Geriatrics

Only a small fraction of older adults in the early stages of Alzheimer’s disease (AD) meet eligibility criteria to receive treatment with newly approved antiamyloid drugs, largely because of the presence of medical conditions or neuroimaging findings, new research shows. 

Applying the clinical trial criteria, only about 8%-17% of amyloid-positive individuals with early AD would be eligible for lecanemab (Leqembi), and even fewer, 5%-9%, would be eligible for aducanumab (Aduhelm), the researchers found.

This study highlights the “limited suitability” of most adults with mild cognitive impairment (MCI) or mild dementia with elevated brain amyloid for treatment with these anti–beta amyloid monoclonal antibodies, write Maria Vassilaki, MD, PhD, and colleagues with Mayo Clinic, Rochester, Minn.

The study was published online in Neurology 

The authors of an accompanying editorial write that this study “provides an important estimate of treatment eligibility for amyloid-lowering monoclonal antibodies for early AD to help health systems make realistic plans for providing these treatments.”
 

More real-world data needed

Dr. Vassilaki and colleagues applied eligibility criteria for lecanemab and aducanumab to 237 older adults with MCI or mild dementia and increased brain amyloid burden from the Mayo Clinic Study of Aging (MCSA). Their mean age was 80.9 years, 55% were men, and most were White. 

After applying lecanemab’s inclusion criteria, less than half of the study population was eligible to receive treatment (112 of 237, or 47%). 

A total of 21 people were excluded because of a body mass index less than 17 or greater than or equal to 35; 48 due to a Clinical Dementia Rating (CDR) global score other than 0.5 or 1.0; 46 because they did not meet WMS-R Logical Memory II scores for age; 8 because of a Mini Mental State Examination (MMSE) score outside the bounds of 22-30; and two because of a CDR memory score less than 0.5. 

Applying lecanemab’s exclusion criteria further narrowed the number of eligible participants from 112 to 19 (8% of 237). 

Notable exclusions included cardiopulmonary contraindications, central nervous system–related exclusions such as brain cancer, Parkinson’s disease, epilepsy or brain injury, imaging findings, and history of cancer. 

The results were similar for aducanumab, with 104 of the 237 participants (44%) meeting the trial’s inclusion criteria. Applying aducanumab’s exclusion criteria further reduced the number of eligible participants to 12 (5% of 237).

A sensitivity analysis including participants with MCI, without CDR global, MMSE, or WMS-R Logical Memory II score restrictions, resulted in a somewhat higher percentage of eligible participants (17.4% for lecanemab and 8.9% for aducanumab). 
 

Shared decision-making

“Clinicians and health systems should be aware that by applying the clinical trial criteria, a smaller percentage might be eligible for these treatments than originally anticipated,” Dr. Vassilaki told this news organization. To help clinicians, there are published recommendations for the appropriate use of these treatments, she noted. 

Given that clinical trial participants are typically healthier than the general population, Dr. Vassilaki said that research is needed to examine the safety and efficacy of antiamyloid therapies in larger, more diverse populations as well as in less healthy populations, before these therapies may be more widely available to people with AD. 

“We can take advantage of the postmarketing surveillance of side effects, and also enrollment of patients receiving these treatments to registries could provide us with data useful for any necessary adjustment to drug use,” Dr. Vassilaki told this news organization. 
 

‘Sharp focus’

This study “brings the issue of eligibility for amyloid-lowering antibody treatment into sharp focus,” Matthew Howe, MD, PhD, with Butler Hospital Memory & Aging Program, Providence, R.I., and colleagues note in their editorial. 

“The results underscore the importance of careful patient selection to help identify patients most likely to benefit from treatment and exclude those at risk for serious outcomes,” they write. 

They also write that appropriate use recommendations for lecanemab and aducanumab “will be revisited as more real-world data emerge, especially about safety.”

For now, clinicians “must exercise clinical judgment in selecting patients for treatment with shared decision-making with patients and families,” they add. 

The study was supported by the National Institutes of Health, the National Institute on Aging, the Alexander Family Alzheimer’s Disease Research Professorship of the Mayo Clinic, the Mayo Foundation for Medical Education and Research, the Liston Award, the GHR Foundation and the Schuler Foundation. Dr. Vassilaki has consulted for F. Hoffmann-La Roche and has equity ownership in Abbott Laboratories, Johnson & Johnson, Medtronic, Merck, and Amgen. Dr. Howe has no conflicts of interest. 

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

Only a small fraction of older adults in the early stages of Alzheimer’s disease (AD) meet eligibility criteria to receive treatment with newly approved antiamyloid drugs, largely because of the presence of medical conditions or neuroimaging findings, new research shows. 

Applying the clinical trial criteria, only about 8%-17% of amyloid-positive individuals with early AD would be eligible for lecanemab (Leqembi), and even fewer, 5%-9%, would be eligible for aducanumab (Aduhelm), the researchers found.

This study highlights the “limited suitability” of most adults with mild cognitive impairment (MCI) or mild dementia with elevated brain amyloid for treatment with these anti–beta amyloid monoclonal antibodies, write Maria Vassilaki, MD, PhD, and colleagues with Mayo Clinic, Rochester, Minn.

The study was published online in Neurology 

The authors of an accompanying editorial write that this study “provides an important estimate of treatment eligibility for amyloid-lowering monoclonal antibodies for early AD to help health systems make realistic plans for providing these treatments.”
 

More real-world data needed

Dr. Vassilaki and colleagues applied eligibility criteria for lecanemab and aducanumab to 237 older adults with MCI or mild dementia and increased brain amyloid burden from the Mayo Clinic Study of Aging (MCSA). Their mean age was 80.9 years, 55% were men, and most were White. 

After applying lecanemab’s inclusion criteria, less than half of the study population was eligible to receive treatment (112 of 237, or 47%). 

A total of 21 people were excluded because of a body mass index less than 17 or greater than or equal to 35; 48 due to a Clinical Dementia Rating (CDR) global score other than 0.5 or 1.0; 46 because they did not meet WMS-R Logical Memory II scores for age; 8 because of a Mini Mental State Examination (MMSE) score outside the bounds of 22-30; and two because of a CDR memory score less than 0.5. 

Applying lecanemab’s exclusion criteria further narrowed the number of eligible participants from 112 to 19 (8% of 237). 

Notable exclusions included cardiopulmonary contraindications, central nervous system–related exclusions such as brain cancer, Parkinson’s disease, epilepsy or brain injury, imaging findings, and history of cancer. 

The results were similar for aducanumab, with 104 of the 237 participants (44%) meeting the trial’s inclusion criteria. Applying aducanumab’s exclusion criteria further reduced the number of eligible participants to 12 (5% of 237).

A sensitivity analysis including participants with MCI, without CDR global, MMSE, or WMS-R Logical Memory II score restrictions, resulted in a somewhat higher percentage of eligible participants (17.4% for lecanemab and 8.9% for aducanumab). 
 

Shared decision-making

“Clinicians and health systems should be aware that by applying the clinical trial criteria, a smaller percentage might be eligible for these treatments than originally anticipated,” Dr. Vassilaki told this news organization. To help clinicians, there are published recommendations for the appropriate use of these treatments, she noted. 

Given that clinical trial participants are typically healthier than the general population, Dr. Vassilaki said that research is needed to examine the safety and efficacy of antiamyloid therapies in larger, more diverse populations as well as in less healthy populations, before these therapies may be more widely available to people with AD. 

“We can take advantage of the postmarketing surveillance of side effects, and also enrollment of patients receiving these treatments to registries could provide us with data useful for any necessary adjustment to drug use,” Dr. Vassilaki told this news organization. 
 

‘Sharp focus’

This study “brings the issue of eligibility for amyloid-lowering antibody treatment into sharp focus,” Matthew Howe, MD, PhD, with Butler Hospital Memory & Aging Program, Providence, R.I., and colleagues note in their editorial. 

“The results underscore the importance of careful patient selection to help identify patients most likely to benefit from treatment and exclude those at risk for serious outcomes,” they write. 

They also write that appropriate use recommendations for lecanemab and aducanumab “will be revisited as more real-world data emerge, especially about safety.”

For now, clinicians “must exercise clinical judgment in selecting patients for treatment with shared decision-making with patients and families,” they add. 

The study was supported by the National Institutes of Health, the National Institute on Aging, the Alexander Family Alzheimer’s Disease Research Professorship of the Mayo Clinic, the Mayo Foundation for Medical Education and Research, the Liston Award, the GHR Foundation and the Schuler Foundation. Dr. Vassilaki has consulted for F. Hoffmann-La Roche and has equity ownership in Abbott Laboratories, Johnson & Johnson, Medtronic, Merck, and Amgen. Dr. Howe has no conflicts of interest. 

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

Only a small fraction of older adults in the early stages of Alzheimer’s disease (AD) meet eligibility criteria to receive treatment with newly approved antiamyloid drugs, largely because of the presence of medical conditions or neuroimaging findings, new research shows. 

Applying the clinical trial criteria, only about 8%-17% of amyloid-positive individuals with early AD would be eligible for lecanemab (Leqembi), and even fewer, 5%-9%, would be eligible for aducanumab (Aduhelm), the researchers found.

This study highlights the “limited suitability” of most adults with mild cognitive impairment (MCI) or mild dementia with elevated brain amyloid for treatment with these anti–beta amyloid monoclonal antibodies, write Maria Vassilaki, MD, PhD, and colleagues with Mayo Clinic, Rochester, Minn.

The study was published online in Neurology 

The authors of an accompanying editorial write that this study “provides an important estimate of treatment eligibility for amyloid-lowering monoclonal antibodies for early AD to help health systems make realistic plans for providing these treatments.”
 

More real-world data needed

Dr. Vassilaki and colleagues applied eligibility criteria for lecanemab and aducanumab to 237 older adults with MCI or mild dementia and increased brain amyloid burden from the Mayo Clinic Study of Aging (MCSA). Their mean age was 80.9 years, 55% were men, and most were White. 

After applying lecanemab’s inclusion criteria, less than half of the study population was eligible to receive treatment (112 of 237, or 47%). 

A total of 21 people were excluded because of a body mass index less than 17 or greater than or equal to 35; 48 due to a Clinical Dementia Rating (CDR) global score other than 0.5 or 1.0; 46 because they did not meet WMS-R Logical Memory II scores for age; 8 because of a Mini Mental State Examination (MMSE) score outside the bounds of 22-30; and two because of a CDR memory score less than 0.5. 

Applying lecanemab’s exclusion criteria further narrowed the number of eligible participants from 112 to 19 (8% of 237). 

Notable exclusions included cardiopulmonary contraindications, central nervous system–related exclusions such as brain cancer, Parkinson’s disease, epilepsy or brain injury, imaging findings, and history of cancer. 

The results were similar for aducanumab, with 104 of the 237 participants (44%) meeting the trial’s inclusion criteria. Applying aducanumab’s exclusion criteria further reduced the number of eligible participants to 12 (5% of 237).

A sensitivity analysis including participants with MCI, without CDR global, MMSE, or WMS-R Logical Memory II score restrictions, resulted in a somewhat higher percentage of eligible participants (17.4% for lecanemab and 8.9% for aducanumab). 
 

Shared decision-making

“Clinicians and health systems should be aware that by applying the clinical trial criteria, a smaller percentage might be eligible for these treatments than originally anticipated,” Dr. Vassilaki told this news organization. To help clinicians, there are published recommendations for the appropriate use of these treatments, she noted. 

Given that clinical trial participants are typically healthier than the general population, Dr. Vassilaki said that research is needed to examine the safety and efficacy of antiamyloid therapies in larger, more diverse populations as well as in less healthy populations, before these therapies may be more widely available to people with AD. 

“We can take advantage of the postmarketing surveillance of side effects, and also enrollment of patients receiving these treatments to registries could provide us with data useful for any necessary adjustment to drug use,” Dr. Vassilaki told this news organization. 
 

‘Sharp focus’

This study “brings the issue of eligibility for amyloid-lowering antibody treatment into sharp focus,” Matthew Howe, MD, PhD, with Butler Hospital Memory & Aging Program, Providence, R.I., and colleagues note in their editorial. 

“The results underscore the importance of careful patient selection to help identify patients most likely to benefit from treatment and exclude those at risk for serious outcomes,” they write. 

They also write that appropriate use recommendations for lecanemab and aducanumab “will be revisited as more real-world data emerge, especially about safety.”

For now, clinicians “must exercise clinical judgment in selecting patients for treatment with shared decision-making with patients and families,” they add. 

The study was supported by the National Institutes of Health, the National Institute on Aging, the Alexander Family Alzheimer’s Disease Research Professorship of the Mayo Clinic, the Mayo Foundation for Medical Education and Research, the Liston Award, the GHR Foundation and the Schuler Foundation. Dr. Vassilaki has consulted for F. Hoffmann-La Roche and has equity ownership in Abbott Laboratories, Johnson & Johnson, Medtronic, Merck, and Amgen. Dr. Howe has no conflicts of interest. 

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

Every 4 years, an interprofessional panel of experts from the American Geriatrics Society provides updated guidelines on safe prescribing of medications in older adults, known as the Beers Criteria. A 2023 update was released in May 2023 after panel review of more 1,500 clinical trials and research studies published since the last update.

Anticoagulants

Notable changes to the 2023 guidelines include updated recommendations for anticoagulation. Warfarin should be avoided as initial therapy for venous thromboembolism or nonvalvular atrial fibrillation unless there are contraindications to direct oral anticoagulants (DOACs) or other substantial barriers to use.

Rivaroxaban should also be avoided, and dabigatran used with caution in favor of apixaban, which is felt to have a better safety profile in older adults. Rivaroxaban may be considered if once daily dosing is deemed to be more clinically appropriate. Financial barriers regarding drug coverage and formulary options were acknowledged as a significant barrier to equitable access to preferred direct oral anticoagulants in older adults.
 

Diabetes medication

Regarding diabetes management, short-acting sulfonylureas should be avoided in addition to long-acting sulfonylureas, because of the increased risk of hypoglycemia, and cardiovascular and all-cause mortality in older adults. Sodium-glucose cotransporter 2 inhibitors as an entire class are recommended to be used with caution, as older adults are at higher risk of euglycemic ketoacidosis and urogenital infections, particularly in women in the first month of initiating treatment.

Like DOACs, the panel acknowledged that financial considerations may lead to limited options for oral diabetic treatment. In circumstances where a sulfonylurea is used, short-acting forms are preferred over long acting to reduce the risk of prolonged hypoglycemia.
 

Aspirin for primary prevention

Alongside the U.S. Preventive Services Task Force guideline update in 2022 regarding aspirin for primary prevention of cardiovascular disease and stroke, the Beer’s Criteria recommend against initiation of aspirin for primary prevention in older adults. Ticagrelor and prasugrel should be used with caution because of the increased risk of major bleeding in older adults over the age of 75, compared with clopidogrel. If prasugrel is used, a lower dose of 5 mg is recommended, in line with guidelines by the American College of Cardiology and American Heart Association.

Pain medication

For pain management, the Beer’s Criteria updated recommendations to avoid NSAIDs, particularly when used in combination with steroids or anticoagulants. The panel highlights that even short-term use of NSAIDs is high risk when used in combination with steroids or anticoagulants. If no other alternatives are possible, patients should be placed on a proton pump inhibitor or misoprostol while taking NSAIDs.

Baclofen should be avoided in older adults with renal insufficiency (estimated glomerular filtration rate < 60 mL/min per 1.73 m²) because of the increased risk of encephalopathy, and when used, should be given at the lowest effective dose with close monitoring for mental status changes.
 

Androgen and estrogen replacement therapy

For androgen replacement therapy, the panel notes that testosterone supplementation should be avoided because of cardiovascular risks unless there is confirmed hypogonadism. The panel revised their recommendation on the basis of emerging data that a history of prostate cancer is not an absolute contraindication for exogenous testosterone. A risk versus benefit discussion about exogenous testosterone should be had with a medical oncologist or urologist in those with a history of prostate cancer.

Regarding estrogen, systemic formulations should not be initiated in women over the age of 60 because of increased risk of cardiovascular events, venous thromboembolism, and dementia. In women with a history of breast cancer, vaginal estrogens are generally felt to be safe to use at low doses, such as less than 25 mcg twice weekly.

Dr. Wang is a geriatrician and general internist at Harborview Medical Center, Seattle.

Every 4 years, an interprofessional panel of experts from the American Geriatrics Society provides updated guidelines on safe prescribing of medications in older adults, known as the Beers Criteria. A 2023 update was released in May 2023 after panel review of more 1,500 clinical trials and research studies published since the last update.

Anticoagulants

Notable changes to the 2023 guidelines include updated recommendations for anticoagulation. Warfarin should be avoided as initial therapy for venous thromboembolism or nonvalvular atrial fibrillation unless there are contraindications to direct oral anticoagulants (DOACs) or other substantial barriers to use.

Rivaroxaban should also be avoided, and dabigatran used with caution in favor of apixaban, which is felt to have a better safety profile in older adults. Rivaroxaban may be considered if once daily dosing is deemed to be more clinically appropriate. Financial barriers regarding drug coverage and formulary options were acknowledged as a significant barrier to equitable access to preferred direct oral anticoagulants in older adults.
 

Diabetes medication

Regarding diabetes management, short-acting sulfonylureas should be avoided in addition to long-acting sulfonylureas, because of the increased risk of hypoglycemia, and cardiovascular and all-cause mortality in older adults. Sodium-glucose cotransporter 2 inhibitors as an entire class are recommended to be used with caution, as older adults are at higher risk of euglycemic ketoacidosis and urogenital infections, particularly in women in the first month of initiating treatment.

Like DOACs, the panel acknowledged that financial considerations may lead to limited options for oral diabetic treatment. In circumstances where a sulfonylurea is used, short-acting forms are preferred over long acting to reduce the risk of prolonged hypoglycemia.
 

Aspirin for primary prevention

Alongside the U.S. Preventive Services Task Force guideline update in 2022 regarding aspirin for primary prevention of cardiovascular disease and stroke, the Beer’s Criteria recommend against initiation of aspirin for primary prevention in older adults. Ticagrelor and prasugrel should be used with caution because of the increased risk of major bleeding in older adults over the age of 75, compared with clopidogrel. If prasugrel is used, a lower dose of 5 mg is recommended, in line with guidelines by the American College of Cardiology and American Heart Association.

Pain medication

For pain management, the Beer’s Criteria updated recommendations to avoid NSAIDs, particularly when used in combination with steroids or anticoagulants. The panel highlights that even short-term use of NSAIDs is high risk when used in combination with steroids or anticoagulants. If no other alternatives are possible, patients should be placed on a proton pump inhibitor or misoprostol while taking NSAIDs.

Baclofen should be avoided in older adults with renal insufficiency (estimated glomerular filtration rate < 60 mL/min per 1.73 m²) because of the increased risk of encephalopathy, and when used, should be given at the lowest effective dose with close monitoring for mental status changes.
 

Androgen and estrogen replacement therapy

For androgen replacement therapy, the panel notes that testosterone supplementation should be avoided because of cardiovascular risks unless there is confirmed hypogonadism. The panel revised their recommendation on the basis of emerging data that a history of prostate cancer is not an absolute contraindication for exogenous testosterone. A risk versus benefit discussion about exogenous testosterone should be had with a medical oncologist or urologist in those with a history of prostate cancer.

Regarding estrogen, systemic formulations should not be initiated in women over the age of 60 because of increased risk of cardiovascular events, venous thromboembolism, and dementia. In women with a history of breast cancer, vaginal estrogens are generally felt to be safe to use at low doses, such as less than 25 mcg twice weekly.

Dr. Wang is a geriatrician and general internist at Harborview Medical Center, Seattle.

Every 4 years, an interprofessional panel of experts from the American Geriatrics Society provides updated guidelines on safe prescribing of medications in older adults, known as the Beers Criteria. A 2023 update was released in May 2023 after panel review of more 1,500 clinical trials and research studies published since the last update.

Anticoagulants

Notable changes to the 2023 guidelines include updated recommendations for anticoagulation. Warfarin should be avoided as initial therapy for venous thromboembolism or nonvalvular atrial fibrillation unless there are contraindications to direct oral anticoagulants (DOACs) or other substantial barriers to use.

Rivaroxaban should also be avoided, and dabigatran used with caution in favor of apixaban, which is felt to have a better safety profile in older adults. Rivaroxaban may be considered if once daily dosing is deemed to be more clinically appropriate. Financial barriers regarding drug coverage and formulary options were acknowledged as a significant barrier to equitable access to preferred direct oral anticoagulants in older adults.
 

Diabetes medication

Regarding diabetes management, short-acting sulfonylureas should be avoided in addition to long-acting sulfonylureas, because of the increased risk of hypoglycemia, and cardiovascular and all-cause mortality in older adults. Sodium-glucose cotransporter 2 inhibitors as an entire class are recommended to be used with caution, as older adults are at higher risk of euglycemic ketoacidosis and urogenital infections, particularly in women in the first month of initiating treatment.

Like DOACs, the panel acknowledged that financial considerations may lead to limited options for oral diabetic treatment. In circumstances where a sulfonylurea is used, short-acting forms are preferred over long acting to reduce the risk of prolonged hypoglycemia.
 

Aspirin for primary prevention

Alongside the U.S. Preventive Services Task Force guideline update in 2022 regarding aspirin for primary prevention of cardiovascular disease and stroke, the Beer’s Criteria recommend against initiation of aspirin for primary prevention in older adults. Ticagrelor and prasugrel should be used with caution because of the increased risk of major bleeding in older adults over the age of 75, compared with clopidogrel. If prasugrel is used, a lower dose of 5 mg is recommended, in line with guidelines by the American College of Cardiology and American Heart Association.

Pain medication

For pain management, the Beer’s Criteria updated recommendations to avoid NSAIDs, particularly when used in combination with steroids or anticoagulants. The panel highlights that even short-term use of NSAIDs is high risk when used in combination with steroids or anticoagulants. If no other alternatives are possible, patients should be placed on a proton pump inhibitor or misoprostol while taking NSAIDs.

Baclofen should be avoided in older adults with renal insufficiency (estimated glomerular filtration rate < 60 mL/min per 1.73 m²) because of the increased risk of encephalopathy, and when used, should be given at the lowest effective dose with close monitoring for mental status changes.
 

Androgen and estrogen replacement therapy

For androgen replacement therapy, the panel notes that testosterone supplementation should be avoided because of cardiovascular risks unless there is confirmed hypogonadism. The panel revised their recommendation on the basis of emerging data that a history of prostate cancer is not an absolute contraindication for exogenous testosterone. A risk versus benefit discussion about exogenous testosterone should be had with a medical oncologist or urologist in those with a history of prostate cancer.

Regarding estrogen, systemic formulations should not be initiated in women over the age of 60 because of increased risk of cardiovascular events, venous thromboembolism, and dementia. In women with a history of breast cancer, vaginal estrogens are generally felt to be safe to use at low doses, such as less than 25 mcg twice weekly.

Dr. Wang is a geriatrician and general internist at Harborview Medical Center, Seattle.

The anti–amyloid-beta monoclonal antibodies lecanemab and aducanumab have introduced a new class of drugs for targeting early stage Alzheimer’s disease, but fewer than 10% of older adults with early signs of the disease would meet eligibility requirements to receive either treatment, a cross sectional study has found.

Reporting in the journal Neurology, researchers from the Mayo Clinic in Rochester, Minn., and the University of Chicago found that only a small percentage of patients in the Mayo Clinic Study of Aging (MCSA) with mild cognitive impairment (MCI) or mild dementia due to Alzheimer’s disease would meet the clinical trial eligibility requirements of either agent.

Mayo Clinic

“Our study results show only a small percentage of people with early Alzheimer’s disease may be eligible to receive treatment, mostly due to chronic health conditions and brain scan abnormalities common in older adults,” said lead researcher Maria Vassilaki, MD, PhD, an epidemiologist at Mayo Clinic in Rochester, Minn.
 

Applying clinical trial exclusion criteria to a broader population

The study included 237 people aged 50-90, 222 who had MCI and 15 with mild dementia, and whose brain scans showed increased amounts of amyloid-beta plaques. Average age of the participants was 80.9 years and 97.5% were White (99.6% not Hispanic or Latino).

The researchers then looked at the eligibility criteria for the pivotal clinical trials for lecanemab, which the U.S. Food and Drug Administration approved in January this year, and aducanumab, which the FDA cleared in 2021. Both drugs received FDA accelerated approval.

For lecanemab, clinical trial inclusion required specific scores for the Clinical Dementia Rating (CDR) (other than 0.5 or 1.0), Wechsler Memory Scale (WMS-R) Logical Memory II (which varied with age group), or Mini-Mental State Examination (MMSE) (22 to 30). A body mass index between 17 and 35 kg/m² was also an inclusion criteria. Only 112 people, or 47%, met the inclusion criteria. Exclusion criteria included a history of cardiovascular disease or cancer, Parkinson’s disease, or brain injury, or a positive brain scan. When the exclusion criteria were applied, only 19 people, or 8%, qualified for the lecanemab trial.

When the researchers modified the exclusion criteria to include all study participants with MCI but not applying results from additional cognitive tests, 17.4% of MCSA patients would have been eligible for the lecanemab trial.

Aducanumab clinical trial inclusion criteria were a CDR global score other than 0.5 and an MMSE below 24, with an age cutoff of 85 years. Only 104 of the MCSA population, or 44%, met the clinical trial criteria. When the researchers applied the exclusion criteria for cardiovascular disease, central nervous system-related exclusions (such as brain cancer or epilepsy), a history of cancer, or brain scan abnormalities, they found that only 12 people, or 5%, would have been eligible for an aducanumab trial.

“Clinical trials often have strict eligibility criteria and could exclude those with other conditions that could be common in older adults,” Dr. Vassilaki said in emailed comments. “Thus, we wanted to examine if we apply these criteria to a study that recruits participants from the community, how many of the individuals in the early symptomatic stages, mild cognitive impairment or mild dementia due to Alzheimer’s disease, would be eligible for the treatment.”

Dr. Vassilaki said these drugs need to be studied in larger, more diverse populations, as well as in less healthy populations, before they’re more widely available to people with Alzheimer’s disease. “In addition,” she said, “we can learn more from the postmarketing surveillance of side effects and also from registries of patients receiving these treatments.”

One limitation of the study Dr. Vassilaki pointed out is the overwhelmingly White population. Evaluating the clinical trial eligibility criteria in more diverse populations is crucial, she said.
 

Estimating the number of patients who would qualify for treatment

In an accompanying commentary, Matthew Howes, MD, of Butler Hospital and Brown University in Providence, R.I., and colleagues wrote that the study findings provide health systems planning to offer amyloid-lowering antibodies for Alzheimer’s disease an estimate of how many patients would be eligible for the treatments. “Providers must exercise clinical judgment in selecting patients for treatment with shared decision-making with patients and families,” the commentators wrote.

The study was supported by the National Institutes of Health, the National Institute on Aging, the Alexander Family Alzheimer’s Disease Research Professorship of the Mayo Clinic, the Mayo Foundation for Medical Education and Research, the Liston Award, the GHR Foundation, and the Schuler Foundation. Dr. Vassilaki disclosed relationships with F. Hoffmann-La Roche, Abbott Laboratories, Johnson & Johnson, Medtronic, Merck, and Amgen. Dr. Howe has no relevant disclosures.
 

The anti–amyloid-beta monoclonal antibodies lecanemab and aducanumab have introduced a new class of drugs for targeting early stage Alzheimer’s disease, but fewer than 10% of older adults with early signs of the disease would meet eligibility requirements to receive either treatment, a cross sectional study has found.

Reporting in the journal Neurology, researchers from the Mayo Clinic in Rochester, Minn., and the University of Chicago found that only a small percentage of patients in the Mayo Clinic Study of Aging (MCSA) with mild cognitive impairment (MCI) or mild dementia due to Alzheimer’s disease would meet the clinical trial eligibility requirements of either agent.

Mayo Clinic

“Our study results show only a small percentage of people with early Alzheimer’s disease may be eligible to receive treatment, mostly due to chronic health conditions and brain scan abnormalities common in older adults,” said lead researcher Maria Vassilaki, MD, PhD, an epidemiologist at Mayo Clinic in Rochester, Minn.
 

Applying clinical trial exclusion criteria to a broader population

The study included 237 people aged 50-90, 222 who had MCI and 15 with mild dementia, and whose brain scans showed increased amounts of amyloid-beta plaques. Average age of the participants was 80.9 years and 97.5% were White (99.6% not Hispanic or Latino).

The researchers then looked at the eligibility criteria for the pivotal clinical trials for lecanemab, which the U.S. Food and Drug Administration approved in January this year, and aducanumab, which the FDA cleared in 2021. Both drugs received FDA accelerated approval.

For lecanemab, clinical trial inclusion required specific scores for the Clinical Dementia Rating (CDR) (other than 0.5 or 1.0), Wechsler Memory Scale (WMS-R) Logical Memory II (which varied with age group), or Mini-Mental State Examination (MMSE) (22 to 30). A body mass index between 17 and 35 kg/m² was also an inclusion criteria. Only 112 people, or 47%, met the inclusion criteria. Exclusion criteria included a history of cardiovascular disease or cancer, Parkinson’s disease, or brain injury, or a positive brain scan. When the exclusion criteria were applied, only 19 people, or 8%, qualified for the lecanemab trial.

When the researchers modified the exclusion criteria to include all study participants with MCI but not applying results from additional cognitive tests, 17.4% of MCSA patients would have been eligible for the lecanemab trial.

Aducanumab clinical trial inclusion criteria were a CDR global score other than 0.5 and an MMSE below 24, with an age cutoff of 85 years. Only 104 of the MCSA population, or 44%, met the clinical trial criteria. When the researchers applied the exclusion criteria for cardiovascular disease, central nervous system-related exclusions (such as brain cancer or epilepsy), a history of cancer, or brain scan abnormalities, they found that only 12 people, or 5%, would have been eligible for an aducanumab trial.

“Clinical trials often have strict eligibility criteria and could exclude those with other conditions that could be common in older adults,” Dr. Vassilaki said in emailed comments. “Thus, we wanted to examine if we apply these criteria to a study that recruits participants from the community, how many of the individuals in the early symptomatic stages, mild cognitive impairment or mild dementia due to Alzheimer’s disease, would be eligible for the treatment.”

Dr. Vassilaki said these drugs need to be studied in larger, more diverse populations, as well as in less healthy populations, before they’re more widely available to people with Alzheimer’s disease. “In addition,” she said, “we can learn more from the postmarketing surveillance of side effects and also from registries of patients receiving these treatments.”

One limitation of the study Dr. Vassilaki pointed out is the overwhelmingly White population. Evaluating the clinical trial eligibility criteria in more diverse populations is crucial, she said.
 

Estimating the number of patients who would qualify for treatment

In an accompanying commentary, Matthew Howes, MD, of Butler Hospital and Brown University in Providence, R.I., and colleagues wrote that the study findings provide health systems planning to offer amyloid-lowering antibodies for Alzheimer’s disease an estimate of how many patients would be eligible for the treatments. “Providers must exercise clinical judgment in selecting patients for treatment with shared decision-making with patients and families,” the commentators wrote.

The study was supported by the National Institutes of Health, the National Institute on Aging, the Alexander Family Alzheimer’s Disease Research Professorship of the Mayo Clinic, the Mayo Foundation for Medical Education and Research, the Liston Award, the GHR Foundation, and the Schuler Foundation. Dr. Vassilaki disclosed relationships with F. Hoffmann-La Roche, Abbott Laboratories, Johnson & Johnson, Medtronic, Merck, and Amgen. Dr. Howe has no relevant disclosures.
 

The anti–amyloid-beta monoclonal antibodies lecanemab and aducanumab have introduced a new class of drugs for targeting early stage Alzheimer’s disease, but fewer than 10% of older adults with early signs of the disease would meet eligibility requirements to receive either treatment, a cross sectional study has found.

Reporting in the journal Neurology, researchers from the Mayo Clinic in Rochester, Minn., and the University of Chicago found that only a small percentage of patients in the Mayo Clinic Study of Aging (MCSA) with mild cognitive impairment (MCI) or mild dementia due to Alzheimer’s disease would meet the clinical trial eligibility requirements of either agent.

Mayo Clinic

“Our study results show only a small percentage of people with early Alzheimer’s disease may be eligible to receive treatment, mostly due to chronic health conditions and brain scan abnormalities common in older adults,” said lead researcher Maria Vassilaki, MD, PhD, an epidemiologist at Mayo Clinic in Rochester, Minn.
 

Applying clinical trial exclusion criteria to a broader population

The study included 237 people aged 50-90, 222 who had MCI and 15 with mild dementia, and whose brain scans showed increased amounts of amyloid-beta plaques. Average age of the participants was 80.9 years and 97.5% were White (99.6% not Hispanic or Latino).

The researchers then looked at the eligibility criteria for the pivotal clinical trials for lecanemab, which the U.S. Food and Drug Administration approved in January this year, and aducanumab, which the FDA cleared in 2021. Both drugs received FDA accelerated approval.

For lecanemab, clinical trial inclusion required specific scores for the Clinical Dementia Rating (CDR) (other than 0.5 or 1.0), Wechsler Memory Scale (WMS-R) Logical Memory II (which varied with age group), or Mini-Mental State Examination (MMSE) (22 to 30). A body mass index between 17 and 35 kg/m² was also an inclusion criteria. Only 112 people, or 47%, met the inclusion criteria. Exclusion criteria included a history of cardiovascular disease or cancer, Parkinson’s disease, or brain injury, or a positive brain scan. When the exclusion criteria were applied, only 19 people, or 8%, qualified for the lecanemab trial.

When the researchers modified the exclusion criteria to include all study participants with MCI but not applying results from additional cognitive tests, 17.4% of MCSA patients would have been eligible for the lecanemab trial.

Aducanumab clinical trial inclusion criteria were a CDR global score other than 0.5 and an MMSE below 24, with an age cutoff of 85 years. Only 104 of the MCSA population, or 44%, met the clinical trial criteria. When the researchers applied the exclusion criteria for cardiovascular disease, central nervous system-related exclusions (such as brain cancer or epilepsy), a history of cancer, or brain scan abnormalities, they found that only 12 people, or 5%, would have been eligible for an aducanumab trial.

“Clinical trials often have strict eligibility criteria and could exclude those with other conditions that could be common in older adults,” Dr. Vassilaki said in emailed comments. “Thus, we wanted to examine if we apply these criteria to a study that recruits participants from the community, how many of the individuals in the early symptomatic stages, mild cognitive impairment or mild dementia due to Alzheimer’s disease, would be eligible for the treatment.”

Dr. Vassilaki said these drugs need to be studied in larger, more diverse populations, as well as in less healthy populations, before they’re more widely available to people with Alzheimer’s disease. “In addition,” she said, “we can learn more from the postmarketing surveillance of side effects and also from registries of patients receiving these treatments.”

One limitation of the study Dr. Vassilaki pointed out is the overwhelmingly White population. Evaluating the clinical trial eligibility criteria in more diverse populations is crucial, she said.
 

Estimating the number of patients who would qualify for treatment

In an accompanying commentary, Matthew Howes, MD, of Butler Hospital and Brown University in Providence, R.I., and colleagues wrote that the study findings provide health systems planning to offer amyloid-lowering antibodies for Alzheimer’s disease an estimate of how many patients would be eligible for the treatments. “Providers must exercise clinical judgment in selecting patients for treatment with shared decision-making with patients and families,” the commentators wrote.

The study was supported by the National Institutes of Health, the National Institute on Aging, the Alexander Family Alzheimer’s Disease Research Professorship of the Mayo Clinic, the Mayo Foundation for Medical Education and Research, the Liston Award, the GHR Foundation, and the Schuler Foundation. Dr. Vassilaki disclosed relationships with F. Hoffmann-La Roche, Abbott Laboratories, Johnson & Johnson, Medtronic, Merck, and Amgen. Dr. Howe has no relevant disclosures.
 

Women who continued breast cancer screenings when they reached age 70 had no lower chance of dying from the disease, and just getting a mammogram could instead set them on a path toward unnecessary risks, according to a new study from Yale University.

The findings, published in Annals of Internal Medicine, suggest that between 31% and 54% of all breast cancer diagnoses in women aged 70 years and older could be considered overdiagnoses, meaning that the cancer found during the screening would not have caused symptoms in a person’s lifetime. (For context, the average life expectancy of a woman in the U.S. is 79 years, according to the Centers for Disease Control and Prevention.) 

Overdiagnosis can be harmful because it carries the risks of complications from overtreatment, plus financial and emotional hardships and unnecessary use of limited resources.

For the study, researchers analyzed data for 54,635 women aged 70 and older and compared the rate of breast cancer diagnosis and death among women who did and did not have mammograms during a 15-year follow-up period. 

The rate of breast cancer in the study among women aged 70-74 was 6% for women who were screened and 4% for women who were not screened. The researchers estimated that 31% of the cases were potentially overdiagnosed. Among women aged 75-84, breast cancer was found in 5% of women who were screened, compared to less than 3% of unscreened women. Their estimated overdiagnosis rate was 47%. Finally, 3% of women aged 85 and older who were screened had breast cancer detected, compared with 1% of women in the unscreened group. For the older group, the overdiagnosis rate was 54%.

Yale University

“While our study focused on overdiagnosis, it is important to acknowledge that overdiagnosis is just one of many considerations when deciding whether to continue screening,” researcher and Yale assistant professor of medicine Ilana Richman, MD, said in a statement. “A patient’s preferences and values, personal risk factors, and the overall balance of risks and benefits from screening are also important to take into account when making screening decisions.”

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

Women who continued breast cancer screenings when they reached age 70 had no lower chance of dying from the disease, and just getting a mammogram could instead set them on a path toward unnecessary risks, according to a new study from Yale University.

The findings, published in Annals of Internal Medicine, suggest that between 31% and 54% of all breast cancer diagnoses in women aged 70 years and older could be considered overdiagnoses, meaning that the cancer found during the screening would not have caused symptoms in a person’s lifetime. (For context, the average life expectancy of a woman in the U.S. is 79 years, according to the Centers for Disease Control and Prevention.) 

Overdiagnosis can be harmful because it carries the risks of complications from overtreatment, plus financial and emotional hardships and unnecessary use of limited resources.

For the study, researchers analyzed data for 54,635 women aged 70 and older and compared the rate of breast cancer diagnosis and death among women who did and did not have mammograms during a 15-year follow-up period. 

The rate of breast cancer in the study among women aged 70-74 was 6% for women who were screened and 4% for women who were not screened. The researchers estimated that 31% of the cases were potentially overdiagnosed. Among women aged 75-84, breast cancer was found in 5% of women who were screened, compared to less than 3% of unscreened women. Their estimated overdiagnosis rate was 47%. Finally, 3% of women aged 85 and older who were screened had breast cancer detected, compared with 1% of women in the unscreened group. For the older group, the overdiagnosis rate was 54%.

Yale University

“While our study focused on overdiagnosis, it is important to acknowledge that overdiagnosis is just one of many considerations when deciding whether to continue screening,” researcher and Yale assistant professor of medicine Ilana Richman, MD, said in a statement. “A patient’s preferences and values, personal risk factors, and the overall balance of risks and benefits from screening are also important to take into account when making screening decisions.”

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

Women who continued breast cancer screenings when they reached age 70 had no lower chance of dying from the disease, and just getting a mammogram could instead set them on a path toward unnecessary risks, according to a new study from Yale University.

The findings, published in Annals of Internal Medicine, suggest that between 31% and 54% of all breast cancer diagnoses in women aged 70 years and older could be considered overdiagnoses, meaning that the cancer found during the screening would not have caused symptoms in a person’s lifetime. (For context, the average life expectancy of a woman in the U.S. is 79 years, according to the Centers for Disease Control and Prevention.) 

Overdiagnosis can be harmful because it carries the risks of complications from overtreatment, plus financial and emotional hardships and unnecessary use of limited resources.

For the study, researchers analyzed data for 54,635 women aged 70 and older and compared the rate of breast cancer diagnosis and death among women who did and did not have mammograms during a 15-year follow-up period. 

The rate of breast cancer in the study among women aged 70-74 was 6% for women who were screened and 4% for women who were not screened. The researchers estimated that 31% of the cases were potentially overdiagnosed. Among women aged 75-84, breast cancer was found in 5% of women who were screened, compared to less than 3% of unscreened women. Their estimated overdiagnosis rate was 47%. Finally, 3% of women aged 85 and older who were screened had breast cancer detected, compared with 1% of women in the unscreened group. For the older group, the overdiagnosis rate was 54%.

Yale University

“While our study focused on overdiagnosis, it is important to acknowledge that overdiagnosis is just one of many considerations when deciding whether to continue screening,” researcher and Yale assistant professor of medicine Ilana Richman, MD, said in a statement. “A patient’s preferences and values, personal risk factors, and the overall balance of risks and benefits from screening are also important to take into account when making screening decisions.”

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

Measuring levels of the synaptic protein NPTX2 in cerebrospinal fluid (CSF) may serve as an early predictor of mild cognitive impairment (MCI) years before symptoms appear, new research indicates.

“Our study shows that low NPTX2 levels are predictive of MCI symptom onset more than 7 years in advance, including among individuals who are in late middle age,” said study investigator Anja Soldan, PhD, associate professor of neurology, Johns Hopkins University School of Medicine, Baltimore.

NPTX2 is still considered an “emerging biomarker” because knowledge about this protein is limited, Dr. Soldan noted.

Prior studies have shown that levels of NPTX2 are lower in people with MCI and dementia than in those with normal cognition and that low levels of this protein in people with MCI are associated with an increased risk of developing dementia.

“Our study extends these prior findings by showing that low protein levels are also associated with the onset of MCI symptoms,” Dr. Soldan said.

The study was published online in Annals of Neurology.
 

New therapeutic target?

The researchers measured NPTX2, as well as amyloid beta 42/40, phosphorylated (p)-tau181, and total (t)-tau in CSF collected longitudinally from 269 cognitively normal adults from the BIOCARD study.

The average age at baseline was 57.7 years. Nearly all were White, 59% were women, most were college educated, and three-quarters had a close relative with Alzheimer’s disease.

During a mean follow-up average of 16 years, 77 participants progressed to MCI or dementia within or after 7 years of baseline measurements.

In Cox regression models, lower baseline NPTX2 levels were associated with an earlier time to MCI symptom onset (hazard ratio, 0.76; P = .023). This association was significant for progression within 7 years (P = .036) and after 7 years from baseline (P = .001), the investigators reported.

Adults who progressed to MCI had, on average, about 15% lower levels of NPTX2 at baseline, compared with adults who remained cognitively normal.

Baseline NPTX2 levels improved prediction of time to MCI symptom onset after accounting for baseline Alzheimer’s disease biomarker levels (P < .01), and NPTX2 did not interact with the CSF Alzheimer’s disease biomarkers or APOE-ε4 genetic status.

Higher baseline levels of p-tau181 and t-tau were associated with higher baseline NPTX2 levels (both P < .001) and with greater declines in NPTX2 over time, suggesting that NPTX2 may decline in response to tau pathology, the investigators suggested.

Dr. Soldan said NPTX2 may be “a novel target” for developing new therapeutics for Alzheimer’s disease and other dementing and neurodegenerative disorders, as it is not an Alzheimer’s disease–specific protein.

“Efforts are underway for developing a sensitive way to measure NPTX2 brain levels in blood, which could then help clinicians identify individuals at greatest risk for cognitive decline,” she explained.

“Other next steps are to examine how changes in NPTX2 over time relate to changes in brain structure and function and to identify factors that alter levels of NPTX2, including genetic factors and potentially modifiable lifestyle factors,” Dr. Soldan said.

“If having higher levels of NPTX2 in the brain provides some resilience against developing symptoms of Alzheimer’s disease, it would be great if we could somehow increase levels of the protein,” she noted.
 

Caveats, cautionary notes

Commenting on this research, Christopher Weber, PhD, Alzheimer’s Association director of global science initiatives, said, “Research has shown that when NPTX2 levels are low, it may lead to weaker connections between neurons and could potentially affect cognitive functions, including memory and learning.”

“This new study found an association between lower levels of NPTX2 in CSF and earlier time to MCI symptom onset, and when combined with other established Alzheimer’s biomarkers, they found that NPTX2 improved the prediction of Alzheimer’s symptom onset,” Dr. Weber said.

“This is in line with previous research that suggests NPTX2 levels are associated with an increased risk of progression from MCI to Alzheimer’s dementia,” Dr. Weber said.

However, he noted some limitations of the study. “Participants were primarily White [and] highly educated, and therefore findings may not be generalizable to a real-world population,” he cautioned.

Dr. Weber said it’s also important to note that NPTX2 is not considered an Alzheimer’s-specific biomarker but rather a marker of synaptic activity and neurodegeneration. “The exact role of NPTX2 in predicting dementia is unknown,” Dr. Weber said.

He said that more studies with larger, more diverse cohorts are needed to fully understand its significance as a biomarker or therapeutic target for neurodegenerative diseases, as well as to develop a blood test for NPTX2.  

The study was supported by the National Institutes of Health. Dr. Soldan and Dr. Weber report no relevant financial relationships.

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

Measuring levels of the synaptic protein NPTX2 in cerebrospinal fluid (CSF) may serve as an early predictor of mild cognitive impairment (MCI) years before symptoms appear, new research indicates.

“Our study shows that low NPTX2 levels are predictive of MCI symptom onset more than 7 years in advance, including among individuals who are in late middle age,” said study investigator Anja Soldan, PhD, associate professor of neurology, Johns Hopkins University School of Medicine, Baltimore.

NPTX2 is still considered an “emerging biomarker” because knowledge about this protein is limited, Dr. Soldan noted.

Prior studies have shown that levels of NPTX2 are lower in people with MCI and dementia than in those with normal cognition and that low levels of this protein in people with MCI are associated with an increased risk of developing dementia.

“Our study extends these prior findings by showing that low protein levels are also associated with the onset of MCI symptoms,” Dr. Soldan said.

The study was published online in Annals of Neurology.
 

New therapeutic target?

The researchers measured NPTX2, as well as amyloid beta 42/40, phosphorylated (p)-tau181, and total (t)-tau in CSF collected longitudinally from 269 cognitively normal adults from the BIOCARD study.

The average age at baseline was 57.7 years. Nearly all were White, 59% were women, most were college educated, and three-quarters had a close relative with Alzheimer’s disease.

During a mean follow-up average of 16 years, 77 participants progressed to MCI or dementia within or after 7 years of baseline measurements.

In Cox regression models, lower baseline NPTX2 levels were associated with an earlier time to MCI symptom onset (hazard ratio, 0.76; P = .023). This association was significant for progression within 7 years (P = .036) and after 7 years from baseline (P = .001), the investigators reported.

Adults who progressed to MCI had, on average, about 15% lower levels of NPTX2 at baseline, compared with adults who remained cognitively normal.

Baseline NPTX2 levels improved prediction of time to MCI symptom onset after accounting for baseline Alzheimer’s disease biomarker levels (P < .01), and NPTX2 did not interact with the CSF Alzheimer’s disease biomarkers or APOE-ε4 genetic status.

Higher baseline levels of p-tau181 and t-tau were associated with higher baseline NPTX2 levels (both P < .001) and with greater declines in NPTX2 over time, suggesting that NPTX2 may decline in response to tau pathology, the investigators suggested.

Dr. Soldan said NPTX2 may be “a novel target” for developing new therapeutics for Alzheimer’s disease and other dementing and neurodegenerative disorders, as it is not an Alzheimer’s disease–specific protein.

“Efforts are underway for developing a sensitive way to measure NPTX2 brain levels in blood, which could then help clinicians identify individuals at greatest risk for cognitive decline,” she explained.

“Other next steps are to examine how changes in NPTX2 over time relate to changes in brain structure and function and to identify factors that alter levels of NPTX2, including genetic factors and potentially modifiable lifestyle factors,” Dr. Soldan said.

“If having higher levels of NPTX2 in the brain provides some resilience against developing symptoms of Alzheimer’s disease, it would be great if we could somehow increase levels of the protein,” she noted.
 

Caveats, cautionary notes

Commenting on this research, Christopher Weber, PhD, Alzheimer’s Association director of global science initiatives, said, “Research has shown that when NPTX2 levels are low, it may lead to weaker connections between neurons and could potentially affect cognitive functions, including memory and learning.”

“This new study found an association between lower levels of NPTX2 in CSF and earlier time to MCI symptom onset, and when combined with other established Alzheimer’s biomarkers, they found that NPTX2 improved the prediction of Alzheimer’s symptom onset,” Dr. Weber said.

“This is in line with previous research that suggests NPTX2 levels are associated with an increased risk of progression from MCI to Alzheimer’s dementia,” Dr. Weber said.

However, he noted some limitations of the study. “Participants were primarily White [and] highly educated, and therefore findings may not be generalizable to a real-world population,” he cautioned.

Dr. Weber said it’s also important to note that NPTX2 is not considered an Alzheimer’s-specific biomarker but rather a marker of synaptic activity and neurodegeneration. “The exact role of NPTX2 in predicting dementia is unknown,” Dr. Weber said.

He said that more studies with larger, more diverse cohorts are needed to fully understand its significance as a biomarker or therapeutic target for neurodegenerative diseases, as well as to develop a blood test for NPTX2.  

The study was supported by the National Institutes of Health. Dr. Soldan and Dr. Weber report no relevant financial relationships.

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

Measuring levels of the synaptic protein NPTX2 in cerebrospinal fluid (CSF) may serve as an early predictor of mild cognitive impairment (MCI) years before symptoms appear, new research indicates.

“Our study shows that low NPTX2 levels are predictive of MCI symptom onset more than 7 years in advance, including among individuals who are in late middle age,” said study investigator Anja Soldan, PhD, associate professor of neurology, Johns Hopkins University School of Medicine, Baltimore.

NPTX2 is still considered an “emerging biomarker” because knowledge about this protein is limited, Dr. Soldan noted.

Prior studies have shown that levels of NPTX2 are lower in people with MCI and dementia than in those with normal cognition and that low levels of this protein in people with MCI are associated with an increased risk of developing dementia.

“Our study extends these prior findings by showing that low protein levels are also associated with the onset of MCI symptoms,” Dr. Soldan said.

The study was published online in Annals of Neurology.
 

New therapeutic target?

The researchers measured NPTX2, as well as amyloid beta 42/40, phosphorylated (p)-tau181, and total (t)-tau in CSF collected longitudinally from 269 cognitively normal adults from the BIOCARD study.

The average age at baseline was 57.7 years. Nearly all were White, 59% were women, most were college educated, and three-quarters had a close relative with Alzheimer’s disease.

During a mean follow-up average of 16 years, 77 participants progressed to MCI or dementia within or after 7 years of baseline measurements.

In Cox regression models, lower baseline NPTX2 levels were associated with an earlier time to MCI symptom onset (hazard ratio, 0.76; P = .023). This association was significant for progression within 7 years (P = .036) and after 7 years from baseline (P = .001), the investigators reported.

Adults who progressed to MCI had, on average, about 15% lower levels of NPTX2 at baseline, compared with adults who remained cognitively normal.

Baseline NPTX2 levels improved prediction of time to MCI symptom onset after accounting for baseline Alzheimer’s disease biomarker levels (P < .01), and NPTX2 did not interact with the CSF Alzheimer’s disease biomarkers or APOE-ε4 genetic status.

Higher baseline levels of p-tau181 and t-tau were associated with higher baseline NPTX2 levels (both P < .001) and with greater declines in NPTX2 over time, suggesting that NPTX2 may decline in response to tau pathology, the investigators suggested.

Dr. Soldan said NPTX2 may be “a novel target” for developing new therapeutics for Alzheimer’s disease and other dementing and neurodegenerative disorders, as it is not an Alzheimer’s disease–specific protein.

“Efforts are underway for developing a sensitive way to measure NPTX2 brain levels in blood, which could then help clinicians identify individuals at greatest risk for cognitive decline,” she explained.

“Other next steps are to examine how changes in NPTX2 over time relate to changes in brain structure and function and to identify factors that alter levels of NPTX2, including genetic factors and potentially modifiable lifestyle factors,” Dr. Soldan said.

“If having higher levels of NPTX2 in the brain provides some resilience against developing symptoms of Alzheimer’s disease, it would be great if we could somehow increase levels of the protein,” she noted.
 

Caveats, cautionary notes

Commenting on this research, Christopher Weber, PhD, Alzheimer’s Association director of global science initiatives, said, “Research has shown that when NPTX2 levels are low, it may lead to weaker connections between neurons and could potentially affect cognitive functions, including memory and learning.”

“This new study found an association between lower levels of NPTX2 in CSF and earlier time to MCI symptom onset, and when combined with other established Alzheimer’s biomarkers, they found that NPTX2 improved the prediction of Alzheimer’s symptom onset,” Dr. Weber said.

“This is in line with previous research that suggests NPTX2 levels are associated with an increased risk of progression from MCI to Alzheimer’s dementia,” Dr. Weber said.

However, he noted some limitations of the study. “Participants were primarily White [and] highly educated, and therefore findings may not be generalizable to a real-world population,” he cautioned.

Dr. Weber said it’s also important to note that NPTX2 is not considered an Alzheimer’s-specific biomarker but rather a marker of synaptic activity and neurodegeneration. “The exact role of NPTX2 in predicting dementia is unknown,” Dr. Weber said.

He said that more studies with larger, more diverse cohorts are needed to fully understand its significance as a biomarker or therapeutic target for neurodegenerative diseases, as well as to develop a blood test for NPTX2.  

The study was supported by the National Institutes of Health. Dr. Soldan and Dr. Weber report no relevant financial relationships.

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

Adults with depression have more than double the risk of developing dementia and the risk persists regardless of when in life depression is diagnosed, a large population-based study shows.

That the association between depression and dementia persisted even among individuals first diagnosed with depression in early or mid-life provides “strong evidence that depression is not only an early symptom of dementia, but also that depression increases dementia risk,” study investigator Holly Elser, MD, PhD, epidemiologist and resident physician, University of Pennsylvania, Philadelphia, told this news organization.

The study was published online in JAMA Neurology.
 

Double the risk

Several prior studies that have examined the relationship between depression and dementia over the life course have consistently shown depression later in life is associated with subsequent dementia.

“Late-life depression is generally thought to be an early symptom of dementia or a reaction to subclinical cognitive decline,” said Dr. Elser.

The investigators wanted to examine whether the association between depression and dementia persists even when depression is diagnosed earlier in life, which may suggest it increases the risk of dementia.

“To my knowledge, ours is the largest study on this topic to date, leveraging routinely and prospectively collected data from more than 1.4 million Danish citizens followed from 1977 to 2018,” Dr. Elser noted.

The cohort included 246,499 individuals diagnosed with depression and 1,190,302 individuals without depression. 

In both groups, the median age was 50 years and 65% were women. Roughly two-thirds (68%) of those diagnosed with depression were diagnosed before age 60 years.

In Cox proportional hazards regression models, the overall hazard of dementia was more than doubled in those diagnosed with depression (hazard ratio [HR] 2.41). The risk of dementia with depression was more pronounced for men (HR, 2.98) than in women (HR, 2.21).

This association persisted even when the time elapsed from depression diagnosis was between 20 and 39 years (HR, 1.79) and whether depression was diagnosed in early life (18-44 years: HR, 3.08), mid-life (45-59 years: HR, 2.95), or late life (≥ 60 years: HR, 2.31).

It remains unclear whether effective treatment of depression modifies the risk of dementia, as the current study explored the role of antidepressants in a “very limited fashion,” Dr. Elser said.

Specifically, the researchers considered whether an individual was treated with an antidepressant within 6 months of the initial depression diagnosis and found no evidence of a difference in dementia risk between the treated and untreated groups.

“Research that explores implications of the timing and duration of treatment with antidepressants for dementia, treatment with cognitive behavioral therapy, and is able to evaluate the effectiveness of those treatments will be extremely important,” Dr. Elser said.
 

‘An assault on the brain’

Reached for comment, John Showalter, MD, chief product officer at Linus Health, said one of the most “intriguing” findings of the study is that a depression diagnosis earlier in adulthood conferred a greater risk of developing vascular dementia (HR, 3.28) than did dementia due to Alzheimer’s disease (HR, 1.73).

“The difference in risk for subtypes of dementia is a meaningful addition to our understanding of depression’s connection to dementia,” said Dr. Showalter, who was not involved in the study.

Also weighing in, Shaheen Lakhan, MD, PhD, a neurologist and researcher in Boston, said the findings from this “far-reaching investigation leave little room for doubt – depression unleashes a devastating storm within the brain, wreaking havoc on the lives of those ensnared by its grip.

“This massive, multi-decade, and high-data quality registry study adds another brick to the growing edifice of evidence attesting to the profound connection between psychiatric health and the very essence of brain health,” said Dr. Lakhan, who was not involved in the study.

“In a resounding declaration, this research underscores that psychiatric health should be perceived as an integral component of overall health – a paradigm shift that challenges long-standing misconceptions and stigmas surrounding mental disorders. Depression, once marginalized, now claims its rightful place on the pedestal of health concerns that must be addressed with unwavering resolve,” said Dr. Lakhan.

He noted that depression is “not just a mental battle, it’s a profound assault on the very fabric of the brain, leaving lives in turmoil and hearts in search of hope. No longer shrouded in silence, depression demands society’s attention.”

The study had no specific funding. Dr. Elser, Dr. Showalter, and Dr. Lakhan have reported no relevant financial relationships.

A version of this article appeared on Medscape.com.

Adults with depression have more than double the risk of developing dementia and the risk persists regardless of when in life depression is diagnosed, a large population-based study shows.

That the association between depression and dementia persisted even among individuals first diagnosed with depression in early or mid-life provides “strong evidence that depression is not only an early symptom of dementia, but also that depression increases dementia risk,” study investigator Holly Elser, MD, PhD, epidemiologist and resident physician, University of Pennsylvania, Philadelphia, told this news organization.

The study was published online in JAMA Neurology.
 

Double the risk

Several prior studies that have examined the relationship between depression and dementia over the life course have consistently shown depression later in life is associated with subsequent dementia.

“Late-life depression is generally thought to be an early symptom of dementia or a reaction to subclinical cognitive decline,” said Dr. Elser.

The investigators wanted to examine whether the association between depression and dementia persists even when depression is diagnosed earlier in life, which may suggest it increases the risk of dementia.

“To my knowledge, ours is the largest study on this topic to date, leveraging routinely and prospectively collected data from more than 1.4 million Danish citizens followed from 1977 to 2018,” Dr. Elser noted.

The cohort included 246,499 individuals diagnosed with depression and 1,190,302 individuals without depression. 

In both groups, the median age was 50 years and 65% were women. Roughly two-thirds (68%) of those diagnosed with depression were diagnosed before age 60 years.

In Cox proportional hazards regression models, the overall hazard of dementia was more than doubled in those diagnosed with depression (hazard ratio [HR] 2.41). The risk of dementia with depression was more pronounced for men (HR, 2.98) than in women (HR, 2.21).

This association persisted even when the time elapsed from depression diagnosis was between 20 and 39 years (HR, 1.79) and whether depression was diagnosed in early life (18-44 years: HR, 3.08), mid-life (45-59 years: HR, 2.95), or late life (≥ 60 years: HR, 2.31).

It remains unclear whether effective treatment of depression modifies the risk of dementia, as the current study explored the role of antidepressants in a “very limited fashion,” Dr. Elser said.

Specifically, the researchers considered whether an individual was treated with an antidepressant within 6 months of the initial depression diagnosis and found no evidence of a difference in dementia risk between the treated and untreated groups.

“Research that explores implications of the timing and duration of treatment with antidepressants for dementia, treatment with cognitive behavioral therapy, and is able to evaluate the effectiveness of those treatments will be extremely important,” Dr. Elser said.
 

‘An assault on the brain’

Reached for comment, John Showalter, MD, chief product officer at Linus Health, said one of the most “intriguing” findings of the study is that a depression diagnosis earlier in adulthood conferred a greater risk of developing vascular dementia (HR, 3.28) than did dementia due to Alzheimer’s disease (HR, 1.73).

“The difference in risk for subtypes of dementia is a meaningful addition to our understanding of depression’s connection to dementia,” said Dr. Showalter, who was not involved in the study.

Also weighing in, Shaheen Lakhan, MD, PhD, a neurologist and researcher in Boston, said the findings from this “far-reaching investigation leave little room for doubt – depression unleashes a devastating storm within the brain, wreaking havoc on the lives of those ensnared by its grip.

“This massive, multi-decade, and high-data quality registry study adds another brick to the growing edifice of evidence attesting to the profound connection between psychiatric health and the very essence of brain health,” said Dr. Lakhan, who was not involved in the study.

“In a resounding declaration, this research underscores that psychiatric health should be perceived as an integral component of overall health – a paradigm shift that challenges long-standing misconceptions and stigmas surrounding mental disorders. Depression, once marginalized, now claims its rightful place on the pedestal of health concerns that must be addressed with unwavering resolve,” said Dr. Lakhan.

He noted that depression is “not just a mental battle, it’s a profound assault on the very fabric of the brain, leaving lives in turmoil and hearts in search of hope. No longer shrouded in silence, depression demands society’s attention.”

The study had no specific funding. Dr. Elser, Dr. Showalter, and Dr. Lakhan have reported no relevant financial relationships.

A version of this article appeared on Medscape.com.

Adults with depression have more than double the risk of developing dementia and the risk persists regardless of when in life depression is diagnosed, a large population-based study shows.

That the association between depression and dementia persisted even among individuals first diagnosed with depression in early or mid-life provides “strong evidence that depression is not only an early symptom of dementia, but also that depression increases dementia risk,” study investigator Holly Elser, MD, PhD, epidemiologist and resident physician, University of Pennsylvania, Philadelphia, told this news organization.

The study was published online in JAMA Neurology.
 

Double the risk

Several prior studies that have examined the relationship between depression and dementia over the life course have consistently shown depression later in life is associated with subsequent dementia.

“Late-life depression is generally thought to be an early symptom of dementia or a reaction to subclinical cognitive decline,” said Dr. Elser.

The investigators wanted to examine whether the association between depression and dementia persists even when depression is diagnosed earlier in life, which may suggest it increases the risk of dementia.

“To my knowledge, ours is the largest study on this topic to date, leveraging routinely and prospectively collected data from more than 1.4 million Danish citizens followed from 1977 to 2018,” Dr. Elser noted.

The cohort included 246,499 individuals diagnosed with depression and 1,190,302 individuals without depression. 

In both groups, the median age was 50 years and 65% were women. Roughly two-thirds (68%) of those diagnosed with depression were diagnosed before age 60 years.

In Cox proportional hazards regression models, the overall hazard of dementia was more than doubled in those diagnosed with depression (hazard ratio [HR] 2.41). The risk of dementia with depression was more pronounced for men (HR, 2.98) than in women (HR, 2.21).

This association persisted even when the time elapsed from depression diagnosis was between 20 and 39 years (HR, 1.79) and whether depression was diagnosed in early life (18-44 years: HR, 3.08), mid-life (45-59 years: HR, 2.95), or late life (≥ 60 years: HR, 2.31).

It remains unclear whether effective treatment of depression modifies the risk of dementia, as the current study explored the role of antidepressants in a “very limited fashion,” Dr. Elser said.

Specifically, the researchers considered whether an individual was treated with an antidepressant within 6 months of the initial depression diagnosis and found no evidence of a difference in dementia risk between the treated and untreated groups.

“Research that explores implications of the timing and duration of treatment with antidepressants for dementia, treatment with cognitive behavioral therapy, and is able to evaluate the effectiveness of those treatments will be extremely important,” Dr. Elser said.
 

‘An assault on the brain’

Reached for comment, John Showalter, MD, chief product officer at Linus Health, said one of the most “intriguing” findings of the study is that a depression diagnosis earlier in adulthood conferred a greater risk of developing vascular dementia (HR, 3.28) than did dementia due to Alzheimer’s disease (HR, 1.73).

“The difference in risk for subtypes of dementia is a meaningful addition to our understanding of depression’s connection to dementia,” said Dr. Showalter, who was not involved in the study.

Also weighing in, Shaheen Lakhan, MD, PhD, a neurologist and researcher in Boston, said the findings from this “far-reaching investigation leave little room for doubt – depression unleashes a devastating storm within the brain, wreaking havoc on the lives of those ensnared by its grip.

“This massive, multi-decade, and high-data quality registry study adds another brick to the growing edifice of evidence attesting to the profound connection between psychiatric health and the very essence of brain health,” said Dr. Lakhan, who was not involved in the study.

“In a resounding declaration, this research underscores that psychiatric health should be perceived as an integral component of overall health – a paradigm shift that challenges long-standing misconceptions and stigmas surrounding mental disorders. Depression, once marginalized, now claims its rightful place on the pedestal of health concerns that must be addressed with unwavering resolve,” said Dr. Lakhan.

He noted that depression is “not just a mental battle, it’s a profound assault on the very fabric of the brain, leaving lives in turmoil and hearts in search of hope. No longer shrouded in silence, depression demands society’s attention.”

The study had no specific funding. Dr. Elser, Dr. Showalter, and Dr. Lakhan have reported no relevant financial relationships.

A version of this article appeared on Medscape.com.

Under a new Medicare pilot program that will begin in 2024, the federal government will pay clinicians to coordinate at-home dementia support services, including respite care for family members.

A Department of Health & Human Services initiative, part of the aim of the Guiding an Improved Dementia Experience (GUIDE) program is to help Medicare beneficiaries with dementia stay in the community for as long as possible. It is estimated that there are 6.7 million Americans living with Alzheimer’s disease or some other form of dementia, said HHS.

The program is voluntary and will be open to Medicare-enrolled clinicians and other providers who can assemble an interdisciplinary care team and meet the program’s participation criteria.

“Our new GUIDE Model has the potential to improve the quality of life for people with dementia and alleviate the significant strain on our families,” said HHS Secretary Xavier Becerra, in a statement.

“Not only is dementia care management a proven way to improve the quality of care and quality of life for those living with Alzheimer’s and other dementia, but now we know that it would also save the federal government billions of dollars,” Robert Egge, Alzheimer’s Association chief public policy officer and Alzheimer’s Impact Movement (AIM) executive director, said in a statement.

Mr. Egge cited a recent analysis commissioned by AIM that found that dementia care management would save the federal government nearly $21 billion over 10 years.

“People living with dementia and their caregivers too often struggle to manage their health care and connect with key supports that can allow them to remain in their homes and communities,” said Centers for Medicare & Medicaid Services Administrator Chiquita Brooks-LaSure, in the HHS statement.

“Fragmented care contributes to the mental and physical health strain of caring for someone with dementia, as well as the substantial financial burden,” she said, adding that Black, Hispanic, Asian American, Native Hawaiian, and Pacific Islander populations have been especially disadvantaged.

The GUIDE Model will provide new resources and greater access to specialty care to those communities, said Ms. Brooks-LaSure.

Care teams that seek to participate in the GUIDE model must have a care navigator who has received required training in dementia, assessment, and care planning.

The teams also must have a clinician with dementia proficiency as recognized by experience caring for adults with cognitive impairment; experience caring for patients aged 65 years old or older; or specialty designation in neurology, psychiatry, geriatrics, geriatric psychiatry, behavioral neurology, or geriatric neurology.

Medicare beneficiaries will be eligible if they are not residing in a nursing home; are not enrolled in hospice; and have a confirmed dementia diagnosis.

Beneficiaries who receive care from GUIDE participants will be placed in one of five “tiers,” based on a combination of disease stage and caregiver status. Beneficiary needs, and care intensity and payment, increase by tier.

GUIDE teams will receive a monthly, per-beneficiary amount for providing care management and coordination and caregiver education and support services. They can also bill for respite services – up to an annual cap – for Medicare beneficiaries who have an unpaid caregiver.

Clinicians seeking to participate in GUIDE can apply beginning in the fall. The program will run for 8 years beginning July 1, 2024.

Alzheimer’s Association President and CEO Joanne Pike, DrPH, said in a statement that the organization had “advocated for this approach for years, believing it [to be] the key to addressing systemic challenges faced by those with dementia, their families and those who provide them with care and support.”

The John A. Hartford Foundation noted that it also had long pushed for a comprehensive dementia care program. “Comprehensive dementia care supports both the medical and nonmedical needs of patients and their family caregivers,” said Foundation President Terry Fulmer, PhD, RN, FAAN, in a statement.

“Notably and necessarily, the model will help improve equity in access to care for underserved communities by addressing unpaid caregiver needs, including respite services and screening for health-related social needs,” added Dr. Fulmer.

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

Under a new Medicare pilot program that will begin in 2024, the federal government will pay clinicians to coordinate at-home dementia support services, including respite care for family members.

A Department of Health & Human Services initiative, part of the aim of the Guiding an Improved Dementia Experience (GUIDE) program is to help Medicare beneficiaries with dementia stay in the community for as long as possible. It is estimated that there are 6.7 million Americans living with Alzheimer’s disease or some other form of dementia, said HHS.

The program is voluntary and will be open to Medicare-enrolled clinicians and other providers who can assemble an interdisciplinary care team and meet the program’s participation criteria.

“Our new GUIDE Model has the potential to improve the quality of life for people with dementia and alleviate the significant strain on our families,” said HHS Secretary Xavier Becerra, in a statement.

“Not only is dementia care management a proven way to improve the quality of care and quality of life for those living with Alzheimer’s and other dementia, but now we know that it would also save the federal government billions of dollars,” Robert Egge, Alzheimer’s Association chief public policy officer and Alzheimer’s Impact Movement (AIM) executive director, said in a statement.

Mr. Egge cited a recent analysis commissioned by AIM that found that dementia care management would save the federal government nearly $21 billion over 10 years.

“People living with dementia and their caregivers too often struggle to manage their health care and connect with key supports that can allow them to remain in their homes and communities,” said Centers for Medicare & Medicaid Services Administrator Chiquita Brooks-LaSure, in the HHS statement.

“Fragmented care contributes to the mental and physical health strain of caring for someone with dementia, as well as the substantial financial burden,” she said, adding that Black, Hispanic, Asian American, Native Hawaiian, and Pacific Islander populations have been especially disadvantaged.

The GUIDE Model will provide new resources and greater access to specialty care to those communities, said Ms. Brooks-LaSure.

Care teams that seek to participate in the GUIDE model must have a care navigator who has received required training in dementia, assessment, and care planning.

The teams also must have a clinician with dementia proficiency as recognized by experience caring for adults with cognitive impairment; experience caring for patients aged 65 years old or older; or specialty designation in neurology, psychiatry, geriatrics, geriatric psychiatry, behavioral neurology, or geriatric neurology.

Medicare beneficiaries will be eligible if they are not residing in a nursing home; are not enrolled in hospice; and have a confirmed dementia diagnosis.

Beneficiaries who receive care from GUIDE participants will be placed in one of five “tiers,” based on a combination of disease stage and caregiver status. Beneficiary needs, and care intensity and payment, increase by tier.

GUIDE teams will receive a monthly, per-beneficiary amount for providing care management and coordination and caregiver education and support services. They can also bill for respite services – up to an annual cap – for Medicare beneficiaries who have an unpaid caregiver.

Clinicians seeking to participate in GUIDE can apply beginning in the fall. The program will run for 8 years beginning July 1, 2024.

Alzheimer’s Association President and CEO Joanne Pike, DrPH, said in a statement that the organization had “advocated for this approach for years, believing it [to be] the key to addressing systemic challenges faced by those with dementia, their families and those who provide them with care and support.”

The John A. Hartford Foundation noted that it also had long pushed for a comprehensive dementia care program. “Comprehensive dementia care supports both the medical and nonmedical needs of patients and their family caregivers,” said Foundation President Terry Fulmer, PhD, RN, FAAN, in a statement.

“Notably and necessarily, the model will help improve equity in access to care for underserved communities by addressing unpaid caregiver needs, including respite services and screening for health-related social needs,” added Dr. Fulmer.

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

Under a new Medicare pilot program that will begin in 2024, the federal government will pay clinicians to coordinate at-home dementia support services, including respite care for family members.

A Department of Health & Human Services initiative, part of the aim of the Guiding an Improved Dementia Experience (GUIDE) program is to help Medicare beneficiaries with dementia stay in the community for as long as possible. It is estimated that there are 6.7 million Americans living with Alzheimer’s disease or some other form of dementia, said HHS.

The program is voluntary and will be open to Medicare-enrolled clinicians and other providers who can assemble an interdisciplinary care team and meet the program’s participation criteria.

“Our new GUIDE Model has the potential to improve the quality of life for people with dementia and alleviate the significant strain on our families,” said HHS Secretary Xavier Becerra, in a statement.

“Not only is dementia care management a proven way to improve the quality of care and quality of life for those living with Alzheimer’s and other dementia, but now we know that it would also save the federal government billions of dollars,” Robert Egge, Alzheimer’s Association chief public policy officer and Alzheimer’s Impact Movement (AIM) executive director, said in a statement.

Mr. Egge cited a recent analysis commissioned by AIM that found that dementia care management would save the federal government nearly $21 billion over 10 years.

“People living with dementia and their caregivers too often struggle to manage their health care and connect with key supports that can allow them to remain in their homes and communities,” said Centers for Medicare & Medicaid Services Administrator Chiquita Brooks-LaSure, in the HHS statement.

“Fragmented care contributes to the mental and physical health strain of caring for someone with dementia, as well as the substantial financial burden,” she said, adding that Black, Hispanic, Asian American, Native Hawaiian, and Pacific Islander populations have been especially disadvantaged.

The GUIDE Model will provide new resources and greater access to specialty care to those communities, said Ms. Brooks-LaSure.

Care teams that seek to participate in the GUIDE model must have a care navigator who has received required training in dementia, assessment, and care planning.

The teams also must have a clinician with dementia proficiency as recognized by experience caring for adults with cognitive impairment; experience caring for patients aged 65 years old or older; or specialty designation in neurology, psychiatry, geriatrics, geriatric psychiatry, behavioral neurology, or geriatric neurology.

Medicare beneficiaries will be eligible if they are not residing in a nursing home; are not enrolled in hospice; and have a confirmed dementia diagnosis.

Beneficiaries who receive care from GUIDE participants will be placed in one of five “tiers,” based on a combination of disease stage and caregiver status. Beneficiary needs, and care intensity and payment, increase by tier.

GUIDE teams will receive a monthly, per-beneficiary amount for providing care management and coordination and caregiver education and support services. They can also bill for respite services – up to an annual cap – for Medicare beneficiaries who have an unpaid caregiver.

Clinicians seeking to participate in GUIDE can apply beginning in the fall. The program will run for 8 years beginning July 1, 2024.

Alzheimer’s Association President and CEO Joanne Pike, DrPH, said in a statement that the organization had “advocated for this approach for years, believing it [to be] the key to addressing systemic challenges faced by those with dementia, their families and those who provide them with care and support.”

The John A. Hartford Foundation noted that it also had long pushed for a comprehensive dementia care program. “Comprehensive dementia care supports both the medical and nonmedical needs of patients and their family caregivers,” said Foundation President Terry Fulmer, PhD, RN, FAAN, in a statement.

“Notably and necessarily, the model will help improve equity in access to care for underserved communities by addressing unpaid caregiver needs, including respite services and screening for health-related social needs,” added Dr. Fulmer.

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

Sadly, the medical business has descended to this: Some insurers are combing health records to find and target customers with a 50% chance of dying in the next 18 months. Those companies then work to persuade customers to switch into palliative and hospice care.

I’ve personally witnessed these insurer-driven interventions by companies that are rewarded financially when hospice enrollments increase. And more of this automated end-of-life medicine appears to be on the way.

What’s gained is cost savings. What’s lost is empathy and humanity.

Doctor colleagues have warned for decades about the rise of the bean-counters in medicine. Yes, health care is a business, but it should be a higher calling, too. We serve, we heal, we protect, and we comfort.

There are times, however, when the people who try to squeeze the most money out of medicine try to gain too much influence over the people who actually engage in medicine. I think the rise of phone bank boiler rooms, built on business incentives to move patients into cheaper hospice care, should be a bridge too far for our profession.

End-of-life care is one of the most sensitive and emotionally rewarding things a doctor can do. Hospice can be an excellent choice for fully informed patients and families, but we should not be turning over these decisions to artificial intelligence, spreadsheets, and crunchers of big data.

At the same time, we should realize that the end-of-life phone banks have not evolved from nowhere. The reality is that dying is expensive. The last year of life accounts for 13%-25% of all spending on Medicare, according to numerous studies. That’s more than $200 billion a year for just one part of one federal health care program. Much of that money goes to hospitals, where end-of-life patients amass average charges of $6,000 per day.

All this spending runs counter to the wishes of most Americans. According to a Kaiser Family Foundation poll, 9 out of 10 adults say they don’t want their families to be burdened financially by their end-of-life medical care. Given the choice, 7 out of 10 Americans say they want to die at home; fewer than 1 in 10 say they want to die in a hospital.

And far more people (71%) think it’s more important to die without pain or stress than to extend life as long as possible (19%).

It’s crucial for us to get this right. Within 11 years, the U.S. Census projects that seniors will outnumber kids for the first time in history: We’ll have 77 million people age 65 or older and 76.5 million age 18 or under. And many of those seniors have medical and functional conditions that signal they are nearing end of life.

As chief medical officer of a complete senior health company, and as a physician with more than 3 decades of personal experience in geriatrics, I know we can improve the final chapter of life for our older adults and our taxpayers. If medical professionals don’t do a better job with patients at the end of life, then key decisions increasingly will be driven by the money-centered phone banks.

The single biggest improvement is having a frank and direct talk with senior patients about end-of-life wishes. Remarkably, only 1 in 10 Americans say they’ve ever had an end-of-life conversation with their doctor or health care provider – no heartfelt talk about what quality of life looks like under different treatment options. Only half ever discussed the topic with a spouse or loved one.

As a result, the default end-of-life care regimen for many is to extend life at any cost, even though most Americans tell pollsters they don’t truly want that. Doctors must focus on thorough informed consent with patients before major medical crises hurt patient cognition.

Another key is for specialists and general care doctors to do a better job consulting with each other. Two of every 3 seniors have several chronic conditions, or multimorbidities; that status worsens to include 8 of every 10 seniors after age 80. That means seniors often have multiple doctors who work in their own silos and fail to communicate the competing risks and benefits of diagnostic and treatment options. The result is fragmented plans that are difficult to follow and often as likely to harm complex patients as help them.

We all know that 90-year-old people shouldn’t be on 15 drugs, and yet too many are. Big Pharma has made it easy for doctors to add new medications, but I don’t think there’s even a class in medical school to teach clinicians how to trim the medicine list. When a drug is causing side effects, the sad reality is that most doctors add another medication to treat the side effect, as opposed to removing the offending agent. We need to end this practice known as drug cascading.

Doctors need training on how to unwind prescriptions. For example, too many seniors are being prescribed atypical antipsychotics off label for dementia. Overtreatment of geriatric diabetes and hypertension causes weakness and falls. Overprescribing antibiotics for frail patients whose bladders are colonized with bacteria too often leads to colitis. We need to question why our seniors are on so many drugs.

Doctors, patients, and families should be discussing quality of life as much as quantity of life.

I’ve spent my career taking care of older people. It’s rare for me to get a phone call saying an older person died and nobody expected it. We all know that we will die, but we spend so little time talking about it and preparing for it. A great disservice will be done to patients, doctors, and the medical profession if we let the phone banks take over.

Dr. Schneeman is a geriatrician and chief medical officer for Lifespark, a senior health company based in Minneapolis.

A version of this article appeared on Medscape.com.

Sadly, the medical business has descended to this: Some insurers are combing health records to find and target customers with a 50% chance of dying in the next 18 months. Those companies then work to persuade customers to switch into palliative and hospice care.

I’ve personally witnessed these insurer-driven interventions by companies that are rewarded financially when hospice enrollments increase. And more of this automated end-of-life medicine appears to be on the way.

What’s gained is cost savings. What’s lost is empathy and humanity.

Doctor colleagues have warned for decades about the rise of the bean-counters in medicine. Yes, health care is a business, but it should be a higher calling, too. We serve, we heal, we protect, and we comfort.

There are times, however, when the people who try to squeeze the most money out of medicine try to gain too much influence over the people who actually engage in medicine. I think the rise of phone bank boiler rooms, built on business incentives to move patients into cheaper hospice care, should be a bridge too far for our profession.

End-of-life care is one of the most sensitive and emotionally rewarding things a doctor can do. Hospice can be an excellent choice for fully informed patients and families, but we should not be turning over these decisions to artificial intelligence, spreadsheets, and crunchers of big data.

At the same time, we should realize that the end-of-life phone banks have not evolved from nowhere. The reality is that dying is expensive. The last year of life accounts for 13%-25% of all spending on Medicare, according to numerous studies. That’s more than $200 billion a year for just one part of one federal health care program. Much of that money goes to hospitals, where end-of-life patients amass average charges of $6,000 per day.

All this spending runs counter to the wishes of most Americans. According to a Kaiser Family Foundation poll, 9 out of 10 adults say they don’t want their families to be burdened financially by their end-of-life medical care. Given the choice, 7 out of 10 Americans say they want to die at home; fewer than 1 in 10 say they want to die in a hospital.

And far more people (71%) think it’s more important to die without pain or stress than to extend life as long as possible (19%).

It’s crucial for us to get this right. Within 11 years, the U.S. Census projects that seniors will outnumber kids for the first time in history: We’ll have 77 million people age 65 or older and 76.5 million age 18 or under. And many of those seniors have medical and functional conditions that signal they are nearing end of life.

As chief medical officer of a complete senior health company, and as a physician with more than 3 decades of personal experience in geriatrics, I know we can improve the final chapter of life for our older adults and our taxpayers. If medical professionals don’t do a better job with patients at the end of life, then key decisions increasingly will be driven by the money-centered phone banks.

The single biggest improvement is having a frank and direct talk with senior patients about end-of-life wishes. Remarkably, only 1 in 10 Americans say they’ve ever had an end-of-life conversation with their doctor or health care provider – no heartfelt talk about what quality of life looks like under different treatment options. Only half ever discussed the topic with a spouse or loved one.

As a result, the default end-of-life care regimen for many is to extend life at any cost, even though most Americans tell pollsters they don’t truly want that. Doctors must focus on thorough informed consent with patients before major medical crises hurt patient cognition.

Another key is for specialists and general care doctors to do a better job consulting with each other. Two of every 3 seniors have several chronic conditions, or multimorbidities; that status worsens to include 8 of every 10 seniors after age 80. That means seniors often have multiple doctors who work in their own silos and fail to communicate the competing risks and benefits of diagnostic and treatment options. The result is fragmented plans that are difficult to follow and often as likely to harm complex patients as help them.

We all know that 90-year-old people shouldn’t be on 15 drugs, and yet too many are. Big Pharma has made it easy for doctors to add new medications, but I don’t think there’s even a class in medical school to teach clinicians how to trim the medicine list. When a drug is causing side effects, the sad reality is that most doctors add another medication to treat the side effect, as opposed to removing the offending agent. We need to end this practice known as drug cascading.

Doctors need training on how to unwind prescriptions. For example, too many seniors are being prescribed atypical antipsychotics off label for dementia. Overtreatment of geriatric diabetes and hypertension causes weakness and falls. Overprescribing antibiotics for frail patients whose bladders are colonized with bacteria too often leads to colitis. We need to question why our seniors are on so many drugs.

Doctors, patients, and families should be discussing quality of life as much as quantity of life.

I’ve spent my career taking care of older people. It’s rare for me to get a phone call saying an older person died and nobody expected it. We all know that we will die, but we spend so little time talking about it and preparing for it. A great disservice will be done to patients, doctors, and the medical profession if we let the phone banks take over.

Dr. Schneeman is a geriatrician and chief medical officer for Lifespark, a senior health company based in Minneapolis.

A version of this article appeared on Medscape.com.

Sadly, the medical business has descended to this: Some insurers are combing health records to find and target customers with a 50% chance of dying in the next 18 months. Those companies then work to persuade customers to switch into palliative and hospice care.

I’ve personally witnessed these insurer-driven interventions by companies that are rewarded financially when hospice enrollments increase. And more of this automated end-of-life medicine appears to be on the way.

What’s gained is cost savings. What’s lost is empathy and humanity.

Doctor colleagues have warned for decades about the rise of the bean-counters in medicine. Yes, health care is a business, but it should be a higher calling, too. We serve, we heal, we protect, and we comfort.

There are times, however, when the people who try to squeeze the most money out of medicine try to gain too much influence over the people who actually engage in medicine. I think the rise of phone bank boiler rooms, built on business incentives to move patients into cheaper hospice care, should be a bridge too far for our profession.

End-of-life care is one of the most sensitive and emotionally rewarding things a doctor can do. Hospice can be an excellent choice for fully informed patients and families, but we should not be turning over these decisions to artificial intelligence, spreadsheets, and crunchers of big data.

At the same time, we should realize that the end-of-life phone banks have not evolved from nowhere. The reality is that dying is expensive. The last year of life accounts for 13%-25% of all spending on Medicare, according to numerous studies. That’s more than $200 billion a year for just one part of one federal health care program. Much of that money goes to hospitals, where end-of-life patients amass average charges of $6,000 per day.

All this spending runs counter to the wishes of most Americans. According to a Kaiser Family Foundation poll, 9 out of 10 adults say they don’t want their families to be burdened financially by their end-of-life medical care. Given the choice, 7 out of 10 Americans say they want to die at home; fewer than 1 in 10 say they want to die in a hospital.

And far more people (71%) think it’s more important to die without pain or stress than to extend life as long as possible (19%).

It’s crucial for us to get this right. Within 11 years, the U.S. Census projects that seniors will outnumber kids for the first time in history: We’ll have 77 million people age 65 or older and 76.5 million age 18 or under. And many of those seniors have medical and functional conditions that signal they are nearing end of life.

As chief medical officer of a complete senior health company, and as a physician with more than 3 decades of personal experience in geriatrics, I know we can improve the final chapter of life for our older adults and our taxpayers. If medical professionals don’t do a better job with patients at the end of life, then key decisions increasingly will be driven by the money-centered phone banks.

The single biggest improvement is having a frank and direct talk with senior patients about end-of-life wishes. Remarkably, only 1 in 10 Americans say they’ve ever had an end-of-life conversation with their doctor or health care provider – no heartfelt talk about what quality of life looks like under different treatment options. Only half ever discussed the topic with a spouse or loved one.

As a result, the default end-of-life care regimen for many is to extend life at any cost, even though most Americans tell pollsters they don’t truly want that. Doctors must focus on thorough informed consent with patients before major medical crises hurt patient cognition.

Another key is for specialists and general care doctors to do a better job consulting with each other. Two of every 3 seniors have several chronic conditions, or multimorbidities; that status worsens to include 8 of every 10 seniors after age 80. That means seniors often have multiple doctors who work in their own silos and fail to communicate the competing risks and benefits of diagnostic and treatment options. The result is fragmented plans that are difficult to follow and often as likely to harm complex patients as help them.

We all know that 90-year-old people shouldn’t be on 15 drugs, and yet too many are. Big Pharma has made it easy for doctors to add new medications, but I don’t think there’s even a class in medical school to teach clinicians how to trim the medicine list. When a drug is causing side effects, the sad reality is that most doctors add another medication to treat the side effect, as opposed to removing the offending agent. We need to end this practice known as drug cascading.

Doctors need training on how to unwind prescriptions. For example, too many seniors are being prescribed atypical antipsychotics off label for dementia. Overtreatment of geriatric diabetes and hypertension causes weakness and falls. Overprescribing antibiotics for frail patients whose bladders are colonized with bacteria too often leads to colitis. We need to question why our seniors are on so many drugs.

Doctors, patients, and families should be discussing quality of life as much as quantity of life.

I’ve spent my career taking care of older people. It’s rare for me to get a phone call saying an older person died and nobody expected it. We all know that we will die, but we spend so little time talking about it and preparing for it. A great disservice will be done to patients, doctors, and the medical profession if we let the phone banks take over.

Dr. Schneeman is a geriatrician and chief medical officer for Lifespark, a senior health company based in Minneapolis.

A version of this article appeared on Medscape.com.

Not so fast with earlier screening for colorectal cancer (CRC), at least according to one professional group.

The American College of Physicians published updated clinical guidance maintaining 50 as the age when clinicians should start screening for CRC in patients who are asymptomatic and at average risk.

The recommendation conflicts with guidelines from the American Cancer Society and the U.S. Preventive Services Task Force, which lowered the recommended age to start screening to age 45.

Although the rate of CRC has increased among adults aged 45-49, the incidence is 35.1 cases per 100,000 people, much lower than among persons aged 50-64 (71.9 per 100,000) and those aged 65-74 (128.9 per 100,000), the guidance notes.

“The net benefit of screening is much less favorable in average-risk adults between ages 45 and 49 years than in those aged 50-75 years,” the authors wrote. “Clinicians should discuss the uncertainty around benefits and harms of screening in this population.”

The ACP’s updated guidance is provocative and should be considered in the context of other groups’ recommendations, not as superseding them just because it is the most recently published document, according to Jeffrey A. Meyerhardt, MD, MPH, codirector of the Colon and Rectal Cancer Center at Dana-Farber Cancer Institute, Boston.

“As with a lot of the things we do in medicine, it is balancing risk and potential benefit,” Dr. Meyerhardt said in an interview. “If a patient is informed that at a younger age doing screening is very likely not to find anything and there are some risks to screening, that patient could then weigh the risks and benefit with their provider.”
 

Three screening approaches

The new guidance statement is based on a critical review of existing clinical guidelines, evidence reviews, and modeling studies. The guidance does not apply to patients who have long-standing inflammatory bowel disease and those with a family history of CRC.

The guideline also addresses when clinicians should stop screening – at age 75 – and what types of tests patients should choose from.

After discussing the benefits, harms, cost, availability, and patient preferences, clinicians and patients should select one of three screening approaches, according to the ACP: a fecal immunochemical or high-sensitivity guaiac fecal occult blood test every 2 years; colonoscopy every 10 years; or flexible sigmoidoscopy every 10 years plus a fecal immunochemical test every 2 years.

They should avoid CRC screening tests that use stool DNA, CT colonography, capsule endoscopy, urine, or serum, according to the guidance.
 

A balancing act

Some physicians view starting screenings at age 45 as a settled argument.

“The entire nation is now focused on increasing screening capacity and getting everyone screened,” said Richard C. Wender, MD, professor and chair of family medicine and community health at the University of Pennsylvania, Philadelphia, who was not involved in the new guidelines. “There is not a controversy about age to start, and I anticipate that this paper won’t create a new one.”

The epidemiology of CRC is changing rapidly, Dr. Wender said.

“While CRC mortality is going down in older age groups, mortality is now rising in younger people,” he said. “While cancer incidence is lower in the 45- to 49-years-old group, the precursors to cancer are present and can be found in a substantial percentage of patients – the same percentage as 50- to 55-year-olds.”

Dr. Meyerhardt said in an interview that the recommendation to start screening at age 45 was reasonable but that more people need to be screened to detect CRC than the older population.

“Ultimately, one’s going to have to consider the various recommendations from these different societies when having a patient in front of you as a primary care or other physician to discuss screening in someone who’s what we call average risk,” he said.

Younger patients who notice any possible symptoms of CRC such as blood in stool or changes in bowel habits should discuss them with a physician, he said.

The ACP also differs from other groups in not recommending stool DNA tests such as Cologuard (Exact Sciences). Dr. Wender said this test is the least cost effective based on comparing adherence for other options. “If Cologuard can lead to higher adherence and there are data suggesting it can, then relative cost-effectiveness looks better.”
 

Why 50

In weighing the risks and benefits of screening, the ACP noted that CRC screening can entail risk for serious bleeding and perforation in the case of colonoscopy.

Overdiagnosis and associated overtreatment, as well as costly follow-ups for findings that are clinically unimportant, are additional factors to consider with various cancer screening tests, said Amir Qaseem, MD, PhD, MHA, the ACP’s chief science officer and the corresponding author of the updated guidance.

Despite some differences between various groups’ recommendations, Dr. Qaseem saw important similarities.

“We need to get everyone between 50 and 75 screened,” Dr. Qaseem said. On that point, “there is no disagreement.”

One guideline author reported receiving salary from the ACP. Dr. Qaseem reported no conflicts of interest.

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

Not so fast with earlier screening for colorectal cancer (CRC), at least according to one professional group.

The American College of Physicians published updated clinical guidance maintaining 50 as the age when clinicians should start screening for CRC in patients who are asymptomatic and at average risk.

The recommendation conflicts with guidelines from the American Cancer Society and the U.S. Preventive Services Task Force, which lowered the recommended age to start screening to age 45.

Although the rate of CRC has increased among adults aged 45-49, the incidence is 35.1 cases per 100,000 people, much lower than among persons aged 50-64 (71.9 per 100,000) and those aged 65-74 (128.9 per 100,000), the guidance notes.

“The net benefit of screening is much less favorable in average-risk adults between ages 45 and 49 years than in those aged 50-75 years,” the authors wrote. “Clinicians should discuss the uncertainty around benefits and harms of screening in this population.”

The ACP’s updated guidance is provocative and should be considered in the context of other groups’ recommendations, not as superseding them just because it is the most recently published document, according to Jeffrey A. Meyerhardt, MD, MPH, codirector of the Colon and Rectal Cancer Center at Dana-Farber Cancer Institute, Boston.

“As with a lot of the things we do in medicine, it is balancing risk and potential benefit,” Dr. Meyerhardt said in an interview. “If a patient is informed that at a younger age doing screening is very likely not to find anything and there are some risks to screening, that patient could then weigh the risks and benefit with their provider.”
 

Three screening approaches

The new guidance statement is based on a critical review of existing clinical guidelines, evidence reviews, and modeling studies. The guidance does not apply to patients who have long-standing inflammatory bowel disease and those with a family history of CRC.

The guideline also addresses when clinicians should stop screening – at age 75 – and what types of tests patients should choose from.

After discussing the benefits, harms, cost, availability, and patient preferences, clinicians and patients should select one of three screening approaches, according to the ACP: a fecal immunochemical or high-sensitivity guaiac fecal occult blood test every 2 years; colonoscopy every 10 years; or flexible sigmoidoscopy every 10 years plus a fecal immunochemical test every 2 years.

They should avoid CRC screening tests that use stool DNA, CT colonography, capsule endoscopy, urine, or serum, according to the guidance.
 

A balancing act

Some physicians view starting screenings at age 45 as a settled argument.

“The entire nation is now focused on increasing screening capacity and getting everyone screened,” said Richard C. Wender, MD, professor and chair of family medicine and community health at the University of Pennsylvania, Philadelphia, who was not involved in the new guidelines. “There is not a controversy about age to start, and I anticipate that this paper won’t create a new one.”

The epidemiology of CRC is changing rapidly, Dr. Wender said.

“While CRC mortality is going down in older age groups, mortality is now rising in younger people,” he said. “While cancer incidence is lower in the 45- to 49-years-old group, the precursors to cancer are present and can be found in a substantial percentage of patients – the same percentage as 50- to 55-year-olds.”

Dr. Meyerhardt said in an interview that the recommendation to start screening at age 45 was reasonable but that more people need to be screened to detect CRC than the older population.

“Ultimately, one’s going to have to consider the various recommendations from these different societies when having a patient in front of you as a primary care or other physician to discuss screening in someone who’s what we call average risk,” he said.

Younger patients who notice any possible symptoms of CRC such as blood in stool or changes in bowel habits should discuss them with a physician, he said.

The ACP also differs from other groups in not recommending stool DNA tests such as Cologuard (Exact Sciences). Dr. Wender said this test is the least cost effective based on comparing adherence for other options. “If Cologuard can lead to higher adherence and there are data suggesting it can, then relative cost-effectiveness looks better.”
 

Why 50

In weighing the risks and benefits of screening, the ACP noted that CRC screening can entail risk for serious bleeding and perforation in the case of colonoscopy.

Overdiagnosis and associated overtreatment, as well as costly follow-ups for findings that are clinically unimportant, are additional factors to consider with various cancer screening tests, said Amir Qaseem, MD, PhD, MHA, the ACP’s chief science officer and the corresponding author of the updated guidance.

Despite some differences between various groups’ recommendations, Dr. Qaseem saw important similarities.

“We need to get everyone between 50 and 75 screened,” Dr. Qaseem said. On that point, “there is no disagreement.”

One guideline author reported receiving salary from the ACP. Dr. Qaseem reported no conflicts of interest.

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

Not so fast with earlier screening for colorectal cancer (CRC), at least according to one professional group.

The American College of Physicians published updated clinical guidance maintaining 50 as the age when clinicians should start screening for CRC in patients who are asymptomatic and at average risk.

The recommendation conflicts with guidelines from the American Cancer Society and the U.S. Preventive Services Task Force, which lowered the recommended age to start screening to age 45.

Although the rate of CRC has increased among adults aged 45-49, the incidence is 35.1 cases per 100,000 people, much lower than among persons aged 50-64 (71.9 per 100,000) and those aged 65-74 (128.9 per 100,000), the guidance notes.

“The net benefit of screening is much less favorable in average-risk adults between ages 45 and 49 years than in those aged 50-75 years,” the authors wrote. “Clinicians should discuss the uncertainty around benefits and harms of screening in this population.”

The ACP’s updated guidance is provocative and should be considered in the context of other groups’ recommendations, not as superseding them just because it is the most recently published document, according to Jeffrey A. Meyerhardt, MD, MPH, codirector of the Colon and Rectal Cancer Center at Dana-Farber Cancer Institute, Boston.

“As with a lot of the things we do in medicine, it is balancing risk and potential benefit,” Dr. Meyerhardt said in an interview. “If a patient is informed that at a younger age doing screening is very likely not to find anything and there are some risks to screening, that patient could then weigh the risks and benefit with their provider.”
 

Three screening approaches

The new guidance statement is based on a critical review of existing clinical guidelines, evidence reviews, and modeling studies. The guidance does not apply to patients who have long-standing inflammatory bowel disease and those with a family history of CRC.

The guideline also addresses when clinicians should stop screening – at age 75 – and what types of tests patients should choose from.

After discussing the benefits, harms, cost, availability, and patient preferences, clinicians and patients should select one of three screening approaches, according to the ACP: a fecal immunochemical or high-sensitivity guaiac fecal occult blood test every 2 years; colonoscopy every 10 years; or flexible sigmoidoscopy every 10 years plus a fecal immunochemical test every 2 years.

They should avoid CRC screening tests that use stool DNA, CT colonography, capsule endoscopy, urine, or serum, according to the guidance.
 

A balancing act

Some physicians view starting screenings at age 45 as a settled argument.

“The entire nation is now focused on increasing screening capacity and getting everyone screened,” said Richard C. Wender, MD, professor and chair of family medicine and community health at the University of Pennsylvania, Philadelphia, who was not involved in the new guidelines. “There is not a controversy about age to start, and I anticipate that this paper won’t create a new one.”

The epidemiology of CRC is changing rapidly, Dr. Wender said.

“While CRC mortality is going down in older age groups, mortality is now rising in younger people,” he said. “While cancer incidence is lower in the 45- to 49-years-old group, the precursors to cancer are present and can be found in a substantial percentage of patients – the same percentage as 50- to 55-year-olds.”

Dr. Meyerhardt said in an interview that the recommendation to start screening at age 45 was reasonable but that more people need to be screened to detect CRC than the older population.

“Ultimately, one’s going to have to consider the various recommendations from these different societies when having a patient in front of you as a primary care or other physician to discuss screening in someone who’s what we call average risk,” he said.

Younger patients who notice any possible symptoms of CRC such as blood in stool or changes in bowel habits should discuss them with a physician, he said.

The ACP also differs from other groups in not recommending stool DNA tests such as Cologuard (Exact Sciences). Dr. Wender said this test is the least cost effective based on comparing adherence for other options. “If Cologuard can lead to higher adherence and there are data suggesting it can, then relative cost-effectiveness looks better.”
 

Why 50

In weighing the risks and benefits of screening, the ACP noted that CRC screening can entail risk for serious bleeding and perforation in the case of colonoscopy.

Overdiagnosis and associated overtreatment, as well as costly follow-ups for findings that are clinically unimportant, are additional factors to consider with various cancer screening tests, said Amir Qaseem, MD, PhD, MHA, the ACP’s chief science officer and the corresponding author of the updated guidance.

Despite some differences between various groups’ recommendations, Dr. Qaseem saw important similarities.

“We need to get everyone between 50 and 75 screened,” Dr. Qaseem said. On that point, “there is no disagreement.”

One guideline author reported receiving salary from the ACP. Dr. Qaseem reported no conflicts of interest.

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

Daily low-dose aspirin increased the risk of intracranial bleeding, including hemorrhagic stroke, by 38% among healthy older people with no history of cardiovascular events, and did not help prevent ischemic stroke, according to results from a large randomized trial.

The findings, published in JAMA Network Open, bolster recommendations published in 2022 by the U.S. Preventive Services Task Force against daily aspirin for primary prevention of stroke in older adults and add to a mounting consensus that it should be avoided in the healthy elderly, for whom bleeding risks outweigh potential benefits.

Stroke was a preplanned secondary outcome of the Aspirin in Reducing Events in the Elderly (ASPREE) trial, which randomized 19,114 community-living people in Australia and the United States (56% women, 91% White) to 100 mg. daily aspirin or placebo. Participants were aged 70 and older, with the exception of U.S. Black and Hispanic individuals, who could be as young as 65. Participants did not have disability or known cardiovascular disease at baseline, and blood pressure was adequately controlled.
 

ASPEE findings

In 2018 the ASPREE authors, led by John McNeil, PhD, of Monash University, Melbourne, published their findings that aspirin did not reduce mortality or cardiovascular events (including stroke) in the same large cohort.

The new analysis, led by Geoffrey Cloud, MB, BS, of Monash University, focuses on stroke and intracranial bleeding outcomes. At 5 years’ follow up, the ASPREE investigators saw no significant reduction in ischemic stroke incidence associated with aspirin (hazard ratio, 0.89; 95% confidence interval, 0.71-1.11), while incidence of all types of intracranial bleeding, including hemorrhagic stroke, was significantly increased (HR, 1.38; 95% CI, 1.03-1.84).

Altogether 108 of participants taking aspirin (1.1%) experienced some form of intracranial bleeding (subdural, extradural, and/or subarachnoid), compared with 79 (0.8%) in the placebo group. Aspirin-treated patients also saw more hemorrhagic stroke (0.5% vs. 0.4%). As the ASPREE investigators had reported in an earlier paper, upper gastrointestinal bleeding occurred in significantly more aspirin-treated patients than those on placebo (HR, 1.87; 95% CI, 1.32-2.66).

“These outcomes may alter the balance of risks and benefits of an antiplatelet drug, especially if given to individuals at low risk in a primary prevention setting. This concern is relevant given the high stroke risk in older individuals, worldwide increases in populations of older individuals, and the importance of evaluating preventive strategies in this age group,” the investigators wrote.

The investigators cited the study’s large size as a strength while noting among its weaknesses that fewer stroke and bleeding events occurred during follow-up than expected, and that not all ischemic stroke events among older participants were thoroughly investigated.
 

Patients need to know their risk

In an interview, Shlee Song, MD, director of the stroke center at Cedars-Sinai, Los Angeles, said that the new ASPREE findings underscore the importance of careful communication with patients and their families, who may be confused about which risk group they belong to and either cease taking aspirin when it is in fact indicated, or take it when it could harm them.

“We need to be clear for our patients whether these results are relevant to them or not,” Dr. Song said. “People with a history of ischemic stroke need to know aspirin therapy is helpful in reducing risk of another stroke.”

Some patients may come to believe that because their stroke occurred a long time ago, they are in a lower-risk group. “But people need to understand that with a history of a heart attack or stroke, you’re always a separate group,” Dr. Song said. “Our job is also surveillance screening – have you had a fall this past year? Have you had a change in bowel movements? The bleeding events seen in ASPREE include bleeding in the head and bleeding in the gut.”

A key issue to stress with patients, Dr. Song said, is blood pressure management. “Patients might take aspirin because a family member had a stroke, without controlling blood pressure first. That could be the perfect storm for a head bleed: uncontrolled hypertension and an antiplatelet agent.”

The ASPREE study was funded by the National Institutes of Health in the United States and Monash University and the Victorian Cancer Agency in Australia. Three coauthors reported receiving funding or fees from drug manufacturers. Dr. Song disclosed no financial conflicts related to her comments.

Daily low-dose aspirin increased the risk of intracranial bleeding, including hemorrhagic stroke, by 38% among healthy older people with no history of cardiovascular events, and did not help prevent ischemic stroke, according to results from a large randomized trial.

The findings, published in JAMA Network Open, bolster recommendations published in 2022 by the U.S. Preventive Services Task Force against daily aspirin for primary prevention of stroke in older adults and add to a mounting consensus that it should be avoided in the healthy elderly, for whom bleeding risks outweigh potential benefits.

Stroke was a preplanned secondary outcome of the Aspirin in Reducing Events in the Elderly (ASPREE) trial, which randomized 19,114 community-living people in Australia and the United States (56% women, 91% White) to 100 mg. daily aspirin or placebo. Participants were aged 70 and older, with the exception of U.S. Black and Hispanic individuals, who could be as young as 65. Participants did not have disability or known cardiovascular disease at baseline, and blood pressure was adequately controlled.
 

ASPEE findings

In 2018 the ASPREE authors, led by John McNeil, PhD, of Monash University, Melbourne, published their findings that aspirin did not reduce mortality or cardiovascular events (including stroke) in the same large cohort.

The new analysis, led by Geoffrey Cloud, MB, BS, of Monash University, focuses on stroke and intracranial bleeding outcomes. At 5 years’ follow up, the ASPREE investigators saw no significant reduction in ischemic stroke incidence associated with aspirin (hazard ratio, 0.89; 95% confidence interval, 0.71-1.11), while incidence of all types of intracranial bleeding, including hemorrhagic stroke, was significantly increased (HR, 1.38; 95% CI, 1.03-1.84).

Altogether 108 of participants taking aspirin (1.1%) experienced some form of intracranial bleeding (subdural, extradural, and/or subarachnoid), compared with 79 (0.8%) in the placebo group. Aspirin-treated patients also saw more hemorrhagic stroke (0.5% vs. 0.4%). As the ASPREE investigators had reported in an earlier paper, upper gastrointestinal bleeding occurred in significantly more aspirin-treated patients than those on placebo (HR, 1.87; 95% CI, 1.32-2.66).

“These outcomes may alter the balance of risks and benefits of an antiplatelet drug, especially if given to individuals at low risk in a primary prevention setting. This concern is relevant given the high stroke risk in older individuals, worldwide increases in populations of older individuals, and the importance of evaluating preventive strategies in this age group,” the investigators wrote.

The investigators cited the study’s large size as a strength while noting among its weaknesses that fewer stroke and bleeding events occurred during follow-up than expected, and that not all ischemic stroke events among older participants were thoroughly investigated.
 

Patients need to know their risk

In an interview, Shlee Song, MD, director of the stroke center at Cedars-Sinai, Los Angeles, said that the new ASPREE findings underscore the importance of careful communication with patients and their families, who may be confused about which risk group they belong to and either cease taking aspirin when it is in fact indicated, or take it when it could harm them.

“We need to be clear for our patients whether these results are relevant to them or not,” Dr. Song said. “People with a history of ischemic stroke need to know aspirin therapy is helpful in reducing risk of another stroke.”

Some patients may come to believe that because their stroke occurred a long time ago, they are in a lower-risk group. “But people need to understand that with a history of a heart attack or stroke, you’re always a separate group,” Dr. Song said. “Our job is also surveillance screening – have you had a fall this past year? Have you had a change in bowel movements? The bleeding events seen in ASPREE include bleeding in the head and bleeding in the gut.”

A key issue to stress with patients, Dr. Song said, is blood pressure management. “Patients might take aspirin because a family member had a stroke, without controlling blood pressure first. That could be the perfect storm for a head bleed: uncontrolled hypertension and an antiplatelet agent.”

The ASPREE study was funded by the National Institutes of Health in the United States and Monash University and the Victorian Cancer Agency in Australia. Three coauthors reported receiving funding or fees from drug manufacturers. Dr. Song disclosed no financial conflicts related to her comments.

Daily low-dose aspirin increased the risk of intracranial bleeding, including hemorrhagic stroke, by 38% among healthy older people with no history of cardiovascular events, and did not help prevent ischemic stroke, according to results from a large randomized trial.

The findings, published in JAMA Network Open, bolster recommendations published in 2022 by the U.S. Preventive Services Task Force against daily aspirin for primary prevention of stroke in older adults and add to a mounting consensus that it should be avoided in the healthy elderly, for whom bleeding risks outweigh potential benefits.

Stroke was a preplanned secondary outcome of the Aspirin in Reducing Events in the Elderly (ASPREE) trial, which randomized 19,114 community-living people in Australia and the United States (56% women, 91% White) to 100 mg. daily aspirin or placebo. Participants were aged 70 and older, with the exception of U.S. Black and Hispanic individuals, who could be as young as 65. Participants did not have disability or known cardiovascular disease at baseline, and blood pressure was adequately controlled.
 

ASPEE findings

In 2018 the ASPREE authors, led by John McNeil, PhD, of Monash University, Melbourne, published their findings that aspirin did not reduce mortality or cardiovascular events (including stroke) in the same large cohort.

The new analysis, led by Geoffrey Cloud, MB, BS, of Monash University, focuses on stroke and intracranial bleeding outcomes. At 5 years’ follow up, the ASPREE investigators saw no significant reduction in ischemic stroke incidence associated with aspirin (hazard ratio, 0.89; 95% confidence interval, 0.71-1.11), while incidence of all types of intracranial bleeding, including hemorrhagic stroke, was significantly increased (HR, 1.38; 95% CI, 1.03-1.84).

Altogether 108 of participants taking aspirin (1.1%) experienced some form of intracranial bleeding (subdural, extradural, and/or subarachnoid), compared with 79 (0.8%) in the placebo group. Aspirin-treated patients also saw more hemorrhagic stroke (0.5% vs. 0.4%). As the ASPREE investigators had reported in an earlier paper, upper gastrointestinal bleeding occurred in significantly more aspirin-treated patients than those on placebo (HR, 1.87; 95% CI, 1.32-2.66).

“These outcomes may alter the balance of risks and benefits of an antiplatelet drug, especially if given to individuals at low risk in a primary prevention setting. This concern is relevant given the high stroke risk in older individuals, worldwide increases in populations of older individuals, and the importance of evaluating preventive strategies in this age group,” the investigators wrote.

The investigators cited the study’s large size as a strength while noting among its weaknesses that fewer stroke and bleeding events occurred during follow-up than expected, and that not all ischemic stroke events among older participants were thoroughly investigated.
 

Patients need to know their risk

In an interview, Shlee Song, MD, director of the stroke center at Cedars-Sinai, Los Angeles, said that the new ASPREE findings underscore the importance of careful communication with patients and their families, who may be confused about which risk group they belong to and either cease taking aspirin when it is in fact indicated, or take it when it could harm them.

“We need to be clear for our patients whether these results are relevant to them or not,” Dr. Song said. “People with a history of ischemic stroke need to know aspirin therapy is helpful in reducing risk of another stroke.”

Some patients may come to believe that because their stroke occurred a long time ago, they are in a lower-risk group. “But people need to understand that with a history of a heart attack or stroke, you’re always a separate group,” Dr. Song said. “Our job is also surveillance screening – have you had a fall this past year? Have you had a change in bowel movements? The bleeding events seen in ASPREE include bleeding in the head and bleeding in the gut.”

A key issue to stress with patients, Dr. Song said, is blood pressure management. “Patients might take aspirin because a family member had a stroke, without controlling blood pressure first. That could be the perfect storm for a head bleed: uncontrolled hypertension and an antiplatelet agent.”

The ASPREE study was funded by the National Institutes of Health in the United States and Monash University and the Victorian Cancer Agency in Australia. Three coauthors reported receiving funding or fees from drug manufacturers. Dr. Song disclosed no financial conflicts related to her comments.