team-based care,” he pointed out. The trained interventionists in the study, called village doctors, collaborated with primary care physicians and initiated medications. “They stayed on a simple treatment protocol, and they were able to assist patients to ensure they had free medications, health coaching for lifestyle, home blood pressure measurement, and ensuring adherence.”

So, Dr. Ferdinand added, “one of the questions is whether this is a model we can use in other places around the globe, in places with low resources, and in the United States in disadvantaged populations.”

Public health priority

It’s estimated that the global number of those living with dementia will increase from 57.4 million in 2019 to 152.8 million by 2050, Dr. He said. “In the absence of curative treatment, the primary prevention of dementia through risk factor reduction, such as blood pressure lowering, becomes a public health priority.”

Previous randomized trials have lacked sample size and duration but have reported a nonsignificant reduction in dementia associated with antihypertensive treatment in patients with hypertension or a history of stroke, Dr. He noted.

This new trial aimed to test the effectiveness of intensive BP intervention to reduce the risk of all-cause dementia and cognitive impairment over a 48-month intervention period versus usual care.

It was an open-label, blinded-endpoint, cluster-randomized trial, and included 33,995 individual patients from 325 villages in China, aged 40 years and older, with untreated hypertension. The villages were randomly assigned to an intervention group or usual care, stratified by province, county, and township.

Patients were eligible if they had mean untreated systolic BP greater than 140 mm Hg and/or diastolic BP greater than 90 mm Hg or mean treated systolic BP of greater than 130 and/or diastolic greater than 80 mm Hg. Patients with a history of cardiovascular disease, chronic kidney disease, or diabetes and a mean systolic BP greater than 130 mm Hg and/or diastolic BP greater than 80 mm Hg from six measures on two different days were also eligible.

All were enrolled in the China New Rural Cooperative Medical Scheme, which covers 99% of rural residents for health care services, Dr. He noted.

The intervention was a simple stepped-care protocol for hypertension treatment, aimed at achieving a target systolic BP of less than 130 mm Hg and diastolic of less than 80 mm Hg.

Village doctors started and titrated antihypertensive treatment based on a protocol and were able to deliver discounted and free medications to patients. They also did health coaching on lifestyle modification and adherence to medication, and instructed patients on home BP monitoring.

Patients were provided training, supervision, and consultation by primary care physicians and hypertension specialists.

At the month 48 follow-up visit, the participants were assessed by neurologists who were blinded to randomization assignments. Neurologists did a variety of tests and assessments including collecting data on the patient’s medical and psychiatric history and risk factors for dementia, as well as neurologic assessment using the Mini-Mental State Examination, the Functional Activities Questionnaire, and the Quick Dementia Rating System.

The primary outcome was all-cause dementia, defined according to recommendations from the National Institute on Aging–Alzheimer’s Association work groups on diagnostic guidelines for Alzheimer’s disease.

Secondary outcomes included CIND, a composite outcome of dementia or CIND, and a composite of dementia or deaths.

The final diagnosis of all-cause dementia or CIND was made by an expert adjudication panel blinded to the intervention assignment.

At 48 months, 91.3% of patients completed the follow-up for clinical outcomes. Participants were an average of 63 years of age, 61% were female, and 23% had less than a primary school education, Dr. He noted.

The net group differences in systolic and diastolic BP reduction were 22 and 9.3 mm Hg, respectively (P < .0001).

Significant differences were also seen between the groups in the primary outcome of all-cause dementia, as well as secondary outcomes of CIND, dementia or cognitive impairment, or dementia or deaths.

Serious adverse events were more common in the usual care group, and there was no difference between groups in the occurrence of falls or syncope.

The effect was consistent across subgroups, Dr. He said, including age, sex, education, cigarette smoking, body mass index, systolic BP, and fasting plasma glucose at baseline.

First definitive evidence

Invited discussant for the trial, Daniel W. Jones, MD, University of Mississippi Medical Center, Jackson, and past president of the AHA, pointed out that previous results from CRHCP on cardiovascular outcomes, reported earlier in 2023 in The Lancet, showed that, similar to results of the large SPRINT trial, lowering systolic BP to a goal of less than 130 mm Hg reduced a composite endpoint of MI, stroke, heart failure requiring hospitalization, and cardiovascular disease death over the 36-month follow-up.

The SPRINT findings also suggested a possible reduction in dementia, Dr. Jones said.

Now, in these new CRHCP results, “there was a clear benefit for intensive BP control in reducing risk for dementia and cognitive dysfunction,” he said. “This is, importantly, the first definitive evidence of dementia risk reduction demonstrated in a randomized controlled clinical trial. This outcome supports observational data that shows a strong relationship between BP and dementia.”

Since it is the first of its kind though, replication of the results will be important, he noted.

The study also showed that the intervention, using minimally trained village doctors, sustained BP control for 48 months. “This model could be used in any setting with modifications, including in the United States,” Dr. Jones said.

The study was supported by the Ministry of Science and Technology of China; U.S. investigators did not receive financial support from this study. The researchers and Dr. Jones disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

This patient's symptoms go beyond just memory problems: She has difficulty with daily tasks, shows behavioral changes, and has significant communication difficulties — symptoms not found in mild cognitive impairment. While the patient has some behavioral changes, she does not exhibit the pronounced personality changes typical of frontotemporal dementia. Finally, the patient's cognitive decline is gradual and consistent without the stepwise progression typical of vascular dementia. Given the comprehensive presentation of the patient's symptoms and the results of her clinical investigations, middle-stage Alzheimer's disease is the most fitting diagnosis.

Alzheimer's disease is a progressive and irreversible brain disorder that affects memory, behavior, and cognitive skills. This condition causes the degeneration and death of brain cells, leading to various cognitive issues. Alzheimer's disease is the most common cause of dementia and accounts for 60%-80% of dementia cases. Although the exact cause is unknown, it is believed to result from genetic, lifestyle, and environmental factors. Alzheimer's disease progresses through stages — mild (early stage), moderate (middle stage), and severe (late stage) — and each stage has different signs and symptoms.

Alzheimer's disease is commonly observed in individuals 65 years or older, as age is the most significant risk factor. Another risk factor for Alzheimer's disease is family history; individuals who have parents or siblings with Alzheimer's disease are more likely to develop the disease. The risk increases with the number of family members diagnosed with the disease. Genetics also contribute to the development of Alzheimer's disease. Genes for developing Alzheimer's disease have been classified as deterministic and risk genes, which imply that they can cause the disease or increase the risk of developing it; however, the deterministic gene, which almost guarantees the occurrence of Alzheimer's, is rare and is found in less than 1% of cases. Experiencing a head injury is also a possible risk factor for Alzheimer's disease.

Accurate diagnosis of Alzheimer's disease requires a thorough history and physical examination. Gathering information from the patient's family and caregivers is important because some patients may not be aware of their condition. It is common for Alzheimer's disease patients to experience "sundowning," which causes confusion, agitation, and behavioral issues in the evening. A comprehensive physical examination, including a detailed neurologic and mental status exam, is necessary to determine the stage of the disease and rule out other conditions. Typically, the neurologic exam of Alzheimer's disease patients is normal.

Volumetric MRI is a recent technique that allows precise measurement of changes in brain volume. In Alzheimer's disease, shrinkage in the medial temporal lobe is visible through volumetric MRI. However, hippocampal atrophy is also a normal part of age-related memory decline, which raises doubts about the appropriateness of using volumetric MRI for early detection of Alzheimer's disease. The full potential of volumetric MRI in aiding the diagnosis of Alzheimer's disease is yet to be fully established.

Alzheimer's disease has no known cure, and treatment options are limited to addressing symptoms. Currently, three types of drugs are approved for treating the moderate or severe stages of the disease: cholinesterase inhibitors, partial N-methyl D-aspartate (NMDA) antagonists, and amyloid-directed antibodies. Cholinesterase inhibitors increase acetylcholine levels, a chemical crucial for cognitive functions such as memory and learning. NMDA antagonists (memantine) blocks NMDA receptors whose overactivation is implicated in Alzheimer's disease and related to synaptic dysfunction. Antiamyloid monoclonal antibodies bind to and promote the clearance of amyloid-beta peptides, thereby reducing amyloid plaques in the brain, which are associated with Alzheimer's disease.

Jasvinder Chawla, MD, Professor of Neurology, Loyola University Medical Center, Maywood; Director, Clinical Neurophysiology Lab, Department of Neurology, Hines VA Hospital, Hines, IL.

Jasvinder Chawla, MD, has disclosed no relevant financial relationships.

Image Quizzes are fictional or fictionalized clinical scenarios intended to provide evidence-based educational takeaways.

This patient's symptoms go beyond just memory problems: She has difficulty with daily tasks, shows behavioral changes, and has significant communication difficulties — symptoms not found in mild cognitive impairment. While the patient has some behavioral changes, she does not exhibit the pronounced personality changes typical of frontotemporal dementia. Finally, the patient's cognitive decline is gradual and consistent without the stepwise progression typical of vascular dementia. Given the comprehensive presentation of the patient's symptoms and the results of her clinical investigations, middle-stage Alzheimer's disease is the most fitting diagnosis.

Alzheimer's disease is a progressive and irreversible brain disorder that affects memory, behavior, and cognitive skills. This condition causes the degeneration and death of brain cells, leading to various cognitive issues. Alzheimer's disease is the most common cause of dementia and accounts for 60%-80% of dementia cases. Although the exact cause is unknown, it is believed to result from genetic, lifestyle, and environmental factors. Alzheimer's disease progresses through stages — mild (early stage), moderate (middle stage), and severe (late stage) — and each stage has different signs and symptoms.

Alzheimer's disease is commonly observed in individuals 65 years or older, as age is the most significant risk factor. Another risk factor for Alzheimer's disease is family history; individuals who have parents or siblings with Alzheimer's disease are more likely to develop the disease. The risk increases with the number of family members diagnosed with the disease. Genetics also contribute to the development of Alzheimer's disease. Genes for developing Alzheimer's disease have been classified as deterministic and risk genes, which imply that they can cause the disease or increase the risk of developing it; however, the deterministic gene, which almost guarantees the occurrence of Alzheimer's, is rare and is found in less than 1% of cases. Experiencing a head injury is also a possible risk factor for Alzheimer's disease.

Accurate diagnosis of Alzheimer's disease requires a thorough history and physical examination. Gathering information from the patient's family and caregivers is important because some patients may not be aware of their condition. It is common for Alzheimer's disease patients to experience "sundowning," which causes confusion, agitation, and behavioral issues in the evening. A comprehensive physical examination, including a detailed neurologic and mental status exam, is necessary to determine the stage of the disease and rule out other conditions. Typically, the neurologic exam of Alzheimer's disease patients is normal.

Volumetric MRI is a recent technique that allows precise measurement of changes in brain volume. In Alzheimer's disease, shrinkage in the medial temporal lobe is visible through volumetric MRI. However, hippocampal atrophy is also a normal part of age-related memory decline, which raises doubts about the appropriateness of using volumetric MRI for early detection of Alzheimer's disease. The full potential of volumetric MRI in aiding the diagnosis of Alzheimer's disease is yet to be fully established.

Alzheimer's disease has no known cure, and treatment options are limited to addressing symptoms. Currently, three types of drugs are approved for treating the moderate or severe stages of the disease: cholinesterase inhibitors, partial N-methyl D-aspartate (NMDA) antagonists, and amyloid-directed antibodies. Cholinesterase inhibitors increase acetylcholine levels, a chemical crucial for cognitive functions such as memory and learning. NMDA antagonists (memantine) blocks NMDA receptors whose overactivation is implicated in Alzheimer's disease and related to synaptic dysfunction. Antiamyloid monoclonal antibodies bind to and promote the clearance of amyloid-beta peptides, thereby reducing amyloid plaques in the brain, which are associated with Alzheimer's disease.

Jasvinder Chawla, MD, Professor of Neurology, Loyola University Medical Center, Maywood; Director, Clinical Neurophysiology Lab, Department of Neurology, Hines VA Hospital, Hines, IL.

Jasvinder Chawla, MD, has disclosed no relevant financial relationships.

Image Quizzes are fictional or fictionalized clinical scenarios intended to provide evidence-based educational takeaways.

This patient's symptoms go beyond just memory problems: She has difficulty with daily tasks, shows behavioral changes, and has significant communication difficulties — symptoms not found in mild cognitive impairment. While the patient has some behavioral changes, she does not exhibit the pronounced personality changes typical of frontotemporal dementia. Finally, the patient's cognitive decline is gradual and consistent without the stepwise progression typical of vascular dementia. Given the comprehensive presentation of the patient's symptoms and the results of her clinical investigations, middle-stage Alzheimer's disease is the most fitting diagnosis.

Alzheimer's disease is a progressive and irreversible brain disorder that affects memory, behavior, and cognitive skills. This condition causes the degeneration and death of brain cells, leading to various cognitive issues. Alzheimer's disease is the most common cause of dementia and accounts for 60%-80% of dementia cases. Although the exact cause is unknown, it is believed to result from genetic, lifestyle, and environmental factors. Alzheimer's disease progresses through stages — mild (early stage), moderate (middle stage), and severe (late stage) — and each stage has different signs and symptoms.

Alzheimer's disease is commonly observed in individuals 65 years or older, as age is the most significant risk factor. Another risk factor for Alzheimer's disease is family history; individuals who have parents or siblings with Alzheimer's disease are more likely to develop the disease. The risk increases with the number of family members diagnosed with the disease. Genetics also contribute to the development of Alzheimer's disease. Genes for developing Alzheimer's disease have been classified as deterministic and risk genes, which imply that they can cause the disease or increase the risk of developing it; however, the deterministic gene, which almost guarantees the occurrence of Alzheimer's, is rare and is found in less than 1% of cases. Experiencing a head injury is also a possible risk factor for Alzheimer's disease.

Accurate diagnosis of Alzheimer's disease requires a thorough history and physical examination. Gathering information from the patient's family and caregivers is important because some patients may not be aware of their condition. It is common for Alzheimer's disease patients to experience "sundowning," which causes confusion, agitation, and behavioral issues in the evening. A comprehensive physical examination, including a detailed neurologic and mental status exam, is necessary to determine the stage of the disease and rule out other conditions. Typically, the neurologic exam of Alzheimer's disease patients is normal.

Volumetric MRI is a recent technique that allows precise measurement of changes in brain volume. In Alzheimer's disease, shrinkage in the medial temporal lobe is visible through volumetric MRI. However, hippocampal atrophy is also a normal part of age-related memory decline, which raises doubts about the appropriateness of using volumetric MRI for early detection of Alzheimer's disease. The full potential of volumetric MRI in aiding the diagnosis of Alzheimer's disease is yet to be fully established.

Alzheimer's disease has no known cure, and treatment options are limited to addressing symptoms. Currently, three types of drugs are approved for treating the moderate or severe stages of the disease: cholinesterase inhibitors, partial N-methyl D-aspartate (NMDA) antagonists, and amyloid-directed antibodies. Cholinesterase inhibitors increase acetylcholine levels, a chemical crucial for cognitive functions such as memory and learning. NMDA antagonists (memantine) blocks NMDA receptors whose overactivation is implicated in Alzheimer's disease and related to synaptic dysfunction. Antiamyloid monoclonal antibodies bind to and promote the clearance of amyloid-beta peptides, thereby reducing amyloid plaques in the brain, which are associated with Alzheimer's disease.

Jasvinder Chawla, MD, Professor of Neurology, Loyola University Medical Center, Maywood; Director, Clinical Neurophysiology Lab, Department of Neurology, Hines VA Hospital, Hines, IL.

Jasvinder Chawla, MD, has disclosed no relevant financial relationships.

Image Quizzes are fictional or fictionalized clinical scenarios intended to provide evidence-based educational takeaways.

BOSTON – An investigational natural killer cell (NK) therapy has shown promise in the treatment of Alzheimer’s disease, in a small phase 1 proof-of-concept clinical trial.

SNK01, being developed by NKGen Biotech, is an autologous, nongenetically modified NK cell product that has enhanced cytotoxicity and activating receptor expression.

“When we give these enhanced natural killer cells intravenously, not only do they get into the brain, but we’ve shown, through CSF biomarker data, that they reduce both amyloid and tau proteins, dramatically reducing the neuroinflammation,” said Paul Song, MD, chief executive officer of NKGen Biotech.

“Remarkably,” in the first 6 months, 90% of patients with Alzheimer’s disease demonstrated improvement or maintained stable cognitive function, based on the Alzheimer’s Disease Composite Score (ADCOMS), suggesting that SNK01 may do more than simply slow disease progression, Dr. Song said.

The findings were presented at the 16th Clinical Trials on Alzheimer’s Disease (CTAD) conference.
 

Sound rationale

NK cells are an essential part of the innate immune system that can shape the adaptive response by eliminating activated (not resting) autologous CD4+ T cells. Weak or deficient NK cells have been found to correlate with various diseases, including autoimmune diseases, and emerging data suggest an autoimmune component to Alzheimer’s disease.

The phase 1 study evaluated the safety, tolerability, and exploratory efficacy of SNK01 given intravenously in escalating doses every 3 weeks (four treatments in total).

Participants included 10 patients with Alzheimer’s disease confirmed by imaging. Five had mild Alzheimer’s disease, three had moderate Alzheimer’s disease, and two had advanced Alzheimer’s disease, based on baseline Clinical Dementia Rating–Sum of Boxes (CDR-SB) scores. Median baseline CDR-SB score was 9 (range, 4-18).

Cognitive assessments included CDR-SB, Mini-Mental State Examination (MMSE), Alzheimer’s disease Assessment Scale-Cognitive Subscale (ADAS-Cog) and ADCOMS. CSF biomarker analyses were performed at baseline and at 1 and 12 weeks after the final dose (weeks 11 and 22, respectively).

NK cells were successfully activated and expanded in all 10 patients and no treatment-related adverse events were observed.

Based on the CSF biomarker data, SNK01 crossed the blood–brain barrier and reduced CSF amyloid-beta 42/40 and pTau181 levels and neuroinflammation, as measured by glial fibrillary acid protein (GFAP), and the effects appeared to persist 12 weeks after the final dose.

The exploratory efficacy data show that, 1 week after final dose (week 11), compared with baseline, 30% of patients showed clinical improvement on the composite ADCOMS and 60% had a stable ADCOMS score; 50%-70% of patients were stable or improved on the CDR-SB, ADAS-Cog and/or MMSE.

“One patient went from a MMSE score of 14, which is moderate dementia, to 22, which is mild cognitive impairment,” said Dr. Song.

At 12 weeks after the final dose (week 22), 44%-89% of patients remained stable or improved in all cognitive scores compared with week 11; and 50% of the patients with stable ADCOMS scores at week 11 remained stable.

Based on the positive phase 1 data, the Food and Drug Administration has approved a phase 1/2a study in patients with moderate Alzheimer’s disease. “The trial will use a much higher dose and a prolonged dosing regimen and we think we’ll see even more dramatic results with more sustained higher dosing,” Dr. Song said.

Down the road, it will be interesting to see how NK cell therapy could “complement” anti-amyloid and anti-tau therapies, he added.
 

Ideal treatment approach

Commenting on this research, Shaheen Lakhan, MD, PhD, a neurologist and researcher in Boston, said NK cells have “natural abilities that could make them an ideal treatment approach for Alzheimer’s and similar neurodegenerative diseases.

“NK cells have properties that allow them to recognize and destroy diseased brain cells while leaving healthy cells intact, without causing excessive inflammation or autoimmune issues. It has historically been difficult to get immune cells to access the privileged immunological environment of the brain,” Dr. Lakhan explained.

“However, this line of early research shows that NK cells safely crosses the blood–brain barrier, infiltrates brain tissue, and may stave off Alzheimer’s disease as measured by biomarkers and clinical symptoms,” he noted.

“This emerging cell-based immunotherapy is highly-specific to the cells responsible for Alzheimer’s, avoids drug resistance, has long-lasting results, and has fewer side effects than drug counterparts,” Dr. Lakhan said.

The trial was sponsored by NKGen Biotech. Dr. Song and six coauthors are employees and shareholders in the company. Dr. Lakhan reports no relevant financial relationships.
 

A version of this article appeared on Medscape.com.

BOSTON – An investigational natural killer cell (NK) therapy has shown promise in the treatment of Alzheimer’s disease, in a small phase 1 proof-of-concept clinical trial.

SNK01, being developed by NKGen Biotech, is an autologous, nongenetically modified NK cell product that has enhanced cytotoxicity and activating receptor expression.

“When we give these enhanced natural killer cells intravenously, not only do they get into the brain, but we’ve shown, through CSF biomarker data, that they reduce both amyloid and tau proteins, dramatically reducing the neuroinflammation,” said Paul Song, MD, chief executive officer of NKGen Biotech.

“Remarkably,” in the first 6 months, 90% of patients with Alzheimer’s disease demonstrated improvement or maintained stable cognitive function, based on the Alzheimer’s Disease Composite Score (ADCOMS), suggesting that SNK01 may do more than simply slow disease progression, Dr. Song said.

The findings were presented at the 16th Clinical Trials on Alzheimer’s Disease (CTAD) conference.
 

Sound rationale

NK cells are an essential part of the innate immune system that can shape the adaptive response by eliminating activated (not resting) autologous CD4+ T cells. Weak or deficient NK cells have been found to correlate with various diseases, including autoimmune diseases, and emerging data suggest an autoimmune component to Alzheimer’s disease.

The phase 1 study evaluated the safety, tolerability, and exploratory efficacy of SNK01 given intravenously in escalating doses every 3 weeks (four treatments in total).

Participants included 10 patients with Alzheimer’s disease confirmed by imaging. Five had mild Alzheimer’s disease, three had moderate Alzheimer’s disease, and two had advanced Alzheimer’s disease, based on baseline Clinical Dementia Rating–Sum of Boxes (CDR-SB) scores. Median baseline CDR-SB score was 9 (range, 4-18).

Cognitive assessments included CDR-SB, Mini-Mental State Examination (MMSE), Alzheimer’s disease Assessment Scale-Cognitive Subscale (ADAS-Cog) and ADCOMS. CSF biomarker analyses were performed at baseline and at 1 and 12 weeks after the final dose (weeks 11 and 22, respectively).

NK cells were successfully activated and expanded in all 10 patients and no treatment-related adverse events were observed.

Based on the CSF biomarker data, SNK01 crossed the blood–brain barrier and reduced CSF amyloid-beta 42/40 and pTau181 levels and neuroinflammation, as measured by glial fibrillary acid protein (GFAP), and the effects appeared to persist 12 weeks after the final dose.

The exploratory efficacy data show that, 1 week after final dose (week 11), compared with baseline, 30% of patients showed clinical improvement on the composite ADCOMS and 60% had a stable ADCOMS score; 50%-70% of patients were stable or improved on the CDR-SB, ADAS-Cog and/or MMSE.

“One patient went from a MMSE score of 14, which is moderate dementia, to 22, which is mild cognitive impairment,” said Dr. Song.

At 12 weeks after the final dose (week 22), 44%-89% of patients remained stable or improved in all cognitive scores compared with week 11; and 50% of the patients with stable ADCOMS scores at week 11 remained stable.

Based on the positive phase 1 data, the Food and Drug Administration has approved a phase 1/2a study in patients with moderate Alzheimer’s disease. “The trial will use a much higher dose and a prolonged dosing regimen and we think we’ll see even more dramatic results with more sustained higher dosing,” Dr. Song said.

Down the road, it will be interesting to see how NK cell therapy could “complement” anti-amyloid and anti-tau therapies, he added.
 

Ideal treatment approach

Commenting on this research, Shaheen Lakhan, MD, PhD, a neurologist and researcher in Boston, said NK cells have “natural abilities that could make them an ideal treatment approach for Alzheimer’s and similar neurodegenerative diseases.

“NK cells have properties that allow them to recognize and destroy diseased brain cells while leaving healthy cells intact, without causing excessive inflammation or autoimmune issues. It has historically been difficult to get immune cells to access the privileged immunological environment of the brain,” Dr. Lakhan explained.

“However, this line of early research shows that NK cells safely crosses the blood–brain barrier, infiltrates brain tissue, and may stave off Alzheimer’s disease as measured by biomarkers and clinical symptoms,” he noted.

“This emerging cell-based immunotherapy is highly-specific to the cells responsible for Alzheimer’s, avoids drug resistance, has long-lasting results, and has fewer side effects than drug counterparts,” Dr. Lakhan said.

The trial was sponsored by NKGen Biotech. Dr. Song and six coauthors are employees and shareholders in the company. Dr. Lakhan reports no relevant financial relationships.
 

A version of this article appeared on Medscape.com.

BOSTON – An investigational natural killer cell (NK) therapy has shown promise in the treatment of Alzheimer’s disease, in a small phase 1 proof-of-concept clinical trial.

SNK01, being developed by NKGen Biotech, is an autologous, nongenetically modified NK cell product that has enhanced cytotoxicity and activating receptor expression.

“When we give these enhanced natural killer cells intravenously, not only do they get into the brain, but we’ve shown, through CSF biomarker data, that they reduce both amyloid and tau proteins, dramatically reducing the neuroinflammation,” said Paul Song, MD, chief executive officer of NKGen Biotech.

“Remarkably,” in the first 6 months, 90% of patients with Alzheimer’s disease demonstrated improvement or maintained stable cognitive function, based on the Alzheimer’s Disease Composite Score (ADCOMS), suggesting that SNK01 may do more than simply slow disease progression, Dr. Song said.

The findings were presented at the 16th Clinical Trials on Alzheimer’s Disease (CTAD) conference.
 

Sound rationale

NK cells are an essential part of the innate immune system that can shape the adaptive response by eliminating activated (not resting) autologous CD4+ T cells. Weak or deficient NK cells have been found to correlate with various diseases, including autoimmune diseases, and emerging data suggest an autoimmune component to Alzheimer’s disease.

The phase 1 study evaluated the safety, tolerability, and exploratory efficacy of SNK01 given intravenously in escalating doses every 3 weeks (four treatments in total).

Participants included 10 patients with Alzheimer’s disease confirmed by imaging. Five had mild Alzheimer’s disease, three had moderate Alzheimer’s disease, and two had advanced Alzheimer’s disease, based on baseline Clinical Dementia Rating–Sum of Boxes (CDR-SB) scores. Median baseline CDR-SB score was 9 (range, 4-18).

Cognitive assessments included CDR-SB, Mini-Mental State Examination (MMSE), Alzheimer’s disease Assessment Scale-Cognitive Subscale (ADAS-Cog) and ADCOMS. CSF biomarker analyses were performed at baseline and at 1 and 12 weeks after the final dose (weeks 11 and 22, respectively).

NK cells were successfully activated and expanded in all 10 patients and no treatment-related adverse events were observed.

Based on the CSF biomarker data, SNK01 crossed the blood–brain barrier and reduced CSF amyloid-beta 42/40 and pTau181 levels and neuroinflammation, as measured by glial fibrillary acid protein (GFAP), and the effects appeared to persist 12 weeks after the final dose.

The exploratory efficacy data show that, 1 week after final dose (week 11), compared with baseline, 30% of patients showed clinical improvement on the composite ADCOMS and 60% had a stable ADCOMS score; 50%-70% of patients were stable or improved on the CDR-SB, ADAS-Cog and/or MMSE.

“One patient went from a MMSE score of 14, which is moderate dementia, to 22, which is mild cognitive impairment,” said Dr. Song.

At 12 weeks after the final dose (week 22), 44%-89% of patients remained stable or improved in all cognitive scores compared with week 11; and 50% of the patients with stable ADCOMS scores at week 11 remained stable.

Based on the positive phase 1 data, the Food and Drug Administration has approved a phase 1/2a study in patients with moderate Alzheimer’s disease. “The trial will use a much higher dose and a prolonged dosing regimen and we think we’ll see even more dramatic results with more sustained higher dosing,” Dr. Song said.

Down the road, it will be interesting to see how NK cell therapy could “complement” anti-amyloid and anti-tau therapies, he added.
 

Ideal treatment approach

Commenting on this research, Shaheen Lakhan, MD, PhD, a neurologist and researcher in Boston, said NK cells have “natural abilities that could make them an ideal treatment approach for Alzheimer’s and similar neurodegenerative diseases.

“NK cells have properties that allow them to recognize and destroy diseased brain cells while leaving healthy cells intact, without causing excessive inflammation or autoimmune issues. It has historically been difficult to get immune cells to access the privileged immunological environment of the brain,” Dr. Lakhan explained.

“However, this line of early research shows that NK cells safely crosses the blood–brain barrier, infiltrates brain tissue, and may stave off Alzheimer’s disease as measured by biomarkers and clinical symptoms,” he noted.

“This emerging cell-based immunotherapy is highly-specific to the cells responsible for Alzheimer’s, avoids drug resistance, has long-lasting results, and has fewer side effects than drug counterparts,” Dr. Lakhan said.

The trial was sponsored by NKGen Biotech. Dr. Song and six coauthors are employees and shareholders in the company. Dr. Lakhan reports no relevant financial relationships.
 

A version of this article appeared on Medscape.com.

TOPLINE:

Atrial fibrillation (AF) is associated with a 45% increased risk of mild cognitive impairment (MCI), an outcome that’s linked to cardiovascular risk factors and multi-comorbidity, results of a new study suggest.

METHODOLOGY:

• From over 4.3 million people in the UK primary electronic health record (EHR) database, researchers identified 233,833 (5.4%) with AF (mean age, 74.2 years) and randomly selected one age- and sex-matched control person without AF for each AF case patient.
• The primary outcome was incidence of mild cognitive impairment (MCI).
• The authors adjusted for age, sex, year at study entry, socioeconomic status, smoking, and a number of comorbid conditions.
• During a median of 5.3 years of follow-up, there were 4,269 incident MCI cases among both AF and non-AF patients.

TAKEAWAY:

• Individuals with AF had a higher risk of MCI than that of those without AF (adjusted hazard ratio [aHR], 1.45; 95% confidence interval [CI], 1.35-1.56).
• Besides AF, older age (risk ratio [RR], 1.08) and history of depression (RR, 1.44) were associated with greater risk of MCI, as were female sex, greater socioeconomic deprivation, stroke, and multimorbidity, including, for example, diabetes, hypercholesterolemia, and peripheral artery disease (all P < .001).
• Individuals with AF who received oral anticoagulants or amiodarone were not at increased risk of MCI, as was the case for those treated with digoxin.
• Individuals with AF and MCI were at greater risk of dementia (aHR, 1.25; 95% CI, 1.09-1.42). Sex, smoking, chronic kidney disease, and multi-comorbidity were among factors linked to elevated dementia risk.

IN PRACTICE:

The findings emphasize the association of multi-comorbidity and cardiovascular risk factors with development of MCI and progression to dementia in AF patients, the authors wrote. They noted that the data suggest combining anticoagulation and symptom and comorbidity management may prevent cognitive deterioration.

SOURCE:

The study was conducted by Sheng-Chia Chung, PhD, Institute of Health informatics Research, University College London, and colleagues. It was published online Oct. 25, 2023, as a research letter in the Journal of the American College of Cardiology (JACC): Advances. 

LIMITATIONS:

The EHR dataset may have lacked granularity and detail, and some risk factors or comorbidities may not have been measured. While those with AF receiving digoxin or amiodarone treatment had no higher risk of MCI than their non-AF peers, the study’s observational design and very wide confidence intervals for these subgroups prevent making solid inferences about causality or a potential protective role of these drugs.

DISCLOSURES:

Dr. Chung is supported by the National Institute of Health and Care Research (NIHR) Author Rui Providencia, MD, PhD, of the Institute of Health informatics Research, University College London, is supported by the University College London British Heart Foundation and NIHR. All other authors report no relevant conflicts of interest.
 

A version of this article appeared on Medscape.com.

TOPLINE:

Atrial fibrillation (AF) is associated with a 45% increased risk of mild cognitive impairment (MCI), an outcome that’s linked to cardiovascular risk factors and multi-comorbidity, results of a new study suggest.

METHODOLOGY:

• From over 4.3 million people in the UK primary electronic health record (EHR) database, researchers identified 233,833 (5.4%) with AF (mean age, 74.2 years) and randomly selected one age- and sex-matched control person without AF for each AF case patient.
• The primary outcome was incidence of mild cognitive impairment (MCI).
• The authors adjusted for age, sex, year at study entry, socioeconomic status, smoking, and a number of comorbid conditions.
• During a median of 5.3 years of follow-up, there were 4,269 incident MCI cases among both AF and non-AF patients.

TAKEAWAY:

• Individuals with AF had a higher risk of MCI than that of those without AF (adjusted hazard ratio [aHR], 1.45; 95% confidence interval [CI], 1.35-1.56).
• Besides AF, older age (risk ratio [RR], 1.08) and history of depression (RR, 1.44) were associated with greater risk of MCI, as were female sex, greater socioeconomic deprivation, stroke, and multimorbidity, including, for example, diabetes, hypercholesterolemia, and peripheral artery disease (all P < .001).
• Individuals with AF who received oral anticoagulants or amiodarone were not at increased risk of MCI, as was the case for those treated with digoxin.
• Individuals with AF and MCI were at greater risk of dementia (aHR, 1.25; 95% CI, 1.09-1.42). Sex, smoking, chronic kidney disease, and multi-comorbidity were among factors linked to elevated dementia risk.

IN PRACTICE:

The findings emphasize the association of multi-comorbidity and cardiovascular risk factors with development of MCI and progression to dementia in AF patients, the authors wrote. They noted that the data suggest combining anticoagulation and symptom and comorbidity management may prevent cognitive deterioration.

SOURCE:

The study was conducted by Sheng-Chia Chung, PhD, Institute of Health informatics Research, University College London, and colleagues. It was published online Oct. 25, 2023, as a research letter in the Journal of the American College of Cardiology (JACC): Advances. 

LIMITATIONS:

The EHR dataset may have lacked granularity and detail, and some risk factors or comorbidities may not have been measured. While those with AF receiving digoxin or amiodarone treatment had no higher risk of MCI than their non-AF peers, the study’s observational design and very wide confidence intervals for these subgroups prevent making solid inferences about causality or a potential protective role of these drugs.

DISCLOSURES:

Dr. Chung is supported by the National Institute of Health and Care Research (NIHR) Author Rui Providencia, MD, PhD, of the Institute of Health informatics Research, University College London, is supported by the University College London British Heart Foundation and NIHR. All other authors report no relevant conflicts of interest.
 

A version of this article appeared on Medscape.com.

TOPLINE:

Atrial fibrillation (AF) is associated with a 45% increased risk of mild cognitive impairment (MCI), an outcome that’s linked to cardiovascular risk factors and multi-comorbidity, results of a new study suggest.

METHODOLOGY:

• From over 4.3 million people in the UK primary electronic health record (EHR) database, researchers identified 233,833 (5.4%) with AF (mean age, 74.2 years) and randomly selected one age- and sex-matched control person without AF for each AF case patient.
• The primary outcome was incidence of mild cognitive impairment (MCI).
• The authors adjusted for age, sex, year at study entry, socioeconomic status, smoking, and a number of comorbid conditions.
• During a median of 5.3 years of follow-up, there were 4,269 incident MCI cases among both AF and non-AF patients.

TAKEAWAY:

• Individuals with AF had a higher risk of MCI than that of those without AF (adjusted hazard ratio [aHR], 1.45; 95% confidence interval [CI], 1.35-1.56).
• Besides AF, older age (risk ratio [RR], 1.08) and history of depression (RR, 1.44) were associated with greater risk of MCI, as were female sex, greater socioeconomic deprivation, stroke, and multimorbidity, including, for example, diabetes, hypercholesterolemia, and peripheral artery disease (all P < .001).
• Individuals with AF who received oral anticoagulants or amiodarone were not at increased risk of MCI, as was the case for those treated with digoxin.
• Individuals with AF and MCI were at greater risk of dementia (aHR, 1.25; 95% CI, 1.09-1.42). Sex, smoking, chronic kidney disease, and multi-comorbidity were among factors linked to elevated dementia risk.

IN PRACTICE:

The findings emphasize the association of multi-comorbidity and cardiovascular risk factors with development of MCI and progression to dementia in AF patients, the authors wrote. They noted that the data suggest combining anticoagulation and symptom and comorbidity management may prevent cognitive deterioration.

SOURCE:

The study was conducted by Sheng-Chia Chung, PhD, Institute of Health informatics Research, University College London, and colleagues. It was published online Oct. 25, 2023, as a research letter in the Journal of the American College of Cardiology (JACC): Advances. 

LIMITATIONS:

The EHR dataset may have lacked granularity and detail, and some risk factors or comorbidities may not have been measured. While those with AF receiving digoxin or amiodarone treatment had no higher risk of MCI than their non-AF peers, the study’s observational design and very wide confidence intervals for these subgroups prevent making solid inferences about causality or a potential protective role of these drugs.

DISCLOSURES:

Dr. Chung is supported by the National Institute of Health and Care Research (NIHR) Author Rui Providencia, MD, PhD, of the Institute of Health informatics Research, University College London, is supported by the University College London British Heart Foundation and NIHR. All other authors report no relevant conflicts of interest.
 

A version of this article appeared on Medscape.com.

Patients age 65 and older who receive thyroid hormone therapy and experience low thyrotropin are at increased risk for dementia and other cognitive problems, according to new research published in JAMA Internal Medicine.

The study found that these patients with thyrotoxicosis had a higher likelihood of incident cognitive disorder (adjusted hazard ratio, 1.39; 95% confidence interval, 1.18-1.64; P < .001). Broken down between internal and external causes of thyrotoxicosis, exogenous thyrotoxicosis continued to be a significant risk factor (aHR, 1.34: 95% CI, 1.10-1.63; P = .003), while endogenous thyrotoxicosis did not show a statistically significant risk estimates (aHR, 1.38; 95% CI, 0.96-1.98; P = .08).

The study also found that women were more likely to have low levels of thyrotropin (thyroid-stimulating hormone/TSH) than men and were more likely to be overtreated.

Previous studies looking at the correlation between hyperthyroidism and cognitive disorders often did not include participants who were already taking thyroid hormones, according to Jennifer S. Mammen, MD, PhD, assistant professor of medicine at the Asthma and Allergy Center at John Hopkins University, Baltimore, and the senior author of the study.

“The fact that we see the signal both in people who are being overtreated with thyroid hormone and in people who have endogenous hyperthyroidism is one way that we think that this supports the fact that it’s not just confounding, it’s not just bias,” Dr. Mammen said. “There’s two different sources of hyperthyroidism, and they’re both showing the same relationship.”

In the study, Dr. Mammen and colleagues analyzed electronic health records for patients aged 65 years and older who received primary care in the Johns Hopkins Community Physicians Network over a 10-year period starting in 2014. Patients had to have a minimum of two visits 30 days apart. None had a history of low TSH levels or cognitive disorder diagnoses within 6 months of their first doctor visit.

More than 65,000 patients were included in the study. Slightly more than half (56%) were female, almost 70% were White, 19.3% were Black, 4.6% were Asian, and 0.4% were American Indian. Almost 25,000 low TSH measurements among 2,710 patients were recorded during the study period. The majority of low TSH measurements were exogenous (14,875), followed by origins of unknown cause (5,833), and endogenous (4,159).

During the follow-up period, 7.2% (4,779) patients received a new cognitive disorder diagnosis, which was dementia in 77% of cases.

Dr. Mammen said primary care physicians should carefully consider whether thyroid hormone therapy is necessary for older patients, and, if so, great care should be taken to avoid overtreatment.

“This is yet another reason for us to be vigilant about not overtreating people with thyroid hormone, especially in older adults,” Dr. Mammen said. “We already know that atrial fibrillation rates are increased in people who are hyperthyroid. We know that fracture and osteoporosis is affected by hyperthyroidism. And now we also have an association with higher rates of cognitive disorders.”

Taking a cautious approach to prescribing thyroid hormone therapy for older patients is paramount, according to Jean Chen, MD, partner at Texas Diabetes & Endocrinology, who was not affiliated with the study.

“All medical providers need to be aware that the 65 and older population does not need to be treated as aggressively with their thyroid hormone,” Dr. Chen said. “We are finding more and more complications from overtreatment rather than benefit in this population.”

Often, older patients may complain of symptoms such as constipation, feeling cold, or tiredness, which can be symptoms of hypothyroidism. But these symptoms could also be from anemia, vitamin deficiencies, depression, perimenopause, menopause, insulin resistance, and sleep apnea. If necessary, Dr. Chen recommended primary care physicians consult with an endocrinologist regarding a possible treatment plan and making a differential diagnosis.

In addition, Dr. Chen said other studies have shown that treating patients with thyroid hormone either did not resolve the condition or negatively impacted anxiety, muscle strength, and bone density, or it increased the risk for arrhythmia. Therefore, it’s important to weight the risks versus the benefits.

“There’s so much gray zone here,” Dr. Chen said.

The study was supported by the Richman Family Precision Medicine Center of Excellence in Alzheimer’s Disease, the Richman Family Foundation, the Rick Sharp Alzheimer’s Foundation, the Sharp Family Foundation, among others. The work was also supported by grants from the National Institutes of Health. One coauthor reported personal fees from Karuna, MapLight Therapeutics, Axsome Therapeutics, GIA, GW Research Limited, Merck, EXCIVA, Otsuka, IntraCellular Therapies, and Medesis Pharma for consulting for treatment development in Alzheimer’s disease outside the submitted work. No other disclosures were reported.

A version of this article appeared on Medscape.com.

Patients age 65 and older who receive thyroid hormone therapy and experience low thyrotropin are at increased risk for dementia and other cognitive problems, according to new research published in JAMA Internal Medicine.

The study found that these patients with thyrotoxicosis had a higher likelihood of incident cognitive disorder (adjusted hazard ratio, 1.39; 95% confidence interval, 1.18-1.64; P < .001). Broken down between internal and external causes of thyrotoxicosis, exogenous thyrotoxicosis continued to be a significant risk factor (aHR, 1.34: 95% CI, 1.10-1.63; P = .003), while endogenous thyrotoxicosis did not show a statistically significant risk estimates (aHR, 1.38; 95% CI, 0.96-1.98; P = .08).

The study also found that women were more likely to have low levels of thyrotropin (thyroid-stimulating hormone/TSH) than men and were more likely to be overtreated.

Previous studies looking at the correlation between hyperthyroidism and cognitive disorders often did not include participants who were already taking thyroid hormones, according to Jennifer S. Mammen, MD, PhD, assistant professor of medicine at the Asthma and Allergy Center at John Hopkins University, Baltimore, and the senior author of the study.

“The fact that we see the signal both in people who are being overtreated with thyroid hormone and in people who have endogenous hyperthyroidism is one way that we think that this supports the fact that it’s not just confounding, it’s not just bias,” Dr. Mammen said. “There’s two different sources of hyperthyroidism, and they’re both showing the same relationship.”

In the study, Dr. Mammen and colleagues analyzed electronic health records for patients aged 65 years and older who received primary care in the Johns Hopkins Community Physicians Network over a 10-year period starting in 2014. Patients had to have a minimum of two visits 30 days apart. None had a history of low TSH levels or cognitive disorder diagnoses within 6 months of their first doctor visit.

More than 65,000 patients were included in the study. Slightly more than half (56%) were female, almost 70% were White, 19.3% were Black, 4.6% were Asian, and 0.4% were American Indian. Almost 25,000 low TSH measurements among 2,710 patients were recorded during the study period. The majority of low TSH measurements were exogenous (14,875), followed by origins of unknown cause (5,833), and endogenous (4,159).

During the follow-up period, 7.2% (4,779) patients received a new cognitive disorder diagnosis, which was dementia in 77% of cases.

Dr. Mammen said primary care physicians should carefully consider whether thyroid hormone therapy is necessary for older patients, and, if so, great care should be taken to avoid overtreatment.

“This is yet another reason for us to be vigilant about not overtreating people with thyroid hormone, especially in older adults,” Dr. Mammen said. “We already know that atrial fibrillation rates are increased in people who are hyperthyroid. We know that fracture and osteoporosis is affected by hyperthyroidism. And now we also have an association with higher rates of cognitive disorders.”

Taking a cautious approach to prescribing thyroid hormone therapy for older patients is paramount, according to Jean Chen, MD, partner at Texas Diabetes & Endocrinology, who was not affiliated with the study.

“All medical providers need to be aware that the 65 and older population does not need to be treated as aggressively with their thyroid hormone,” Dr. Chen said. “We are finding more and more complications from overtreatment rather than benefit in this population.”

Often, older patients may complain of symptoms such as constipation, feeling cold, or tiredness, which can be symptoms of hypothyroidism. But these symptoms could also be from anemia, vitamin deficiencies, depression, perimenopause, menopause, insulin resistance, and sleep apnea. If necessary, Dr. Chen recommended primary care physicians consult with an endocrinologist regarding a possible treatment plan and making a differential diagnosis.

In addition, Dr. Chen said other studies have shown that treating patients with thyroid hormone either did not resolve the condition or negatively impacted anxiety, muscle strength, and bone density, or it increased the risk for arrhythmia. Therefore, it’s important to weight the risks versus the benefits.

“There’s so much gray zone here,” Dr. Chen said.

The study was supported by the Richman Family Precision Medicine Center of Excellence in Alzheimer’s Disease, the Richman Family Foundation, the Rick Sharp Alzheimer’s Foundation, the Sharp Family Foundation, among others. The work was also supported by grants from the National Institutes of Health. One coauthor reported personal fees from Karuna, MapLight Therapeutics, Axsome Therapeutics, GIA, GW Research Limited, Merck, EXCIVA, Otsuka, IntraCellular Therapies, and Medesis Pharma for consulting for treatment development in Alzheimer’s disease outside the submitted work. No other disclosures were reported.

A version of this article appeared on Medscape.com.

Patients age 65 and older who receive thyroid hormone therapy and experience low thyrotropin are at increased risk for dementia and other cognitive problems, according to new research published in JAMA Internal Medicine.

The study found that these patients with thyrotoxicosis had a higher likelihood of incident cognitive disorder (adjusted hazard ratio, 1.39; 95% confidence interval, 1.18-1.64; P < .001). Broken down between internal and external causes of thyrotoxicosis, exogenous thyrotoxicosis continued to be a significant risk factor (aHR, 1.34: 95% CI, 1.10-1.63; P = .003), while endogenous thyrotoxicosis did not show a statistically significant risk estimates (aHR, 1.38; 95% CI, 0.96-1.98; P = .08).

The study also found that women were more likely to have low levels of thyrotropin (thyroid-stimulating hormone/TSH) than men and were more likely to be overtreated.

Previous studies looking at the correlation between hyperthyroidism and cognitive disorders often did not include participants who were already taking thyroid hormones, according to Jennifer S. Mammen, MD, PhD, assistant professor of medicine at the Asthma and Allergy Center at John Hopkins University, Baltimore, and the senior author of the study.

“The fact that we see the signal both in people who are being overtreated with thyroid hormone and in people who have endogenous hyperthyroidism is one way that we think that this supports the fact that it’s not just confounding, it’s not just bias,” Dr. Mammen said. “There’s two different sources of hyperthyroidism, and they’re both showing the same relationship.”

In the study, Dr. Mammen and colleagues analyzed electronic health records for patients aged 65 years and older who received primary care in the Johns Hopkins Community Physicians Network over a 10-year period starting in 2014. Patients had to have a minimum of two visits 30 days apart. None had a history of low TSH levels or cognitive disorder diagnoses within 6 months of their first doctor visit.

More than 65,000 patients were included in the study. Slightly more than half (56%) were female, almost 70% were White, 19.3% were Black, 4.6% were Asian, and 0.4% were American Indian. Almost 25,000 low TSH measurements among 2,710 patients were recorded during the study period. The majority of low TSH measurements were exogenous (14,875), followed by origins of unknown cause (5,833), and endogenous (4,159).

During the follow-up period, 7.2% (4,779) patients received a new cognitive disorder diagnosis, which was dementia in 77% of cases.

Dr. Mammen said primary care physicians should carefully consider whether thyroid hormone therapy is necessary for older patients, and, if so, great care should be taken to avoid overtreatment.

“This is yet another reason for us to be vigilant about not overtreating people with thyroid hormone, especially in older adults,” Dr. Mammen said. “We already know that atrial fibrillation rates are increased in people who are hyperthyroid. We know that fracture and osteoporosis is affected by hyperthyroidism. And now we also have an association with higher rates of cognitive disorders.”

Taking a cautious approach to prescribing thyroid hormone therapy for older patients is paramount, according to Jean Chen, MD, partner at Texas Diabetes & Endocrinology, who was not affiliated with the study.

“All medical providers need to be aware that the 65 and older population does not need to be treated as aggressively with their thyroid hormone,” Dr. Chen said. “We are finding more and more complications from overtreatment rather than benefit in this population.”

Often, older patients may complain of symptoms such as constipation, feeling cold, or tiredness, which can be symptoms of hypothyroidism. But these symptoms could also be from anemia, vitamin deficiencies, depression, perimenopause, menopause, insulin resistance, and sleep apnea. If necessary, Dr. Chen recommended primary care physicians consult with an endocrinologist regarding a possible treatment plan and making a differential diagnosis.

In addition, Dr. Chen said other studies have shown that treating patients with thyroid hormone either did not resolve the condition or negatively impacted anxiety, muscle strength, and bone density, or it increased the risk for arrhythmia. Therefore, it’s important to weight the risks versus the benefits.

“There’s so much gray zone here,” Dr. Chen said.

The study was supported by the Richman Family Precision Medicine Center of Excellence in Alzheimer’s Disease, the Richman Family Foundation, the Rick Sharp Alzheimer’s Foundation, the Sharp Family Foundation, among others. The work was also supported by grants from the National Institutes of Health. One coauthor reported personal fees from Karuna, MapLight Therapeutics, Axsome Therapeutics, GIA, GW Research Limited, Merck, EXCIVA, Otsuka, IntraCellular Therapies, and Medesis Pharma for consulting for treatment development in Alzheimer’s disease outside the submitted work. No other disclosures were reported.

A version of this article appeared on Medscape.com.

TOPLINE:

New research suggests terminating metformin may raise the risk for dementia in older adults with type 2 diabetes, providing more evidence of metformin’s potential neuroprotective effects.

METHODOLOGY:

• Researchers evaluated the association between discontinuing metformin for reasons unrelated to kidney dysfunction and dementia incidence.
• The cohort included 12,220 Kaiser Permanente Northern California members who stopped metformin early (with normal kidney function) and 29,126 routine metformin users.
• The cohort of early terminators was 46% women with an average age of 59 years at the start of metformin prescription. The cohort continuing metformin was 47% women, with a start age of 61 years.

TAKEAWAY:

• Adults who stopped metformin early were 21% more likely to be diagnosed with dementia during follow up (hazard ratio, 1.21; 95% confidence interval, 1.12-1.30), compared with routine metformin users.
• This association was largely independent of changes in A1c level and insulin usage.

IN PRACTICE:

The findings “corroborate the largely consistent evidence from other observational studies showing an association between metformin use and lower dementia incidence [and] may have important implications for clinical treatment of adults with diabetes,” the authors write.

SOURCE:

The study, with first author Scott Zimmerman, MPH, University of California, San Francisco, was published online  in JAMA Network Open.

LIMITATIONS:

Dementia diagnosis was obtained based on medical records. Factors such as race, ethnicity, or time on metformin were not evaluated. Information on the exact reason for stopping metformin was not available.

DISCLOSURES:

The study was funded by grants from the National Institutes of Health, National Institute on Aging. Mr. Zimmerman owns stock in AbbVie, Gilead Sciences, CRISPR Therapeutics, and Abbott Laboratories. Disclosure for the other study authors can be found with the original article.

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

TOPLINE:

New research suggests terminating metformin may raise the risk for dementia in older adults with type 2 diabetes, providing more evidence of metformin’s potential neuroprotective effects.

METHODOLOGY:

• Researchers evaluated the association between discontinuing metformin for reasons unrelated to kidney dysfunction and dementia incidence.
• The cohort included 12,220 Kaiser Permanente Northern California members who stopped metformin early (with normal kidney function) and 29,126 routine metformin users.
• The cohort of early terminators was 46% women with an average age of 59 years at the start of metformin prescription. The cohort continuing metformin was 47% women, with a start age of 61 years.

TAKEAWAY:

• Adults who stopped metformin early were 21% more likely to be diagnosed with dementia during follow up (hazard ratio, 1.21; 95% confidence interval, 1.12-1.30), compared with routine metformin users.
• This association was largely independent of changes in A1c level and insulin usage.

IN PRACTICE:

The findings “corroborate the largely consistent evidence from other observational studies showing an association between metformin use and lower dementia incidence [and] may have important implications for clinical treatment of adults with diabetes,” the authors write.

SOURCE:

The study, with first author Scott Zimmerman, MPH, University of California, San Francisco, was published online  in JAMA Network Open.

LIMITATIONS:

Dementia diagnosis was obtained based on medical records. Factors such as race, ethnicity, or time on metformin were not evaluated. Information on the exact reason for stopping metformin was not available.

DISCLOSURES:

The study was funded by grants from the National Institutes of Health, National Institute on Aging. Mr. Zimmerman owns stock in AbbVie, Gilead Sciences, CRISPR Therapeutics, and Abbott Laboratories. Disclosure for the other study authors can be found with the original article.

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

TOPLINE:

New research suggests terminating metformin may raise the risk for dementia in older adults with type 2 diabetes, providing more evidence of metformin’s potential neuroprotective effects.

METHODOLOGY:

• Researchers evaluated the association between discontinuing metformin for reasons unrelated to kidney dysfunction and dementia incidence.
• The cohort included 12,220 Kaiser Permanente Northern California members who stopped metformin early (with normal kidney function) and 29,126 routine metformin users.
• The cohort of early terminators was 46% women with an average age of 59 years at the start of metformin prescription. The cohort continuing metformin was 47% women, with a start age of 61 years.

TAKEAWAY:

• Adults who stopped metformin early were 21% more likely to be diagnosed with dementia during follow up (hazard ratio, 1.21; 95% confidence interval, 1.12-1.30), compared with routine metformin users.
• This association was largely independent of changes in A1c level and insulin usage.

IN PRACTICE:

The findings “corroborate the largely consistent evidence from other observational studies showing an association between metformin use and lower dementia incidence [and] may have important implications for clinical treatment of adults with diabetes,” the authors write.

SOURCE:

The study, with first author Scott Zimmerman, MPH, University of California, San Francisco, was published online  in JAMA Network Open.

LIMITATIONS:

Dementia diagnosis was obtained based on medical records. Factors such as race, ethnicity, or time on metformin were not evaluated. Information on the exact reason for stopping metformin was not available.

DISCLOSURES:

The study was funded by grants from the National Institutes of Health, National Institute on Aging. Mr. Zimmerman owns stock in AbbVie, Gilead Sciences, CRISPR Therapeutics, and Abbott Laboratories. Disclosure for the other study authors can be found with the original article.

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

Should older physicians be forced to undergo cognitive tests to stay on the job? One 84-year-old ophthalmologist is suing her Michigan employer to stop the practice.

Lylas G. Mogk, MD, recently sued Henry Ford Health and Henry Ford Medical Group in federal court, alleging that the mandatory cognitive test violates the Americans with Disabilities Act, the Age Discrimination in Employment Act, and two Michigan laws.

Dr. Mogk’s lawsuit follows a widely watched 2020 case in which the U.S. Equal Employment Opportunity Commission sued Yale New Haven Hospital, the teaching hospital of Yale University, for age discrimination. According to the lawsuit, the hospital illegally required neuropsychological and eye examinations of physicians aged 70 or older who sought to gain or renew staff privileges.

According to the lawsuit, Dr. Mogk is a member of Henry Ford Medical Group, which in 2017 required all members aged 70 and older to undergo cognitive screening tests. The tests would be repeated every 5 years thereafter, the lawsuit said, and anyone who refused would have to resign or be fired.

Dr. Mogk completed the screening, although no information about the results or outcome was mentioned in the lawsuit. It’s not clear whether Henry Ford’s cognitive test mandate remains in place; a spokesperson for Henry Ford Health and attorneys for Dr. Mogk declined to comment.

The number of practicing physicians in their 70s and beyond is rising. A 2021 report found that 12% of U.S. licensed physicians in 2020 were least 70 years old, up from 9% in 2010 and an increase from 75,627 to 120,510. The percentage of doctors aged 60-69 grew to 19% from 16% in 2010.

The number of health systems requiring testing of older physicians isn’t known, although various reports suggest at least a dozen have had mandates.

The University of California, San Diego, offers a physical and mental screening program that health organizations can use to evaluate “late-career physicians,” and a 2021 report noted that “Nebraska’s Children’s Hospital requires physicians aged 70 years and older to undergo an assessment by several peers, a complete physical, and unspecified cognitive screening.” Another system, Hartford HealthCare, mandated an annual reappointment process for clinicians aged 70 or older, requiring them to undergo various exams.

There’s evidence that physician performance declines with age. However, age-based cognitive testing can run afoul of federal and state laws against age discrimination, said Sharona Hoffman, JD, professor of law and bioethics at Case Western Reserve University, Cleveland, in an interview.

Federal law prohibits age-related restrictions on employment but allows exceptions in areas like public safety, said Ms. Hoffman, who’s written about age discrimination and testing requirements. Pilots, law enforcement officers, firefighters, and air controllers, for example, can be forced to retire at specific ages.

It’s not clear how many physicians took the cognitive tests required by Henry Ford Medical Group.

However, details are available about the policy at Yale New Haven Hospital: According to the EEOC lawsuit, from 2016 to 2019, 145 physicians aged 70 or older took the mandatory test. Of those, seven individuals failed either or both of the exams, 14 were listed as “borderline deficient,” and one was listed as “deficient.” Another five refused testing and either resigned or changed their status. The EEOC case against the hospital is still pending.

“You can make an argument that health care is like a public safety job because people put their lives in the hands of doctors,” Ms. Hoffman said.

In defending mandatory cognitive tests, she said, health care systems could say, “it’s not really discrimination; we’re not forcing them to retire, we’re not limiting their work in any way. We’re just doing testing to make sure they perform competently, and the ADA allows us to conduct testing that is job-related.”

Indeed, a Yale New Haven Hospital spokesman made an argument along these lines in a statement regarding the 2020 lawsuit: The “policy is designed to protect our patients from potential harm while including safeguards to ensure that our physicians are treated fairly. The policy is modeled on similar standards in other industries, and we are confident that no discrimination has occurred and will vigorously defend ourselves in this matter.”

However, Ms. Hoffman herself doesn’t buy these arguments. Requiring tests only for older physicians does appear to be discrimination based on age, she said. As an alternative, “employers can do close supervision of people. As soon as there are performance problems or patient complaints, you need to see a doctor or get testing done.”

Another option is to mandate tests at specific ages via licensing boards. “I don’t think that would be legally problematic,” Ms. Hoffman said.

What else can be done to protect patients from clinicians whose skills have significantly declined as they’ve aged? The 2021 report in Neurology Clinical Practice notes that there are disadvantages to several strategies.

One common approach, waiting to evaluate a clinician until an error occurs, can lead to patient harm, the report’s authors wrote. Relying on reporting by peers is problematic because “physicians have been very resistant to reporting colleagues who are impaired” and the “medical apprenticeship model discourages physicians from reporting on senior colleagues.”

Physician self-assessment is yet another option, but “loss of insight may be a component of an individual’s impairment,” the authors wrote.

So what’s the best solution? The authors recommended “a relatively brief cognitive screening followed by more extensive testing for the most impaired individuals.” This approach “appears most reliable in confidentially identifying truly impaired physicians while minimizing the chance of a falsely flagging unimpaired individuals. This strategy allows aging physicians to continue working while safeguarding both their reputations and their patients’ health.”

Ms. Hoffman has no disclosures.

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

Should older physicians be forced to undergo cognitive tests to stay on the job? One 84-year-old ophthalmologist is suing her Michigan employer to stop the practice.

Lylas G. Mogk, MD, recently sued Henry Ford Health and Henry Ford Medical Group in federal court, alleging that the mandatory cognitive test violates the Americans with Disabilities Act, the Age Discrimination in Employment Act, and two Michigan laws.

Dr. Mogk’s lawsuit follows a widely watched 2020 case in which the U.S. Equal Employment Opportunity Commission sued Yale New Haven Hospital, the teaching hospital of Yale University, for age discrimination. According to the lawsuit, the hospital illegally required neuropsychological and eye examinations of physicians aged 70 or older who sought to gain or renew staff privileges.

According to the lawsuit, Dr. Mogk is a member of Henry Ford Medical Group, which in 2017 required all members aged 70 and older to undergo cognitive screening tests. The tests would be repeated every 5 years thereafter, the lawsuit said, and anyone who refused would have to resign or be fired.

Dr. Mogk completed the screening, although no information about the results or outcome was mentioned in the lawsuit. It’s not clear whether Henry Ford’s cognitive test mandate remains in place; a spokesperson for Henry Ford Health and attorneys for Dr. Mogk declined to comment.

The number of practicing physicians in their 70s and beyond is rising. A 2021 report found that 12% of U.S. licensed physicians in 2020 were least 70 years old, up from 9% in 2010 and an increase from 75,627 to 120,510. The percentage of doctors aged 60-69 grew to 19% from 16% in 2010.

The number of health systems requiring testing of older physicians isn’t known, although various reports suggest at least a dozen have had mandates.

The University of California, San Diego, offers a physical and mental screening program that health organizations can use to evaluate “late-career physicians,” and a 2021 report noted that “Nebraska’s Children’s Hospital requires physicians aged 70 years and older to undergo an assessment by several peers, a complete physical, and unspecified cognitive screening.” Another system, Hartford HealthCare, mandated an annual reappointment process for clinicians aged 70 or older, requiring them to undergo various exams.

There’s evidence that physician performance declines with age. However, age-based cognitive testing can run afoul of federal and state laws against age discrimination, said Sharona Hoffman, JD, professor of law and bioethics at Case Western Reserve University, Cleveland, in an interview.

Federal law prohibits age-related restrictions on employment but allows exceptions in areas like public safety, said Ms. Hoffman, who’s written about age discrimination and testing requirements. Pilots, law enforcement officers, firefighters, and air controllers, for example, can be forced to retire at specific ages.

It’s not clear how many physicians took the cognitive tests required by Henry Ford Medical Group.

However, details are available about the policy at Yale New Haven Hospital: According to the EEOC lawsuit, from 2016 to 2019, 145 physicians aged 70 or older took the mandatory test. Of those, seven individuals failed either or both of the exams, 14 were listed as “borderline deficient,” and one was listed as “deficient.” Another five refused testing and either resigned or changed their status. The EEOC case against the hospital is still pending.

“You can make an argument that health care is like a public safety job because people put their lives in the hands of doctors,” Ms. Hoffman said.

In defending mandatory cognitive tests, she said, health care systems could say, “it’s not really discrimination; we’re not forcing them to retire, we’re not limiting their work in any way. We’re just doing testing to make sure they perform competently, and the ADA allows us to conduct testing that is job-related.”

Indeed, a Yale New Haven Hospital spokesman made an argument along these lines in a statement regarding the 2020 lawsuit: The “policy is designed to protect our patients from potential harm while including safeguards to ensure that our physicians are treated fairly. The policy is modeled on similar standards in other industries, and we are confident that no discrimination has occurred and will vigorously defend ourselves in this matter.”

However, Ms. Hoffman herself doesn’t buy these arguments. Requiring tests only for older physicians does appear to be discrimination based on age, she said. As an alternative, “employers can do close supervision of people. As soon as there are performance problems or patient complaints, you need to see a doctor or get testing done.”

Another option is to mandate tests at specific ages via licensing boards. “I don’t think that would be legally problematic,” Ms. Hoffman said.

What else can be done to protect patients from clinicians whose skills have significantly declined as they’ve aged? The 2021 report in Neurology Clinical Practice notes that there are disadvantages to several strategies.

One common approach, waiting to evaluate a clinician until an error occurs, can lead to patient harm, the report’s authors wrote. Relying on reporting by peers is problematic because “physicians have been very resistant to reporting colleagues who are impaired” and the “medical apprenticeship model discourages physicians from reporting on senior colleagues.”

Physician self-assessment is yet another option, but “loss of insight may be a component of an individual’s impairment,” the authors wrote.

So what’s the best solution? The authors recommended “a relatively brief cognitive screening followed by more extensive testing for the most impaired individuals.” This approach “appears most reliable in confidentially identifying truly impaired physicians while minimizing the chance of a falsely flagging unimpaired individuals. This strategy allows aging physicians to continue working while safeguarding both their reputations and their patients’ health.”

Ms. Hoffman has no disclosures.

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

Should older physicians be forced to undergo cognitive tests to stay on the job? One 84-year-old ophthalmologist is suing her Michigan employer to stop the practice.

Lylas G. Mogk, MD, recently sued Henry Ford Health and Henry Ford Medical Group in federal court, alleging that the mandatory cognitive test violates the Americans with Disabilities Act, the Age Discrimination in Employment Act, and two Michigan laws.

Dr. Mogk’s lawsuit follows a widely watched 2020 case in which the U.S. Equal Employment Opportunity Commission sued Yale New Haven Hospital, the teaching hospital of Yale University, for age discrimination. According to the lawsuit, the hospital illegally required neuropsychological and eye examinations of physicians aged 70 or older who sought to gain or renew staff privileges.

According to the lawsuit, Dr. Mogk is a member of Henry Ford Medical Group, which in 2017 required all members aged 70 and older to undergo cognitive screening tests. The tests would be repeated every 5 years thereafter, the lawsuit said, and anyone who refused would have to resign or be fired.

Dr. Mogk completed the screening, although no information about the results or outcome was mentioned in the lawsuit. It’s not clear whether Henry Ford’s cognitive test mandate remains in place; a spokesperson for Henry Ford Health and attorneys for Dr. Mogk declined to comment.

The number of practicing physicians in their 70s and beyond is rising. A 2021 report found that 12% of U.S. licensed physicians in 2020 were least 70 years old, up from 9% in 2010 and an increase from 75,627 to 120,510. The percentage of doctors aged 60-69 grew to 19% from 16% in 2010.

The number of health systems requiring testing of older physicians isn’t known, although various reports suggest at least a dozen have had mandates.

The University of California, San Diego, offers a physical and mental screening program that health organizations can use to evaluate “late-career physicians,” and a 2021 report noted that “Nebraska’s Children’s Hospital requires physicians aged 70 years and older to undergo an assessment by several peers, a complete physical, and unspecified cognitive screening.” Another system, Hartford HealthCare, mandated an annual reappointment process for clinicians aged 70 or older, requiring them to undergo various exams.

There’s evidence that physician performance declines with age. However, age-based cognitive testing can run afoul of federal and state laws against age discrimination, said Sharona Hoffman, JD, professor of law and bioethics at Case Western Reserve University, Cleveland, in an interview.

Federal law prohibits age-related restrictions on employment but allows exceptions in areas like public safety, said Ms. Hoffman, who’s written about age discrimination and testing requirements. Pilots, law enforcement officers, firefighters, and air controllers, for example, can be forced to retire at specific ages.

It’s not clear how many physicians took the cognitive tests required by Henry Ford Medical Group.

However, details are available about the policy at Yale New Haven Hospital: According to the EEOC lawsuit, from 2016 to 2019, 145 physicians aged 70 or older took the mandatory test. Of those, seven individuals failed either or both of the exams, 14 were listed as “borderline deficient,” and one was listed as “deficient.” Another five refused testing and either resigned or changed their status. The EEOC case against the hospital is still pending.

“You can make an argument that health care is like a public safety job because people put their lives in the hands of doctors,” Ms. Hoffman said.

In defending mandatory cognitive tests, she said, health care systems could say, “it’s not really discrimination; we’re not forcing them to retire, we’re not limiting their work in any way. We’re just doing testing to make sure they perform competently, and the ADA allows us to conduct testing that is job-related.”

Indeed, a Yale New Haven Hospital spokesman made an argument along these lines in a statement regarding the 2020 lawsuit: The “policy is designed to protect our patients from potential harm while including safeguards to ensure that our physicians are treated fairly. The policy is modeled on similar standards in other industries, and we are confident that no discrimination has occurred and will vigorously defend ourselves in this matter.”

However, Ms. Hoffman herself doesn’t buy these arguments. Requiring tests only for older physicians does appear to be discrimination based on age, she said. As an alternative, “employers can do close supervision of people. As soon as there are performance problems or patient complaints, you need to see a doctor or get testing done.”

Another option is to mandate tests at specific ages via licensing boards. “I don’t think that would be legally problematic,” Ms. Hoffman said.

What else can be done to protect patients from clinicians whose skills have significantly declined as they’ve aged? The 2021 report in Neurology Clinical Practice notes that there are disadvantages to several strategies.

One common approach, waiting to evaluate a clinician until an error occurs, can lead to patient harm, the report’s authors wrote. Relying on reporting by peers is problematic because “physicians have been very resistant to reporting colleagues who are impaired” and the “medical apprenticeship model discourages physicians from reporting on senior colleagues.”

Physician self-assessment is yet another option, but “loss of insight may be a component of an individual’s impairment,” the authors wrote.

So what’s the best solution? The authors recommended “a relatively brief cognitive screening followed by more extensive testing for the most impaired individuals.” This approach “appears most reliable in confidentially identifying truly impaired physicians while minimizing the chance of a falsely flagging unimpaired individuals. This strategy allows aging physicians to continue working while safeguarding both their reputations and their patients’ health.”

Ms. Hoffman has no disclosures.

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

TOPLINE:

Higher triglyceride levels – a main energy source for the brain – are associated with lower risk for dementia that is not mediated by age, sex, or APOE epsilon-4 allele status, a large study of community-dwelling older adults suggests.

METHODOLOGY:

• The analysis included 18,294 participants, median age 75 years and median triglyceride level 106 mg/dL, from the Aspirin in Reducing Events in the Elderly (ASPREE) study, a placebo-controlled, randomized trial of daily low-dose aspirin in older people without dementia or history of cardiovascular disease (CVD) at recruitment.
• Researchers repeated their main analyses in a sub-cohort of 13,976 subjects with APOE epsilon-4 genetic data, and an external cohort of 68,200 participants, mean age 66.9 years and a median nonfasting triglyceride of 139 mg/dL, from the UK biobank, followed for a median of 12.5 years.
• The main outcome was incident dementia over 6.4 years and secondary outcomes included changes in composite cognitive function and domain-specific cognition.
• Researchers controlled for a number of potential confounders, including age, sex, race, smoking, alcohol consumption, education, family history of dementia, diabetes, hypertension, and statin use.

TAKEAWAY:

• Every doubling of baseline triglycerides was associated with an 18% lower risk of incident dementia across the entire study cohort (adjusted hazard ratio, 0.82) and in participants with genotypic data (aHR, 0.82) and a 17% lower risk in the external UK Biobank cohort (aHR, 0.83) (P ≤ .01 for all).
• In the entire cohort, the risk for dementia was 15% lower in those with triglyceride levels at 63-106 mg/dL (aHR, 0.85); 24% lower in those at 107-186 mg/dL (aHR, 0.76); and 36% lower for those with levels higher than 187 mg/dL (aHR, 0.64), compared with individuals with levels below 62 mg/dL (P for trend <.001).
• The direction and magnitude of the inverse association between triglycerides and dementia risk were not modified by age, sex, or risk factors related to triglycerides or dementia.
• In the entire study cohort, higher triglyceride levels were significantly associated with slower decline in global cognition (P = .02), composite cognition (P = .03), and a borderline significantly slower decline in episodic memory (P = .05).

IN PRACTICE:

“Triglyceride levels may serve as a useful predictor for dementia risk and cognitive decline in older populations,” the investigators write. Higher triglyceride levels may reflect better overall health and/or lifestyle behaviors that protect against dementia.

SOURCE:

The study was led by Zhen Zhou, of Monash University, Melbourne. It was published online in Neurology.

LIMITATIONS:

The study can’t establish a causal relationship between triglyceride levels and dementia or fully exclude reverse causality. As most ASPREE participants had normal to high-normal triglyceride levels, the results can’t be generalized to those with severe hypertriglyceridemia. The findings are unique to older people without CVD and may not be generalizable to other populations.

DISCLOSURES:

The study received support from the Royal Australian College of General Practitioners (RACGP)/HCF Research Foundation. Dr. Zhou reported receiving salary from the RACGP/HCF Research Foundation.

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

TOPLINE:

Higher triglyceride levels – a main energy source for the brain – are associated with lower risk for dementia that is not mediated by age, sex, or APOE epsilon-4 allele status, a large study of community-dwelling older adults suggests.

METHODOLOGY:

• The analysis included 18,294 participants, median age 75 years and median triglyceride level 106 mg/dL, from the Aspirin in Reducing Events in the Elderly (ASPREE) study, a placebo-controlled, randomized trial of daily low-dose aspirin in older people without dementia or history of cardiovascular disease (CVD) at recruitment.
• Researchers repeated their main analyses in a sub-cohort of 13,976 subjects with APOE epsilon-4 genetic data, and an external cohort of 68,200 participants, mean age 66.9 years and a median nonfasting triglyceride of 139 mg/dL, from the UK biobank, followed for a median of 12.5 years.
• The main outcome was incident dementia over 6.4 years and secondary outcomes included changes in composite cognitive function and domain-specific cognition.
• Researchers controlled for a number of potential confounders, including age, sex, race, smoking, alcohol consumption, education, family history of dementia, diabetes, hypertension, and statin use.

TAKEAWAY:

• Every doubling of baseline triglycerides was associated with an 18% lower risk of incident dementia across the entire study cohort (adjusted hazard ratio, 0.82) and in participants with genotypic data (aHR, 0.82) and a 17% lower risk in the external UK Biobank cohort (aHR, 0.83) (P ≤ .01 for all).
• In the entire cohort, the risk for dementia was 15% lower in those with triglyceride levels at 63-106 mg/dL (aHR, 0.85); 24% lower in those at 107-186 mg/dL (aHR, 0.76); and 36% lower for those with levels higher than 187 mg/dL (aHR, 0.64), compared with individuals with levels below 62 mg/dL (P for trend <.001).
• The direction and magnitude of the inverse association between triglycerides and dementia risk were not modified by age, sex, or risk factors related to triglycerides or dementia.
• In the entire study cohort, higher triglyceride levels were significantly associated with slower decline in global cognition (P = .02), composite cognition (P = .03), and a borderline significantly slower decline in episodic memory (P = .05).

IN PRACTICE:

“Triglyceride levels may serve as a useful predictor for dementia risk and cognitive decline in older populations,” the investigators write. Higher triglyceride levels may reflect better overall health and/or lifestyle behaviors that protect against dementia.

SOURCE:

The study was led by Zhen Zhou, of Monash University, Melbourne. It was published online in Neurology.

LIMITATIONS:

The study can’t establish a causal relationship between triglyceride levels and dementia or fully exclude reverse causality. As most ASPREE participants had normal to high-normal triglyceride levels, the results can’t be generalized to those with severe hypertriglyceridemia. The findings are unique to older people without CVD and may not be generalizable to other populations.

DISCLOSURES:

The study received support from the Royal Australian College of General Practitioners (RACGP)/HCF Research Foundation. Dr. Zhou reported receiving salary from the RACGP/HCF Research Foundation.

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

TOPLINE:

Higher triglyceride levels – a main energy source for the brain – are associated with lower risk for dementia that is not mediated by age, sex, or APOE epsilon-4 allele status, a large study of community-dwelling older adults suggests.

METHODOLOGY:

• The analysis included 18,294 participants, median age 75 years and median triglyceride level 106 mg/dL, from the Aspirin in Reducing Events in the Elderly (ASPREE) study, a placebo-controlled, randomized trial of daily low-dose aspirin in older people without dementia or history of cardiovascular disease (CVD) at recruitment.
• Researchers repeated their main analyses in a sub-cohort of 13,976 subjects with APOE epsilon-4 genetic data, and an external cohort of 68,200 participants, mean age 66.9 years and a median nonfasting triglyceride of 139 mg/dL, from the UK biobank, followed for a median of 12.5 years.
• The main outcome was incident dementia over 6.4 years and secondary outcomes included changes in composite cognitive function and domain-specific cognition.
• Researchers controlled for a number of potential confounders, including age, sex, race, smoking, alcohol consumption, education, family history of dementia, diabetes, hypertension, and statin use.

TAKEAWAY:

• Every doubling of baseline triglycerides was associated with an 18% lower risk of incident dementia across the entire study cohort (adjusted hazard ratio, 0.82) and in participants with genotypic data (aHR, 0.82) and a 17% lower risk in the external UK Biobank cohort (aHR, 0.83) (P ≤ .01 for all).
• In the entire cohort, the risk for dementia was 15% lower in those with triglyceride levels at 63-106 mg/dL (aHR, 0.85); 24% lower in those at 107-186 mg/dL (aHR, 0.76); and 36% lower for those with levels higher than 187 mg/dL (aHR, 0.64), compared with individuals with levels below 62 mg/dL (P for trend <.001).
• The direction and magnitude of the inverse association between triglycerides and dementia risk were not modified by age, sex, or risk factors related to triglycerides or dementia.
• In the entire study cohort, higher triglyceride levels were significantly associated with slower decline in global cognition (P = .02), composite cognition (P = .03), and a borderline significantly slower decline in episodic memory (P = .05).

IN PRACTICE:

“Triglyceride levels may serve as a useful predictor for dementia risk and cognitive decline in older populations,” the investigators write. Higher triglyceride levels may reflect better overall health and/or lifestyle behaviors that protect against dementia.

SOURCE:

The study was led by Zhen Zhou, of Monash University, Melbourne. It was published online in Neurology.

LIMITATIONS:

The study can’t establish a causal relationship between triglyceride levels and dementia or fully exclude reverse causality. As most ASPREE participants had normal to high-normal triglyceride levels, the results can’t be generalized to those with severe hypertriglyceridemia. The findings are unique to older people without CVD and may not be generalizable to other populations.

DISCLOSURES:

The study received support from the Royal Australian College of General Practitioners (RACGP)/HCF Research Foundation. Dr. Zhou reported receiving salary from the RACGP/HCF Research Foundation.

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

TOPLINE:

Detection rates of mild cognitive impairment (MCI) in primary care are extremely low, with only about 8% of expected cases diagnosed on average, a finding that points to an urgent need to improve early detection in primary care.

METHODOLOGY:

• Researchers estimated MCI detection rates among 226,756 primary care clinicians and 54,597 practices that had at least 25 patients enrolled in Medicare between 2017 and 2019. 
• They compared the expected number of MCI cases, based on a predictive model, to actual diagnosed cases as documented in claims and encounter data.
• They accounted for uncertainty in these estimates to determine whether detection rates are within the expected range or significantly higher or lower.

TAKEAWAY:

• More than 25% of clinicians and practices did not have a single patient with diagnosed MCI; the average detection rate was 0.01 for both clinicians and practices.
• The modeled expected MCI detection rate, however, was much higher (average 0.19 for clinicians and 0.20 for practices).
• Average detection rates for clinicians and practices was 0.08, with more than 99% of clinicians and practices underdiagnosing MCI; clinicians practicing geriatric medicine had higher detection rates than others.

IN PRACTICE:

The findings are “concerning not only because patients might not get identified for a disease-modifying AD treatment in time, but also because numerous causes of MCI – such as hypothyroidism and medication side effects – are reversible, and the condition itself can be stabilized by lifestyle modification interventions,” the authors write.

SOURCE:

The study was published online in the Journal of Prevention of Alzheimer’s Disease. The first author was Ying Liu, PhD, of the University of Southern California, Los Angeles.

LIMITATIONS:

The predictive model based on demographic information has only moderate accuracy. Expected prevalence of MCI was based on cognitive test scores, which is not the same as a true clinical diagnosis.

DISCLOSURES:

The study was partially funded by a contract from Genentech to the University of Southern California. Coauthors Soeren Mattke and Christopher Wallick have disclosed relationships with Genentech.

A version of this article appeared on Medscape.com.

TOPLINE:

Detection rates of mild cognitive impairment (MCI) in primary care are extremely low, with only about 8% of expected cases diagnosed on average, a finding that points to an urgent need to improve early detection in primary care.

METHODOLOGY:

• Researchers estimated MCI detection rates among 226,756 primary care clinicians and 54,597 practices that had at least 25 patients enrolled in Medicare between 2017 and 2019. 
• They compared the expected number of MCI cases, based on a predictive model, to actual diagnosed cases as documented in claims and encounter data.
• They accounted for uncertainty in these estimates to determine whether detection rates are within the expected range or significantly higher or lower.

TAKEAWAY:

• More than 25% of clinicians and practices did not have a single patient with diagnosed MCI; the average detection rate was 0.01 for both clinicians and practices.
• The modeled expected MCI detection rate, however, was much higher (average 0.19 for clinicians and 0.20 for practices).
• Average detection rates for clinicians and practices was 0.08, with more than 99% of clinicians and practices underdiagnosing MCI; clinicians practicing geriatric medicine had higher detection rates than others.

IN PRACTICE:

The findings are “concerning not only because patients might not get identified for a disease-modifying AD treatment in time, but also because numerous causes of MCI – such as hypothyroidism and medication side effects – are reversible, and the condition itself can be stabilized by lifestyle modification interventions,” the authors write.

SOURCE:

The study was published online in the Journal of Prevention of Alzheimer’s Disease. The first author was Ying Liu, PhD, of the University of Southern California, Los Angeles.

LIMITATIONS:

The predictive model based on demographic information has only moderate accuracy. Expected prevalence of MCI was based on cognitive test scores, which is not the same as a true clinical diagnosis.

DISCLOSURES:

The study was partially funded by a contract from Genentech to the University of Southern California. Coauthors Soeren Mattke and Christopher Wallick have disclosed relationships with Genentech.

A version of this article appeared on Medscape.com.

TOPLINE:

Detection rates of mild cognitive impairment (MCI) in primary care are extremely low, with only about 8% of expected cases diagnosed on average, a finding that points to an urgent need to improve early detection in primary care.

METHODOLOGY:

• Researchers estimated MCI detection rates among 226,756 primary care clinicians and 54,597 practices that had at least 25 patients enrolled in Medicare between 2017 and 2019. 
• They compared the expected number of MCI cases, based on a predictive model, to actual diagnosed cases as documented in claims and encounter data.
• They accounted for uncertainty in these estimates to determine whether detection rates are within the expected range or significantly higher or lower.

TAKEAWAY:

• More than 25% of clinicians and practices did not have a single patient with diagnosed MCI; the average detection rate was 0.01 for both clinicians and practices.
• The modeled expected MCI detection rate, however, was much higher (average 0.19 for clinicians and 0.20 for practices).
• Average detection rates for clinicians and practices was 0.08, with more than 99% of clinicians and practices underdiagnosing MCI; clinicians practicing geriatric medicine had higher detection rates than others.

IN PRACTICE:

The findings are “concerning not only because patients might not get identified for a disease-modifying AD treatment in time, but also because numerous causes of MCI – such as hypothyroidism and medication side effects – are reversible, and the condition itself can be stabilized by lifestyle modification interventions,” the authors write.

SOURCE:

The study was published online in the Journal of Prevention of Alzheimer’s Disease. The first author was Ying Liu, PhD, of the University of Southern California, Los Angeles.

LIMITATIONS:

The predictive model based on demographic information has only moderate accuracy. Expected prevalence of MCI was based on cognitive test scores, which is not the same as a true clinical diagnosis.

DISCLOSURES:

The study was partially funded by a contract from Genentech to the University of Southern California. Coauthors Soeren Mattke and Christopher Wallick have disclosed relationships with Genentech.

A version of this article appeared on Medscape.com.