Geriatrics

Daily use of low-dose aspirin offers no significant protection against stroke and was linked to a higher rate of bleeding in the brain, according to new research published in JAMA.

The research matches other evidence advising that healthy older adults without a history of heart conditions or warning signs of stroke should not take low-dose aspirin. 

The findings also support the recommendation from the U.S. Preventive Services Task Force that low-dose aspirin should not be prescribed for preventing a first heart attack or stroke in healthy older adults, The New York Times reported.

“We can be very emphatic that healthy people who are not on aspirin and do not have multiple risk factors should not be starting it now,” said Randall Stafford, MD, of Stanford (Calif.) University, who was not involved in the study, in the Times.

It’s not as clear for others, he said.

“The longer you’ve been on aspirin and the more risk factors you have for heart attacks and strokes, the murkier it gets,” he said.

Some cardiac and stroke experts say daily aspirin should remain part of the regimen for people who have had a heart attack or stroke.

The JAMA report was based on data from a randomized control trial of 19,000 people from Australia and America. Participants were over the age of 70 and did not have heart disease. 

The data covered an average of almost 4.7 years and revealed that aspirin lowered the rate of ischemic stroke but not significantly. An ischemic stroke happens when a clot forms in a blood vessel that sends blood to the brain. 

There was also a 38% higher rate of brain bleeds for people who took aspirin daily, compared with those who took a placebo.

The Times wrote, “In the past, some doctors regarded aspirin as something of a wonder drug, capable of protecting healthy patients against a future heart attack or stroke. But recent studies have shown that the powerful drug has limited protective power among people who have not yet had such an event, and it comes with dangerous side effects.”

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

Daily use of low-dose aspirin offers no significant protection against stroke and was linked to a higher rate of bleeding in the brain, according to new research published in JAMA.

The research matches other evidence advising that healthy older adults without a history of heart conditions or warning signs of stroke should not take low-dose aspirin. 

The findings also support the recommendation from the U.S. Preventive Services Task Force that low-dose aspirin should not be prescribed for preventing a first heart attack or stroke in healthy older adults, The New York Times reported.

“We can be very emphatic that healthy people who are not on aspirin and do not have multiple risk factors should not be starting it now,” said Randall Stafford, MD, of Stanford (Calif.) University, who was not involved in the study, in the Times.

It’s not as clear for others, he said.

“The longer you’ve been on aspirin and the more risk factors you have for heart attacks and strokes, the murkier it gets,” he said.

Some cardiac and stroke experts say daily aspirin should remain part of the regimen for people who have had a heart attack or stroke.

The JAMA report was based on data from a randomized control trial of 19,000 people from Australia and America. Participants were over the age of 70 and did not have heart disease. 

The data covered an average of almost 4.7 years and revealed that aspirin lowered the rate of ischemic stroke but not significantly. An ischemic stroke happens when a clot forms in a blood vessel that sends blood to the brain. 

There was also a 38% higher rate of brain bleeds for people who took aspirin daily, compared with those who took a placebo.

The Times wrote, “In the past, some doctors regarded aspirin as something of a wonder drug, capable of protecting healthy patients against a future heart attack or stroke. But recent studies have shown that the powerful drug has limited protective power among people who have not yet had such an event, and it comes with dangerous side effects.”

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

Daily use of low-dose aspirin offers no significant protection against stroke and was linked to a higher rate of bleeding in the brain, according to new research published in JAMA.

The research matches other evidence advising that healthy older adults without a history of heart conditions or warning signs of stroke should not take low-dose aspirin. 

The findings also support the recommendation from the U.S. Preventive Services Task Force that low-dose aspirin should not be prescribed for preventing a first heart attack or stroke in healthy older adults, The New York Times reported.

“We can be very emphatic that healthy people who are not on aspirin and do not have multiple risk factors should not be starting it now,” said Randall Stafford, MD, of Stanford (Calif.) University, who was not involved in the study, in the Times.

It’s not as clear for others, he said.

“The longer you’ve been on aspirin and the more risk factors you have for heart attacks and strokes, the murkier it gets,” he said.

Some cardiac and stroke experts say daily aspirin should remain part of the regimen for people who have had a heart attack or stroke.

The JAMA report was based on data from a randomized control trial of 19,000 people from Australia and America. Participants were over the age of 70 and did not have heart disease. 

The data covered an average of almost 4.7 years and revealed that aspirin lowered the rate of ischemic stroke but not significantly. An ischemic stroke happens when a clot forms in a blood vessel that sends blood to the brain. 

There was also a 38% higher rate of brain bleeds for people who took aspirin daily, compared with those who took a placebo.

The Times wrote, “In the past, some doctors regarded aspirin as something of a wonder drug, capable of protecting healthy patients against a future heart attack or stroke. But recent studies have shown that the powerful drug has limited protective power among people who have not yet had such an event, and it comes with dangerous side effects.”

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

Gum disease and tooth loss are linked to hippocampal atrophy and may have a more negative impact on the brain than aging, new research suggests.

Investigators found that in a late middle-aged and older cohort, among patients with mild periodontitis, having fewer teeth was linked to a faster rate of left hippocampal atrophy. For those with severe gum disease, each additional lost tooth was associated with a faster rate of brain shrinkage, equivalent to 1.3 years of brain aging.

“Tooth loss and gum disease, which is inflammation of the tissue around the teeth that can cause shrinkage of the gums and loosening of the teeth, are very common, so evaluating a potential link with dementia is incredibly important,” study investigator Satoshi Yamaguchi, PhD, DDS, of Tohoku University, in Sendai, Japan, said in a release.

“Our study found that these conditions may play a role in the health of the brain area that controls thinking and memory, giving people another reason to take better care of their teeth,” Dr. Yamaguchi noted.

The findings were published online in Neurology.
 

Greater effect than aging

Although previous research suggests that tooth loss and periodontitis are risk factors for Alzheimer’s disease, longitudinal research has not shown a significant correlation between these conditions and hippocampal atrophy.

To clarify this association, the investigators followed 172 men and women (average age, 67 years) who had undergone two MRI brain scans 4 years apart and had had a dental examination. None of the participants had any signs of cognitive decline at baseline.

At study outset, information on cerebrovascular and cardiovascular disease, alcohol consumption, smoking, depression history, and cognitive function was gathered. The Mini Mental State Exam and dental exams were administered at baseline and at 4-year follow-up.

For each participant, the number of teeth was counted, and all participants were assessed for gum disease via periodontal probing depth (PD).

Healthy gums typically measure between 1 and 3 mm in depth. Mild gum disease is signified by measurements of 3-4 mm in several areas. Severe gum disease involves measurements of 5-6 mm and is accompanied by greater bone loss, leading to potential tooth loss.

Multiple regression analysis was performed, with the annual symmetric percentage change (SPC) of hippocampal volume as the dependent variable. The analysis included an interaction term between the number of teeth present (NTP) and mean PD.

Over the 4-year study period, the investigators found that the qualitative interaction between NTP and mean PD was significant for the annual SPC in the left hippocampus.

Among those with mild periodontitis, having fewer teeth correlated with more rapid atrophy of the left hippocampus, such that every tooth lost was equivalent to nearly 1 year of brain aging.

In contrast, having more teeth was associated with a faster rate of left hippocampal atrophy among those with severe periodontitis and was equivalent to 1.3 years of brain aging.

For those with severe gum disease, each additional lost tooth corresponded to a faster rate of brain shrinkage, equivalent to 1.3 years of brain aging.

“This finding indicates that periodontitis may have a greater association with left hippocampal atrophy than the association exhibited by age. Furthermore, in cases of mild periodontitis, fewer teeth may be associated with a subsequent decline in cognitive function,” the investigators write.

The study’s results, they add, highlight the importance of preserving oral health, not just the retaining of teeth. “These findings suggest that retaining teeth with severe gum disease is associated with brain atrophy,” said Dr. Yamaguchi.

“Controlling the progression of gum disease through regular dental visits is crucial, and teeth with severe gum disease may need to be extracted and replaced with appropriate prosthetic devices,” he added.

The researchers note that further studies are needed to confirm these findings.

The study was supported the Japanese Ministry of Education, Culture, Sports, Science, and Technology; Kelo University; Japan Arteriosclerosis Prevention Fund; Japanese Ministry of Health, Labor, and Welfare; Teiko University; Pfizer Japan; Bayer Yakuhin; Chugai Pharmaceutical; Daiichi Sankyo; Astrellas Pharma; Takeda Pharmaceutical; the Health Care Science Institute; the Health Science Center; and the Takeda Science Foundation. The investigators reported no relevant financial relationships.

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

Gum disease and tooth loss are linked to hippocampal atrophy and may have a more negative impact on the brain than aging, new research suggests.

Investigators found that in a late middle-aged and older cohort, among patients with mild periodontitis, having fewer teeth was linked to a faster rate of left hippocampal atrophy. For those with severe gum disease, each additional lost tooth was associated with a faster rate of brain shrinkage, equivalent to 1.3 years of brain aging.

“Tooth loss and gum disease, which is inflammation of the tissue around the teeth that can cause shrinkage of the gums and loosening of the teeth, are very common, so evaluating a potential link with dementia is incredibly important,” study investigator Satoshi Yamaguchi, PhD, DDS, of Tohoku University, in Sendai, Japan, said in a release.

“Our study found that these conditions may play a role in the health of the brain area that controls thinking and memory, giving people another reason to take better care of their teeth,” Dr. Yamaguchi noted.

The findings were published online in Neurology.
 

Greater effect than aging

Although previous research suggests that tooth loss and periodontitis are risk factors for Alzheimer’s disease, longitudinal research has not shown a significant correlation between these conditions and hippocampal atrophy.

To clarify this association, the investigators followed 172 men and women (average age, 67 years) who had undergone two MRI brain scans 4 years apart and had had a dental examination. None of the participants had any signs of cognitive decline at baseline.

At study outset, information on cerebrovascular and cardiovascular disease, alcohol consumption, smoking, depression history, and cognitive function was gathered. The Mini Mental State Exam and dental exams were administered at baseline and at 4-year follow-up.

For each participant, the number of teeth was counted, and all participants were assessed for gum disease via periodontal probing depth (PD).

Healthy gums typically measure between 1 and 3 mm in depth. Mild gum disease is signified by measurements of 3-4 mm in several areas. Severe gum disease involves measurements of 5-6 mm and is accompanied by greater bone loss, leading to potential tooth loss.

Multiple regression analysis was performed, with the annual symmetric percentage change (SPC) of hippocampal volume as the dependent variable. The analysis included an interaction term between the number of teeth present (NTP) and mean PD.

Over the 4-year study period, the investigators found that the qualitative interaction between NTP and mean PD was significant for the annual SPC in the left hippocampus.

Among those with mild periodontitis, having fewer teeth correlated with more rapid atrophy of the left hippocampus, such that every tooth lost was equivalent to nearly 1 year of brain aging.

In contrast, having more teeth was associated with a faster rate of left hippocampal atrophy among those with severe periodontitis and was equivalent to 1.3 years of brain aging.

For those with severe gum disease, each additional lost tooth corresponded to a faster rate of brain shrinkage, equivalent to 1.3 years of brain aging.

“This finding indicates that periodontitis may have a greater association with left hippocampal atrophy than the association exhibited by age. Furthermore, in cases of mild periodontitis, fewer teeth may be associated with a subsequent decline in cognitive function,” the investigators write.

The study’s results, they add, highlight the importance of preserving oral health, not just the retaining of teeth. “These findings suggest that retaining teeth with severe gum disease is associated with brain atrophy,” said Dr. Yamaguchi.

“Controlling the progression of gum disease through regular dental visits is crucial, and teeth with severe gum disease may need to be extracted and replaced with appropriate prosthetic devices,” he added.

The researchers note that further studies are needed to confirm these findings.

The study was supported the Japanese Ministry of Education, Culture, Sports, Science, and Technology; Kelo University; Japan Arteriosclerosis Prevention Fund; Japanese Ministry of Health, Labor, and Welfare; Teiko University; Pfizer Japan; Bayer Yakuhin; Chugai Pharmaceutical; Daiichi Sankyo; Astrellas Pharma; Takeda Pharmaceutical; the Health Care Science Institute; the Health Science Center; and the Takeda Science Foundation. The investigators reported no relevant financial relationships.

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

Gum disease and tooth loss are linked to hippocampal atrophy and may have a more negative impact on the brain than aging, new research suggests.

Investigators found that in a late middle-aged and older cohort, among patients with mild periodontitis, having fewer teeth was linked to a faster rate of left hippocampal atrophy. For those with severe gum disease, each additional lost tooth was associated with a faster rate of brain shrinkage, equivalent to 1.3 years of brain aging.

“Tooth loss and gum disease, which is inflammation of the tissue around the teeth that can cause shrinkage of the gums and loosening of the teeth, are very common, so evaluating a potential link with dementia is incredibly important,” study investigator Satoshi Yamaguchi, PhD, DDS, of Tohoku University, in Sendai, Japan, said in a release.

“Our study found that these conditions may play a role in the health of the brain area that controls thinking and memory, giving people another reason to take better care of their teeth,” Dr. Yamaguchi noted.

The findings were published online in Neurology.
 

Greater effect than aging

Although previous research suggests that tooth loss and periodontitis are risk factors for Alzheimer’s disease, longitudinal research has not shown a significant correlation between these conditions and hippocampal atrophy.

To clarify this association, the investigators followed 172 men and women (average age, 67 years) who had undergone two MRI brain scans 4 years apart and had had a dental examination. None of the participants had any signs of cognitive decline at baseline.

At study outset, information on cerebrovascular and cardiovascular disease, alcohol consumption, smoking, depression history, and cognitive function was gathered. The Mini Mental State Exam and dental exams were administered at baseline and at 4-year follow-up.

For each participant, the number of teeth was counted, and all participants were assessed for gum disease via periodontal probing depth (PD).

Healthy gums typically measure between 1 and 3 mm in depth. Mild gum disease is signified by measurements of 3-4 mm in several areas. Severe gum disease involves measurements of 5-6 mm and is accompanied by greater bone loss, leading to potential tooth loss.

Multiple regression analysis was performed, with the annual symmetric percentage change (SPC) of hippocampal volume as the dependent variable. The analysis included an interaction term between the number of teeth present (NTP) and mean PD.

Over the 4-year study period, the investigators found that the qualitative interaction between NTP and mean PD was significant for the annual SPC in the left hippocampus.

Among those with mild periodontitis, having fewer teeth correlated with more rapid atrophy of the left hippocampus, such that every tooth lost was equivalent to nearly 1 year of brain aging.

In contrast, having more teeth was associated with a faster rate of left hippocampal atrophy among those with severe periodontitis and was equivalent to 1.3 years of brain aging.

For those with severe gum disease, each additional lost tooth corresponded to a faster rate of brain shrinkage, equivalent to 1.3 years of brain aging.

“This finding indicates that periodontitis may have a greater association with left hippocampal atrophy than the association exhibited by age. Furthermore, in cases of mild periodontitis, fewer teeth may be associated with a subsequent decline in cognitive function,” the investigators write.

The study’s results, they add, highlight the importance of preserving oral health, not just the retaining of teeth. “These findings suggest that retaining teeth with severe gum disease is associated with brain atrophy,” said Dr. Yamaguchi.

“Controlling the progression of gum disease through regular dental visits is crucial, and teeth with severe gum disease may need to be extracted and replaced with appropriate prosthetic devices,” he added.

The researchers note that further studies are needed to confirm these findings.

The study was supported the Japanese Ministry of Education, Culture, Sports, Science, and Technology; Kelo University; Japan Arteriosclerosis Prevention Fund; Japanese Ministry of Health, Labor, and Welfare; Teiko University; Pfizer Japan; Bayer Yakuhin; Chugai Pharmaceutical; Daiichi Sankyo; Astrellas Pharma; Takeda Pharmaceutical; the Health Care Science Institute; the Health Science Center; and the Takeda Science Foundation. The investigators reported no relevant financial relationships.

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

With the Food and Drug Administration’s full stamp of approval in hand, Leqembi (lecanemab) is poised to catapult us into a new era of treatment for Alzheimer’s disease. And now that the donanemab trial data are out, there’s another antiamyloid drug waiting in the wings.

To finally have true disease-modifying therapies for Alzheimer’s disease is a massive step forward for a field that’s been plagued with disappointment. But these drugs come with serious concerns and unknowns. They will require complex decision-making, putting doctors, patients, and their families in a medical quandary.

Striking the right balance between cautious optimism and realistic expectations will be a formidable challenge.
 

Managing patient and family expectations

These drugs are no magic bullet. They slow down the dementia’s progression, buying patients more time (on the order of months) before they begin to experience significant worsening. We’ll need a lot more information from research and clinical experience before we can understand how meaningful that treatment effect is. Right now, it is unclear whether eligible patients and their families will even perceive tangible differences.

In the CLARITY-AD trial, participants on lecanemab experienced a 27% slowing in the rate of cognitive decline over 18 months. Donanemab was shown to slow decline in memory and cognition by about 35% over the same time frame in the TRAILBLAZER-ALZ 2 trial. That translates to more time for patients and their families to enjoy independence, maintain normal life, and stave off the most distressing parts of the disease.

But what happens after 18 months of treatment – will the treatment effect magnify or dissipate? How much time are we really buying in the long run? Counseling patients and their families is made all the more difficult when the answers to important questions like these remain to be seen.
 

Only a sliver of Alzheimer’s patients are current candidates

The fact is that most patients living with Alzheimer’s disease will not qualify for treatment with these drugs. Lecanemab is approved for people with early-stage disease, meaning their dementia is mild or they have mild cognitive impairment, which is a precursor to full-blown Alzheimer’s disease. Of the 6 million people in the United States living with Alzheimer’s, about 1.5 million are estimated to fall into that category. We can expect to see a similar qualifier for donanemab if it receives FDA approval, especially because that trial suggested a more pronounced treatment effect for patients in the earliest stages of the disease.

Even if a patient hits the sweet spot where they have just enough cognitive impairment, but not too much, they aren’t technically therapeutic candidates until prerequisite testing confirms amyloid protein accumulation in the brain via PET scan or cerebrospinal fluid analysis.

Even then, the FDA’s boxed warning for lecanemab recommends that patients undergo genetic testing for the apo E4 mutation to identify those at a particularly high risk for severe adverse effects including brain bleeding and swelling. This recommendation is not unreasonable considering that 15% of the Alzheimer’s population has two copies of the apo E4 mutation and fall into that high-risk group.
 

Significant risks

Antiamyloid drugs are well-known to cause serious side effects. In the lecanemab trial, 13% of participants receiving Leqembi experienced brain swelling (vs. 2% of participants receiving placebo) and 17% of participants had brain bleeding (vs. 9% of participants on placebo). In the donanemab trial, brain bleeding occurred in 31.4% of participants on the drug (vs. 13.6% on placebo) and swelling occurred in 24% (vs. 2.1% receiving placebo). Thankfully, in both trials, most of these adverse events did not produce significant symptoms, but in rare cases these events caused severe or catastrophic neurologic injury, including death.

How can we best guide patients and their families to weigh the uncertain benefits against potentially serious risks? We can start by considering the patient characteristics most likely to portend increased risk for serious side effects: apo E4 mutations, blood thinner use, and the presence of microhemorrhages on brain imaging. But after that, we’re left with a lot of uncertainty in terms of which patients are most likely to see meaningful clinical improvements from the drug and unknown factors that may increase the risks of treatment.
 

A costly therapy

Medicare plans to cover 80% of lecanemab’s steep cost of $26,500 per year. Still, that will leave many patients with a hefty copay, potentially over $6,000 per year. But that only scratches the surface. Consider the frequent medical visits, repeated brain scans, laboratory tests, and infusion center appointments. It’s been estimated that all-in, the treatment will actually cost about $90,000 per year.

Yes, Medicare will reimburse a large portion of that cost, but it adds up to an estimated $2 billion per year for about 85,000 patients. This will probably spur increases to Medicare premiums, among other economic consequences for the health care system.

We’ll probably have to wait for an FDA approval decision before we know where donanemab will be priced.
 

Logistical challenges could be a rate-limiting step

Ask anyone who’s tried to see a neurologist recently, and they’ll tell you that the wait for a new patient appointment is months long. The shortage of neurologists in the United States is already a crisis, and there are even fewer cognitive neurologists. How long will patients be forced to wait for their diagnosis?

Many geriatricians will get comfortable prescribing these drugs, but will our already overburdened primary care providers have the bandwidth to do the same? It’s a tall order.

A new world of Alzheimer’s treatments also means that the infrastructure of our health care systems will need to be ramped up. Lecanemab infusions are administered every 2 weeks and donanemab every 4 weeks. Infusion centers will need to accommodate a lot more patients. And those patients will need frequent brain scans, so neuroimaging centers will need to increase their capacity to perform many more brain MRI and PET scans.
 

Antiamyloid drugs: An exciting first step

The bottom line is that these drugs aren’t the Alzheimer’s holy grail: An accessible treatment that could stop the disease in its tracks or reverse cognitive impairment. They are, however, a very promising breakthrough.

Yes, there are a ton of kinks to work out here, but this is an exciting start. Alzheimer’s research is entering a renaissance era that will hopefully bring more groundbreaking developments. Better biomarkers to facilitate faster, easier diagnosis. More drugs that go beyond amyloid proteins for their therapeutic targets. Treatments for later-stage disease. Drugs that prevent dementia altogether.

Ultimately, these new antiamyloid beta drugs are an exciting indication that we will eventually have a toolkit of Alzheimer’s drugs to choose from. For now, we’ve taken a solid step forward and there is ample reason to be hopeful for the future.

Dr. Croll is assistant professor of neurology at Temple University, Philadelphia. She reported no relevant conflicts of interest.

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

With the Food and Drug Administration’s full stamp of approval in hand, Leqembi (lecanemab) is poised to catapult us into a new era of treatment for Alzheimer’s disease. And now that the donanemab trial data are out, there’s another antiamyloid drug waiting in the wings.

To finally have true disease-modifying therapies for Alzheimer’s disease is a massive step forward for a field that’s been plagued with disappointment. But these drugs come with serious concerns and unknowns. They will require complex decision-making, putting doctors, patients, and their families in a medical quandary.

Striking the right balance between cautious optimism and realistic expectations will be a formidable challenge.
 

Managing patient and family expectations

These drugs are no magic bullet. They slow down the dementia’s progression, buying patients more time (on the order of months) before they begin to experience significant worsening. We’ll need a lot more information from research and clinical experience before we can understand how meaningful that treatment effect is. Right now, it is unclear whether eligible patients and their families will even perceive tangible differences.

In the CLARITY-AD trial, participants on lecanemab experienced a 27% slowing in the rate of cognitive decline over 18 months. Donanemab was shown to slow decline in memory and cognition by about 35% over the same time frame in the TRAILBLAZER-ALZ 2 trial. That translates to more time for patients and their families to enjoy independence, maintain normal life, and stave off the most distressing parts of the disease.

But what happens after 18 months of treatment – will the treatment effect magnify or dissipate? How much time are we really buying in the long run? Counseling patients and their families is made all the more difficult when the answers to important questions like these remain to be seen.
 

Only a sliver of Alzheimer’s patients are current candidates

The fact is that most patients living with Alzheimer’s disease will not qualify for treatment with these drugs. Lecanemab is approved for people with early-stage disease, meaning their dementia is mild or they have mild cognitive impairment, which is a precursor to full-blown Alzheimer’s disease. Of the 6 million people in the United States living with Alzheimer’s, about 1.5 million are estimated to fall into that category. We can expect to see a similar qualifier for donanemab if it receives FDA approval, especially because that trial suggested a more pronounced treatment effect for patients in the earliest stages of the disease.

Even if a patient hits the sweet spot where they have just enough cognitive impairment, but not too much, they aren’t technically therapeutic candidates until prerequisite testing confirms amyloid protein accumulation in the brain via PET scan or cerebrospinal fluid analysis.

Even then, the FDA’s boxed warning for lecanemab recommends that patients undergo genetic testing for the apo E4 mutation to identify those at a particularly high risk for severe adverse effects including brain bleeding and swelling. This recommendation is not unreasonable considering that 15% of the Alzheimer’s population has two copies of the apo E4 mutation and fall into that high-risk group.
 

Significant risks

Antiamyloid drugs are well-known to cause serious side effects. In the lecanemab trial, 13% of participants receiving Leqembi experienced brain swelling (vs. 2% of participants receiving placebo) and 17% of participants had brain bleeding (vs. 9% of participants on placebo). In the donanemab trial, brain bleeding occurred in 31.4% of participants on the drug (vs. 13.6% on placebo) and swelling occurred in 24% (vs. 2.1% receiving placebo). Thankfully, in both trials, most of these adverse events did not produce significant symptoms, but in rare cases these events caused severe or catastrophic neurologic injury, including death.

How can we best guide patients and their families to weigh the uncertain benefits against potentially serious risks? We can start by considering the patient characteristics most likely to portend increased risk for serious side effects: apo E4 mutations, blood thinner use, and the presence of microhemorrhages on brain imaging. But after that, we’re left with a lot of uncertainty in terms of which patients are most likely to see meaningful clinical improvements from the drug and unknown factors that may increase the risks of treatment.
 

A costly therapy

Medicare plans to cover 80% of lecanemab’s steep cost of $26,500 per year. Still, that will leave many patients with a hefty copay, potentially over $6,000 per year. But that only scratches the surface. Consider the frequent medical visits, repeated brain scans, laboratory tests, and infusion center appointments. It’s been estimated that all-in, the treatment will actually cost about $90,000 per year.

Yes, Medicare will reimburse a large portion of that cost, but it adds up to an estimated $2 billion per year for about 85,000 patients. This will probably spur increases to Medicare premiums, among other economic consequences for the health care system.

We’ll probably have to wait for an FDA approval decision before we know where donanemab will be priced.
 

Logistical challenges could be a rate-limiting step

Ask anyone who’s tried to see a neurologist recently, and they’ll tell you that the wait for a new patient appointment is months long. The shortage of neurologists in the United States is already a crisis, and there are even fewer cognitive neurologists. How long will patients be forced to wait for their diagnosis?

Many geriatricians will get comfortable prescribing these drugs, but will our already overburdened primary care providers have the bandwidth to do the same? It’s a tall order.

A new world of Alzheimer’s treatments also means that the infrastructure of our health care systems will need to be ramped up. Lecanemab infusions are administered every 2 weeks and donanemab every 4 weeks. Infusion centers will need to accommodate a lot more patients. And those patients will need frequent brain scans, so neuroimaging centers will need to increase their capacity to perform many more brain MRI and PET scans.
 

Antiamyloid drugs: An exciting first step

The bottom line is that these drugs aren’t the Alzheimer’s holy grail: An accessible treatment that could stop the disease in its tracks or reverse cognitive impairment. They are, however, a very promising breakthrough.

Yes, there are a ton of kinks to work out here, but this is an exciting start. Alzheimer’s research is entering a renaissance era that will hopefully bring more groundbreaking developments. Better biomarkers to facilitate faster, easier diagnosis. More drugs that go beyond amyloid proteins for their therapeutic targets. Treatments for later-stage disease. Drugs that prevent dementia altogether.

Ultimately, these new antiamyloid beta drugs are an exciting indication that we will eventually have a toolkit of Alzheimer’s drugs to choose from. For now, we’ve taken a solid step forward and there is ample reason to be hopeful for the future.

Dr. Croll is assistant professor of neurology at Temple University, Philadelphia. She reported no relevant conflicts of interest.

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

With the Food and Drug Administration’s full stamp of approval in hand, Leqembi (lecanemab) is poised to catapult us into a new era of treatment for Alzheimer’s disease. And now that the donanemab trial data are out, there’s another antiamyloid drug waiting in the wings.

To finally have true disease-modifying therapies for Alzheimer’s disease is a massive step forward for a field that’s been plagued with disappointment. But these drugs come with serious concerns and unknowns. They will require complex decision-making, putting doctors, patients, and their families in a medical quandary.

Striking the right balance between cautious optimism and realistic expectations will be a formidable challenge.
 

Managing patient and family expectations

These drugs are no magic bullet. They slow down the dementia’s progression, buying patients more time (on the order of months) before they begin to experience significant worsening. We’ll need a lot more information from research and clinical experience before we can understand how meaningful that treatment effect is. Right now, it is unclear whether eligible patients and their families will even perceive tangible differences.

In the CLARITY-AD trial, participants on lecanemab experienced a 27% slowing in the rate of cognitive decline over 18 months. Donanemab was shown to slow decline in memory and cognition by about 35% over the same time frame in the TRAILBLAZER-ALZ 2 trial. That translates to more time for patients and their families to enjoy independence, maintain normal life, and stave off the most distressing parts of the disease.

But what happens after 18 months of treatment – will the treatment effect magnify or dissipate? How much time are we really buying in the long run? Counseling patients and their families is made all the more difficult when the answers to important questions like these remain to be seen.
 

Only a sliver of Alzheimer’s patients are current candidates

The fact is that most patients living with Alzheimer’s disease will not qualify for treatment with these drugs. Lecanemab is approved for people with early-stage disease, meaning their dementia is mild or they have mild cognitive impairment, which is a precursor to full-blown Alzheimer’s disease. Of the 6 million people in the United States living with Alzheimer’s, about 1.5 million are estimated to fall into that category. We can expect to see a similar qualifier for donanemab if it receives FDA approval, especially because that trial suggested a more pronounced treatment effect for patients in the earliest stages of the disease.

Even if a patient hits the sweet spot where they have just enough cognitive impairment, but not too much, they aren’t technically therapeutic candidates until prerequisite testing confirms amyloid protein accumulation in the brain via PET scan or cerebrospinal fluid analysis.

Even then, the FDA’s boxed warning for lecanemab recommends that patients undergo genetic testing for the apo E4 mutation to identify those at a particularly high risk for severe adverse effects including brain bleeding and swelling. This recommendation is not unreasonable considering that 15% of the Alzheimer’s population has two copies of the apo E4 mutation and fall into that high-risk group.
 

Significant risks

Antiamyloid drugs are well-known to cause serious side effects. In the lecanemab trial, 13% of participants receiving Leqembi experienced brain swelling (vs. 2% of participants receiving placebo) and 17% of participants had brain bleeding (vs. 9% of participants on placebo). In the donanemab trial, brain bleeding occurred in 31.4% of participants on the drug (vs. 13.6% on placebo) and swelling occurred in 24% (vs. 2.1% receiving placebo). Thankfully, in both trials, most of these adverse events did not produce significant symptoms, but in rare cases these events caused severe or catastrophic neurologic injury, including death.

How can we best guide patients and their families to weigh the uncertain benefits against potentially serious risks? We can start by considering the patient characteristics most likely to portend increased risk for serious side effects: apo E4 mutations, blood thinner use, and the presence of microhemorrhages on brain imaging. But after that, we’re left with a lot of uncertainty in terms of which patients are most likely to see meaningful clinical improvements from the drug and unknown factors that may increase the risks of treatment.
 

A costly therapy

Medicare plans to cover 80% of lecanemab’s steep cost of $26,500 per year. Still, that will leave many patients with a hefty copay, potentially over $6,000 per year. But that only scratches the surface. Consider the frequent medical visits, repeated brain scans, laboratory tests, and infusion center appointments. It’s been estimated that all-in, the treatment will actually cost about $90,000 per year.

Yes, Medicare will reimburse a large portion of that cost, but it adds up to an estimated $2 billion per year for about 85,000 patients. This will probably spur increases to Medicare premiums, among other economic consequences for the health care system.

We’ll probably have to wait for an FDA approval decision before we know where donanemab will be priced.
 

Logistical challenges could be a rate-limiting step

Ask anyone who’s tried to see a neurologist recently, and they’ll tell you that the wait for a new patient appointment is months long. The shortage of neurologists in the United States is already a crisis, and there are even fewer cognitive neurologists. How long will patients be forced to wait for their diagnosis?

Many geriatricians will get comfortable prescribing these drugs, but will our already overburdened primary care providers have the bandwidth to do the same? It’s a tall order.

A new world of Alzheimer’s treatments also means that the infrastructure of our health care systems will need to be ramped up. Lecanemab infusions are administered every 2 weeks and donanemab every 4 weeks. Infusion centers will need to accommodate a lot more patients. And those patients will need frequent brain scans, so neuroimaging centers will need to increase their capacity to perform many more brain MRI and PET scans.
 

Antiamyloid drugs: An exciting first step

The bottom line is that these drugs aren’t the Alzheimer’s holy grail: An accessible treatment that could stop the disease in its tracks or reverse cognitive impairment. They are, however, a very promising breakthrough.

Yes, there are a ton of kinks to work out here, but this is an exciting start. Alzheimer’s research is entering a renaissance era that will hopefully bring more groundbreaking developments. Better biomarkers to facilitate faster, easier diagnosis. More drugs that go beyond amyloid proteins for their therapeutic targets. Treatments for later-stage disease. Drugs that prevent dementia altogether.

Ultimately, these new antiamyloid beta drugs are an exciting indication that we will eventually have a toolkit of Alzheimer’s drugs to choose from. For now, we’ve taken a solid step forward and there is ample reason to be hopeful for the future.

Dr. Croll is assistant professor of neurology at Temple University, Philadelphia. She reported no relevant conflicts of interest.

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

Meditation and foreign language training does not boost cognitive function in cognitively healthy older adults, a new study suggests.

The findings are similar to results from another study published last year but are contrary to previous findings showing cognitive benefits for practicing meditation and learning a new language later in life.

“Based on existing literature, which has provided support for the efficacy of meditation and foreign language training in promoting cognition among older adults, perhaps the most surprising outcome of our study was the lack of evidence indicating cognitive benefits after 18 months of either intervention,” lead author Harriet Demnitz-King, MSc, a doctoral candidate at University College London, said in an interview. The findings were published online  in JAMA Network Open.

Harriet Demnitz-King

Contradictory findings

For the study, 135 French-speaking, cognitively healthy people were randomized to English-language training, meditation, or a control group. All participants were aged 65 years or older, had been retired for at least 1 year, and had completed at least 7 years of education.

The meditation and English-language training interventions were both 18 months long and included a 2-hour weekly group session, daily home practice of at least 20 minutes, and 1-day intensive 5-hour practice.

Researchers found no significant changes in global cognition, episodic memory, executive function, or attention with either intervention, compared with the control group or to each other.

The findings contradict the researchers’ earlier work that found mindfulness meditation boosted cognitive function in older adults with subjective cognitive decline.

“We are still trying to reconcile these findings,” senior author Natalie Marchant, PhD, associate professor in the division of psychiatry at University College London, said. “It may be that mindfulness meditation may not improve cognition beyond normally functioning levels but may help to preserve cognition in the face of cognitive decline.”

Natalie Marchant

More to learn

The results harken to those of a study last year with a similar participant group and similar results. In that work, mindfulness meditation and exercise also failed to boost cognition in healthy adults. But that may not be the whole story, according to Eric Lenze, MD, professor and chair of psychiatry at Washington University School of Medicine, St. Louis.

Dr. Lenze was a lead author on that earlier research, known as the MEDEX trial, but was not involved with this study. He commented on the new findings for this news organization.

“People may read these results, and ours that were published in JAMA in December, as suggesting that lifestyle and cognitive interventions don’t work in older adults, but that’s not what this shows, in my opinion,” Dr. Lenze said. “It shows that we don’t understand the science of the aging brain as much as we would like to.”

Participants in most of these studies were mostly White, highly educated, and in good cognitive health, all characteristics that could have skewed these findings, he added.

“It may be that interventions to improve cognitive function in older adults would be more likely to help people who have more room to benefit,” Dr. Lenze said. “If you’re already highly educated, healthy, and cognitively normal, why should we expect that you could do even better than that?”

The Age-Well study was funded by European Union in Horizon 2020 program and Inserm, Région Normandie, Fondation d’entreprise MMA des Entrepreneurs du Futur. Dr. Marchant reports grants from Alzheimer’s Society and the U.K. Medical Research Council. Dr. Lenze reports funding from Takeda pharmaceuticals and has been a consultant for Pritikin Intensive Cardiac Rehabilitation.

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

Meditation and foreign language training does not boost cognitive function in cognitively healthy older adults, a new study suggests.

The findings are similar to results from another study published last year but are contrary to previous findings showing cognitive benefits for practicing meditation and learning a new language later in life.

“Based on existing literature, which has provided support for the efficacy of meditation and foreign language training in promoting cognition among older adults, perhaps the most surprising outcome of our study was the lack of evidence indicating cognitive benefits after 18 months of either intervention,” lead author Harriet Demnitz-King, MSc, a doctoral candidate at University College London, said in an interview. The findings were published online  in JAMA Network Open.

Harriet Demnitz-King

Contradictory findings

For the study, 135 French-speaking, cognitively healthy people were randomized to English-language training, meditation, or a control group. All participants were aged 65 years or older, had been retired for at least 1 year, and had completed at least 7 years of education.

The meditation and English-language training interventions were both 18 months long and included a 2-hour weekly group session, daily home practice of at least 20 minutes, and 1-day intensive 5-hour practice.

Researchers found no significant changes in global cognition, episodic memory, executive function, or attention with either intervention, compared with the control group or to each other.

The findings contradict the researchers’ earlier work that found mindfulness meditation boosted cognitive function in older adults with subjective cognitive decline.

“We are still trying to reconcile these findings,” senior author Natalie Marchant, PhD, associate professor in the division of psychiatry at University College London, said. “It may be that mindfulness meditation may not improve cognition beyond normally functioning levels but may help to preserve cognition in the face of cognitive decline.”

Natalie Marchant

More to learn

The results harken to those of a study last year with a similar participant group and similar results. In that work, mindfulness meditation and exercise also failed to boost cognition in healthy adults. But that may not be the whole story, according to Eric Lenze, MD, professor and chair of psychiatry at Washington University School of Medicine, St. Louis.

Dr. Lenze was a lead author on that earlier research, known as the MEDEX trial, but was not involved with this study. He commented on the new findings for this news organization.

“People may read these results, and ours that were published in JAMA in December, as suggesting that lifestyle and cognitive interventions don’t work in older adults, but that’s not what this shows, in my opinion,” Dr. Lenze said. “It shows that we don’t understand the science of the aging brain as much as we would like to.”

Participants in most of these studies were mostly White, highly educated, and in good cognitive health, all characteristics that could have skewed these findings, he added.

“It may be that interventions to improve cognitive function in older adults would be more likely to help people who have more room to benefit,” Dr. Lenze said. “If you’re already highly educated, healthy, and cognitively normal, why should we expect that you could do even better than that?”

The Age-Well study was funded by European Union in Horizon 2020 program and Inserm, Région Normandie, Fondation d’entreprise MMA des Entrepreneurs du Futur. Dr. Marchant reports grants from Alzheimer’s Society and the U.K. Medical Research Council. Dr. Lenze reports funding from Takeda pharmaceuticals and has been a consultant for Pritikin Intensive Cardiac Rehabilitation.

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

Meditation and foreign language training does not boost cognitive function in cognitively healthy older adults, a new study suggests.

The findings are similar to results from another study published last year but are contrary to previous findings showing cognitive benefits for practicing meditation and learning a new language later in life.

“Based on existing literature, which has provided support for the efficacy of meditation and foreign language training in promoting cognition among older adults, perhaps the most surprising outcome of our study was the lack of evidence indicating cognitive benefits after 18 months of either intervention,” lead author Harriet Demnitz-King, MSc, a doctoral candidate at University College London, said in an interview. The findings were published online  in JAMA Network Open.

Harriet Demnitz-King

Contradictory findings

For the study, 135 French-speaking, cognitively healthy people were randomized to English-language training, meditation, or a control group. All participants were aged 65 years or older, had been retired for at least 1 year, and had completed at least 7 years of education.

The meditation and English-language training interventions were both 18 months long and included a 2-hour weekly group session, daily home practice of at least 20 minutes, and 1-day intensive 5-hour practice.

Researchers found no significant changes in global cognition, episodic memory, executive function, or attention with either intervention, compared with the control group or to each other.

The findings contradict the researchers’ earlier work that found mindfulness meditation boosted cognitive function in older adults with subjective cognitive decline.

“We are still trying to reconcile these findings,” senior author Natalie Marchant, PhD, associate professor in the division of psychiatry at University College London, said. “It may be that mindfulness meditation may not improve cognition beyond normally functioning levels but may help to preserve cognition in the face of cognitive decline.”

Natalie Marchant

More to learn

The results harken to those of a study last year with a similar participant group and similar results. In that work, mindfulness meditation and exercise also failed to boost cognition in healthy adults. But that may not be the whole story, according to Eric Lenze, MD, professor and chair of psychiatry at Washington University School of Medicine, St. Louis.

Dr. Lenze was a lead author on that earlier research, known as the MEDEX trial, but was not involved with this study. He commented on the new findings for this news organization.

“People may read these results, and ours that were published in JAMA in December, as suggesting that lifestyle and cognitive interventions don’t work in older adults, but that’s not what this shows, in my opinion,” Dr. Lenze said. “It shows that we don’t understand the science of the aging brain as much as we would like to.”

Participants in most of these studies were mostly White, highly educated, and in good cognitive health, all characteristics that could have skewed these findings, he added.

“It may be that interventions to improve cognitive function in older adults would be more likely to help people who have more room to benefit,” Dr. Lenze said. “If you’re already highly educated, healthy, and cognitively normal, why should we expect that you could do even better than that?”

The Age-Well study was funded by European Union in Horizon 2020 program and Inserm, Région Normandie, Fondation d’entreprise MMA des Entrepreneurs du Futur. Dr. Marchant reports grants from Alzheimer’s Society and the U.K. Medical Research Council. Dr. Lenze reports funding from Takeda pharmaceuticals and has been a consultant for Pritikin Intensive Cardiac Rehabilitation.

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

Two newly approved respiratory syncytial virus (RSV) vaccines for adults aged 60 years and older may be able to prevent illness in those at risk for severe RSV disease.

Most adult RSV illness occurs among the older age group and results in an estimated 60,000-160,000 hospitalizations and 6,000-10,000 deaths per year among people aged at least 65 years.

Older adults deciding whether to get the vaccines should weigh risks and their own preferences and make the decision in consultation with their clinicians, said authors of a Centers for Disease Control and Prevention report.

Michael Melgar, MD, with the Coronavirus and Other Respiratory Viruses Division at the CDC, was lead author on the report, published in the Morbidity and Mortality Weekly Report.
 

Two new vaccines

In May, the Food and Drug Administration approved the first of two vaccines for preventing RSV lower respiratory tract disease for adults aged at least 60 years.

On June 21, the Advisory Committee on Immunization Practices (ACIP) recommended that people in that age group receive a single dose of RSV vaccine using shared decision-making.

The recommendation for shared decision-making makes the ACIP decision different from routine and risk-based vaccine recommendations. Rather than targeting all in a particular age group or risk group, the decision calls for consideration of a patients’ risk for disease and their characteristics, preferences, and values; the health care professional’s clinical discretion; and performance of the vaccine.

Dr. Melgar and colleagues reported that vaccination with one dose of the GSK or Pfizer RSV vaccines has proved moderately to highly effective in preventing symptomatic RSV-associated lower respiratory tract disease over two consecutive RSV seasons among people aged 60 and older.

The trials that led to approval weren’t powered to gauge efficacy against RSV-associated hospitalization and death. However, the authors wrote, the prevention of lower respiratory tract disease, including medically attended illness, suggests that the shots might prevent considerable morbidity from RSV disease among those aged 60 and older.

Both vaccines were generally well tolerated with a good safety profile. However, six cases of inflammatory neurologic events (including Guillain-Barré Syndrome, acute disseminated encephalomyelitis, and others) were reported in clinical trials after RSV vaccination.

“Whether these events occurred due to chance, or whether RSV vaccination increases the risk for inflammatory neurologic events, is currently unknown,” the authors wrote.

Postmarketing surveillance may help clarify the existence of any potential risk, but until those results are clearer, the CDC researchers said, RSV vaccinations should be targeted to older adults at highest risk for severe RSV and those most likely to benefit from the shots.
 

At higher risk

Some adults with certain medical conditions have a higher risk for RSV-associated hospitalization, according to the report.

Those conditions include chronic obstructive pulmonary disease, asthma, heart failure, coronary artery disease, cerebrovascular disease, diabetes mellitus, and chronic kidney disease.

People who are frail and of advanced age also are at higher risk for RSV hospitalization. That risk increases with age and the highest risk is for people aged at least 75 years.

The researchers added that RSV can cause severe disease in those with compromised immunity, including people who have received hematopoietic stem cell transplants and patients taking immunosuppressive drugs such as those used with solid organ transplants, cancer treatment, or other conditions.

As for when physicians should offer the vaccinations, shots are optimally given before the start of the RSV season.

However, the COVID-19 pandemic interrupted the seasonality and the timing has not yet returned to prepandemic patterns.

For the 2023-24 season, this report states, clinicians should offer RSV vaccination to adults aged at least 60 years using shared clinical decision-making as early as vaccine supply is available and should continue to offer vaccination to eligible adults who remain unvaccinated.

RSV vaccines can be administered with other adult vaccines during the same visit, the authors confirmed.
 

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

Two newly approved respiratory syncytial virus (RSV) vaccines for adults aged 60 years and older may be able to prevent illness in those at risk for severe RSV disease.

Most adult RSV illness occurs among the older age group and results in an estimated 60,000-160,000 hospitalizations and 6,000-10,000 deaths per year among people aged at least 65 years.

Older adults deciding whether to get the vaccines should weigh risks and their own preferences and make the decision in consultation with their clinicians, said authors of a Centers for Disease Control and Prevention report.

Michael Melgar, MD, with the Coronavirus and Other Respiratory Viruses Division at the CDC, was lead author on the report, published in the Morbidity and Mortality Weekly Report.
 

Two new vaccines

In May, the Food and Drug Administration approved the first of two vaccines for preventing RSV lower respiratory tract disease for adults aged at least 60 years.

On June 21, the Advisory Committee on Immunization Practices (ACIP) recommended that people in that age group receive a single dose of RSV vaccine using shared decision-making.

The recommendation for shared decision-making makes the ACIP decision different from routine and risk-based vaccine recommendations. Rather than targeting all in a particular age group or risk group, the decision calls for consideration of a patients’ risk for disease and their characteristics, preferences, and values; the health care professional’s clinical discretion; and performance of the vaccine.

Dr. Melgar and colleagues reported that vaccination with one dose of the GSK or Pfizer RSV vaccines has proved moderately to highly effective in preventing symptomatic RSV-associated lower respiratory tract disease over two consecutive RSV seasons among people aged 60 and older.

The trials that led to approval weren’t powered to gauge efficacy against RSV-associated hospitalization and death. However, the authors wrote, the prevention of lower respiratory tract disease, including medically attended illness, suggests that the shots might prevent considerable morbidity from RSV disease among those aged 60 and older.

Both vaccines were generally well tolerated with a good safety profile. However, six cases of inflammatory neurologic events (including Guillain-Barré Syndrome, acute disseminated encephalomyelitis, and others) were reported in clinical trials after RSV vaccination.

“Whether these events occurred due to chance, or whether RSV vaccination increases the risk for inflammatory neurologic events, is currently unknown,” the authors wrote.

Postmarketing surveillance may help clarify the existence of any potential risk, but until those results are clearer, the CDC researchers said, RSV vaccinations should be targeted to older adults at highest risk for severe RSV and those most likely to benefit from the shots.
 

At higher risk

Some adults with certain medical conditions have a higher risk for RSV-associated hospitalization, according to the report.

Those conditions include chronic obstructive pulmonary disease, asthma, heart failure, coronary artery disease, cerebrovascular disease, diabetes mellitus, and chronic kidney disease.

People who are frail and of advanced age also are at higher risk for RSV hospitalization. That risk increases with age and the highest risk is for people aged at least 75 years.

The researchers added that RSV can cause severe disease in those with compromised immunity, including people who have received hematopoietic stem cell transplants and patients taking immunosuppressive drugs such as those used with solid organ transplants, cancer treatment, or other conditions.

As for when physicians should offer the vaccinations, shots are optimally given before the start of the RSV season.

However, the COVID-19 pandemic interrupted the seasonality and the timing has not yet returned to prepandemic patterns.

For the 2023-24 season, this report states, clinicians should offer RSV vaccination to adults aged at least 60 years using shared clinical decision-making as early as vaccine supply is available and should continue to offer vaccination to eligible adults who remain unvaccinated.

RSV vaccines can be administered with other adult vaccines during the same visit, the authors confirmed.
 

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

Two newly approved respiratory syncytial virus (RSV) vaccines for adults aged 60 years and older may be able to prevent illness in those at risk for severe RSV disease.

Most adult RSV illness occurs among the older age group and results in an estimated 60,000-160,000 hospitalizations and 6,000-10,000 deaths per year among people aged at least 65 years.

Older adults deciding whether to get the vaccines should weigh risks and their own preferences and make the decision in consultation with their clinicians, said authors of a Centers for Disease Control and Prevention report.

Michael Melgar, MD, with the Coronavirus and Other Respiratory Viruses Division at the CDC, was lead author on the report, published in the Morbidity and Mortality Weekly Report.
 

Two new vaccines

In May, the Food and Drug Administration approved the first of two vaccines for preventing RSV lower respiratory tract disease for adults aged at least 60 years.

On June 21, the Advisory Committee on Immunization Practices (ACIP) recommended that people in that age group receive a single dose of RSV vaccine using shared decision-making.

The recommendation for shared decision-making makes the ACIP decision different from routine and risk-based vaccine recommendations. Rather than targeting all in a particular age group or risk group, the decision calls for consideration of a patients’ risk for disease and their characteristics, preferences, and values; the health care professional’s clinical discretion; and performance of the vaccine.

Dr. Melgar and colleagues reported that vaccination with one dose of the GSK or Pfizer RSV vaccines has proved moderately to highly effective in preventing symptomatic RSV-associated lower respiratory tract disease over two consecutive RSV seasons among people aged 60 and older.

The trials that led to approval weren’t powered to gauge efficacy against RSV-associated hospitalization and death. However, the authors wrote, the prevention of lower respiratory tract disease, including medically attended illness, suggests that the shots might prevent considerable morbidity from RSV disease among those aged 60 and older.

Both vaccines were generally well tolerated with a good safety profile. However, six cases of inflammatory neurologic events (including Guillain-Barré Syndrome, acute disseminated encephalomyelitis, and others) were reported in clinical trials after RSV vaccination.

“Whether these events occurred due to chance, or whether RSV vaccination increases the risk for inflammatory neurologic events, is currently unknown,” the authors wrote.

Postmarketing surveillance may help clarify the existence of any potential risk, but until those results are clearer, the CDC researchers said, RSV vaccinations should be targeted to older adults at highest risk for severe RSV and those most likely to benefit from the shots.
 

At higher risk

Some adults with certain medical conditions have a higher risk for RSV-associated hospitalization, according to the report.

Those conditions include chronic obstructive pulmonary disease, asthma, heart failure, coronary artery disease, cerebrovascular disease, diabetes mellitus, and chronic kidney disease.

People who are frail and of advanced age also are at higher risk for RSV hospitalization. That risk increases with age and the highest risk is for people aged at least 75 years.

The researchers added that RSV can cause severe disease in those with compromised immunity, including people who have received hematopoietic stem cell transplants and patients taking immunosuppressive drugs such as those used with solid organ transplants, cancer treatment, or other conditions.

As for when physicians should offer the vaccinations, shots are optimally given before the start of the RSV season.

However, the COVID-19 pandemic interrupted the seasonality and the timing has not yet returned to prepandemic patterns.

For the 2023-24 season, this report states, clinicians should offer RSV vaccination to adults aged at least 60 years using shared clinical decision-making as early as vaccine supply is available and should continue to offer vaccination to eligible adults who remain unvaccinated.

RSV vaccines can be administered with other adult vaccines during the same visit, the authors confirmed.
 

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

Primary care utilization within a year of emergency general surgery was significantly associated with lower mortality up to 180 days later for older adults, based on data from more than 100,000 individuals.

Although previous research has shown the benefits of routine health and preventive care visits for surgery patients, many individuals in the United States live in areas with a shortage of primary care providers, wrote Sanford E. Roberts, MD, of the University of Pennsylvania, Philadelphia, and colleagues. The effect of primary care use on adverse outcomes after emergency general surgery, including mortality, remains unknown, they said.

In a study published in JAMA Surgery the researchers reviewed data from 102,384 Medicare patients aged 66 years and older who underwent emergency general surgery (EGS) between July 1, 2015, and June 30, 2018. Participants were classified into five EGS categories: colorectal, general abdominal, hepatopancreatobiliary, intestinal obstruction, and upper gastrointestinal. The mean age of the participants was 73.8 years; 8.4% were Black, 91.6% were White.

The primary outcome was mortality in hospital and at 30, 60, 90, and 180 days. In the year before hospitalization for EGS, 88,340 patients (86.3%) had visited a primary care physician.

After adjusting for multiple risk factors, the overall risk of in-hospital mortality was 19% lower for patients who had a history of primary care visits than for those without prior-year exposure to primary care (odds ratio, 0.81).

Mortality at 30 days was 27% lower overall in patients with primary care exposure, compared with those without primary care exposure (OR, 0.73). This trend continued at 60 days (OR, 0.75), 90 days (OR, 0.74), and 180 days (OR, 0.75); mortality rates at each time period were similar for Black and White patients with primary care exposure, both groups had reduced mortality, compared with those without primary care exposure.

However, when analyzed by race, in-hospital mortality was not significantly different for Black patients with and without primary care exposure (OR, 1.09), but in-hospital mortality was 21% less in White patients with primary care exposure (OR, 0.79). Interactions between race and primary care exposure related to mortality were not significantly different at any of the follow-up time points of 30, 60, 90, and 180 days.

“These findings suggest that primary care may be exerting a protective effect on postoperative morbidity and mortality,” the researchers wrote in their discussion. “This protective effect could be mediated through several different paths, such as identifying and managing a patient’s comorbidities, medically optimizing patients preoperatively, earlier detection of the primary EGS condition leading to early referral to treatment, and encouraging better lifestyle decisions,” they said.

The findings were limited by several factors including the retrospective design and inability to extract clinical data from a claims database, the researchers noted. Other limitations included potential confounding of unmeasured factors such as the other beneficial health behaviors often associated with seeking primary care.

Patients who avoid primary care may be more likely to delay presentation to the emergency department, which might promote poorer postoperative outcomes, the researchers said. Consequently, surgeons should consider primary care exposure in preoperative assessment, and perform a more comprehensive presurgical assessment as needed, the researchers said.

More studies are needed to examine trends in racial groups, but the results of the current study suggest that primary care provides similar benefits for Black and White individuals, and therefore could help reduce health disparities, they concluded.
 

Primary care benefits elude many patients

The current study shows a “rather dramatic” association between utilization of primary care within a year before surgery and patient mortality after surgery, wrote Caroline E. Reinke, MD, and David C. Slawson, MD, both of Atrium Health, Charlotte, N.C., in an accompanying editorial. The authors reiterated that possible reasons for the positive effect of primary care on postsurgical mortality included identification and management of comorbidities that could complicate surgery, as well as earlier detection of disease.

However, the editorialists noted that the benefits of primary care exposure depend on patient access to primary care, and on patient adherence to recommendations from their primary care provider. They identified barriers to potential effective interventions with primary care providers including time, money, and transportation.

An unanswered question is “whether the PCP visit itself is the causative factor associated with decreased mortality or if seeing a PCP on an annual basis is a marker of the patient possessing some other ‘magic sauce’ that improves outcomes,” they wrote.

Further, individuals in areas of primary care shortage also are more likely to lack the socioeconomic resources to benefit from primary care, the editorialists said. “Future evaluations of the interaction between PCP visits and social determinants of health may shed light on how to achieve the greatest impact,” they concluded.
 

Study supports value of consistent primary care

The increasingly aging population across the United States may undergo surgical procedures on an emergent basis and the current study provides data on the benefits of established and effective primary care for these individuals, said Noel Deep, MD, in an interview.

“Having data from this study supports the current position of many physicians and health care organizations and medical professional organizations that older individuals in particular, and adults in general, who have regular routine primary care visits tend to lead healthier lives and have better prognosis and quality of life,” said Dr. Deep, a general internist in private practice in Antigo, Wisc., who was not involved in the study. Dr. Deep also serves as chief medical officer and a staff physician at Aspirus Langlade Hospital in Antigo.

The study findings reinforce what most physicians in primary care, himself included, have been advising adult patients, especially older adults about maintaining regular follow-up visits with their physicians for health screening and management of chronic medical conditions, Dr. Deep said in an interview.

However, barriers to the routine use of primary care to improve postsurgical outcomes include health illiteracy, being overwhelmed by a sudden change in health or emergent surgery, and lack of access to primary care physician, as well as issues such as transportation, financial difficulties, and physical limitations, Dr. Deep added.

“Patients who avoid routine health care visits with primary care may be lacking health insurance or financial resources, have time constraints or family responsibilities, or may be unaware of the benefits of routine health care,” he noted.

As for additional research, “I would like to see studies that can document the impact of having primary care physicians comanage these hospitalized patients in the perioperative period with continued follow-up in the postoperative/convalescent period,” said Dr. Deep.

The study was supported by the National Institute on Aging of the National Institutes of Health. Dr. Roberts disclosed grants from the National Institute on Aging and from NIH during the conduct of the study. The editorial author had no financial conflicts to disclose. Dr. Deep had no financial conflicts to disclose and serves on the Editorial Advisory Board of Internal Medicine News.

Primary care utilization within a year of emergency general surgery was significantly associated with lower mortality up to 180 days later for older adults, based on data from more than 100,000 individuals.

Although previous research has shown the benefits of routine health and preventive care visits for surgery patients, many individuals in the United States live in areas with a shortage of primary care providers, wrote Sanford E. Roberts, MD, of the University of Pennsylvania, Philadelphia, and colleagues. The effect of primary care use on adverse outcomes after emergency general surgery, including mortality, remains unknown, they said.

In a study published in JAMA Surgery the researchers reviewed data from 102,384 Medicare patients aged 66 years and older who underwent emergency general surgery (EGS) between July 1, 2015, and June 30, 2018. Participants were classified into five EGS categories: colorectal, general abdominal, hepatopancreatobiliary, intestinal obstruction, and upper gastrointestinal. The mean age of the participants was 73.8 years; 8.4% were Black, 91.6% were White.

The primary outcome was mortality in hospital and at 30, 60, 90, and 180 days. In the year before hospitalization for EGS, 88,340 patients (86.3%) had visited a primary care physician.

After adjusting for multiple risk factors, the overall risk of in-hospital mortality was 19% lower for patients who had a history of primary care visits than for those without prior-year exposure to primary care (odds ratio, 0.81).

Mortality at 30 days was 27% lower overall in patients with primary care exposure, compared with those without primary care exposure (OR, 0.73). This trend continued at 60 days (OR, 0.75), 90 days (OR, 0.74), and 180 days (OR, 0.75); mortality rates at each time period were similar for Black and White patients with primary care exposure, both groups had reduced mortality, compared with those without primary care exposure.

However, when analyzed by race, in-hospital mortality was not significantly different for Black patients with and without primary care exposure (OR, 1.09), but in-hospital mortality was 21% less in White patients with primary care exposure (OR, 0.79). Interactions between race and primary care exposure related to mortality were not significantly different at any of the follow-up time points of 30, 60, 90, and 180 days.

“These findings suggest that primary care may be exerting a protective effect on postoperative morbidity and mortality,” the researchers wrote in their discussion. “This protective effect could be mediated through several different paths, such as identifying and managing a patient’s comorbidities, medically optimizing patients preoperatively, earlier detection of the primary EGS condition leading to early referral to treatment, and encouraging better lifestyle decisions,” they said.

The findings were limited by several factors including the retrospective design and inability to extract clinical data from a claims database, the researchers noted. Other limitations included potential confounding of unmeasured factors such as the other beneficial health behaviors often associated with seeking primary care.

Patients who avoid primary care may be more likely to delay presentation to the emergency department, which might promote poorer postoperative outcomes, the researchers said. Consequently, surgeons should consider primary care exposure in preoperative assessment, and perform a more comprehensive presurgical assessment as needed, the researchers said.

More studies are needed to examine trends in racial groups, but the results of the current study suggest that primary care provides similar benefits for Black and White individuals, and therefore could help reduce health disparities, they concluded.
 

Primary care benefits elude many patients

The current study shows a “rather dramatic” association between utilization of primary care within a year before surgery and patient mortality after surgery, wrote Caroline E. Reinke, MD, and David C. Slawson, MD, both of Atrium Health, Charlotte, N.C., in an accompanying editorial. The authors reiterated that possible reasons for the positive effect of primary care on postsurgical mortality included identification and management of comorbidities that could complicate surgery, as well as earlier detection of disease.

However, the editorialists noted that the benefits of primary care exposure depend on patient access to primary care, and on patient adherence to recommendations from their primary care provider. They identified barriers to potential effective interventions with primary care providers including time, money, and transportation.

An unanswered question is “whether the PCP visit itself is the causative factor associated with decreased mortality or if seeing a PCP on an annual basis is a marker of the patient possessing some other ‘magic sauce’ that improves outcomes,” they wrote.

Further, individuals in areas of primary care shortage also are more likely to lack the socioeconomic resources to benefit from primary care, the editorialists said. “Future evaluations of the interaction between PCP visits and social determinants of health may shed light on how to achieve the greatest impact,” they concluded.
 

Study supports value of consistent primary care

The increasingly aging population across the United States may undergo surgical procedures on an emergent basis and the current study provides data on the benefits of established and effective primary care for these individuals, said Noel Deep, MD, in an interview.

“Having data from this study supports the current position of many physicians and health care organizations and medical professional organizations that older individuals in particular, and adults in general, who have regular routine primary care visits tend to lead healthier lives and have better prognosis and quality of life,” said Dr. Deep, a general internist in private practice in Antigo, Wisc., who was not involved in the study. Dr. Deep also serves as chief medical officer and a staff physician at Aspirus Langlade Hospital in Antigo.

The study findings reinforce what most physicians in primary care, himself included, have been advising adult patients, especially older adults about maintaining regular follow-up visits with their physicians for health screening and management of chronic medical conditions, Dr. Deep said in an interview.

However, barriers to the routine use of primary care to improve postsurgical outcomes include health illiteracy, being overwhelmed by a sudden change in health or emergent surgery, and lack of access to primary care physician, as well as issues such as transportation, financial difficulties, and physical limitations, Dr. Deep added.

“Patients who avoid routine health care visits with primary care may be lacking health insurance or financial resources, have time constraints or family responsibilities, or may be unaware of the benefits of routine health care,” he noted.

As for additional research, “I would like to see studies that can document the impact of having primary care physicians comanage these hospitalized patients in the perioperative period with continued follow-up in the postoperative/convalescent period,” said Dr. Deep.

The study was supported by the National Institute on Aging of the National Institutes of Health. Dr. Roberts disclosed grants from the National Institute on Aging and from NIH during the conduct of the study. The editorial author had no financial conflicts to disclose. Dr. Deep had no financial conflicts to disclose and serves on the Editorial Advisory Board of Internal Medicine News.

Primary care utilization within a year of emergency general surgery was significantly associated with lower mortality up to 180 days later for older adults, based on data from more than 100,000 individuals.

Although previous research has shown the benefits of routine health and preventive care visits for surgery patients, many individuals in the United States live in areas with a shortage of primary care providers, wrote Sanford E. Roberts, MD, of the University of Pennsylvania, Philadelphia, and colleagues. The effect of primary care use on adverse outcomes after emergency general surgery, including mortality, remains unknown, they said.

In a study published in JAMA Surgery the researchers reviewed data from 102,384 Medicare patients aged 66 years and older who underwent emergency general surgery (EGS) between July 1, 2015, and June 30, 2018. Participants were classified into five EGS categories: colorectal, general abdominal, hepatopancreatobiliary, intestinal obstruction, and upper gastrointestinal. The mean age of the participants was 73.8 years; 8.4% were Black, 91.6% were White.

The primary outcome was mortality in hospital and at 30, 60, 90, and 180 days. In the year before hospitalization for EGS, 88,340 patients (86.3%) had visited a primary care physician.

After adjusting for multiple risk factors, the overall risk of in-hospital mortality was 19% lower for patients who had a history of primary care visits than for those without prior-year exposure to primary care (odds ratio, 0.81).

Mortality at 30 days was 27% lower overall in patients with primary care exposure, compared with those without primary care exposure (OR, 0.73). This trend continued at 60 days (OR, 0.75), 90 days (OR, 0.74), and 180 days (OR, 0.75); mortality rates at each time period were similar for Black and White patients with primary care exposure, both groups had reduced mortality, compared with those without primary care exposure.

However, when analyzed by race, in-hospital mortality was not significantly different for Black patients with and without primary care exposure (OR, 1.09), but in-hospital mortality was 21% less in White patients with primary care exposure (OR, 0.79). Interactions between race and primary care exposure related to mortality were not significantly different at any of the follow-up time points of 30, 60, 90, and 180 days.

“These findings suggest that primary care may be exerting a protective effect on postoperative morbidity and mortality,” the researchers wrote in their discussion. “This protective effect could be mediated through several different paths, such as identifying and managing a patient’s comorbidities, medically optimizing patients preoperatively, earlier detection of the primary EGS condition leading to early referral to treatment, and encouraging better lifestyle decisions,” they said.

The findings were limited by several factors including the retrospective design and inability to extract clinical data from a claims database, the researchers noted. Other limitations included potential confounding of unmeasured factors such as the other beneficial health behaviors often associated with seeking primary care.

Patients who avoid primary care may be more likely to delay presentation to the emergency department, which might promote poorer postoperative outcomes, the researchers said. Consequently, surgeons should consider primary care exposure in preoperative assessment, and perform a more comprehensive presurgical assessment as needed, the researchers said.

More studies are needed to examine trends in racial groups, but the results of the current study suggest that primary care provides similar benefits for Black and White individuals, and therefore could help reduce health disparities, they concluded.
 

Primary care benefits elude many patients

The current study shows a “rather dramatic” association between utilization of primary care within a year before surgery and patient mortality after surgery, wrote Caroline E. Reinke, MD, and David C. Slawson, MD, both of Atrium Health, Charlotte, N.C., in an accompanying editorial. The authors reiterated that possible reasons for the positive effect of primary care on postsurgical mortality included identification and management of comorbidities that could complicate surgery, as well as earlier detection of disease.

However, the editorialists noted that the benefits of primary care exposure depend on patient access to primary care, and on patient adherence to recommendations from their primary care provider. They identified barriers to potential effective interventions with primary care providers including time, money, and transportation.

An unanswered question is “whether the PCP visit itself is the causative factor associated with decreased mortality or if seeing a PCP on an annual basis is a marker of the patient possessing some other ‘magic sauce’ that improves outcomes,” they wrote.

Further, individuals in areas of primary care shortage also are more likely to lack the socioeconomic resources to benefit from primary care, the editorialists said. “Future evaluations of the interaction between PCP visits and social determinants of health may shed light on how to achieve the greatest impact,” they concluded.
 

Study supports value of consistent primary care

The increasingly aging population across the United States may undergo surgical procedures on an emergent basis and the current study provides data on the benefits of established and effective primary care for these individuals, said Noel Deep, MD, in an interview.

“Having data from this study supports the current position of many physicians and health care organizations and medical professional organizations that older individuals in particular, and adults in general, who have regular routine primary care visits tend to lead healthier lives and have better prognosis and quality of life,” said Dr. Deep, a general internist in private practice in Antigo, Wisc., who was not involved in the study. Dr. Deep also serves as chief medical officer and a staff physician at Aspirus Langlade Hospital in Antigo.

The study findings reinforce what most physicians in primary care, himself included, have been advising adult patients, especially older adults about maintaining regular follow-up visits with their physicians for health screening and management of chronic medical conditions, Dr. Deep said in an interview.

However, barriers to the routine use of primary care to improve postsurgical outcomes include health illiteracy, being overwhelmed by a sudden change in health or emergent surgery, and lack of access to primary care physician, as well as issues such as transportation, financial difficulties, and physical limitations, Dr. Deep added.

“Patients who avoid routine health care visits with primary care may be lacking health insurance or financial resources, have time constraints or family responsibilities, or may be unaware of the benefits of routine health care,” he noted.

As for additional research, “I would like to see studies that can document the impact of having primary care physicians comanage these hospitalized patients in the perioperative period with continued follow-up in the postoperative/convalescent period,” said Dr. Deep.

The study was supported by the National Institute on Aging of the National Institutes of Health. Dr. Roberts disclosed grants from the National Institute on Aging and from NIH during the conduct of the study. The editorial author had no financial conflicts to disclose. Dr. Deep had no financial conflicts to disclose and serves on the Editorial Advisory Board of Internal Medicine News.

Treatment with an experimental oral tau aggregation inhibitor, hydromethylthionine mesylate (HMTM), led to a statistically significant reduction in an established biomarker of neurodegeneration in Alzheimer’s disease (AD) in the LUCIDITY phase 3 trial.
 

Blood concentrations of neurofilament light chain (NfL) showed a 93% reduction in change over 12 months in participants receiving HMTM at the target dose of 16 mg/day relative to the control group, which correlated significantly with a tau biomarker (p-tau 181) in blood and changes in cognitive test scores.

“This is the first tau aggregation inhibitor to reach the phase 3 stage of development and to produce results like this,” Claude Wischik, PhD, executive chairman of TauRx Therapeutics, which is developing the drug, noted in an interview.

“NfL is one of the best studied biomarkers in the business because it goes off the rails in a range of neurodegenerative disorders. In AD, it correlates with disease severity, and it tracks ongoing damage to neurons,” Dr. Wischik explained.

Oral HMTM was designed to reduce tau pathology in AD, and the noted changes in NfL concentration by HMTM indicate a “direct impact on disease pathology,” Dr. Wischik said.

The findings, from a prespecified blood biomarker analysis of the LUCIDITY phase 3 trial, were presented at the annual Alzheimer’s Association International Conference.
 

Support for tau inhibitor

Topline results from the LUCIDITY trial showed improvement in cognition over 18 months in participants with mild cognitive impairment (MCI) caused by AD who were treated with a 16-mg/day dose of HMTM.

However, in an odd twist, participants in the control group who received a low dose of methylthioninium chloride (MTC) also showed cognitive improvement.

As a result, HMTM 16 mg/day failed to reach its two primary endpoints – change from baseline on the Alzheimer’s Disease Assessment Scale–Cognitive Subscale (ADAS-Cog11) and the Alzheimer’s Disease Cooperative Study/Activities of Daily Living Inventory (ADCS-ADL23) – relative to the MTC control group.

That’s likely because treatment with MTC, which is a variant of HMTM, unexpectedly achieved blood levels of active drug above the threshold needed to produce a clinical effect.

For the prespecified biomarker analysis reported at AAIC 2023, baseline and 12-month NfL plasma levels were available in 161 of 185 participants receiving HMTM 16 mg/day, 38 of 48 receiving HMTM 8 mg/day and 136 of 185 receiving MTC 8 mg/week.

Blood concentrations of NfL showed a statistically significant 93% reduction in change over 12 months in participants receiving HMTM at a dose of 16 mg/day relative to the control group (P = .0278), Dr. Wischik reported.

In addition, the p-tau 181 increase over 12 months “reduced to zero” with HMTM 16 mg/day and there was significant correlation between change in NfL and p-tau 181 concentration, he noted.

NfL reductions were significantly correlated with change in ADAS-Cog11 (P = .0038) and whole brain volume (P = .0359) over 24 months.
 

‘Exciting’ biomarker data

Commenting on the new data in an interview, Christopher Weber, PhD, director of global science initiatives at the Alzheimer’s Association, said the phase 3 LUCIDITY results “suggest that HMTM could be a potential therapeutic for slowing down neurodegenerative processes in Alzheimer’s disease.”

“Plasma NfL is an interesting biomarker which is used more and more in clinical trials because it’s noninvasive, accessible, and can assist in diagnosing and monitoring the disease in the early stages. Elevated NfL levels suggest that neurons are being affected in the brain, which could indicate the presence or progression of Alzheimer’s disease,” Dr. Weber said in an interview.

He said the biomarker data from the LUCIDITY study are “exciting.”

“However, due to the relatively small sample size, we look forward to seeing additional research on HMTM in larger, and even more diverse cohorts to better understand the performance of this treatment and the role of NfL in Alzheimer’s disease,” Dr. Weber said.

Also providing outside perspective, Howard Fillit, MD, founding executive director of the Alzheimer’s Drug Discovery Foundation, noted that currently “there is a lot of effort in trying to address the abnormal tau that occurs in Alzheimer’s disease.”

The biomarker data from LUCIDITY show that HMTM “seems to markedly decrease the amount of NfL in plasma and there is some correlation with cognitive scores. The obvious unknown is whether these changes in plasma NfL will predict clinical benefit,” Dr. Fillit said in an interview.

“This is an oral drug that has a good safety profile, and the mechanism of action makes sense, but we need to see the clinical data,” Dr. Fillit said.

Final 2-year data from the LUCIDITY trial are expected to be released later in 2023.

In the United Kingdom, TauRx has entered an accelerated approval process for the drug, and the company said it plans to seek regulatory approval in the United States and Canada in 2023.

The study was funded by TauRx Therapeutics. Dr. Wischik is an employee of the University of Aberdeen (Scotland), and TauRx Therapeutics. Dr. Weber and Dr. Fillit reported no relevant financial relationships.

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

Treatment with an experimental oral tau aggregation inhibitor, hydromethylthionine mesylate (HMTM), led to a statistically significant reduction in an established biomarker of neurodegeneration in Alzheimer’s disease (AD) in the LUCIDITY phase 3 trial.
 

Blood concentrations of neurofilament light chain (NfL) showed a 93% reduction in change over 12 months in participants receiving HMTM at the target dose of 16 mg/day relative to the control group, which correlated significantly with a tau biomarker (p-tau 181) in blood and changes in cognitive test scores.

“This is the first tau aggregation inhibitor to reach the phase 3 stage of development and to produce results like this,” Claude Wischik, PhD, executive chairman of TauRx Therapeutics, which is developing the drug, noted in an interview.

“NfL is one of the best studied biomarkers in the business because it goes off the rails in a range of neurodegenerative disorders. In AD, it correlates with disease severity, and it tracks ongoing damage to neurons,” Dr. Wischik explained.

Oral HMTM was designed to reduce tau pathology in AD, and the noted changes in NfL concentration by HMTM indicate a “direct impact on disease pathology,” Dr. Wischik said.

The findings, from a prespecified blood biomarker analysis of the LUCIDITY phase 3 trial, were presented at the annual Alzheimer’s Association International Conference.
 

Support for tau inhibitor

Topline results from the LUCIDITY trial showed improvement in cognition over 18 months in participants with mild cognitive impairment (MCI) caused by AD who were treated with a 16-mg/day dose of HMTM.

However, in an odd twist, participants in the control group who received a low dose of methylthioninium chloride (MTC) also showed cognitive improvement.

As a result, HMTM 16 mg/day failed to reach its two primary endpoints – change from baseline on the Alzheimer’s Disease Assessment Scale–Cognitive Subscale (ADAS-Cog11) and the Alzheimer’s Disease Cooperative Study/Activities of Daily Living Inventory (ADCS-ADL23) – relative to the MTC control group.

That’s likely because treatment with MTC, which is a variant of HMTM, unexpectedly achieved blood levels of active drug above the threshold needed to produce a clinical effect.

For the prespecified biomarker analysis reported at AAIC 2023, baseline and 12-month NfL plasma levels were available in 161 of 185 participants receiving HMTM 16 mg/day, 38 of 48 receiving HMTM 8 mg/day and 136 of 185 receiving MTC 8 mg/week.

Blood concentrations of NfL showed a statistically significant 93% reduction in change over 12 months in participants receiving HMTM at a dose of 16 mg/day relative to the control group (P = .0278), Dr. Wischik reported.

In addition, the p-tau 181 increase over 12 months “reduced to zero” with HMTM 16 mg/day and there was significant correlation between change in NfL and p-tau 181 concentration, he noted.

NfL reductions were significantly correlated with change in ADAS-Cog11 (P = .0038) and whole brain volume (P = .0359) over 24 months.
 

‘Exciting’ biomarker data

Commenting on the new data in an interview, Christopher Weber, PhD, director of global science initiatives at the Alzheimer’s Association, said the phase 3 LUCIDITY results “suggest that HMTM could be a potential therapeutic for slowing down neurodegenerative processes in Alzheimer’s disease.”

“Plasma NfL is an interesting biomarker which is used more and more in clinical trials because it’s noninvasive, accessible, and can assist in diagnosing and monitoring the disease in the early stages. Elevated NfL levels suggest that neurons are being affected in the brain, which could indicate the presence or progression of Alzheimer’s disease,” Dr. Weber said in an interview.

He said the biomarker data from the LUCIDITY study are “exciting.”

“However, due to the relatively small sample size, we look forward to seeing additional research on HMTM in larger, and even more diverse cohorts to better understand the performance of this treatment and the role of NfL in Alzheimer’s disease,” Dr. Weber said.

Also providing outside perspective, Howard Fillit, MD, founding executive director of the Alzheimer’s Drug Discovery Foundation, noted that currently “there is a lot of effort in trying to address the abnormal tau that occurs in Alzheimer’s disease.”

The biomarker data from LUCIDITY show that HMTM “seems to markedly decrease the amount of NfL in plasma and there is some correlation with cognitive scores. The obvious unknown is whether these changes in plasma NfL will predict clinical benefit,” Dr. Fillit said in an interview.

“This is an oral drug that has a good safety profile, and the mechanism of action makes sense, but we need to see the clinical data,” Dr. Fillit said.

Final 2-year data from the LUCIDITY trial are expected to be released later in 2023.

In the United Kingdom, TauRx has entered an accelerated approval process for the drug, and the company said it plans to seek regulatory approval in the United States and Canada in 2023.

The study was funded by TauRx Therapeutics. Dr. Wischik is an employee of the University of Aberdeen (Scotland), and TauRx Therapeutics. Dr. Weber and Dr. Fillit reported no relevant financial relationships.

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

Treatment with an experimental oral tau aggregation inhibitor, hydromethylthionine mesylate (HMTM), led to a statistically significant reduction in an established biomarker of neurodegeneration in Alzheimer’s disease (AD) in the LUCIDITY phase 3 trial.
 

Blood concentrations of neurofilament light chain (NfL) showed a 93% reduction in change over 12 months in participants receiving HMTM at the target dose of 16 mg/day relative to the control group, which correlated significantly with a tau biomarker (p-tau 181) in blood and changes in cognitive test scores.

“This is the first tau aggregation inhibitor to reach the phase 3 stage of development and to produce results like this,” Claude Wischik, PhD, executive chairman of TauRx Therapeutics, which is developing the drug, noted in an interview.

“NfL is one of the best studied biomarkers in the business because it goes off the rails in a range of neurodegenerative disorders. In AD, it correlates with disease severity, and it tracks ongoing damage to neurons,” Dr. Wischik explained.

Oral HMTM was designed to reduce tau pathology in AD, and the noted changes in NfL concentration by HMTM indicate a “direct impact on disease pathology,” Dr. Wischik said.

The findings, from a prespecified blood biomarker analysis of the LUCIDITY phase 3 trial, were presented at the annual Alzheimer’s Association International Conference.
 

Support for tau inhibitor

Topline results from the LUCIDITY trial showed improvement in cognition over 18 months in participants with mild cognitive impairment (MCI) caused by AD who were treated with a 16-mg/day dose of HMTM.

However, in an odd twist, participants in the control group who received a low dose of methylthioninium chloride (MTC) also showed cognitive improvement.

As a result, HMTM 16 mg/day failed to reach its two primary endpoints – change from baseline on the Alzheimer’s Disease Assessment Scale–Cognitive Subscale (ADAS-Cog11) and the Alzheimer’s Disease Cooperative Study/Activities of Daily Living Inventory (ADCS-ADL23) – relative to the MTC control group.

That’s likely because treatment with MTC, which is a variant of HMTM, unexpectedly achieved blood levels of active drug above the threshold needed to produce a clinical effect.

For the prespecified biomarker analysis reported at AAIC 2023, baseline and 12-month NfL plasma levels were available in 161 of 185 participants receiving HMTM 16 mg/day, 38 of 48 receiving HMTM 8 mg/day and 136 of 185 receiving MTC 8 mg/week.

Blood concentrations of NfL showed a statistically significant 93% reduction in change over 12 months in participants receiving HMTM at a dose of 16 mg/day relative to the control group (P = .0278), Dr. Wischik reported.

In addition, the p-tau 181 increase over 12 months “reduced to zero” with HMTM 16 mg/day and there was significant correlation between change in NfL and p-tau 181 concentration, he noted.

NfL reductions were significantly correlated with change in ADAS-Cog11 (P = .0038) and whole brain volume (P = .0359) over 24 months.
 

‘Exciting’ biomarker data

Commenting on the new data in an interview, Christopher Weber, PhD, director of global science initiatives at the Alzheimer’s Association, said the phase 3 LUCIDITY results “suggest that HMTM could be a potential therapeutic for slowing down neurodegenerative processes in Alzheimer’s disease.”

“Plasma NfL is an interesting biomarker which is used more and more in clinical trials because it’s noninvasive, accessible, and can assist in diagnosing and monitoring the disease in the early stages. Elevated NfL levels suggest that neurons are being affected in the brain, which could indicate the presence or progression of Alzheimer’s disease,” Dr. Weber said in an interview.

He said the biomarker data from the LUCIDITY study are “exciting.”

“However, due to the relatively small sample size, we look forward to seeing additional research on HMTM in larger, and even more diverse cohorts to better understand the performance of this treatment and the role of NfL in Alzheimer’s disease,” Dr. Weber said.

Also providing outside perspective, Howard Fillit, MD, founding executive director of the Alzheimer’s Drug Discovery Foundation, noted that currently “there is a lot of effort in trying to address the abnormal tau that occurs in Alzheimer’s disease.”

The biomarker data from LUCIDITY show that HMTM “seems to markedly decrease the amount of NfL in plasma and there is some correlation with cognitive scores. The obvious unknown is whether these changes in plasma NfL will predict clinical benefit,” Dr. Fillit said in an interview.

“This is an oral drug that has a good safety profile, and the mechanism of action makes sense, but we need to see the clinical data,” Dr. Fillit said.

Final 2-year data from the LUCIDITY trial are expected to be released later in 2023.

In the United Kingdom, TauRx has entered an accelerated approval process for the drug, and the company said it plans to seek regulatory approval in the United States and Canada in 2023.

The study was funded by TauRx Therapeutics. Dr. Wischik is an employee of the University of Aberdeen (Scotland), and TauRx Therapeutics. Dr. Weber and Dr. Fillit reported no relevant financial relationships.

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

Opioid initiation for older adults with dementia is linked to a significantly increased risk of death, especially in the first 2 weeks, when the risk is elevated 11-fold, new research shows.

“We expected that opioids would be associated with an increased risk of death, but we are surprised by the magnitude,” study investigator Christina Jensen-Dahm, MD, PhD, with the Danish Dementia Research Centre, Copenhagen University Hospital, Rigshospitalet, Denmark, told this news organization.

“It’s important that physicians carefully evaluate the risk and benefits if considering initiating an opioid, and this is particularly important in elderly with dementia,” Dr. Jensen-Dahm added.

The findings were presented at the Alzheimer’s Association International Conference.
 

Risky business

Using Danish nationwide registries, the researchers analyzed data on all 75,471 adults in Denmark who were aged 65 and older and had been diagnosed with dementia between 2008 and 2018. A total of 31,619 individuals (42%) filled a prescription for an opioid. These “exposed” individuals were matched to 63,235 unexposed individuals.

Among the exposed group, 10,474 (33%) died within 180 days after starting opioid therapy, compared with 3,980 (6.4%) in the unexposed group.

After adjusting for potential differences between groups, new use of an opioid was associated with a greater than fourfold excess mortality risk (adjusted hazard ratio, 4.16; 95% confidence interval, 4.00-4.33).

New use of a strong opioid – defined as morphine, oxycodone, ketobemidone, hydromorphone, pethidine, buprenorphine, and fentanyl – was associated with a greater than sixfold increase in mortality risk (aHR, 6.42; 95% CI, 6.08-6.79).

Among those who used fentanyl patches as their first opioid, 65% died within the first 180 days, compared with 6.7% in the unexposed – an eightfold increased mortality risk (aHR, 8.04; 95% CI, 7.01-9.22).

For all opioids, the risk was greatest in the first 14 days, with a nearly 11-fold increased risk of mortality (aHR, 10.8; 95% CI, 9.74-11.99). However, there remained a twofold increase in risk after taking opioids for 90 days (aHR, 2.32; 95% CI, 2.17-2.48).

“Opioids are associated with severe and well-known side effects, such as sedation, confusion, respiratory depression, falls, and in the most severe cases, death. In the general population, opioids have been associated with an increased risk of death, and similar to ours, greatest in the first 14 days,” said Dr. Jensen-Dahm.
 

Need to weigh risks, benefits

Commenting on the study, Percy Griffin, PhD, director of scientific engagement at the Alzheimer’s Association, told this news organization that the use of strong opioids has “increased considerably over the past decade among older people with dementia. Opioid therapy should only be considered for pain if the benefits are anticipated to outweigh the risks in individuals who are living with dementia.”

“Opioids are very powerful drugs, and while we need to see additional research in more diverse populations, these initial findings indicate they may put older adults with dementia at much higher risk of death,” Nicole Purcell, DO, neurologist and senior director of clinical practice at the Alzheimer’s Association, added in a conference statement.

“Pain should not go undiagnosed or untreated, in particular in people living with dementia, who may not be able to effectively articulate the location and severity of the pain,” Dr. Purcell added.

These new findings further emphasize the need for discussion between patient, family, and physician. Decisions about prescribing pain medication should be thought through carefully, and if used, there needs to be careful monitoring of the patient, said Dr. Purcell.

The study was supported by a grant from the Capital Region of Denmark. Dr. Jensen-Dahm, Dr. Griffin, and Dr. Purcell have no relevant disclosures.

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

Opioid initiation for older adults with dementia is linked to a significantly increased risk of death, especially in the first 2 weeks, when the risk is elevated 11-fold, new research shows.

“We expected that opioids would be associated with an increased risk of death, but we are surprised by the magnitude,” study investigator Christina Jensen-Dahm, MD, PhD, with the Danish Dementia Research Centre, Copenhagen University Hospital, Rigshospitalet, Denmark, told this news organization.

“It’s important that physicians carefully evaluate the risk and benefits if considering initiating an opioid, and this is particularly important in elderly with dementia,” Dr. Jensen-Dahm added.

The findings were presented at the Alzheimer’s Association International Conference.
 

Risky business

Using Danish nationwide registries, the researchers analyzed data on all 75,471 adults in Denmark who were aged 65 and older and had been diagnosed with dementia between 2008 and 2018. A total of 31,619 individuals (42%) filled a prescription for an opioid. These “exposed” individuals were matched to 63,235 unexposed individuals.

Among the exposed group, 10,474 (33%) died within 180 days after starting opioid therapy, compared with 3,980 (6.4%) in the unexposed group.

After adjusting for potential differences between groups, new use of an opioid was associated with a greater than fourfold excess mortality risk (adjusted hazard ratio, 4.16; 95% confidence interval, 4.00-4.33).

New use of a strong opioid – defined as morphine, oxycodone, ketobemidone, hydromorphone, pethidine, buprenorphine, and fentanyl – was associated with a greater than sixfold increase in mortality risk (aHR, 6.42; 95% CI, 6.08-6.79).

Among those who used fentanyl patches as their first opioid, 65% died within the first 180 days, compared with 6.7% in the unexposed – an eightfold increased mortality risk (aHR, 8.04; 95% CI, 7.01-9.22).

For all opioids, the risk was greatest in the first 14 days, with a nearly 11-fold increased risk of mortality (aHR, 10.8; 95% CI, 9.74-11.99). However, there remained a twofold increase in risk after taking opioids for 90 days (aHR, 2.32; 95% CI, 2.17-2.48).

“Opioids are associated with severe and well-known side effects, such as sedation, confusion, respiratory depression, falls, and in the most severe cases, death. In the general population, opioids have been associated with an increased risk of death, and similar to ours, greatest in the first 14 days,” said Dr. Jensen-Dahm.
 

Need to weigh risks, benefits

Commenting on the study, Percy Griffin, PhD, director of scientific engagement at the Alzheimer’s Association, told this news organization that the use of strong opioids has “increased considerably over the past decade among older people with dementia. Opioid therapy should only be considered for pain if the benefits are anticipated to outweigh the risks in individuals who are living with dementia.”

“Opioids are very powerful drugs, and while we need to see additional research in more diverse populations, these initial findings indicate they may put older adults with dementia at much higher risk of death,” Nicole Purcell, DO, neurologist and senior director of clinical practice at the Alzheimer’s Association, added in a conference statement.

“Pain should not go undiagnosed or untreated, in particular in people living with dementia, who may not be able to effectively articulate the location and severity of the pain,” Dr. Purcell added.

These new findings further emphasize the need for discussion between patient, family, and physician. Decisions about prescribing pain medication should be thought through carefully, and if used, there needs to be careful monitoring of the patient, said Dr. Purcell.

The study was supported by a grant from the Capital Region of Denmark. Dr. Jensen-Dahm, Dr. Griffin, and Dr. Purcell have no relevant disclosures.

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

Opioid initiation for older adults with dementia is linked to a significantly increased risk of death, especially in the first 2 weeks, when the risk is elevated 11-fold, new research shows.

“We expected that opioids would be associated with an increased risk of death, but we are surprised by the magnitude,” study investigator Christina Jensen-Dahm, MD, PhD, with the Danish Dementia Research Centre, Copenhagen University Hospital, Rigshospitalet, Denmark, told this news organization.

“It’s important that physicians carefully evaluate the risk and benefits if considering initiating an opioid, and this is particularly important in elderly with dementia,” Dr. Jensen-Dahm added.

The findings were presented at the Alzheimer’s Association International Conference.
 

Risky business

Using Danish nationwide registries, the researchers analyzed data on all 75,471 adults in Denmark who were aged 65 and older and had been diagnosed with dementia between 2008 and 2018. A total of 31,619 individuals (42%) filled a prescription for an opioid. These “exposed” individuals were matched to 63,235 unexposed individuals.

Among the exposed group, 10,474 (33%) died within 180 days after starting opioid therapy, compared with 3,980 (6.4%) in the unexposed group.

After adjusting for potential differences between groups, new use of an opioid was associated with a greater than fourfold excess mortality risk (adjusted hazard ratio, 4.16; 95% confidence interval, 4.00-4.33).

New use of a strong opioid – defined as morphine, oxycodone, ketobemidone, hydromorphone, pethidine, buprenorphine, and fentanyl – was associated with a greater than sixfold increase in mortality risk (aHR, 6.42; 95% CI, 6.08-6.79).

Among those who used fentanyl patches as their first opioid, 65% died within the first 180 days, compared with 6.7% in the unexposed – an eightfold increased mortality risk (aHR, 8.04; 95% CI, 7.01-9.22).

For all opioids, the risk was greatest in the first 14 days, with a nearly 11-fold increased risk of mortality (aHR, 10.8; 95% CI, 9.74-11.99). However, there remained a twofold increase in risk after taking opioids for 90 days (aHR, 2.32; 95% CI, 2.17-2.48).

“Opioids are associated with severe and well-known side effects, such as sedation, confusion, respiratory depression, falls, and in the most severe cases, death. In the general population, opioids have been associated with an increased risk of death, and similar to ours, greatest in the first 14 days,” said Dr. Jensen-Dahm.
 

Need to weigh risks, benefits

Commenting on the study, Percy Griffin, PhD, director of scientific engagement at the Alzheimer’s Association, told this news organization that the use of strong opioids has “increased considerably over the past decade among older people with dementia. Opioid therapy should only be considered for pain if the benefits are anticipated to outweigh the risks in individuals who are living with dementia.”

“Opioids are very powerful drugs, and while we need to see additional research in more diverse populations, these initial findings indicate they may put older adults with dementia at much higher risk of death,” Nicole Purcell, DO, neurologist and senior director of clinical practice at the Alzheimer’s Association, added in a conference statement.

“Pain should not go undiagnosed or untreated, in particular in people living with dementia, who may not be able to effectively articulate the location and severity of the pain,” Dr. Purcell added.

These new findings further emphasize the need for discussion between patient, family, and physician. Decisions about prescribing pain medication should be thought through carefully, and if used, there needs to be careful monitoring of the patient, said Dr. Purcell.

The study was supported by a grant from the Capital Region of Denmark. Dr. Jensen-Dahm, Dr. Griffin, and Dr. Purcell have no relevant disclosures.

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

Recent news highlights advancements in the understanding of Alzheimer’s disease: Increased information on biomarkers to be used for evaluation and diagnosis and recent studies on lifestyle factors or medications that do and do not correlate with Alzheimer’s disease.

It is helpful for family medicine physicians and other primary care physicians to be aware of this information to better help our patients and their families. When we have patients with strong family history of cognitive decline, they often will ask us for an early assessment or help with next steps and requests for treatment. Patients and their families want to understand what testing will be done by the neurologist they will likely be seeing.

An article published in Alzheimer’s and Dementia put forward a consensus statement by 11 European scientific societies on diagnosis and management of the disease. These societies defined work flows for processes to utilize biomarkers to diagnose Alzheimer’s disease. Although these work flows may help with diagnosis, they are not able to definitively rule out other causes of dementia. However, they may lead to consistency in how treatments are determined.¹ More consistency will be helpful in counseling patients and their families on the next steps in the treatment plan.

Another study evaluated the correlation between lean mass and dementia. This study demonstrated a decreased risk of dementia in patients with higher lean mass. It is unclear from this study whether the higher lean mass is protective or if decreased cognitive function decreases the amount of lean mass. However, this study does provide hope in two possible ways: it provides potentially predictive information on who may be more at risk of declining cognitive function as well as a modifiable risk factor to address.² Family physicians may use this as part of their counseling for patients who are concerned about their potential risk of dementia. It is yet another reason why we may counsel on healthy diet and weight-bearing exercise to help maintain lean mass.

Other associations related to dementia have been disproven. An article in Gastroenterology discussed the association between cognitive decline and use of proton pump inhibitors and H₂ blockers – indicating that there is no association.³ Although there are reasons why we want to limit the use of these medications – particularly when they are not needed, it is a relief that they are not causing cognitive decline in patients.

Most of these studies provide information that is helpful for both family medicine physicians and patients. We are learning more about cognitive decline and Alzheimer’s disease. This gives hope to patients with strong family history that we may be able to reduce their risks. These studies also give us possible risk factors on which we can counsel our patients.

Developments in Alzheimer’s disease research are speeding ahead and give family physicians a bit more information to discuss with patients and their families as they face the challenging symptoms of cognitive decline. Future research, it is hoped, will help with treatment plans and modifiable risk factors to improve the outcomes for patients at high risk of cognitive decline.

Dr. Wheat is associate professor of family and community medicine at Northwestern University in Chicago. She has no conflicts of interest.

References

1. Massa F et al. Alzheimer’s and Dementia. 2023;19(S2):e062216.

2. Daghlas I et al. BMJ Medicine. 2023;2(1):e000354.

3. Mehta R et al. Gastroenterology. 2023 Jun 12. doi: 10.1053/j.gastro.2023.05.052.

Recent news highlights advancements in the understanding of Alzheimer’s disease: Increased information on biomarkers to be used for evaluation and diagnosis and recent studies on lifestyle factors or medications that do and do not correlate with Alzheimer’s disease.

It is helpful for family medicine physicians and other primary care physicians to be aware of this information to better help our patients and their families. When we have patients with strong family history of cognitive decline, they often will ask us for an early assessment or help with next steps and requests for treatment. Patients and their families want to understand what testing will be done by the neurologist they will likely be seeing.

An article published in Alzheimer’s and Dementia put forward a consensus statement by 11 European scientific societies on diagnosis and management of the disease. These societies defined work flows for processes to utilize biomarkers to diagnose Alzheimer’s disease. Although these work flows may help with diagnosis, they are not able to definitively rule out other causes of dementia. However, they may lead to consistency in how treatments are determined.¹ More consistency will be helpful in counseling patients and their families on the next steps in the treatment plan.

Another study evaluated the correlation between lean mass and dementia. This study demonstrated a decreased risk of dementia in patients with higher lean mass. It is unclear from this study whether the higher lean mass is protective or if decreased cognitive function decreases the amount of lean mass. However, this study does provide hope in two possible ways: it provides potentially predictive information on who may be more at risk of declining cognitive function as well as a modifiable risk factor to address.² Family physicians may use this as part of their counseling for patients who are concerned about their potential risk of dementia. It is yet another reason why we may counsel on healthy diet and weight-bearing exercise to help maintain lean mass.

Other associations related to dementia have been disproven. An article in Gastroenterology discussed the association between cognitive decline and use of proton pump inhibitors and H₂ blockers – indicating that there is no association.³ Although there are reasons why we want to limit the use of these medications – particularly when they are not needed, it is a relief that they are not causing cognitive decline in patients.

Most of these studies provide information that is helpful for both family medicine physicians and patients. We are learning more about cognitive decline and Alzheimer’s disease. This gives hope to patients with strong family history that we may be able to reduce their risks. These studies also give us possible risk factors on which we can counsel our patients.

Developments in Alzheimer’s disease research are speeding ahead and give family physicians a bit more information to discuss with patients and their families as they face the challenging symptoms of cognitive decline. Future research, it is hoped, will help with treatment plans and modifiable risk factors to improve the outcomes for patients at high risk of cognitive decline.

Dr. Wheat is associate professor of family and community medicine at Northwestern University in Chicago. She has no conflicts of interest.

References

1. Massa F et al. Alzheimer’s and Dementia. 2023;19(S2):e062216.

2. Daghlas I et al. BMJ Medicine. 2023;2(1):e000354.

3. Mehta R et al. Gastroenterology. 2023 Jun 12. doi: 10.1053/j.gastro.2023.05.052.

Recent news highlights advancements in the understanding of Alzheimer’s disease: Increased information on biomarkers to be used for evaluation and diagnosis and recent studies on lifestyle factors or medications that do and do not correlate with Alzheimer’s disease.

It is helpful for family medicine physicians and other primary care physicians to be aware of this information to better help our patients and their families. When we have patients with strong family history of cognitive decline, they often will ask us for an early assessment or help with next steps and requests for treatment. Patients and their families want to understand what testing will be done by the neurologist they will likely be seeing.

An article published in Alzheimer’s and Dementia put forward a consensus statement by 11 European scientific societies on diagnosis and management of the disease. These societies defined work flows for processes to utilize biomarkers to diagnose Alzheimer’s disease. Although these work flows may help with diagnosis, they are not able to definitively rule out other causes of dementia. However, they may lead to consistency in how treatments are determined.¹ More consistency will be helpful in counseling patients and their families on the next steps in the treatment plan.

Another study evaluated the correlation between lean mass and dementia. This study demonstrated a decreased risk of dementia in patients with higher lean mass. It is unclear from this study whether the higher lean mass is protective or if decreased cognitive function decreases the amount of lean mass. However, this study does provide hope in two possible ways: it provides potentially predictive information on who may be more at risk of declining cognitive function as well as a modifiable risk factor to address.² Family physicians may use this as part of their counseling for patients who are concerned about their potential risk of dementia. It is yet another reason why we may counsel on healthy diet and weight-bearing exercise to help maintain lean mass.

Other associations related to dementia have been disproven. An article in Gastroenterology discussed the association between cognitive decline and use of proton pump inhibitors and H₂ blockers – indicating that there is no association.³ Although there are reasons why we want to limit the use of these medications – particularly when they are not needed, it is a relief that they are not causing cognitive decline in patients.

Most of these studies provide information that is helpful for both family medicine physicians and patients. We are learning more about cognitive decline and Alzheimer’s disease. This gives hope to patients with strong family history that we may be able to reduce their risks. These studies also give us possible risk factors on which we can counsel our patients.

Developments in Alzheimer’s disease research are speeding ahead and give family physicians a bit more information to discuss with patients and their families as they face the challenging symptoms of cognitive decline. Future research, it is hoped, will help with treatment plans and modifiable risk factors to improve the outcomes for patients at high risk of cognitive decline.

Dr. Wheat is associate professor of family and community medicine at Northwestern University in Chicago. She has no conflicts of interest.

References

1. Massa F et al. Alzheimer’s and Dementia. 2023;19(S2):e062216.

2. Daghlas I et al. BMJ Medicine. 2023;2(1):e000354.

3. Mehta R et al. Gastroenterology. 2023 Jun 12. doi: 10.1053/j.gastro.2023.05.052.

Kathy Blackwell is not going to allow a couple of aching joints stop her from living her best life.
 

The 73-year-old resident of Simi Valley, Calif., a bedroom community about 30 miles northwest of downtown Los Angeles, organizes regular activities for her group of seniors. The 20- to 30-member-strong band of seasoned citizens, mostly women, keep active. Over the coming weeks, they plan to catch the Beach Boys at the historic Hollywood Bowl and take a cruise to Alaska. 

The busy schedule is why Ms. Blackwell intends to delay her second hip replacement surgery, opting instead for a cortisone shot in hopes of easing the pain enough to enjoy the upcoming excursions.

Not that she is shy about joint replacement. If her orthopedic surgeon offered a frequent customer punch card like the ones you get at the local coffee shop, hers would be nearly full. Ms. Blackwell’s knees and a hip have been replaced, and her other hip will be, too, once her calendar clears up.

“If you go on enough with chronic pain where there’s no relief, you get cranky,” Ms. Blackwell said.
 

More than 1 million new knees, hips

Joint replacements are getting more common, with about 790,000 total knee replacements and more than 450,000 hip replacements performed annually in the United States, according to the American College of Rheumatology.

Experts agree age is not a factor when considering candidates for joint replacement. Rafael Sierra, MD, of the Mayo Clinic, Rochester, Minn., said he’s done hip replacements on patients as young as 12 and as old as 102. Orthopedic surgeon John Wang, MD, of the Hospital for Special Surgery, New York, has performed a total knee arthroscopy on a patient in their mid-90s. At 73, Ms. Blackwell is on the older side of the average age of 66 for a hip replacement.

“A lot of research and studies have shown that no matter what the age ranges, people end up doing great,” Dr. Wang said.

More importantly than age, older patients should be prepared for postsurgery therapy and treatment. For younger patients, the biggest drawback is outliving the estimated 25-year life span of a joint replacement. Complications are rare and occur in about 2% of procedures. These include infection, dislocation of the joint, and blood clots; other health issues you also have are not a factor.

Considering Ms. Blackwell’s hard time with her first knee replacement, it’s no small wonder that she ever set foot in a surgeon’s office again.

After putting it off for 7 years, Ms. Blackwell finally agreed to her doctor’s advice to replace her left knee in 2017 to relieve what she described as a “grinding,” chronic, bone-on-bone pain.

“It got to the point where there were no alternatives,” she said.

But her first orthopedic surgeon did a “lousy job,” leaving her with a gaping, festering wound that resulted in sepsis and required wound vacuum therapy to close the lesion. She eventually found another surgeon who removed and cleaned up her artificial knee before replacing the prosthesis. Luckily, the sepsis didn’t spread, and eight surgeries later, she was in the clear.

Ms. Blackwell’s second knee replacement in 2018 was a textbook surgery, as was a hip replacement in late 2019 .

“Your whole attitude changes,” she said.
 

What generalists should know

Orthopedic surgeons recommend that primary care doctors ask two things when weighing joint replacements: Have they exhausted nonsurgical treatments, and is the pain intolerable? They also advise avoiding narcotics to treat the symptoms.

The top issue to consider for a primary care doctor when weighing whether their patient may be a candidate for joint replacement is if the pain and the imaging are bad enough to warrant surgery.

“You don’t want to do it too soon,” Dr. Sierra said.

Dr. Sierra likes to tell the story of the golfer whose knee stiffens after playing 18 holes. To those patients, he recommends dialing back the activity; in this case, using a cart or playing only nine holes.

Dr. Wang agrees, asking if the pain is “lifestyle altering” and if the patient was unresponsive to nonsurgical treatments such as over-the-counter medications, anti-inflammatory medication and shots, home exercises or physical therapy, wearing a brace or sleeve, or simply changing their activity.

And no addictive pain pills to treat arthritis that can lead to other serious issues.

“This is not going to heal itself,” Dr. Wang said. “It’s not going to improve on its own. So, we don’t want to throw narcotics at it just to cover it up.”

Karen Smith, MD, has been a family doctor in rural North Carolina for more than 30 years. When she sees patients complaining about their joints, she first looks at function and pain. From there, she explores why they’re having discomfort. For example, is the problem an ergonomic issue at work or the result of carrying a lot of body weight?

“We look at those areas to determine what can be modified,” she said. “All of that’s done even before we get to having the orthopedic involvement.”

Dr. Smith said she also considers things beyond basic medicine: What is the patient’s mental status and tolerance for pain? Do they have a support system at home for post-operative care? And can they afford to miss work?

“We look at all of those factors together because that is going to determine the outcome that we’re hoping to achieve,” Dr. Smith said.
 

Great expectations

A recent study shows that older patients respond better to knee replacements than younger patients, particularly with pain relief and quality of life. The reason for this is believed to boil down to expectations. Whereas a younger person may want to return to the racquetball court and perform like they used to, older patients may just wish to walk down the hall without discomfort.

“It’s possible that these under 55-age-old patients may just take a little longer to heal to be satisfied,” Dr. Wang said. “We really can’t speak to why this is happening, but it’s possible that the younger patients are more active, and they expect more out of their knee.”

Jeevan Sall, MD, is a primary care sports medicine doctor with Providence Mission Heritage Medical Group in Laguna Niguel, Calif. He first discusses conservative management for patients struggling with arthritis in their joints. These measures include rehabilitation exercises, braces, shoe inserts, medication, and weight loss efforts. If these steps don’t improve a patient’s pain or lifestyle, surgery is on the table. Managing expectations is a significant factor.

“Is the patient mentally ready for surgery?” Dr. Sall said. “This includes what they hope to achieve with surgery as well as the risk and benefits of the procedure.”

Ms. Blackwell’s hip and knee pain came simply from a life well lived, with no marathon running or life-changing accident to speak of. She worked as a housewife raising her two children and owned an elevator company with her late husband, Robert Blackwell.

Yes, the elevator construction business has jokes.

“We have our ups and downs,” Ms. Blackwell said.

And with her new joints, so does she.

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

Kathy Blackwell is not going to allow a couple of aching joints stop her from living her best life.
 

The 73-year-old resident of Simi Valley, Calif., a bedroom community about 30 miles northwest of downtown Los Angeles, organizes regular activities for her group of seniors. The 20- to 30-member-strong band of seasoned citizens, mostly women, keep active. Over the coming weeks, they plan to catch the Beach Boys at the historic Hollywood Bowl and take a cruise to Alaska. 

The busy schedule is why Ms. Blackwell intends to delay her second hip replacement surgery, opting instead for a cortisone shot in hopes of easing the pain enough to enjoy the upcoming excursions.

Not that she is shy about joint replacement. If her orthopedic surgeon offered a frequent customer punch card like the ones you get at the local coffee shop, hers would be nearly full. Ms. Blackwell’s knees and a hip have been replaced, and her other hip will be, too, once her calendar clears up.

“If you go on enough with chronic pain where there’s no relief, you get cranky,” Ms. Blackwell said.
 

More than 1 million new knees, hips

Joint replacements are getting more common, with about 790,000 total knee replacements and more than 450,000 hip replacements performed annually in the United States, according to the American College of Rheumatology.

Experts agree age is not a factor when considering candidates for joint replacement. Rafael Sierra, MD, of the Mayo Clinic, Rochester, Minn., said he’s done hip replacements on patients as young as 12 and as old as 102. Orthopedic surgeon John Wang, MD, of the Hospital for Special Surgery, New York, has performed a total knee arthroscopy on a patient in their mid-90s. At 73, Ms. Blackwell is on the older side of the average age of 66 for a hip replacement.

“A lot of research and studies have shown that no matter what the age ranges, people end up doing great,” Dr. Wang said.

More importantly than age, older patients should be prepared for postsurgery therapy and treatment. For younger patients, the biggest drawback is outliving the estimated 25-year life span of a joint replacement. Complications are rare and occur in about 2% of procedures. These include infection, dislocation of the joint, and blood clots; other health issues you also have are not a factor.

Considering Ms. Blackwell’s hard time with her first knee replacement, it’s no small wonder that she ever set foot in a surgeon’s office again.

After putting it off for 7 years, Ms. Blackwell finally agreed to her doctor’s advice to replace her left knee in 2017 to relieve what she described as a “grinding,” chronic, bone-on-bone pain.

“It got to the point where there were no alternatives,” she said.

But her first orthopedic surgeon did a “lousy job,” leaving her with a gaping, festering wound that resulted in sepsis and required wound vacuum therapy to close the lesion. She eventually found another surgeon who removed and cleaned up her artificial knee before replacing the prosthesis. Luckily, the sepsis didn’t spread, and eight surgeries later, she was in the clear.

Ms. Blackwell’s second knee replacement in 2018 was a textbook surgery, as was a hip replacement in late 2019 .

“Your whole attitude changes,” she said.
 

What generalists should know

Orthopedic surgeons recommend that primary care doctors ask two things when weighing joint replacements: Have they exhausted nonsurgical treatments, and is the pain intolerable? They also advise avoiding narcotics to treat the symptoms.

The top issue to consider for a primary care doctor when weighing whether their patient may be a candidate for joint replacement is if the pain and the imaging are bad enough to warrant surgery.

“You don’t want to do it too soon,” Dr. Sierra said.

Dr. Sierra likes to tell the story of the golfer whose knee stiffens after playing 18 holes. To those patients, he recommends dialing back the activity; in this case, using a cart or playing only nine holes.

Dr. Wang agrees, asking if the pain is “lifestyle altering” and if the patient was unresponsive to nonsurgical treatments such as over-the-counter medications, anti-inflammatory medication and shots, home exercises or physical therapy, wearing a brace or sleeve, or simply changing their activity.

And no addictive pain pills to treat arthritis that can lead to other serious issues.

“This is not going to heal itself,” Dr. Wang said. “It’s not going to improve on its own. So, we don’t want to throw narcotics at it just to cover it up.”

Karen Smith, MD, has been a family doctor in rural North Carolina for more than 30 years. When she sees patients complaining about their joints, she first looks at function and pain. From there, she explores why they’re having discomfort. For example, is the problem an ergonomic issue at work or the result of carrying a lot of body weight?

“We look at those areas to determine what can be modified,” she said. “All of that’s done even before we get to having the orthopedic involvement.”

Dr. Smith said she also considers things beyond basic medicine: What is the patient’s mental status and tolerance for pain? Do they have a support system at home for post-operative care? And can they afford to miss work?

“We look at all of those factors together because that is going to determine the outcome that we’re hoping to achieve,” Dr. Smith said.
 

Great expectations

A recent study shows that older patients respond better to knee replacements than younger patients, particularly with pain relief and quality of life. The reason for this is believed to boil down to expectations. Whereas a younger person may want to return to the racquetball court and perform like they used to, older patients may just wish to walk down the hall without discomfort.

“It’s possible that these under 55-age-old patients may just take a little longer to heal to be satisfied,” Dr. Wang said. “We really can’t speak to why this is happening, but it’s possible that the younger patients are more active, and they expect more out of their knee.”

Jeevan Sall, MD, is a primary care sports medicine doctor with Providence Mission Heritage Medical Group in Laguna Niguel, Calif. He first discusses conservative management for patients struggling with arthritis in their joints. These measures include rehabilitation exercises, braces, shoe inserts, medication, and weight loss efforts. If these steps don’t improve a patient’s pain or lifestyle, surgery is on the table. Managing expectations is a significant factor.

“Is the patient mentally ready for surgery?” Dr. Sall said. “This includes what they hope to achieve with surgery as well as the risk and benefits of the procedure.”

Ms. Blackwell’s hip and knee pain came simply from a life well lived, with no marathon running or life-changing accident to speak of. She worked as a housewife raising her two children and owned an elevator company with her late husband, Robert Blackwell.

Yes, the elevator construction business has jokes.

“We have our ups and downs,” Ms. Blackwell said.

And with her new joints, so does she.

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

Kathy Blackwell is not going to allow a couple of aching joints stop her from living her best life.
 

The 73-year-old resident of Simi Valley, Calif., a bedroom community about 30 miles northwest of downtown Los Angeles, organizes regular activities for her group of seniors. The 20- to 30-member-strong band of seasoned citizens, mostly women, keep active. Over the coming weeks, they plan to catch the Beach Boys at the historic Hollywood Bowl and take a cruise to Alaska. 

The busy schedule is why Ms. Blackwell intends to delay her second hip replacement surgery, opting instead for a cortisone shot in hopes of easing the pain enough to enjoy the upcoming excursions.

Not that she is shy about joint replacement. If her orthopedic surgeon offered a frequent customer punch card like the ones you get at the local coffee shop, hers would be nearly full. Ms. Blackwell’s knees and a hip have been replaced, and her other hip will be, too, once her calendar clears up.

“If you go on enough with chronic pain where there’s no relief, you get cranky,” Ms. Blackwell said.
 

More than 1 million new knees, hips

Joint replacements are getting more common, with about 790,000 total knee replacements and more than 450,000 hip replacements performed annually in the United States, according to the American College of Rheumatology.

Experts agree age is not a factor when considering candidates for joint replacement. Rafael Sierra, MD, of the Mayo Clinic, Rochester, Minn., said he’s done hip replacements on patients as young as 12 and as old as 102. Orthopedic surgeon John Wang, MD, of the Hospital for Special Surgery, New York, has performed a total knee arthroscopy on a patient in their mid-90s. At 73, Ms. Blackwell is on the older side of the average age of 66 for a hip replacement.

“A lot of research and studies have shown that no matter what the age ranges, people end up doing great,” Dr. Wang said.

More importantly than age, older patients should be prepared for postsurgery therapy and treatment. For younger patients, the biggest drawback is outliving the estimated 25-year life span of a joint replacement. Complications are rare and occur in about 2% of procedures. These include infection, dislocation of the joint, and blood clots; other health issues you also have are not a factor.

Considering Ms. Blackwell’s hard time with her first knee replacement, it’s no small wonder that she ever set foot in a surgeon’s office again.

After putting it off for 7 years, Ms. Blackwell finally agreed to her doctor’s advice to replace her left knee in 2017 to relieve what she described as a “grinding,” chronic, bone-on-bone pain.

“It got to the point where there were no alternatives,” she said.

But her first orthopedic surgeon did a “lousy job,” leaving her with a gaping, festering wound that resulted in sepsis and required wound vacuum therapy to close the lesion. She eventually found another surgeon who removed and cleaned up her artificial knee before replacing the prosthesis. Luckily, the sepsis didn’t spread, and eight surgeries later, she was in the clear.

Ms. Blackwell’s second knee replacement in 2018 was a textbook surgery, as was a hip replacement in late 2019 .

“Your whole attitude changes,” she said.
 

What generalists should know

Orthopedic surgeons recommend that primary care doctors ask two things when weighing joint replacements: Have they exhausted nonsurgical treatments, and is the pain intolerable? They also advise avoiding narcotics to treat the symptoms.

The top issue to consider for a primary care doctor when weighing whether their patient may be a candidate for joint replacement is if the pain and the imaging are bad enough to warrant surgery.

“You don’t want to do it too soon,” Dr. Sierra said.

Dr. Sierra likes to tell the story of the golfer whose knee stiffens after playing 18 holes. To those patients, he recommends dialing back the activity; in this case, using a cart or playing only nine holes.

Dr. Wang agrees, asking if the pain is “lifestyle altering” and if the patient was unresponsive to nonsurgical treatments such as over-the-counter medications, anti-inflammatory medication and shots, home exercises or physical therapy, wearing a brace or sleeve, or simply changing their activity.

And no addictive pain pills to treat arthritis that can lead to other serious issues.

“This is not going to heal itself,” Dr. Wang said. “It’s not going to improve on its own. So, we don’t want to throw narcotics at it just to cover it up.”

Karen Smith, MD, has been a family doctor in rural North Carolina for more than 30 years. When she sees patients complaining about their joints, she first looks at function and pain. From there, she explores why they’re having discomfort. For example, is the problem an ergonomic issue at work or the result of carrying a lot of body weight?

“We look at those areas to determine what can be modified,” she said. “All of that’s done even before we get to having the orthopedic involvement.”

Dr. Smith said she also considers things beyond basic medicine: What is the patient’s mental status and tolerance for pain? Do they have a support system at home for post-operative care? And can they afford to miss work?

“We look at all of those factors together because that is going to determine the outcome that we’re hoping to achieve,” Dr. Smith said.
 

Great expectations

A recent study shows that older patients respond better to knee replacements than younger patients, particularly with pain relief and quality of life. The reason for this is believed to boil down to expectations. Whereas a younger person may want to return to the racquetball court and perform like they used to, older patients may just wish to walk down the hall without discomfort.

“It’s possible that these under 55-age-old patients may just take a little longer to heal to be satisfied,” Dr. Wang said. “We really can’t speak to why this is happening, but it’s possible that the younger patients are more active, and they expect more out of their knee.”

Jeevan Sall, MD, is a primary care sports medicine doctor with Providence Mission Heritage Medical Group in Laguna Niguel, Calif. He first discusses conservative management for patients struggling with arthritis in their joints. These measures include rehabilitation exercises, braces, shoe inserts, medication, and weight loss efforts. If these steps don’t improve a patient’s pain or lifestyle, surgery is on the table. Managing expectations is a significant factor.

“Is the patient mentally ready for surgery?” Dr. Sall said. “This includes what they hope to achieve with surgery as well as the risk and benefits of the procedure.”

Ms. Blackwell’s hip and knee pain came simply from a life well lived, with no marathon running or life-changing accident to speak of. She worked as a housewife raising her two children and owned an elevator company with her late husband, Robert Blackwell.

Yes, the elevator construction business has jokes.

“We have our ups and downs,” Ms. Blackwell said.

And with her new joints, so does she.

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