User login
In Lecanemab Alzheimer Extension Study, Placebo Roll-Over Group Does Not Catch Up
DENVER — , according to a first report of 6-month OLE data.
Due to the steady disease progression observed after the switch of placebo to active therapy, the message of these data is that “early initiation of lecanemab is important,” according to Michael Irizarry, MD, the senior vice president of clinical research at Eisai Ltd, which markets lecanemab.
The 6-month OLE data along with data from a tau PET substudy were presented by Dr. Irizarry at the 2024 annual meeting of the American Academy of Neurology.
From the start of the OLE through the 6-month follow-up, the downward trajectory of cognitive function, as measured with the Clinical Dementia Rating – Sum of Boxes (CDR-SB), has been parallel for the lecanemab-start and switch arms. As a result, the degree of separation between active and placebo groups over the course of the OLE has remained unchanged from the end of the randomized trial.
This does not rule out any benefit in the switch arm, according to Dr. Irizarry. Although there was no discernible change in the trajectory of decline among placebo patients after they were switched to lecanemab, Dr. Irizarry postulated that this might overlook the greater likely decline over time with no treatment.
“There was no placebo group in the OLE to compare with those on active treatment,” he pointed out. He then juxtaposed data from the Alzheimer’s Disease Neuroimaging Initiative (ADNI). Over the same 6-month timeframe, these data show a hypothetical separation of the curves if no treatment had been received.
The 6-month OLE data provide a preliminary look at outcomes in a planned 4-year follow-up. At the end of the randomized CLARITY trial, the mean decline from the baseline CDR-SB score of 3.2, was 1.21 in the lecanemab group, translating into a 38% decline, and 1.66 in the placebo group, translating into about a 50% decline. Over the 6 months of OLE, there has been a further mean CDR-SB reduction of approximately 0.6 in both arms, suggesting a further 18% decline from baseline.
Additional Data
In the pivotal CLARITY trial, which was published a few months prior to regulatory approval early last year, 1785 patients were randomized to 10 mg/kg lecanemab or placebo infused every 2 weeks. At the end of 18 months, the superiority of lecanemab for the primary endpoint of adverse change in CDR-SB was highly significant (P < .001) as were the differences in key secondary endpoints, such as Alzheimer’s Disease Composite Score (P < .001).
Of those who participated in CLARITY, 1385 patients entered the OLE. Placebo patients were switched to lecanemab which is being maintained in all patients on the trial schedule of 10 mg/kg administered by intravenous infusion every 2 weeks.
In addition to the overall OLE 6-month data, which has not raised any new safety signals, Dr. Irizarry provided a new look at the PET TAU substudy with a focus on patients who entered the study with a low relative tau burden. Of the three classifications, which also included medium and high tau, as measured with positron-emission tomography (PET), the low tau group represented 41.2% of the 342 tau PET substudy participants. With only 2.9% entering the study with a high tau burden, almost all the others fell in the medium stratification.
Due to the potential for a lower therapeutic response, “patients with low Tau are often excluded from trials,” Dr. Irizarry said. But the sizable proportion of low tau patients has permitted an assessment of relative response with lecanemab, which turned out to be substantial.
“Consistent rates of clinical stability or improvements were observed regardless of baseline tau levels with the highest rates of improvements observed for the low tau group after 24 months of follow-up,” Dr. Irizarry reported.
In previously reported results from the tau PET substudy, lecanemab was shown to slow tau spread at least numerically in every section of the brain evaluated, including the frontal, cingulate, parietal, and whole cortical gray matter areas. The reductions reached significance for the medial temporal (P = .0024), meta temporal (P = .012), and temporal (P = .16) portions.
When most recently evaluated in the OLE, the CDR-SB score declined 38% less among those treated with lecanemab than those treated with placebo in the subgroup enrolled in the tau PET substudy.
Relative to those with intermediate or high tau, patients in the low tau had an even greater reduction in cognitive decline than those with higher tau burdens. Although Dr. Irizarry cautioned that greater baseline CDR-SB scores exaggerated the treatment effect in the low tau group, the message is that “a lecanemab treatment effect is seen even when baseline tau levels are low.”
Now, with the recent market withdrawal of aducanumab, another anti-amyloid monoclonal antibody that was previously approved for Alzheimer’s disease, lecanemab is the only therapy currently available for the goal of changing disease progression, not just modifying symptoms.
Looking Long Term
Both sets of data provide important messages for clinicians, according to Marcelo Matiello, MD, a physician investigator at Mass General Hospital and associate professor of neurology at Harvard Medical School, Boston.
“Clinicians are really looking for more data because this remains a relatively new drug,” he said. Both sets of findings presented by Dr. Irizarry “look good but the follow-up is still short, so I think everyone is still looking closely at long-term safety and efficacy.”
The need for continuous indefinite therapy is one concern that Dr. Matiello expressed. As moderator of the session in which these data were presented, Dr. Matiello specifically asked Dr. Irizarry if there are plans to explore whether periods without treatment might be a means to reduce the cost and burden of frequent infusions while preserving cognitive gains.
In response, Dr. Irizarry said that earlier studies showed rapid progression when lecanemab was stopped. On this basis, he thinks therapy must be maintained, but he did say that there are plans to look at less frequent dosing, such as once per month. He also said that a subcutaneous formulation in development might also reduce the burden of prolonged treatment.
Dr. Irizarry is an employee of Eisai Ltd., which manufacturers lecanemab. Dr. Matiello reports no potential conflicts of interest.
DENVER — , according to a first report of 6-month OLE data.
Due to the steady disease progression observed after the switch of placebo to active therapy, the message of these data is that “early initiation of lecanemab is important,” according to Michael Irizarry, MD, the senior vice president of clinical research at Eisai Ltd, which markets lecanemab.
The 6-month OLE data along with data from a tau PET substudy were presented by Dr. Irizarry at the 2024 annual meeting of the American Academy of Neurology.
From the start of the OLE through the 6-month follow-up, the downward trajectory of cognitive function, as measured with the Clinical Dementia Rating – Sum of Boxes (CDR-SB), has been parallel for the lecanemab-start and switch arms. As a result, the degree of separation between active and placebo groups over the course of the OLE has remained unchanged from the end of the randomized trial.
This does not rule out any benefit in the switch arm, according to Dr. Irizarry. Although there was no discernible change in the trajectory of decline among placebo patients after they were switched to lecanemab, Dr. Irizarry postulated that this might overlook the greater likely decline over time with no treatment.
“There was no placebo group in the OLE to compare with those on active treatment,” he pointed out. He then juxtaposed data from the Alzheimer’s Disease Neuroimaging Initiative (ADNI). Over the same 6-month timeframe, these data show a hypothetical separation of the curves if no treatment had been received.
The 6-month OLE data provide a preliminary look at outcomes in a planned 4-year follow-up. At the end of the randomized CLARITY trial, the mean decline from the baseline CDR-SB score of 3.2, was 1.21 in the lecanemab group, translating into a 38% decline, and 1.66 in the placebo group, translating into about a 50% decline. Over the 6 months of OLE, there has been a further mean CDR-SB reduction of approximately 0.6 in both arms, suggesting a further 18% decline from baseline.
Additional Data
In the pivotal CLARITY trial, which was published a few months prior to regulatory approval early last year, 1785 patients were randomized to 10 mg/kg lecanemab or placebo infused every 2 weeks. At the end of 18 months, the superiority of lecanemab for the primary endpoint of adverse change in CDR-SB was highly significant (P < .001) as were the differences in key secondary endpoints, such as Alzheimer’s Disease Composite Score (P < .001).
Of those who participated in CLARITY, 1385 patients entered the OLE. Placebo patients were switched to lecanemab which is being maintained in all patients on the trial schedule of 10 mg/kg administered by intravenous infusion every 2 weeks.
In addition to the overall OLE 6-month data, which has not raised any new safety signals, Dr. Irizarry provided a new look at the PET TAU substudy with a focus on patients who entered the study with a low relative tau burden. Of the three classifications, which also included medium and high tau, as measured with positron-emission tomography (PET), the low tau group represented 41.2% of the 342 tau PET substudy participants. With only 2.9% entering the study with a high tau burden, almost all the others fell in the medium stratification.
Due to the potential for a lower therapeutic response, “patients with low Tau are often excluded from trials,” Dr. Irizarry said. But the sizable proportion of low tau patients has permitted an assessment of relative response with lecanemab, which turned out to be substantial.
“Consistent rates of clinical stability or improvements were observed regardless of baseline tau levels with the highest rates of improvements observed for the low tau group after 24 months of follow-up,” Dr. Irizarry reported.
In previously reported results from the tau PET substudy, lecanemab was shown to slow tau spread at least numerically in every section of the brain evaluated, including the frontal, cingulate, parietal, and whole cortical gray matter areas. The reductions reached significance for the medial temporal (P = .0024), meta temporal (P = .012), and temporal (P = .16) portions.
When most recently evaluated in the OLE, the CDR-SB score declined 38% less among those treated with lecanemab than those treated with placebo in the subgroup enrolled in the tau PET substudy.
Relative to those with intermediate or high tau, patients in the low tau had an even greater reduction in cognitive decline than those with higher tau burdens. Although Dr. Irizarry cautioned that greater baseline CDR-SB scores exaggerated the treatment effect in the low tau group, the message is that “a lecanemab treatment effect is seen even when baseline tau levels are low.”
Now, with the recent market withdrawal of aducanumab, another anti-amyloid monoclonal antibody that was previously approved for Alzheimer’s disease, lecanemab is the only therapy currently available for the goal of changing disease progression, not just modifying symptoms.
Looking Long Term
Both sets of data provide important messages for clinicians, according to Marcelo Matiello, MD, a physician investigator at Mass General Hospital and associate professor of neurology at Harvard Medical School, Boston.
“Clinicians are really looking for more data because this remains a relatively new drug,” he said. Both sets of findings presented by Dr. Irizarry “look good but the follow-up is still short, so I think everyone is still looking closely at long-term safety and efficacy.”
The need for continuous indefinite therapy is one concern that Dr. Matiello expressed. As moderator of the session in which these data were presented, Dr. Matiello specifically asked Dr. Irizarry if there are plans to explore whether periods without treatment might be a means to reduce the cost and burden of frequent infusions while preserving cognitive gains.
In response, Dr. Irizarry said that earlier studies showed rapid progression when lecanemab was stopped. On this basis, he thinks therapy must be maintained, but he did say that there are plans to look at less frequent dosing, such as once per month. He also said that a subcutaneous formulation in development might also reduce the burden of prolonged treatment.
Dr. Irizarry is an employee of Eisai Ltd., which manufacturers lecanemab. Dr. Matiello reports no potential conflicts of interest.
DENVER — , according to a first report of 6-month OLE data.
Due to the steady disease progression observed after the switch of placebo to active therapy, the message of these data is that “early initiation of lecanemab is important,” according to Michael Irizarry, MD, the senior vice president of clinical research at Eisai Ltd, which markets lecanemab.
The 6-month OLE data along with data from a tau PET substudy were presented by Dr. Irizarry at the 2024 annual meeting of the American Academy of Neurology.
From the start of the OLE through the 6-month follow-up, the downward trajectory of cognitive function, as measured with the Clinical Dementia Rating – Sum of Boxes (CDR-SB), has been parallel for the lecanemab-start and switch arms. As a result, the degree of separation between active and placebo groups over the course of the OLE has remained unchanged from the end of the randomized trial.
This does not rule out any benefit in the switch arm, according to Dr. Irizarry. Although there was no discernible change in the trajectory of decline among placebo patients after they were switched to lecanemab, Dr. Irizarry postulated that this might overlook the greater likely decline over time with no treatment.
“There was no placebo group in the OLE to compare with those on active treatment,” he pointed out. He then juxtaposed data from the Alzheimer’s Disease Neuroimaging Initiative (ADNI). Over the same 6-month timeframe, these data show a hypothetical separation of the curves if no treatment had been received.
The 6-month OLE data provide a preliminary look at outcomes in a planned 4-year follow-up. At the end of the randomized CLARITY trial, the mean decline from the baseline CDR-SB score of 3.2, was 1.21 in the lecanemab group, translating into a 38% decline, and 1.66 in the placebo group, translating into about a 50% decline. Over the 6 months of OLE, there has been a further mean CDR-SB reduction of approximately 0.6 in both arms, suggesting a further 18% decline from baseline.
Additional Data
In the pivotal CLARITY trial, which was published a few months prior to regulatory approval early last year, 1785 patients were randomized to 10 mg/kg lecanemab or placebo infused every 2 weeks. At the end of 18 months, the superiority of lecanemab for the primary endpoint of adverse change in CDR-SB was highly significant (P < .001) as were the differences in key secondary endpoints, such as Alzheimer’s Disease Composite Score (P < .001).
Of those who participated in CLARITY, 1385 patients entered the OLE. Placebo patients were switched to lecanemab which is being maintained in all patients on the trial schedule of 10 mg/kg administered by intravenous infusion every 2 weeks.
In addition to the overall OLE 6-month data, which has not raised any new safety signals, Dr. Irizarry provided a new look at the PET TAU substudy with a focus on patients who entered the study with a low relative tau burden. Of the three classifications, which also included medium and high tau, as measured with positron-emission tomography (PET), the low tau group represented 41.2% of the 342 tau PET substudy participants. With only 2.9% entering the study with a high tau burden, almost all the others fell in the medium stratification.
Due to the potential for a lower therapeutic response, “patients with low Tau are often excluded from trials,” Dr. Irizarry said. But the sizable proportion of low tau patients has permitted an assessment of relative response with lecanemab, which turned out to be substantial.
“Consistent rates of clinical stability or improvements were observed regardless of baseline tau levels with the highest rates of improvements observed for the low tau group after 24 months of follow-up,” Dr. Irizarry reported.
In previously reported results from the tau PET substudy, lecanemab was shown to slow tau spread at least numerically in every section of the brain evaluated, including the frontal, cingulate, parietal, and whole cortical gray matter areas. The reductions reached significance for the medial temporal (P = .0024), meta temporal (P = .012), and temporal (P = .16) portions.
When most recently evaluated in the OLE, the CDR-SB score declined 38% less among those treated with lecanemab than those treated with placebo in the subgroup enrolled in the tau PET substudy.
Relative to those with intermediate or high tau, patients in the low tau had an even greater reduction in cognitive decline than those with higher tau burdens. Although Dr. Irizarry cautioned that greater baseline CDR-SB scores exaggerated the treatment effect in the low tau group, the message is that “a lecanemab treatment effect is seen even when baseline tau levels are low.”
Now, with the recent market withdrawal of aducanumab, another anti-amyloid monoclonal antibody that was previously approved for Alzheimer’s disease, lecanemab is the only therapy currently available for the goal of changing disease progression, not just modifying symptoms.
Looking Long Term
Both sets of data provide important messages for clinicians, according to Marcelo Matiello, MD, a physician investigator at Mass General Hospital and associate professor of neurology at Harvard Medical School, Boston.
“Clinicians are really looking for more data because this remains a relatively new drug,” he said. Both sets of findings presented by Dr. Irizarry “look good but the follow-up is still short, so I think everyone is still looking closely at long-term safety and efficacy.”
The need for continuous indefinite therapy is one concern that Dr. Matiello expressed. As moderator of the session in which these data were presented, Dr. Matiello specifically asked Dr. Irizarry if there are plans to explore whether periods without treatment might be a means to reduce the cost and burden of frequent infusions while preserving cognitive gains.
In response, Dr. Irizarry said that earlier studies showed rapid progression when lecanemab was stopped. On this basis, he thinks therapy must be maintained, but he did say that there are plans to look at less frequent dosing, such as once per month. He also said that a subcutaneous formulation in development might also reduce the burden of prolonged treatment.
Dr. Irizarry is an employee of Eisai Ltd., which manufacturers lecanemab. Dr. Matiello reports no potential conflicts of interest.
FROM AAN 2024
Time Wasted to Avoid Penalties
Depression is a serious issue. I want to say that off the top, because nothing below is intended to minimize it.
But does everyone need to be tested for it?
A lot of general practices test for it with every patient and every visit. After all, mandates say you have to or you’ll get penalized a few bucks. Since no one wants to leave any money on the table in the razor-thin margins of running a medical practice, they ask these questions (I don’t blame them for that).
I can see where this might be useful, but does it really do much? Or is it just a mandatory waste of time?
Good question.
A recent review by the American College of Physicians found it was mostly a waste of time (which surprises no one). Only one of the eight measures involved in depression screening (suicide risk assessment) turned out to be useful. So, basically, 88% of the time spent on these questions contributed absolutely nothing of clinical relevance.
Of course, this isn’t unique to family medicine. Every time I see a Medicare or Medicare Advantage patient I have to document whether they’ve had flu and pneumonia vaccines. While there are occasional cases where asking about recent vaccines is critical to the history, for most it’s not. But I do it so I don’t get penalized, even though the answer changes nothing. It’s not like I give vaccines in my practice.
A fair number of people come to me for hospital follow-ups, so I go into the system and review the chart. The notes inevitably contain questions of sexual activity, fear of violence, fear of domestic abuse, food security, recent travel patterns, and so on. Some of them are useful in certain situations, but not in all, or even most. All they do is increase the length of the note until anything of relevance is obscured, and allow someone in coding to check the boxes to raise the billing level. Realistically, the ER staff involved probably didn’t ask any of them, and just clicked “no.”
Once this probably seemed like a good idea, but clearly most of it is now a waste of time. These “quality measures” have turned the art of taking a good history into a session of mouse and box clicking.
Does that really improve care?
Dr. Block has a solo neurology practice in Scottsdale, Arizona.
Depression is a serious issue. I want to say that off the top, because nothing below is intended to minimize it.
But does everyone need to be tested for it?
A lot of general practices test for it with every patient and every visit. After all, mandates say you have to or you’ll get penalized a few bucks. Since no one wants to leave any money on the table in the razor-thin margins of running a medical practice, they ask these questions (I don’t blame them for that).
I can see where this might be useful, but does it really do much? Or is it just a mandatory waste of time?
Good question.
A recent review by the American College of Physicians found it was mostly a waste of time (which surprises no one). Only one of the eight measures involved in depression screening (suicide risk assessment) turned out to be useful. So, basically, 88% of the time spent on these questions contributed absolutely nothing of clinical relevance.
Of course, this isn’t unique to family medicine. Every time I see a Medicare or Medicare Advantage patient I have to document whether they’ve had flu and pneumonia vaccines. While there are occasional cases where asking about recent vaccines is critical to the history, for most it’s not. But I do it so I don’t get penalized, even though the answer changes nothing. It’s not like I give vaccines in my practice.
A fair number of people come to me for hospital follow-ups, so I go into the system and review the chart. The notes inevitably contain questions of sexual activity, fear of violence, fear of domestic abuse, food security, recent travel patterns, and so on. Some of them are useful in certain situations, but not in all, or even most. All they do is increase the length of the note until anything of relevance is obscured, and allow someone in coding to check the boxes to raise the billing level. Realistically, the ER staff involved probably didn’t ask any of them, and just clicked “no.”
Once this probably seemed like a good idea, but clearly most of it is now a waste of time. These “quality measures” have turned the art of taking a good history into a session of mouse and box clicking.
Does that really improve care?
Dr. Block has a solo neurology practice in Scottsdale, Arizona.
Depression is a serious issue. I want to say that off the top, because nothing below is intended to minimize it.
But does everyone need to be tested for it?
A lot of general practices test for it with every patient and every visit. After all, mandates say you have to or you’ll get penalized a few bucks. Since no one wants to leave any money on the table in the razor-thin margins of running a medical practice, they ask these questions (I don’t blame them for that).
I can see where this might be useful, but does it really do much? Or is it just a mandatory waste of time?
Good question.
A recent review by the American College of Physicians found it was mostly a waste of time (which surprises no one). Only one of the eight measures involved in depression screening (suicide risk assessment) turned out to be useful. So, basically, 88% of the time spent on these questions contributed absolutely nothing of clinical relevance.
Of course, this isn’t unique to family medicine. Every time I see a Medicare or Medicare Advantage patient I have to document whether they’ve had flu and pneumonia vaccines. While there are occasional cases where asking about recent vaccines is critical to the history, for most it’s not. But I do it so I don’t get penalized, even though the answer changes nothing. It’s not like I give vaccines in my practice.
A fair number of people come to me for hospital follow-ups, so I go into the system and review the chart. The notes inevitably contain questions of sexual activity, fear of violence, fear of domestic abuse, food security, recent travel patterns, and so on. Some of them are useful in certain situations, but not in all, or even most. All they do is increase the length of the note until anything of relevance is obscured, and allow someone in coding to check the boxes to raise the billing level. Realistically, the ER staff involved probably didn’t ask any of them, and just clicked “no.”
Once this probably seemed like a good idea, but clearly most of it is now a waste of time. These “quality measures” have turned the art of taking a good history into a session of mouse and box clicking.
Does that really improve care?
Dr. Block has a solo neurology practice in Scottsdale, Arizona.
One-Minute Speech Test Could Help Assess Dementia Risk
BUDAPEST, HUNGARY — , suggests research.
János Kálmán, MD, PhD, and colleagues at the University of Szeged in Hungary have developed an automated speech analysis approach called the Speech-Gap Test (S-GAP Test) that is unique because it focuses on the temporal changes made when someone talks. This means it does not overcomplicate matters by also assessing the phonetics and semantics of speech, Dr. Kálmán said.
Dr. Kálmán presented his findings at the 32nd European Congress of Psychiatry.
Temporal Speech Parameters
The test analyzes parameters such as how quickly someone speaks, whether they hesitate when they talk, how long the hesitation lasts, and how many silent pauses they make. This can be done with a mere 60-second sample of speech, Dr. Kálmán said, noting that other automated speech and language tools currently in development need much longer audio samples.
“We tried different approaches and we finally ended up with the temporal speech parameters because these are not culture-dependent, not education-dependent, and could be more reliable than the semantic parts of [speech] analysis,” he explained.
The analysis of temporal speech parameters is also not language-dependent. Although the S-GAP Test was developed using audio samples from native Hungarian speakers, Dr. Kálmán and his collaborators have shown that it works just as well with samples from native English and German speakers. They now plan to validate the test further using samples from native Spanish speakers.
For Screening, Not Diagnosis
Currently, “the only purpose of this tool would be initial screening,” Dr. Kálmán said at the congress. It is not for diagnosis, and there is no intention to get it registered as a medical device.
A national survey of primary care physicians conducted by Dr. Kálmán and collaborators showed that there was little time for performing standard cognitive tests during the average consultation. Thus, the original idea was that the S-GAP Test would be an aid to help primary care physicians quickly flag whether a patient might have cognitive problems that needed further assessment at a memory clinic or by more specialist neurology services.
The goalposts have since been moved, from developing a pure telemedicine solution to a more widespread application that perhaps anyone could buy and download from the internet or using a smartphone.
Dr. Kálmán doesn’t discount developing a more sophisticated version of the S-GAP Test in the future that combines temporal speech parameters with biomarkers for mild cognitive impairment or Alzheimer’s disease and could be used in memory clinics and by neurologists for the purpose of diagnosis.
Detect to Prevent?
The big question is: What happens to all the people that could be flagged as needing further assessment using tools such as the S-GAP Test?
Tackling risk factors for dementia will probably be key, said Robert Perneckzy, MD, MBA, professor of translational dementia research at Ludwig Maximilian University of Munich, Imperial College London, and the University of Sheffield.
According to the Lancet Commission on dementia, there are 12 potentially modifiable risk factors for dementia. Their influence varies throughout the life course, but certain early events, such as the level of education attained, can’t be modified in an older patient.
That said, there are many risk factors that might still be influenced later in life, such as adequately treating comorbid conditions such as diabetes, and addressing alcohol consumption and smoking practices.
“We can do things in terms of personal risk, risk mitigation, which have a huge effect on dementia risk much later in life,” said Dr. Perneckzy.
“The speech-based assessments are another opportunity to save our time as doctors to do assessments before someone comes to the memory clinic,” he said.
The S-GAP Test is under development by the University of Szeged. Dr. Kálmán is a co-inventor. Dr. Perneckzy had no relevant conflicts of interest but has helped validate the S-GAP Test in the German language.
A version of this article appeared on Medscape.com.
BUDAPEST, HUNGARY — , suggests research.
János Kálmán, MD, PhD, and colleagues at the University of Szeged in Hungary have developed an automated speech analysis approach called the Speech-Gap Test (S-GAP Test) that is unique because it focuses on the temporal changes made when someone talks. This means it does not overcomplicate matters by also assessing the phonetics and semantics of speech, Dr. Kálmán said.
Dr. Kálmán presented his findings at the 32nd European Congress of Psychiatry.
Temporal Speech Parameters
The test analyzes parameters such as how quickly someone speaks, whether they hesitate when they talk, how long the hesitation lasts, and how many silent pauses they make. This can be done with a mere 60-second sample of speech, Dr. Kálmán said, noting that other automated speech and language tools currently in development need much longer audio samples.
“We tried different approaches and we finally ended up with the temporal speech parameters because these are not culture-dependent, not education-dependent, and could be more reliable than the semantic parts of [speech] analysis,” he explained.
The analysis of temporal speech parameters is also not language-dependent. Although the S-GAP Test was developed using audio samples from native Hungarian speakers, Dr. Kálmán and his collaborators have shown that it works just as well with samples from native English and German speakers. They now plan to validate the test further using samples from native Spanish speakers.
For Screening, Not Diagnosis
Currently, “the only purpose of this tool would be initial screening,” Dr. Kálmán said at the congress. It is not for diagnosis, and there is no intention to get it registered as a medical device.
A national survey of primary care physicians conducted by Dr. Kálmán and collaborators showed that there was little time for performing standard cognitive tests during the average consultation. Thus, the original idea was that the S-GAP Test would be an aid to help primary care physicians quickly flag whether a patient might have cognitive problems that needed further assessment at a memory clinic or by more specialist neurology services.
The goalposts have since been moved, from developing a pure telemedicine solution to a more widespread application that perhaps anyone could buy and download from the internet or using a smartphone.
Dr. Kálmán doesn’t discount developing a more sophisticated version of the S-GAP Test in the future that combines temporal speech parameters with biomarkers for mild cognitive impairment or Alzheimer’s disease and could be used in memory clinics and by neurologists for the purpose of diagnosis.
Detect to Prevent?
The big question is: What happens to all the people that could be flagged as needing further assessment using tools such as the S-GAP Test?
Tackling risk factors for dementia will probably be key, said Robert Perneckzy, MD, MBA, professor of translational dementia research at Ludwig Maximilian University of Munich, Imperial College London, and the University of Sheffield.
According to the Lancet Commission on dementia, there are 12 potentially modifiable risk factors for dementia. Their influence varies throughout the life course, but certain early events, such as the level of education attained, can’t be modified in an older patient.
That said, there are many risk factors that might still be influenced later in life, such as adequately treating comorbid conditions such as diabetes, and addressing alcohol consumption and smoking practices.
“We can do things in terms of personal risk, risk mitigation, which have a huge effect on dementia risk much later in life,” said Dr. Perneckzy.
“The speech-based assessments are another opportunity to save our time as doctors to do assessments before someone comes to the memory clinic,” he said.
The S-GAP Test is under development by the University of Szeged. Dr. Kálmán is a co-inventor. Dr. Perneckzy had no relevant conflicts of interest but has helped validate the S-GAP Test in the German language.
A version of this article appeared on Medscape.com.
BUDAPEST, HUNGARY — , suggests research.
János Kálmán, MD, PhD, and colleagues at the University of Szeged in Hungary have developed an automated speech analysis approach called the Speech-Gap Test (S-GAP Test) that is unique because it focuses on the temporal changes made when someone talks. This means it does not overcomplicate matters by also assessing the phonetics and semantics of speech, Dr. Kálmán said.
Dr. Kálmán presented his findings at the 32nd European Congress of Psychiatry.
Temporal Speech Parameters
The test analyzes parameters such as how quickly someone speaks, whether they hesitate when they talk, how long the hesitation lasts, and how many silent pauses they make. This can be done with a mere 60-second sample of speech, Dr. Kálmán said, noting that other automated speech and language tools currently in development need much longer audio samples.
“We tried different approaches and we finally ended up with the temporal speech parameters because these are not culture-dependent, not education-dependent, and could be more reliable than the semantic parts of [speech] analysis,” he explained.
The analysis of temporal speech parameters is also not language-dependent. Although the S-GAP Test was developed using audio samples from native Hungarian speakers, Dr. Kálmán and his collaborators have shown that it works just as well with samples from native English and German speakers. They now plan to validate the test further using samples from native Spanish speakers.
For Screening, Not Diagnosis
Currently, “the only purpose of this tool would be initial screening,” Dr. Kálmán said at the congress. It is not for diagnosis, and there is no intention to get it registered as a medical device.
A national survey of primary care physicians conducted by Dr. Kálmán and collaborators showed that there was little time for performing standard cognitive tests during the average consultation. Thus, the original idea was that the S-GAP Test would be an aid to help primary care physicians quickly flag whether a patient might have cognitive problems that needed further assessment at a memory clinic or by more specialist neurology services.
The goalposts have since been moved, from developing a pure telemedicine solution to a more widespread application that perhaps anyone could buy and download from the internet or using a smartphone.
Dr. Kálmán doesn’t discount developing a more sophisticated version of the S-GAP Test in the future that combines temporal speech parameters with biomarkers for mild cognitive impairment or Alzheimer’s disease and could be used in memory clinics and by neurologists for the purpose of diagnosis.
Detect to Prevent?
The big question is: What happens to all the people that could be flagged as needing further assessment using tools such as the S-GAP Test?
Tackling risk factors for dementia will probably be key, said Robert Perneckzy, MD, MBA, professor of translational dementia research at Ludwig Maximilian University of Munich, Imperial College London, and the University of Sheffield.
According to the Lancet Commission on dementia, there are 12 potentially modifiable risk factors for dementia. Their influence varies throughout the life course, but certain early events, such as the level of education attained, can’t be modified in an older patient.
That said, there are many risk factors that might still be influenced later in life, such as adequately treating comorbid conditions such as diabetes, and addressing alcohol consumption and smoking practices.
“We can do things in terms of personal risk, risk mitigation, which have a huge effect on dementia risk much later in life,” said Dr. Perneckzy.
“The speech-based assessments are another opportunity to save our time as doctors to do assessments before someone comes to the memory clinic,” he said.
The S-GAP Test is under development by the University of Szeged. Dr. Kálmán is a co-inventor. Dr. Perneckzy had no relevant conflicts of interest but has helped validate the S-GAP Test in the German language.
A version of this article appeared on Medscape.com.
FROM THE EUROPEAN CONGRESS OF PSYCHIATRY
Delirium Linked to a Threefold Increased Risk for Dementia
, new research showed.
Incident dementia risk was more than three times higher in those who experienced just one episode of delirium, with each additional episode linked to a further 20% increase in dementia risk. The association was strongest in men.
Patients with delirium also had a 39% higher mortality risk than those with no history of delirium.
“We have known for a long time that delirium is dangerous, and this provides evidence that it’s even more dangerous than perhaps we had appreciated,” said study investigator Emily H. Gordon, PhD, MBBS, a geriatrician and senior lecturer at the University of Queensland, Brisbane, Australia.
“But we also know delirium is preventable. There are no excuses anymore; we really need to work together to improve the hospital system, to implement what are known to be effective interventions,” she added.
The findings were published online in The BMJ.
Close Matching
Prior studies that suggested an association between delirium and dementia were relatively small with short follow-up and varied in their adjustment for confounders. They also didn’t account for the competing risk for death, researchers noted.
Investigators used a linked New South Wales (NSW) statewide dataset that includes records of care episodes from all NSW hospitals as well as personal, administrative, clinical, and death information.
The study included an eligible sample of 626,467 older adults without dementia at baseline with at least one hospital admission between 2009 and 2014. For these patients, researchers calculated a hospital frailty risk score and collected other information including primary diagnosis and mean length of hospital stay and stay in the intensive care unit. From diagnostic codes, they categorized patients into no delirium and delirium groups and determined the number of delirium episodes.
Investigators matched patients in the delirium group to patients with no delirium according to characteristics with potential to confound the association between delirium and risk for dementia, including age, gender, frailty, reason for hospitalization, and length of stay in hospital and intensive care.
The matched study sample included 55,211 (mean age, 83 years) each in the delirium and the no delirium groups. Despite matching, the length of hospital stay for the index episode was longer for the delirium group than the no delirium group (mean, 9 days vs 6 days).
The primary outcomes were death and incident dementia, determined via diagnostic codes. During a follow-up of 5.25 years, 58% of patients died, and 17% had a new dementia diagnosis.
Among patients with at least one episode of delirium, the rate of incident dementia was 3.4 times higher than in those without delirium. After accounting for the competing risk for death, incident dementia risk remained three times higher among the delirium group (hazard ratio [HR], 3.00; 95% CI, 2.91-3.10).
This association was stronger for men than women (HR, 3.17 and 2.88, respectively; P = .004).
Sex Differences
The study is thought to be the first to identify a difference between sexes in dementia risk and delirium, Dr. Gordon said. It’s possible delirium in men is more severe in intensity or lasts longer than in women, or the male brain is, for whatever reason, more vulnerable to the effects of delirium, said Dr. Gordon. But she stressed these are only theories.
Investigators also found a mortality rate 1.4 times higher in the delirium group versus those without delirium, equating to a 39% increased risk for death (HR, 1.39; 95% CI, 1.37-1.41). The risk was similar for men and women (interaction P = .62).
When researchers categorized delirium by number of episodes, they found each additional episode was associated with a 10% increased risk for death (HR, 1.10; 95% CI, 1.09-1.12).
In addition to its large size, long follow-up, and close matching, what sets this new study apart from previous research is it accounted for the competing risk for death, said Dr. Gordon.
“This is really important because you’re not going to get dementia if you die, and in this population, the rate of death is incredibly high,” she said. “If we just assume people who died didn’t get dementia, then that screws the results.”
Causal Link?
For those who experienced at least one episode of delirium within the first 12 months, each additional episode of delirium was associated with a 20% increased risk for dementia (HR, 1.20; 95% CI, 1.18-1.23).
That dose-response association suggests a causal link between the two, Dr. Gordon said.
“The number one way to prove causality is to do a randomized controlled trial,” which isn’t feasible with delirium, she said. “By demonstrating a dose-response relationship suggests that it could be a causal pathway.”
Exact mechanisms linking delirium with dementia are unclear. Delirium might uncover preexisting or preclinical dementia, or it might cause dementia by accelerating underlying neuropathologic processes or de novo mechanisms, the authors noted.
Study limitations included the potential for residual confounding from unmeasured variables in the matching criteria. Delirium and dementia diagnoses depended on clinical coding of medical information recorded in the administrative dataset, and under-coding of dementia during hospitalization is well-recognized.
Although the study controlled for length of stay in hospital and in intensive care, this may not have fully captured differences in severity of medical conditions. Data about the duration and severity of delirium episodes were also unavailable, which limited the dose-response analysis.
Commenting on the findings, Christopher Weber, PhD, Alzheimer’s Association as director of Global Science Initiatives, said the results are consistent with other research on the association between delirium and incidents of dementia.
The increased risk for dementia following delirium in males is “an interesting finding,” said Dr. Weber. “This suggests a need for more research to understand the impact of sex differences in delirium, as well as research to see if preventing incidents of delirium could ultimately reduce rates of dementia.”
The study received support from the National Health and Medical Research Council: Partnership Centre for Health System Sustainability. Dr. Gordon and Dr. Weber reported no relevant conflicts of interest.
A version of this article appeared on Medscape.com.
, new research showed.
Incident dementia risk was more than three times higher in those who experienced just one episode of delirium, with each additional episode linked to a further 20% increase in dementia risk. The association was strongest in men.
Patients with delirium also had a 39% higher mortality risk than those with no history of delirium.
“We have known for a long time that delirium is dangerous, and this provides evidence that it’s even more dangerous than perhaps we had appreciated,” said study investigator Emily H. Gordon, PhD, MBBS, a geriatrician and senior lecturer at the University of Queensland, Brisbane, Australia.
“But we also know delirium is preventable. There are no excuses anymore; we really need to work together to improve the hospital system, to implement what are known to be effective interventions,” she added.
The findings were published online in The BMJ.
Close Matching
Prior studies that suggested an association between delirium and dementia were relatively small with short follow-up and varied in their adjustment for confounders. They also didn’t account for the competing risk for death, researchers noted.
Investigators used a linked New South Wales (NSW) statewide dataset that includes records of care episodes from all NSW hospitals as well as personal, administrative, clinical, and death information.
The study included an eligible sample of 626,467 older adults without dementia at baseline with at least one hospital admission between 2009 and 2014. For these patients, researchers calculated a hospital frailty risk score and collected other information including primary diagnosis and mean length of hospital stay and stay in the intensive care unit. From diagnostic codes, they categorized patients into no delirium and delirium groups and determined the number of delirium episodes.
Investigators matched patients in the delirium group to patients with no delirium according to characteristics with potential to confound the association between delirium and risk for dementia, including age, gender, frailty, reason for hospitalization, and length of stay in hospital and intensive care.
The matched study sample included 55,211 (mean age, 83 years) each in the delirium and the no delirium groups. Despite matching, the length of hospital stay for the index episode was longer for the delirium group than the no delirium group (mean, 9 days vs 6 days).
The primary outcomes were death and incident dementia, determined via diagnostic codes. During a follow-up of 5.25 years, 58% of patients died, and 17% had a new dementia diagnosis.
Among patients with at least one episode of delirium, the rate of incident dementia was 3.4 times higher than in those without delirium. After accounting for the competing risk for death, incident dementia risk remained three times higher among the delirium group (hazard ratio [HR], 3.00; 95% CI, 2.91-3.10).
This association was stronger for men than women (HR, 3.17 and 2.88, respectively; P = .004).
Sex Differences
The study is thought to be the first to identify a difference between sexes in dementia risk and delirium, Dr. Gordon said. It’s possible delirium in men is more severe in intensity or lasts longer than in women, or the male brain is, for whatever reason, more vulnerable to the effects of delirium, said Dr. Gordon. But she stressed these are only theories.
Investigators also found a mortality rate 1.4 times higher in the delirium group versus those without delirium, equating to a 39% increased risk for death (HR, 1.39; 95% CI, 1.37-1.41). The risk was similar for men and women (interaction P = .62).
When researchers categorized delirium by number of episodes, they found each additional episode was associated with a 10% increased risk for death (HR, 1.10; 95% CI, 1.09-1.12).
In addition to its large size, long follow-up, and close matching, what sets this new study apart from previous research is it accounted for the competing risk for death, said Dr. Gordon.
“This is really important because you’re not going to get dementia if you die, and in this population, the rate of death is incredibly high,” she said. “If we just assume people who died didn’t get dementia, then that screws the results.”
Causal Link?
For those who experienced at least one episode of delirium within the first 12 months, each additional episode of delirium was associated with a 20% increased risk for dementia (HR, 1.20; 95% CI, 1.18-1.23).
That dose-response association suggests a causal link between the two, Dr. Gordon said.
“The number one way to prove causality is to do a randomized controlled trial,” which isn’t feasible with delirium, she said. “By demonstrating a dose-response relationship suggests that it could be a causal pathway.”
Exact mechanisms linking delirium with dementia are unclear. Delirium might uncover preexisting or preclinical dementia, or it might cause dementia by accelerating underlying neuropathologic processes or de novo mechanisms, the authors noted.
Study limitations included the potential for residual confounding from unmeasured variables in the matching criteria. Delirium and dementia diagnoses depended on clinical coding of medical information recorded in the administrative dataset, and under-coding of dementia during hospitalization is well-recognized.
Although the study controlled for length of stay in hospital and in intensive care, this may not have fully captured differences in severity of medical conditions. Data about the duration and severity of delirium episodes were also unavailable, which limited the dose-response analysis.
Commenting on the findings, Christopher Weber, PhD, Alzheimer’s Association as director of Global Science Initiatives, said the results are consistent with other research on the association between delirium and incidents of dementia.
The increased risk for dementia following delirium in males is “an interesting finding,” said Dr. Weber. “This suggests a need for more research to understand the impact of sex differences in delirium, as well as research to see if preventing incidents of delirium could ultimately reduce rates of dementia.”
The study received support from the National Health and Medical Research Council: Partnership Centre for Health System Sustainability. Dr. Gordon and Dr. Weber reported no relevant conflicts of interest.
A version of this article appeared on Medscape.com.
, new research showed.
Incident dementia risk was more than three times higher in those who experienced just one episode of delirium, with each additional episode linked to a further 20% increase in dementia risk. The association was strongest in men.
Patients with delirium also had a 39% higher mortality risk than those with no history of delirium.
“We have known for a long time that delirium is dangerous, and this provides evidence that it’s even more dangerous than perhaps we had appreciated,” said study investigator Emily H. Gordon, PhD, MBBS, a geriatrician and senior lecturer at the University of Queensland, Brisbane, Australia.
“But we also know delirium is preventable. There are no excuses anymore; we really need to work together to improve the hospital system, to implement what are known to be effective interventions,” she added.
The findings were published online in The BMJ.
Close Matching
Prior studies that suggested an association between delirium and dementia were relatively small with short follow-up and varied in their adjustment for confounders. They also didn’t account for the competing risk for death, researchers noted.
Investigators used a linked New South Wales (NSW) statewide dataset that includes records of care episodes from all NSW hospitals as well as personal, administrative, clinical, and death information.
The study included an eligible sample of 626,467 older adults without dementia at baseline with at least one hospital admission between 2009 and 2014. For these patients, researchers calculated a hospital frailty risk score and collected other information including primary diagnosis and mean length of hospital stay and stay in the intensive care unit. From diagnostic codes, they categorized patients into no delirium and delirium groups and determined the number of delirium episodes.
Investigators matched patients in the delirium group to patients with no delirium according to characteristics with potential to confound the association between delirium and risk for dementia, including age, gender, frailty, reason for hospitalization, and length of stay in hospital and intensive care.
The matched study sample included 55,211 (mean age, 83 years) each in the delirium and the no delirium groups. Despite matching, the length of hospital stay for the index episode was longer for the delirium group than the no delirium group (mean, 9 days vs 6 days).
The primary outcomes were death and incident dementia, determined via diagnostic codes. During a follow-up of 5.25 years, 58% of patients died, and 17% had a new dementia diagnosis.
Among patients with at least one episode of delirium, the rate of incident dementia was 3.4 times higher than in those without delirium. After accounting for the competing risk for death, incident dementia risk remained three times higher among the delirium group (hazard ratio [HR], 3.00; 95% CI, 2.91-3.10).
This association was stronger for men than women (HR, 3.17 and 2.88, respectively; P = .004).
Sex Differences
The study is thought to be the first to identify a difference between sexes in dementia risk and delirium, Dr. Gordon said. It’s possible delirium in men is more severe in intensity or lasts longer than in women, or the male brain is, for whatever reason, more vulnerable to the effects of delirium, said Dr. Gordon. But she stressed these are only theories.
Investigators also found a mortality rate 1.4 times higher in the delirium group versus those without delirium, equating to a 39% increased risk for death (HR, 1.39; 95% CI, 1.37-1.41). The risk was similar for men and women (interaction P = .62).
When researchers categorized delirium by number of episodes, they found each additional episode was associated with a 10% increased risk for death (HR, 1.10; 95% CI, 1.09-1.12).
In addition to its large size, long follow-up, and close matching, what sets this new study apart from previous research is it accounted for the competing risk for death, said Dr. Gordon.
“This is really important because you’re not going to get dementia if you die, and in this population, the rate of death is incredibly high,” she said. “If we just assume people who died didn’t get dementia, then that screws the results.”
Causal Link?
For those who experienced at least one episode of delirium within the first 12 months, each additional episode of delirium was associated with a 20% increased risk for dementia (HR, 1.20; 95% CI, 1.18-1.23).
That dose-response association suggests a causal link between the two, Dr. Gordon said.
“The number one way to prove causality is to do a randomized controlled trial,” which isn’t feasible with delirium, she said. “By demonstrating a dose-response relationship suggests that it could be a causal pathway.”
Exact mechanisms linking delirium with dementia are unclear. Delirium might uncover preexisting or preclinical dementia, or it might cause dementia by accelerating underlying neuropathologic processes or de novo mechanisms, the authors noted.
Study limitations included the potential for residual confounding from unmeasured variables in the matching criteria. Delirium and dementia diagnoses depended on clinical coding of medical information recorded in the administrative dataset, and under-coding of dementia during hospitalization is well-recognized.
Although the study controlled for length of stay in hospital and in intensive care, this may not have fully captured differences in severity of medical conditions. Data about the duration and severity of delirium episodes were also unavailable, which limited the dose-response analysis.
Commenting on the findings, Christopher Weber, PhD, Alzheimer’s Association as director of Global Science Initiatives, said the results are consistent with other research on the association between delirium and incidents of dementia.
The increased risk for dementia following delirium in males is “an interesting finding,” said Dr. Weber. “This suggests a need for more research to understand the impact of sex differences in delirium, as well as research to see if preventing incidents of delirium could ultimately reduce rates of dementia.”
The study received support from the National Health and Medical Research Council: Partnership Centre for Health System Sustainability. Dr. Gordon and Dr. Weber reported no relevant conflicts of interest.
A version of this article appeared on Medscape.com.
FROM THE BMJ
Chronic Pain Linked to Accelerated Brain Aging
, new research showed.
Using structural MRI data from more than 9000 adults with knee osteoarthritis (KOA) from the UK Biobank, investigators developed a brain age model to compare an individual’s brain age with their chronological age. Those with KOA showed a much faster rate of brain aging than healthy individuals.
The acceleration in brain aging was largely driven by the hippocampus and predicted memory decline and incident dementia during follow-up. Researchers identified a gene highly expressed in glial cells as a possible genetic factor for accelerated brain aging.
“We demonstrate the accelerated brain aging and cognitive decline in chronic musculoskeletal pain, in particular knee osteoarthritis, and provide a neural marker for early detection and intervention,” said co-first author Jiao Liu, PhD candidate, Chinese Academy of Sciences, Beijing.
“We are interested to know how to slow down the aging brain in chronic musculoskeletal pain patients. Proper exercise and lifestyle may reduce the risk,” Dr. Liu said.
The study was published online in Nature Mental Health.
Common Condition
CMP affects more than 40% of the world’s population and has been shown to have a harmful impact on cognitive function, although the exact mechanisms remain unclear. Prior research suggests that inflammatory markers associated with brain aging are higher in patients with CMP, suggesting a link between brain aging and CMP.
To investigate further, researchers explored patterns of brain aging in healthy cohorts and cohorts with four common types of CMP — chronic knee pain, chronic back pain, chronic neck pain, and chronic hip pain.
Using their brain age model, investigators observed significantly increased brain aging, or “predicted age difference,” only in individuals with KOA (P < .001). The observation was validated in an independent dataset (P = .020), suggesting a pattern of brain aging acceleration specific to KOA.
This acceleration was primarily driven by key brain regions involved in cognitive processing, including hippocampus and orbitofrontal cortex, and was correlated with longitudinal memory decline and dementia risk.
These data also suggest that the SLC39A8 gene, which is highly expressed in glial cells, might be a key genetic factor underpinning this acceleration.
“We not only revealed the specificity of accelerated brain aging in knee osteoarthritis patients, but importantly, we also provided longitudinal evidence suggesting the ability of our brain aging marker to predict future memory decline and increased dementia risk,” corresponding author Yiheng Tu, PhD, also with Chinese Academy of Sciences, Beijing, said in a news release.
A Future Treatment Target?
Commenting on this research, Shaheen Lakhan, MD, PhD, a neurologist and researcher based in Miami, noted that in this study, people with KOA showed signs of “faster brain aging on scans. Think of it as your brain wearing a disguise, appearing older than its actual years,” Dr. Lakhan said.
“Inflammation, a key player in osteoarthritis, might be playing a double agent, wreaking havoc not just on your joints but potentially on your memory too. Researchers even identified a specific gene linked to both knee pain and faster brain aging, hinting at a potential target for future treatments,” he added.
“Importantly, the increased risk of cognitive decline and dementia associated with chronic pain is likely one of many factors, and probably not a very high one on its own,” Dr. Lakhan noted.
The “good news,” he said, is that there are many “well-established ways to keep your brain sharp. Regular exercise, a healthy diet, and staying mentally stimulated are all proven strategies to reduce dementia risk. Think of chronic pain management as another tool you can add to your brain health toolbox.”
Support for the study was provided by the STI-2030 Major Project, the National Natural Science Foundation of China, the Scientific Foundation of the Institute of Psychology, Chinese Academy of Sciences, and the Young Elite Scientist Sponsorship Program by the China Association for Science and Technology. Dr. Liu and Dr. Lakhan had no relevant disclosures.
A version of this article appeared on Medscape.com.
, new research showed.
Using structural MRI data from more than 9000 adults with knee osteoarthritis (KOA) from the UK Biobank, investigators developed a brain age model to compare an individual’s brain age with their chronological age. Those with KOA showed a much faster rate of brain aging than healthy individuals.
The acceleration in brain aging was largely driven by the hippocampus and predicted memory decline and incident dementia during follow-up. Researchers identified a gene highly expressed in glial cells as a possible genetic factor for accelerated brain aging.
“We demonstrate the accelerated brain aging and cognitive decline in chronic musculoskeletal pain, in particular knee osteoarthritis, and provide a neural marker for early detection and intervention,” said co-first author Jiao Liu, PhD candidate, Chinese Academy of Sciences, Beijing.
“We are interested to know how to slow down the aging brain in chronic musculoskeletal pain patients. Proper exercise and lifestyle may reduce the risk,” Dr. Liu said.
The study was published online in Nature Mental Health.
Common Condition
CMP affects more than 40% of the world’s population and has been shown to have a harmful impact on cognitive function, although the exact mechanisms remain unclear. Prior research suggests that inflammatory markers associated with brain aging are higher in patients with CMP, suggesting a link between brain aging and CMP.
To investigate further, researchers explored patterns of brain aging in healthy cohorts and cohorts with four common types of CMP — chronic knee pain, chronic back pain, chronic neck pain, and chronic hip pain.
Using their brain age model, investigators observed significantly increased brain aging, or “predicted age difference,” only in individuals with KOA (P < .001). The observation was validated in an independent dataset (P = .020), suggesting a pattern of brain aging acceleration specific to KOA.
This acceleration was primarily driven by key brain regions involved in cognitive processing, including hippocampus and orbitofrontal cortex, and was correlated with longitudinal memory decline and dementia risk.
These data also suggest that the SLC39A8 gene, which is highly expressed in glial cells, might be a key genetic factor underpinning this acceleration.
“We not only revealed the specificity of accelerated brain aging in knee osteoarthritis patients, but importantly, we also provided longitudinal evidence suggesting the ability of our brain aging marker to predict future memory decline and increased dementia risk,” corresponding author Yiheng Tu, PhD, also with Chinese Academy of Sciences, Beijing, said in a news release.
A Future Treatment Target?
Commenting on this research, Shaheen Lakhan, MD, PhD, a neurologist and researcher based in Miami, noted that in this study, people with KOA showed signs of “faster brain aging on scans. Think of it as your brain wearing a disguise, appearing older than its actual years,” Dr. Lakhan said.
“Inflammation, a key player in osteoarthritis, might be playing a double agent, wreaking havoc not just on your joints but potentially on your memory too. Researchers even identified a specific gene linked to both knee pain and faster brain aging, hinting at a potential target for future treatments,” he added.
“Importantly, the increased risk of cognitive decline and dementia associated with chronic pain is likely one of many factors, and probably not a very high one on its own,” Dr. Lakhan noted.
The “good news,” he said, is that there are many “well-established ways to keep your brain sharp. Regular exercise, a healthy diet, and staying mentally stimulated are all proven strategies to reduce dementia risk. Think of chronic pain management as another tool you can add to your brain health toolbox.”
Support for the study was provided by the STI-2030 Major Project, the National Natural Science Foundation of China, the Scientific Foundation of the Institute of Psychology, Chinese Academy of Sciences, and the Young Elite Scientist Sponsorship Program by the China Association for Science and Technology. Dr. Liu and Dr. Lakhan had no relevant disclosures.
A version of this article appeared on Medscape.com.
, new research showed.
Using structural MRI data from more than 9000 adults with knee osteoarthritis (KOA) from the UK Biobank, investigators developed a brain age model to compare an individual’s brain age with their chronological age. Those with KOA showed a much faster rate of brain aging than healthy individuals.
The acceleration in brain aging was largely driven by the hippocampus and predicted memory decline and incident dementia during follow-up. Researchers identified a gene highly expressed in glial cells as a possible genetic factor for accelerated brain aging.
“We demonstrate the accelerated brain aging and cognitive decline in chronic musculoskeletal pain, in particular knee osteoarthritis, and provide a neural marker for early detection and intervention,” said co-first author Jiao Liu, PhD candidate, Chinese Academy of Sciences, Beijing.
“We are interested to know how to slow down the aging brain in chronic musculoskeletal pain patients. Proper exercise and lifestyle may reduce the risk,” Dr. Liu said.
The study was published online in Nature Mental Health.
Common Condition
CMP affects more than 40% of the world’s population and has been shown to have a harmful impact on cognitive function, although the exact mechanisms remain unclear. Prior research suggests that inflammatory markers associated with brain aging are higher in patients with CMP, suggesting a link between brain aging and CMP.
To investigate further, researchers explored patterns of brain aging in healthy cohorts and cohorts with four common types of CMP — chronic knee pain, chronic back pain, chronic neck pain, and chronic hip pain.
Using their brain age model, investigators observed significantly increased brain aging, or “predicted age difference,” only in individuals with KOA (P < .001). The observation was validated in an independent dataset (P = .020), suggesting a pattern of brain aging acceleration specific to KOA.
This acceleration was primarily driven by key brain regions involved in cognitive processing, including hippocampus and orbitofrontal cortex, and was correlated with longitudinal memory decline and dementia risk.
These data also suggest that the SLC39A8 gene, which is highly expressed in glial cells, might be a key genetic factor underpinning this acceleration.
“We not only revealed the specificity of accelerated brain aging in knee osteoarthritis patients, but importantly, we also provided longitudinal evidence suggesting the ability of our brain aging marker to predict future memory decline and increased dementia risk,” corresponding author Yiheng Tu, PhD, also with Chinese Academy of Sciences, Beijing, said in a news release.
A Future Treatment Target?
Commenting on this research, Shaheen Lakhan, MD, PhD, a neurologist and researcher based in Miami, noted that in this study, people with KOA showed signs of “faster brain aging on scans. Think of it as your brain wearing a disguise, appearing older than its actual years,” Dr. Lakhan said.
“Inflammation, a key player in osteoarthritis, might be playing a double agent, wreaking havoc not just on your joints but potentially on your memory too. Researchers even identified a specific gene linked to both knee pain and faster brain aging, hinting at a potential target for future treatments,” he added.
“Importantly, the increased risk of cognitive decline and dementia associated with chronic pain is likely one of many factors, and probably not a very high one on its own,” Dr. Lakhan noted.
The “good news,” he said, is that there are many “well-established ways to keep your brain sharp. Regular exercise, a healthy diet, and staying mentally stimulated are all proven strategies to reduce dementia risk. Think of chronic pain management as another tool you can add to your brain health toolbox.”
Support for the study was provided by the STI-2030 Major Project, the National Natural Science Foundation of China, the Scientific Foundation of the Institute of Psychology, Chinese Academy of Sciences, and the Young Elite Scientist Sponsorship Program by the China Association for Science and Technology. Dr. Liu and Dr. Lakhan had no relevant disclosures.
A version of this article appeared on Medscape.com.
FROM NATURE MENTAL HEALTH
Prevalence of Dementia in Homeless Twice That in Housed
, according to the results of a new study.
The findings suggested that dementia occurs earlier in homeless individuals, and that these patients could benefit from proactive screening and housing interventions.
“Whether dementia caused the homelessness or homelessness caused the dementia, it’s a bidirectional relationship,” said lead author Richard G. Booth, PhD, RN, adjunct scientist at ICES (formerly Institute for Clinical Evaluative Sciences) and associate professor of nursing at Western University in London, Ontario, Canada.
The study was published in the April issue of The Lancet Public Health.
Dementia at Early Ages
The investigators used health administrative data from Ontario to compare the prevalence of dementia among homeless people with that among housed individuals in the general population and those living in low-income neighborhoods.
They included individuals aged 45 years or older on January 1, 2019, who visited hospital-based ambulatory care (such as emergency departments), were hospitalized, or visited a community health center in 2019. The researchers identified people as experiencing homelessness if they had one or more healthcare records with an indication of homelessness or unstable housing. The prevalence of dementia was ascertained as of December 31, 2019.
Included in the population-based, cross-sectional comparative analysis were 12,863 homeless people, 475,544 people in the low-income group, and 2,273,068 people in the general population group.
Dementia prevalence was 68.7 per 1000 individuals among the homeless population, 62.6 per 1000 in the low-income group, and 51.0 per 1000 in the general population group.
After adjustments for age, sex, geographical location of residence (urban vs rural), and health conditions associated with dementia, the prevalence ratio of dementia among homeless people was 1.71, compared with the low-income group, and 1.90, compared with the general population group.
Dementia also was detected in the 45- to 55-year age group among homeless people. This age is much earlier than the age at which doctors start screening their patients for cognitive decline (65 years).
“The study was not designed to define the causality but consider: If you have early-stage dementia and you are not intact enough to do basic functions of life, the likelihood of you becoming homeless is definitely increased, and vice versa. If you are homeless and suffer significant environmental and physical traumas just living on the street, you age much quicker, and you will experience geriatric symptoms such as dementia earlier in your life trajectory,” said Dr. Booth.
“The main takeaway here is that if you don’t have housing, bad things are going to happen in life.”
Public Health Problem
In an accompanying editorial, William J. Panenka, MD, associate professor of psychiatry at the University of British Columbia in Vancouver, British Columbia, Canada, and colleagues cited modifiable risk factors for dementia, including lower education, traumatic brain injury, substance use, smoking, mood disorders, and social isolation, many of which are disproportionately prevalent among homeless individuals.
“Ultimately, dementia could contribute to the cycle of homelessness, whereby housing instability increases the risk for brain impairment, and brain impairment makes breaking the cycle of homelessness progressively more challenging,” they wrote.
Dr. Panenka and colleagues also pointed out that the average age of homeless people is increasing. In the United States, it is now approximately 50 years. This fact underscores “the immediacy and gravity of the public health problem. A multifaceted approach that integrates healthcare, housing, and social services is needed to better understand and alleviate the health consequences of homelessness. A concerted effort at all levels is vital to inform future public health efforts and stem the tide of increasing morbidity, compromised function, and early mortality in homelessness,” they concluded.
Stephen Hwang, MD, director of the MAP Centre for Urban Health Solutions at St. Michael’s Hospital and Unity Health in Toronto, said that the study may underestimate the magnitude of the problem of dementia among homeless people.
“The methods used in this research study are very strong because they draw upon data for everyone living in the entire province of Ontario, and this is a very powerful way of looking at this challenging problem. The study probably underestimates the magnitude of the problem because to be diagnosed with dementia, patients have to have contact with healthcare providers that make that diagnosis. Often, people experiencing homelessness don’t have extensive contact with the healthcare system, and so their condition may go undiagnosed,” said Dr. Hwang.
A specialist in internal medicine, Dr. Hwang has provided healthcare for homeless people, and his research focuses on homelessness, housing, and health. He said that the findings from the Canadian study are applicable to the United States.
Forced clearances of homeless people and placing them in encampments, something that has been discussed in Florida, is unlikely to solve the problem, he said.
“The approach that has been shown to be beneficial is to engage with people and offer them housing and services that will allow them to exit homelessness without criminalizing the fact that they’re homeless. There really is no reason to think that this approach of forced clearances is going to help anyone.”
This study was supported by ICES (formerly the Institute for Clinical Evaluative Sciences), which is funded by the Ontario Ministry of Health and Ontario Ministry of Long-Term Care. Dr. Booth and Dr. Hwang reported no relevant financial relationships. Dr. Panenka reported receiving a research grant from the Canadian Institutes of Health Research.
A version of this article appeared on Medscape.com.
, according to the results of a new study.
The findings suggested that dementia occurs earlier in homeless individuals, and that these patients could benefit from proactive screening and housing interventions.
“Whether dementia caused the homelessness or homelessness caused the dementia, it’s a bidirectional relationship,” said lead author Richard G. Booth, PhD, RN, adjunct scientist at ICES (formerly Institute for Clinical Evaluative Sciences) and associate professor of nursing at Western University in London, Ontario, Canada.
The study was published in the April issue of The Lancet Public Health.
Dementia at Early Ages
The investigators used health administrative data from Ontario to compare the prevalence of dementia among homeless people with that among housed individuals in the general population and those living in low-income neighborhoods.
They included individuals aged 45 years or older on January 1, 2019, who visited hospital-based ambulatory care (such as emergency departments), were hospitalized, or visited a community health center in 2019. The researchers identified people as experiencing homelessness if they had one or more healthcare records with an indication of homelessness or unstable housing. The prevalence of dementia was ascertained as of December 31, 2019.
Included in the population-based, cross-sectional comparative analysis were 12,863 homeless people, 475,544 people in the low-income group, and 2,273,068 people in the general population group.
Dementia prevalence was 68.7 per 1000 individuals among the homeless population, 62.6 per 1000 in the low-income group, and 51.0 per 1000 in the general population group.
After adjustments for age, sex, geographical location of residence (urban vs rural), and health conditions associated with dementia, the prevalence ratio of dementia among homeless people was 1.71, compared with the low-income group, and 1.90, compared with the general population group.
Dementia also was detected in the 45- to 55-year age group among homeless people. This age is much earlier than the age at which doctors start screening their patients for cognitive decline (65 years).
“The study was not designed to define the causality but consider: If you have early-stage dementia and you are not intact enough to do basic functions of life, the likelihood of you becoming homeless is definitely increased, and vice versa. If you are homeless and suffer significant environmental and physical traumas just living on the street, you age much quicker, and you will experience geriatric symptoms such as dementia earlier in your life trajectory,” said Dr. Booth.
“The main takeaway here is that if you don’t have housing, bad things are going to happen in life.”
Public Health Problem
In an accompanying editorial, William J. Panenka, MD, associate professor of psychiatry at the University of British Columbia in Vancouver, British Columbia, Canada, and colleagues cited modifiable risk factors for dementia, including lower education, traumatic brain injury, substance use, smoking, mood disorders, and social isolation, many of which are disproportionately prevalent among homeless individuals.
“Ultimately, dementia could contribute to the cycle of homelessness, whereby housing instability increases the risk for brain impairment, and brain impairment makes breaking the cycle of homelessness progressively more challenging,” they wrote.
Dr. Panenka and colleagues also pointed out that the average age of homeless people is increasing. In the United States, it is now approximately 50 years. This fact underscores “the immediacy and gravity of the public health problem. A multifaceted approach that integrates healthcare, housing, and social services is needed to better understand and alleviate the health consequences of homelessness. A concerted effort at all levels is vital to inform future public health efforts and stem the tide of increasing morbidity, compromised function, and early mortality in homelessness,” they concluded.
Stephen Hwang, MD, director of the MAP Centre for Urban Health Solutions at St. Michael’s Hospital and Unity Health in Toronto, said that the study may underestimate the magnitude of the problem of dementia among homeless people.
“The methods used in this research study are very strong because they draw upon data for everyone living in the entire province of Ontario, and this is a very powerful way of looking at this challenging problem. The study probably underestimates the magnitude of the problem because to be diagnosed with dementia, patients have to have contact with healthcare providers that make that diagnosis. Often, people experiencing homelessness don’t have extensive contact with the healthcare system, and so their condition may go undiagnosed,” said Dr. Hwang.
A specialist in internal medicine, Dr. Hwang has provided healthcare for homeless people, and his research focuses on homelessness, housing, and health. He said that the findings from the Canadian study are applicable to the United States.
Forced clearances of homeless people and placing them in encampments, something that has been discussed in Florida, is unlikely to solve the problem, he said.
“The approach that has been shown to be beneficial is to engage with people and offer them housing and services that will allow them to exit homelessness without criminalizing the fact that they’re homeless. There really is no reason to think that this approach of forced clearances is going to help anyone.”
This study was supported by ICES (formerly the Institute for Clinical Evaluative Sciences), which is funded by the Ontario Ministry of Health and Ontario Ministry of Long-Term Care. Dr. Booth and Dr. Hwang reported no relevant financial relationships. Dr. Panenka reported receiving a research grant from the Canadian Institutes of Health Research.
A version of this article appeared on Medscape.com.
, according to the results of a new study.
The findings suggested that dementia occurs earlier in homeless individuals, and that these patients could benefit from proactive screening and housing interventions.
“Whether dementia caused the homelessness or homelessness caused the dementia, it’s a bidirectional relationship,” said lead author Richard G. Booth, PhD, RN, adjunct scientist at ICES (formerly Institute for Clinical Evaluative Sciences) and associate professor of nursing at Western University in London, Ontario, Canada.
The study was published in the April issue of The Lancet Public Health.
Dementia at Early Ages
The investigators used health administrative data from Ontario to compare the prevalence of dementia among homeless people with that among housed individuals in the general population and those living in low-income neighborhoods.
They included individuals aged 45 years or older on January 1, 2019, who visited hospital-based ambulatory care (such as emergency departments), were hospitalized, or visited a community health center in 2019. The researchers identified people as experiencing homelessness if they had one or more healthcare records with an indication of homelessness or unstable housing. The prevalence of dementia was ascertained as of December 31, 2019.
Included in the population-based, cross-sectional comparative analysis were 12,863 homeless people, 475,544 people in the low-income group, and 2,273,068 people in the general population group.
Dementia prevalence was 68.7 per 1000 individuals among the homeless population, 62.6 per 1000 in the low-income group, and 51.0 per 1000 in the general population group.
After adjustments for age, sex, geographical location of residence (urban vs rural), and health conditions associated with dementia, the prevalence ratio of dementia among homeless people was 1.71, compared with the low-income group, and 1.90, compared with the general population group.
Dementia also was detected in the 45- to 55-year age group among homeless people. This age is much earlier than the age at which doctors start screening their patients for cognitive decline (65 years).
“The study was not designed to define the causality but consider: If you have early-stage dementia and you are not intact enough to do basic functions of life, the likelihood of you becoming homeless is definitely increased, and vice versa. If you are homeless and suffer significant environmental and physical traumas just living on the street, you age much quicker, and you will experience geriatric symptoms such as dementia earlier in your life trajectory,” said Dr. Booth.
“The main takeaway here is that if you don’t have housing, bad things are going to happen in life.”
Public Health Problem
In an accompanying editorial, William J. Panenka, MD, associate professor of psychiatry at the University of British Columbia in Vancouver, British Columbia, Canada, and colleagues cited modifiable risk factors for dementia, including lower education, traumatic brain injury, substance use, smoking, mood disorders, and social isolation, many of which are disproportionately prevalent among homeless individuals.
“Ultimately, dementia could contribute to the cycle of homelessness, whereby housing instability increases the risk for brain impairment, and brain impairment makes breaking the cycle of homelessness progressively more challenging,” they wrote.
Dr. Panenka and colleagues also pointed out that the average age of homeless people is increasing. In the United States, it is now approximately 50 years. This fact underscores “the immediacy and gravity of the public health problem. A multifaceted approach that integrates healthcare, housing, and social services is needed to better understand and alleviate the health consequences of homelessness. A concerted effort at all levels is vital to inform future public health efforts and stem the tide of increasing morbidity, compromised function, and early mortality in homelessness,” they concluded.
Stephen Hwang, MD, director of the MAP Centre for Urban Health Solutions at St. Michael’s Hospital and Unity Health in Toronto, said that the study may underestimate the magnitude of the problem of dementia among homeless people.
“The methods used in this research study are very strong because they draw upon data for everyone living in the entire province of Ontario, and this is a very powerful way of looking at this challenging problem. The study probably underestimates the magnitude of the problem because to be diagnosed with dementia, patients have to have contact with healthcare providers that make that diagnosis. Often, people experiencing homelessness don’t have extensive contact with the healthcare system, and so their condition may go undiagnosed,” said Dr. Hwang.
A specialist in internal medicine, Dr. Hwang has provided healthcare for homeless people, and his research focuses on homelessness, housing, and health. He said that the findings from the Canadian study are applicable to the United States.
Forced clearances of homeless people and placing them in encampments, something that has been discussed in Florida, is unlikely to solve the problem, he said.
“The approach that has been shown to be beneficial is to engage with people and offer them housing and services that will allow them to exit homelessness without criminalizing the fact that they’re homeless. There really is no reason to think that this approach of forced clearances is going to help anyone.”
This study was supported by ICES (formerly the Institute for Clinical Evaluative Sciences), which is funded by the Ontario Ministry of Health and Ontario Ministry of Long-Term Care. Dr. Booth and Dr. Hwang reported no relevant financial relationships. Dr. Panenka reported receiving a research grant from the Canadian Institutes of Health Research.
A version of this article appeared on Medscape.com.
From Lancet Public Health
Smartphone App Detects Early Signs of Frontotemporal Dementia
, new research showed.
Cognitive tests administered remotely on the phone “showed similar findings as our gold standard in-clinic cognitive tests and brain imaging,” said study investigator Adam M. Staffaroni, PhD, with the Memory and Aging Center, University of California San Francisco.
“We also provided evidence that these assessments may be useful for detecting early symptoms of the disease at a level that is on par, or perhaps slightly better, than our gold standard in-person tests,” Dr. Staffaroni said.
The study was published online in JAMA Network Open.
Tough to Diagnose
Although relatively rare, FTD is the top cause of dementia in patients younger than 60 years. Patients are usually diagnosed relatively late in the disease because they are young and because their symptoms may be mistaken for psychiatric disorders.
In addition, behavioral and motor symptoms of FTD can make it hard for families to get to an academic center for in-clinic assessments, making remote assessments a huge need.
Dr. Staffaroni and colleagues with the ALLFTD Consortium partnered with software company Datacubed Health to develop the ALLFTD-mApp, which includes cognitive, motor, and speech tasks.
They assessed the reliability and validity of the app, against standard in-clinic assessments, in 350 individuals (mean age, 54 years; 58% women; mean education level, 16.5 years).
Among the 329 individuals with data on disease stage, 195 (59%) were asymptomatic or had preclinical FTD, 66 (20%) had prodromal FTD, and 68 (21%) had symptomatic FTD with a range of clinical syndromes.
The smartphone app showed “moderate to excellent” reliability within a single administration (ie, internally consistent) and across repeated assessments (ie, test-retest reliability), the researchers reported.
Validity was supported by association of smartphones tests with disease severity, criterion-standard neuropsychological tests, and brain volume, they noted.
Of Great Interest
They also reported that a composite of brief smartphone tests accurately distinguished dementia from cognitively unimpaired participants, screening out participants without symptoms, and detected prodromal FTD with greater sensitivity than the Montreal Cognitive Assessment.
“This tool is currently being used in several research studies. The remote aspect of this technology is important because it could allow researchers to collect data more frequently, which may give them a more accurate picture of the disease. Furthermore, researchers can be more inclusive in their study designs and include participants who otherwise might have difficulty traveling to academic centers for standard in-person visits,” said Dr. Staffaroni.
“Because the app appears sensitive to early stages of the disease, it could be also used as a screening tool, possibly alongside other remote data collection, to help identify participants that might be appropriate for a clinical trial. At this point, these technologies are not ready for clinical use and require additional research studies to understand their clinical utility,” he cautioned.
Commenting on the study, Walter Kukull, PhD, director of the National Alzheimer’s Coordinating Center at the University of Washington in Seattle, noted that “remote direct and indirect testing/telemetry are of great interest to the field and are being examined carefully in comparison to in-person means both for validity and possibly earlier recognition.”
This research was supported by grants from the National Institutes of Health, the Association for Frontotemporal Degeneration, the Bluefield Project to Cure FTD, the Rainwater Charitable Foundation, and the Larry L. Hillblom Foundation. Dr. Staffaroni reported being a coinventor of four ALLFTD mobile application tasks (not analyzed in the current study); receiving licensing fees from Datacubed Health and research support from the National Institute on Aging of the NIH, Bluefield Project to Cure FTD, the Alzheimer’s Association, the Larry L. Hillblom Foundation, and the Rainwater Charitable Foundation; and consulting for Alector Inc., Eli Lilly and Company Prevail Therapeutics, Passage Bio Inc, and Takeda Pharmaceuticals. Dr. Kukull participated in the ALLFTD Consortium.
A version of this article appeared on Medscape.com.
, new research showed.
Cognitive tests administered remotely on the phone “showed similar findings as our gold standard in-clinic cognitive tests and brain imaging,” said study investigator Adam M. Staffaroni, PhD, with the Memory and Aging Center, University of California San Francisco.
“We also provided evidence that these assessments may be useful for detecting early symptoms of the disease at a level that is on par, or perhaps slightly better, than our gold standard in-person tests,” Dr. Staffaroni said.
The study was published online in JAMA Network Open.
Tough to Diagnose
Although relatively rare, FTD is the top cause of dementia in patients younger than 60 years. Patients are usually diagnosed relatively late in the disease because they are young and because their symptoms may be mistaken for psychiatric disorders.
In addition, behavioral and motor symptoms of FTD can make it hard for families to get to an academic center for in-clinic assessments, making remote assessments a huge need.
Dr. Staffaroni and colleagues with the ALLFTD Consortium partnered with software company Datacubed Health to develop the ALLFTD-mApp, which includes cognitive, motor, and speech tasks.
They assessed the reliability and validity of the app, against standard in-clinic assessments, in 350 individuals (mean age, 54 years; 58% women; mean education level, 16.5 years).
Among the 329 individuals with data on disease stage, 195 (59%) were asymptomatic or had preclinical FTD, 66 (20%) had prodromal FTD, and 68 (21%) had symptomatic FTD with a range of clinical syndromes.
The smartphone app showed “moderate to excellent” reliability within a single administration (ie, internally consistent) and across repeated assessments (ie, test-retest reliability), the researchers reported.
Validity was supported by association of smartphones tests with disease severity, criterion-standard neuropsychological tests, and brain volume, they noted.
Of Great Interest
They also reported that a composite of brief smartphone tests accurately distinguished dementia from cognitively unimpaired participants, screening out participants without symptoms, and detected prodromal FTD with greater sensitivity than the Montreal Cognitive Assessment.
“This tool is currently being used in several research studies. The remote aspect of this technology is important because it could allow researchers to collect data more frequently, which may give them a more accurate picture of the disease. Furthermore, researchers can be more inclusive in their study designs and include participants who otherwise might have difficulty traveling to academic centers for standard in-person visits,” said Dr. Staffaroni.
“Because the app appears sensitive to early stages of the disease, it could be also used as a screening tool, possibly alongside other remote data collection, to help identify participants that might be appropriate for a clinical trial. At this point, these technologies are not ready for clinical use and require additional research studies to understand their clinical utility,” he cautioned.
Commenting on the study, Walter Kukull, PhD, director of the National Alzheimer’s Coordinating Center at the University of Washington in Seattle, noted that “remote direct and indirect testing/telemetry are of great interest to the field and are being examined carefully in comparison to in-person means both for validity and possibly earlier recognition.”
This research was supported by grants from the National Institutes of Health, the Association for Frontotemporal Degeneration, the Bluefield Project to Cure FTD, the Rainwater Charitable Foundation, and the Larry L. Hillblom Foundation. Dr. Staffaroni reported being a coinventor of four ALLFTD mobile application tasks (not analyzed in the current study); receiving licensing fees from Datacubed Health and research support from the National Institute on Aging of the NIH, Bluefield Project to Cure FTD, the Alzheimer’s Association, the Larry L. Hillblom Foundation, and the Rainwater Charitable Foundation; and consulting for Alector Inc., Eli Lilly and Company Prevail Therapeutics, Passage Bio Inc, and Takeda Pharmaceuticals. Dr. Kukull participated in the ALLFTD Consortium.
A version of this article appeared on Medscape.com.
, new research showed.
Cognitive tests administered remotely on the phone “showed similar findings as our gold standard in-clinic cognitive tests and brain imaging,” said study investigator Adam M. Staffaroni, PhD, with the Memory and Aging Center, University of California San Francisco.
“We also provided evidence that these assessments may be useful for detecting early symptoms of the disease at a level that is on par, or perhaps slightly better, than our gold standard in-person tests,” Dr. Staffaroni said.
The study was published online in JAMA Network Open.
Tough to Diagnose
Although relatively rare, FTD is the top cause of dementia in patients younger than 60 years. Patients are usually diagnosed relatively late in the disease because they are young and because their symptoms may be mistaken for psychiatric disorders.
In addition, behavioral and motor symptoms of FTD can make it hard for families to get to an academic center for in-clinic assessments, making remote assessments a huge need.
Dr. Staffaroni and colleagues with the ALLFTD Consortium partnered with software company Datacubed Health to develop the ALLFTD-mApp, which includes cognitive, motor, and speech tasks.
They assessed the reliability and validity of the app, against standard in-clinic assessments, in 350 individuals (mean age, 54 years; 58% women; mean education level, 16.5 years).
Among the 329 individuals with data on disease stage, 195 (59%) were asymptomatic or had preclinical FTD, 66 (20%) had prodromal FTD, and 68 (21%) had symptomatic FTD with a range of clinical syndromes.
The smartphone app showed “moderate to excellent” reliability within a single administration (ie, internally consistent) and across repeated assessments (ie, test-retest reliability), the researchers reported.
Validity was supported by association of smartphones tests with disease severity, criterion-standard neuropsychological tests, and brain volume, they noted.
Of Great Interest
They also reported that a composite of brief smartphone tests accurately distinguished dementia from cognitively unimpaired participants, screening out participants without symptoms, and detected prodromal FTD with greater sensitivity than the Montreal Cognitive Assessment.
“This tool is currently being used in several research studies. The remote aspect of this technology is important because it could allow researchers to collect data more frequently, which may give them a more accurate picture of the disease. Furthermore, researchers can be more inclusive in their study designs and include participants who otherwise might have difficulty traveling to academic centers for standard in-person visits,” said Dr. Staffaroni.
“Because the app appears sensitive to early stages of the disease, it could be also used as a screening tool, possibly alongside other remote data collection, to help identify participants that might be appropriate for a clinical trial. At this point, these technologies are not ready for clinical use and require additional research studies to understand their clinical utility,” he cautioned.
Commenting on the study, Walter Kukull, PhD, director of the National Alzheimer’s Coordinating Center at the University of Washington in Seattle, noted that “remote direct and indirect testing/telemetry are of great interest to the field and are being examined carefully in comparison to in-person means both for validity and possibly earlier recognition.”
This research was supported by grants from the National Institutes of Health, the Association for Frontotemporal Degeneration, the Bluefield Project to Cure FTD, the Rainwater Charitable Foundation, and the Larry L. Hillblom Foundation. Dr. Staffaroni reported being a coinventor of four ALLFTD mobile application tasks (not analyzed in the current study); receiving licensing fees from Datacubed Health and research support from the National Institute on Aging of the NIH, Bluefield Project to Cure FTD, the Alzheimer’s Association, the Larry L. Hillblom Foundation, and the Rainwater Charitable Foundation; and consulting for Alector Inc., Eli Lilly and Company Prevail Therapeutics, Passage Bio Inc, and Takeda Pharmaceuticals. Dr. Kukull participated in the ALLFTD Consortium.
A version of this article appeared on Medscape.com.
FROM JAMA NETWORK OPEN
Alzheimer’s Transmissible Via Stem Cell Transplantation?
Studies in preclinical models hint that familial Alzheimer’s disease (AD) may be transmissible via bone marrow transplant, but the researchers and outside experts caution against making the immediate leap to humans.
These pathologic features included compromised blood-brain barrier integrity, heightened cerebral vascular neoangiogenesis, elevated brain-associated beta-amyloid levels, and cognitive impairment.
In addition, symptoms of cognitive decline presented rapidly — 6 months after transplant in the APP-knockout mice and 9 months in the wild-type mice vs 12 months shown previously in AD transgenic mice.
“Contrary to prevailing beliefs regarding AD occurring solely in familial or sporadic forms, our study reveals an unexpected transplantable form of AD in a preclinical model, suggesting potential iatrogenic transmission in AD patients,” the investigators, led by Wilfred Jefferies, DPhil, write.
Although this is probably an “infrequent” occurrence, it’s still “concerning,” Dr. Jefferies told this news organization, and it suggests that “human donors of blood, tissue, organ, and stem cells should be screened to prevent its inadvertent transfer of disease during blood product transfusions and cellular therapies.”
The study was published March 28 in Stem Cell Reports.
Intriguing, but Limited Human Relevance
The researchers note the study also demonstrates that beta-amyloid accumulation originating outside of the central nervous system contributes to AD pathology, providing an opportunity for the development of new biomarkers for AD.
Several experts weighed in on this research in a statement from the UK-based nonprofit and independent Science Media Centre (SMC).
David Curtis, MBBS, MD, PhD, with University College London’s Genetics Institute, United Kingdom, noted that the study suggests that “theoretically there could be a risk of acquiring Alzheimer’s disease if one received a stem cell transplant from somebody carrying the severe, familial form of the disease. However, this form is extremely rare so in practice the risk seems low and there are many safeguards around stem cell transplantation. I do not see that the risks extend to other areas such as organ transplantation or blood transfusion because these procedures do not involve large numbers of stem cells which can go on to form glial cells.”
Paul Morgan, PhD, with UK Dementia Research Institute Cardiff, Cardiff University, said the study is “scientifically intriguing” in demonstrating in this “very specific experimental situation, that bone marrow cells are sufficient to transfer the gene and the disease. Relevance to human organ and cell transplant is limited.”
Morgan cautioned against making the “gargantuan leap to propose that tissue, organ and cell transplantation, and even blood transfusion, carry a risk of transferring Alzheimer’s disease and other neuropathologies in man.”
Bart De Strooper, MD, PhD, with University College London, agreed. “There is not sufficient evidence here to suggest that anyone receiving a bone marrow transplant is at risk of developing Alzheimer’s disease as a result of the procedure, and nobody should forgo a transplant for this reason,” he said in the SMC release.
The study had no specific funding. The authors hold equity in the start-up company, Cava Healthcare, which possesses intellectual property related to these findings. This had no role in the study design, data collection, analysis, or interpretation of data, or in the writing of the paper. Morgan, De Strooper, and Curtis have no relevant disclosures.
A version of this article appeared on Medscape.com.
Studies in preclinical models hint that familial Alzheimer’s disease (AD) may be transmissible via bone marrow transplant, but the researchers and outside experts caution against making the immediate leap to humans.
These pathologic features included compromised blood-brain barrier integrity, heightened cerebral vascular neoangiogenesis, elevated brain-associated beta-amyloid levels, and cognitive impairment.
In addition, symptoms of cognitive decline presented rapidly — 6 months after transplant in the APP-knockout mice and 9 months in the wild-type mice vs 12 months shown previously in AD transgenic mice.
“Contrary to prevailing beliefs regarding AD occurring solely in familial or sporadic forms, our study reveals an unexpected transplantable form of AD in a preclinical model, suggesting potential iatrogenic transmission in AD patients,” the investigators, led by Wilfred Jefferies, DPhil, write.
Although this is probably an “infrequent” occurrence, it’s still “concerning,” Dr. Jefferies told this news organization, and it suggests that “human donors of blood, tissue, organ, and stem cells should be screened to prevent its inadvertent transfer of disease during blood product transfusions and cellular therapies.”
The study was published March 28 in Stem Cell Reports.
Intriguing, but Limited Human Relevance
The researchers note the study also demonstrates that beta-amyloid accumulation originating outside of the central nervous system contributes to AD pathology, providing an opportunity for the development of new biomarkers for AD.
Several experts weighed in on this research in a statement from the UK-based nonprofit and independent Science Media Centre (SMC).
David Curtis, MBBS, MD, PhD, with University College London’s Genetics Institute, United Kingdom, noted that the study suggests that “theoretically there could be a risk of acquiring Alzheimer’s disease if one received a stem cell transplant from somebody carrying the severe, familial form of the disease. However, this form is extremely rare so in practice the risk seems low and there are many safeguards around stem cell transplantation. I do not see that the risks extend to other areas such as organ transplantation or blood transfusion because these procedures do not involve large numbers of stem cells which can go on to form glial cells.”
Paul Morgan, PhD, with UK Dementia Research Institute Cardiff, Cardiff University, said the study is “scientifically intriguing” in demonstrating in this “very specific experimental situation, that bone marrow cells are sufficient to transfer the gene and the disease. Relevance to human organ and cell transplant is limited.”
Morgan cautioned against making the “gargantuan leap to propose that tissue, organ and cell transplantation, and even blood transfusion, carry a risk of transferring Alzheimer’s disease and other neuropathologies in man.”
Bart De Strooper, MD, PhD, with University College London, agreed. “There is not sufficient evidence here to suggest that anyone receiving a bone marrow transplant is at risk of developing Alzheimer’s disease as a result of the procedure, and nobody should forgo a transplant for this reason,” he said in the SMC release.
The study had no specific funding. The authors hold equity in the start-up company, Cava Healthcare, which possesses intellectual property related to these findings. This had no role in the study design, data collection, analysis, or interpretation of data, or in the writing of the paper. Morgan, De Strooper, and Curtis have no relevant disclosures.
A version of this article appeared on Medscape.com.
Studies in preclinical models hint that familial Alzheimer’s disease (AD) may be transmissible via bone marrow transplant, but the researchers and outside experts caution against making the immediate leap to humans.
These pathologic features included compromised blood-brain barrier integrity, heightened cerebral vascular neoangiogenesis, elevated brain-associated beta-amyloid levels, and cognitive impairment.
In addition, symptoms of cognitive decline presented rapidly — 6 months after transplant in the APP-knockout mice and 9 months in the wild-type mice vs 12 months shown previously in AD transgenic mice.
“Contrary to prevailing beliefs regarding AD occurring solely in familial or sporadic forms, our study reveals an unexpected transplantable form of AD in a preclinical model, suggesting potential iatrogenic transmission in AD patients,” the investigators, led by Wilfred Jefferies, DPhil, write.
Although this is probably an “infrequent” occurrence, it’s still “concerning,” Dr. Jefferies told this news organization, and it suggests that “human donors of blood, tissue, organ, and stem cells should be screened to prevent its inadvertent transfer of disease during blood product transfusions and cellular therapies.”
The study was published March 28 in Stem Cell Reports.
Intriguing, but Limited Human Relevance
The researchers note the study also demonstrates that beta-amyloid accumulation originating outside of the central nervous system contributes to AD pathology, providing an opportunity for the development of new biomarkers for AD.
Several experts weighed in on this research in a statement from the UK-based nonprofit and independent Science Media Centre (SMC).
David Curtis, MBBS, MD, PhD, with University College London’s Genetics Institute, United Kingdom, noted that the study suggests that “theoretically there could be a risk of acquiring Alzheimer’s disease if one received a stem cell transplant from somebody carrying the severe, familial form of the disease. However, this form is extremely rare so in practice the risk seems low and there are many safeguards around stem cell transplantation. I do not see that the risks extend to other areas such as organ transplantation or blood transfusion because these procedures do not involve large numbers of stem cells which can go on to form glial cells.”
Paul Morgan, PhD, with UK Dementia Research Institute Cardiff, Cardiff University, said the study is “scientifically intriguing” in demonstrating in this “very specific experimental situation, that bone marrow cells are sufficient to transfer the gene and the disease. Relevance to human organ and cell transplant is limited.”
Morgan cautioned against making the “gargantuan leap to propose that tissue, organ and cell transplantation, and even blood transfusion, carry a risk of transferring Alzheimer’s disease and other neuropathologies in man.”
Bart De Strooper, MD, PhD, with University College London, agreed. “There is not sufficient evidence here to suggest that anyone receiving a bone marrow transplant is at risk of developing Alzheimer’s disease as a result of the procedure, and nobody should forgo a transplant for this reason,” he said in the SMC release.
The study had no specific funding. The authors hold equity in the start-up company, Cava Healthcare, which possesses intellectual property related to these findings. This had no role in the study design, data collection, analysis, or interpretation of data, or in the writing of the paper. Morgan, De Strooper, and Curtis have no relevant disclosures.
A version of this article appeared on Medscape.com.
FROM STEM CELL REPORTS
Human Brains Are Getting Bigger: Good News for Dementia Risk?
A secular trends analysis using brain imaging data from the long-running Framingham Heart Study revealed an increase in intracranial volume (ICV), cortical gray matter, white matter, and hippocampal volumes, as well as cortical surface area in people born in the 1970s versus those born in the 1930s.
“We hypothesize that the increased size of the brain will lead to increased ‘reserve’ against the diseases of aging, consequently reducing overall risk of dementia,” said Charles DeCarli, MD, director of the Alzheimer’s Disease Research Center and Imaging of Dementia and Aging Laboratory, Department of Neurology and Center for Neuroscience, University of California at Davis.
The study was published online in JAMA Neurology.
Dementia Protection?
An earlier report from the Framingham Heart Study suggested that dementia incidence is declining.
“This difference occurred among persons with at least a high school education and was not affected by differences in vascular risk. Our work was stimulated by this finding and the possibility that differences in brain size might be occurring over the three generations of the Framingham Heart Study which might explain an increased resilience to dementia,” said Dr. DeCarli.
The cross-sectional study used data from 3226 Framingham participants (53% women) born in the decades 1930–1970. None had dementia or a history of stroke. At a mean age of 57.7 years, they underwent brain MRI.
Compared with the 1930s birth decade, the 1970s birth decade had a 6.6% greater ICV (1321 mL vs 1234 mL), 7.7% greater white matter volume (476.3 mL vs 441.9 mL), 5.7% greater hippocampal volume (6.69 mL vs 6.51 mL), and 14.9% greater cortical surface area (2222 cm2 vs 1933 cm2).
Cortical thickness was thinner by 21% over the same period, coinciding with larger intracranial volume, cerebral white matter volume, and cortical surface area.
“We were surprised to find that the brain is getting larger, but the cortex is thinning very slightly. The apparent thinning of the cortex is related to the increased need for expansion of the cortical ribbon. This is based on hypotheses related to the effects of evolution and cortical development designed to make neuronal integration most efficient,” said Dr. DeCarli.
Repeat analysis applied to a subgroup of 1145 individuals of similar age range born in the 1940s (mean age, 60 years) and 1950s (mean age, 59 years) resulted in similar findings.
“These findings likely reflect both secular improvements in early life environmental influences through health, social-cultural, and educational factors, as well as secular improvements in modifiable dementia risk factors leading to better brain health and reserve,” the authors wrote.
While the effects observed are “likely to be small at the level of the individual, they are likely to be substantial at the population level, adding to growing literature that suggests optimized brain development and ideal health through modification of risk factors could substantially modify the effect of common neurodegenerative diseases such as stroke and Alzheiemer’s disease on dementia incidence,” they added.
Limitations included the predominately non-Hispanic White, healthy, and well-educated population that is the Framingham cohort, which is not representative of the broader US population. The cross-sectional nature of the study also limited causal inference.
Exciting Work
“If these results are confirmed by others and the observed differences by decade are as large as those reported, it has important implications for aging and dementia studies,” Prashanthi Lemuria, PhD, with Mayo Clinic, Rochester, Minnesota, wrote in an accompanying editorial.
“First, studies that use brain charts for the human life span to understand the mechanisms of aging, by stitching together data from individuals across the decades, are significantly overestimating the degree of brain health decline using volumes across the life span because the baseline brain health in individuals who are in their older decades is likely lower to begin with,” Dr. Lemuria noted.
“Second, cortical thickness measurements, often used in dementia studies as a cross-sectional marker for neurodegeneration, showed greatest decline due to secular trends and are not scaled for ICV. Therefore, these should be traded in favor of gray matter volumes after consideration of ICV to estimate the true degree of neurodegeneration,” Dr. Vemuri added.
The data also suggest that longitudinal imaging study designs should be preferred when testing hypotheses on brain health, Dr. Vemuri wrote.
Although this work is “exciting and will bring attention to secular trends in brain health, much work is yet to be done to validate and replicate these findings and, more importantly, understand the mechanistic basis of these trends,” she added.
“Do these secular trends in improvement of brain health underlie the decrease in dementia risk? The jury may be still out, but the authors are commended for investigating new avenues,” Dr. Vemuri concluded.
Support for this research was provided by the National Institute on Aging and the National Institute on Neurological Disorders and Stroke and the National Institutes of Health. Dr. DeCarli reported serving as a consultant to Novartis on a safety study of heart failure during the conduct of the study and receiving consultant fees from Eisai and Novo Nordisk outside the submitted work. Dr. Lemuria had no disclosures.
A version of this article appeared on Medscape.com.
A secular trends analysis using brain imaging data from the long-running Framingham Heart Study revealed an increase in intracranial volume (ICV), cortical gray matter, white matter, and hippocampal volumes, as well as cortical surface area in people born in the 1970s versus those born in the 1930s.
“We hypothesize that the increased size of the brain will lead to increased ‘reserve’ against the diseases of aging, consequently reducing overall risk of dementia,” said Charles DeCarli, MD, director of the Alzheimer’s Disease Research Center and Imaging of Dementia and Aging Laboratory, Department of Neurology and Center for Neuroscience, University of California at Davis.
The study was published online in JAMA Neurology.
Dementia Protection?
An earlier report from the Framingham Heart Study suggested that dementia incidence is declining.
“This difference occurred among persons with at least a high school education and was not affected by differences in vascular risk. Our work was stimulated by this finding and the possibility that differences in brain size might be occurring over the three generations of the Framingham Heart Study which might explain an increased resilience to dementia,” said Dr. DeCarli.
The cross-sectional study used data from 3226 Framingham participants (53% women) born in the decades 1930–1970. None had dementia or a history of stroke. At a mean age of 57.7 years, they underwent brain MRI.
Compared with the 1930s birth decade, the 1970s birth decade had a 6.6% greater ICV (1321 mL vs 1234 mL), 7.7% greater white matter volume (476.3 mL vs 441.9 mL), 5.7% greater hippocampal volume (6.69 mL vs 6.51 mL), and 14.9% greater cortical surface area (2222 cm2 vs 1933 cm2).
Cortical thickness was thinner by 21% over the same period, coinciding with larger intracranial volume, cerebral white matter volume, and cortical surface area.
“We were surprised to find that the brain is getting larger, but the cortex is thinning very slightly. The apparent thinning of the cortex is related to the increased need for expansion of the cortical ribbon. This is based on hypotheses related to the effects of evolution and cortical development designed to make neuronal integration most efficient,” said Dr. DeCarli.
Repeat analysis applied to a subgroup of 1145 individuals of similar age range born in the 1940s (mean age, 60 years) and 1950s (mean age, 59 years) resulted in similar findings.
“These findings likely reflect both secular improvements in early life environmental influences through health, social-cultural, and educational factors, as well as secular improvements in modifiable dementia risk factors leading to better brain health and reserve,” the authors wrote.
While the effects observed are “likely to be small at the level of the individual, they are likely to be substantial at the population level, adding to growing literature that suggests optimized brain development and ideal health through modification of risk factors could substantially modify the effect of common neurodegenerative diseases such as stroke and Alzheiemer’s disease on dementia incidence,” they added.
Limitations included the predominately non-Hispanic White, healthy, and well-educated population that is the Framingham cohort, which is not representative of the broader US population. The cross-sectional nature of the study also limited causal inference.
Exciting Work
“If these results are confirmed by others and the observed differences by decade are as large as those reported, it has important implications for aging and dementia studies,” Prashanthi Lemuria, PhD, with Mayo Clinic, Rochester, Minnesota, wrote in an accompanying editorial.
“First, studies that use brain charts for the human life span to understand the mechanisms of aging, by stitching together data from individuals across the decades, are significantly overestimating the degree of brain health decline using volumes across the life span because the baseline brain health in individuals who are in their older decades is likely lower to begin with,” Dr. Lemuria noted.
“Second, cortical thickness measurements, often used in dementia studies as a cross-sectional marker for neurodegeneration, showed greatest decline due to secular trends and are not scaled for ICV. Therefore, these should be traded in favor of gray matter volumes after consideration of ICV to estimate the true degree of neurodegeneration,” Dr. Vemuri added.
The data also suggest that longitudinal imaging study designs should be preferred when testing hypotheses on brain health, Dr. Vemuri wrote.
Although this work is “exciting and will bring attention to secular trends in brain health, much work is yet to be done to validate and replicate these findings and, more importantly, understand the mechanistic basis of these trends,” she added.
“Do these secular trends in improvement of brain health underlie the decrease in dementia risk? The jury may be still out, but the authors are commended for investigating new avenues,” Dr. Vemuri concluded.
Support for this research was provided by the National Institute on Aging and the National Institute on Neurological Disorders and Stroke and the National Institutes of Health. Dr. DeCarli reported serving as a consultant to Novartis on a safety study of heart failure during the conduct of the study and receiving consultant fees from Eisai and Novo Nordisk outside the submitted work. Dr. Lemuria had no disclosures.
A version of this article appeared on Medscape.com.
A secular trends analysis using brain imaging data from the long-running Framingham Heart Study revealed an increase in intracranial volume (ICV), cortical gray matter, white matter, and hippocampal volumes, as well as cortical surface area in people born in the 1970s versus those born in the 1930s.
“We hypothesize that the increased size of the brain will lead to increased ‘reserve’ against the diseases of aging, consequently reducing overall risk of dementia,” said Charles DeCarli, MD, director of the Alzheimer’s Disease Research Center and Imaging of Dementia and Aging Laboratory, Department of Neurology and Center for Neuroscience, University of California at Davis.
The study was published online in JAMA Neurology.
Dementia Protection?
An earlier report from the Framingham Heart Study suggested that dementia incidence is declining.
“This difference occurred among persons with at least a high school education and was not affected by differences in vascular risk. Our work was stimulated by this finding and the possibility that differences in brain size might be occurring over the three generations of the Framingham Heart Study which might explain an increased resilience to dementia,” said Dr. DeCarli.
The cross-sectional study used data from 3226 Framingham participants (53% women) born in the decades 1930–1970. None had dementia or a history of stroke. At a mean age of 57.7 years, they underwent brain MRI.
Compared with the 1930s birth decade, the 1970s birth decade had a 6.6% greater ICV (1321 mL vs 1234 mL), 7.7% greater white matter volume (476.3 mL vs 441.9 mL), 5.7% greater hippocampal volume (6.69 mL vs 6.51 mL), and 14.9% greater cortical surface area (2222 cm2 vs 1933 cm2).
Cortical thickness was thinner by 21% over the same period, coinciding with larger intracranial volume, cerebral white matter volume, and cortical surface area.
“We were surprised to find that the brain is getting larger, but the cortex is thinning very slightly. The apparent thinning of the cortex is related to the increased need for expansion of the cortical ribbon. This is based on hypotheses related to the effects of evolution and cortical development designed to make neuronal integration most efficient,” said Dr. DeCarli.
Repeat analysis applied to a subgroup of 1145 individuals of similar age range born in the 1940s (mean age, 60 years) and 1950s (mean age, 59 years) resulted in similar findings.
“These findings likely reflect both secular improvements in early life environmental influences through health, social-cultural, and educational factors, as well as secular improvements in modifiable dementia risk factors leading to better brain health and reserve,” the authors wrote.
While the effects observed are “likely to be small at the level of the individual, they are likely to be substantial at the population level, adding to growing literature that suggests optimized brain development and ideal health through modification of risk factors could substantially modify the effect of common neurodegenerative diseases such as stroke and Alzheiemer’s disease on dementia incidence,” they added.
Limitations included the predominately non-Hispanic White, healthy, and well-educated population that is the Framingham cohort, which is not representative of the broader US population. The cross-sectional nature of the study also limited causal inference.
Exciting Work
“If these results are confirmed by others and the observed differences by decade are as large as those reported, it has important implications for aging and dementia studies,” Prashanthi Lemuria, PhD, with Mayo Clinic, Rochester, Minnesota, wrote in an accompanying editorial.
“First, studies that use brain charts for the human life span to understand the mechanisms of aging, by stitching together data from individuals across the decades, are significantly overestimating the degree of brain health decline using volumes across the life span because the baseline brain health in individuals who are in their older decades is likely lower to begin with,” Dr. Lemuria noted.
“Second, cortical thickness measurements, often used in dementia studies as a cross-sectional marker for neurodegeneration, showed greatest decline due to secular trends and are not scaled for ICV. Therefore, these should be traded in favor of gray matter volumes after consideration of ICV to estimate the true degree of neurodegeneration,” Dr. Vemuri added.
The data also suggest that longitudinal imaging study designs should be preferred when testing hypotheses on brain health, Dr. Vemuri wrote.
Although this work is “exciting and will bring attention to secular trends in brain health, much work is yet to be done to validate and replicate these findings and, more importantly, understand the mechanistic basis of these trends,” she added.
“Do these secular trends in improvement of brain health underlie the decrease in dementia risk? The jury may be still out, but the authors are commended for investigating new avenues,” Dr. Vemuri concluded.
Support for this research was provided by the National Institute on Aging and the National Institute on Neurological Disorders and Stroke and the National Institutes of Health. Dr. DeCarli reported serving as a consultant to Novartis on a safety study of heart failure during the conduct of the study and receiving consultant fees from Eisai and Novo Nordisk outside the submitted work. Dr. Lemuria had no disclosures.
A version of this article appeared on Medscape.com.
FROM JAMA NEUROLOGY
Alzheimer’s Prevalence Predicted to Double by 2050
An estimated 6.9 million older adults are living with Alzheimer’s disease (AD) in the United States, and another 200,000 people under age 65 have younger-onset AD, new data showed.
The report also included sobering statistics on AD-related mortality — which increased 141% between 2001 and 2021 — and described “dementia neurology deserts” that will leave some states with less than 10 neurologists per 10,000 people with dementia as early as 2025. The shortages extend to other specialties, clinical professionals, and direct care workers, the report authors wrote.
“Dementia healthcare is a complex maze composed of primary care providers, specialists, social services, medication management, and caregiver support,” Sam Fazio, PhD, senior director, psychosocial research and quality care, Alzheimer’s Association, said in a press release.
“As the number of individuals living with Alzheimer’s continues to grow, ensuring patients, their caregivers, and families have a clear understanding of how to navigate dementia care resources is critical to improving health outcomes,” Dr. Fazio added.
The “2024 Alzheimer’s Disease Facts and Figures” study and accompanying report “Mapping a Better Future for Dementia Care Navigation” were published online on March 20 by the Alzheimer’s Association and will appear in the May issue of Alzheimer’s & Dementia.
Significant Increase in Mortality
The number of people over 65 with AD rose slightly in 2024 to 6.9 million from 6.7 million in 2023. The number of younger-onset AD cases remained roughly the same.
States and counties in the eastern and southeastern United States have the highest percentage of people over 65 with AD, with the District of Columbia reporting 16.8% and New York, Florida, and Mississippi between 12.5% and 12.7%. Alaska has the lowest with 8.8%.
Based on an analysis of death certificate data, the number of deaths from AD increased 141% between 2000 and 2021, while deaths from heart disease — the number-one cause of death — decreased 2.1%. Among people aged 70, 61% of those with AD are expected to die before age 80 compared with 30% of those without AD.
The cost of health and long-term care for people with AD has also risen, the data suggested, with a projected total for 2024 of $360 billion, a $15 billion increase since 2023. That figure does not include unpaid caregiving by family and friends, which the report valued at nearly $350 billion.
With the prevalence of AD expected to rise — the report projected 11.2 million by 2040 and 12.7 million by 2050 — mortality, morbidity, and healthcare costs will only continue to go up. Without new treatments and advancements in care, study authors estimated the cost will reach $1 trillion in 2050.
The report also waded into the issue of workforce deficits. Between 2012 and 2022, the number of direct care workers in the United States increased from 3.2 million to 4.8 million. Study authors estimated more than 1 million additional direct care workers will be needed before 2031.
There is a shortage of clinicians as well, especially for geriatricians, specially trained family physicians, or board-certified internists who can screen for, detect, and diagnose possible dementia. The National Center for Health Workforce Analysis (NCHWA) determined shortages in that specialty began a decade ago, and the projected need for geriatricians is expected to far exceed the supply in every region of the United States by 2050.
The NCHWA also projected a shortfall of neurologists by 2025. The report listed 20 US states as “dementia neurology deserts,” meaning they’re projected to have fewer than 10 neurologists per 10,000 people with dementia in 2025.
Several factors may contribute to the scarcity of specialists. In addition to an aging population, contributors include lower pay for geriatricians and neurologists compared with other specialists, an inadequate number of clinician educators with relevant specialties on faculties of health professional schools, and limited incentives to choose these specialties.
Underestimating a ‘Serious Problem’
The report “probably underestimates” the “serious problem with dementia specialty care in the United States,” David S. Knopman, MD, professor of neurology, Mayo Clinic, Rochester, Minnesota, told this news organization.
Given the complexity of managing treatments for AD, such as the monoclonal antibody lecanemab, or those for dementia with Lewy bodies, “my sense is that very few geriatricians are likely to take an active role in dementia care,” said Dr. Knopman.
Very few neurologists have specialty training in dementia diagnosis and care, he added, and neurologists who do specialize in dementia are generally located exclusively in tertiary medical centers.
“While neurologists are more likely to be able to diagnose dementia subtypes compared to geriatricians or general internists or family physicians, non-specialty neurologists are also unlikely to have the expertise to manage lecanemab therapy or to deal with diagnosis and management of dementia subtypes,” Dr. Knopman said.
“Filling the pipeline with new trainees is going to take a long, long time,” he added.
As it stands, most dementia diagnoses are not made by specialists. The report cited a study of Medicare beneficiaries that found 85% of people living with dementia were diagnosed by providers such as primary care physicians (PCPs).
Barriers to Care
Although screening is now a reimbursable service by Medicare, PCPs experience numerous barriers to detecting cognitive impairment and diagnosing dementia. Routinely used cognitive assessments are time-consuming and labor-intensive, making them challenging to use in a busy clinical setting.
“Even if dementia is diagnosed, providers sometimes wait to disclose this information to the patient due to diagnostic uncertainty, time constraints, stigma, and fear of causing emotional distress,” the authors wrote.
A previous survey by the Alzheimer’s Association uncovered a high degree of uncertainty and discomfort among PCPs in making a dementia diagnosis. While almost a third reported referring patients to specialists, 55% said there were not enough geriatricians and other specialists in their area to meet the demand.
In tackling the theme of dementia care navigation, the report included a survey of 1204 nonphysician healthcare workers, including nurses, physician assistants, and social workers.
About 60% believed the US healthcare system isn’t effectively helping patients and families navigate the system and that training in dementia care navigation is lacking and not standardized. Respondents also said nonmedical professionals are best suited to help people with dementia and their caregivers navigate care.
Respondents identified a range of barriers that make navigating dementia care difficult for patients and families. More than three in four (77%) identified a lack of community-based resources as a barrier. And 70% called out restrictions in current payment models as a barrier, with 41% saying this was the greatest barrier.
Alternative Model
In July, the Centers for Medicare & Medicaid Services will launch a pilot model in dementia care management, the Guiding an Improved Dementia Experience. The program will test a monthly per-patient payment model as a fee-for-service replacement.
Healthcare providers who participate in the program will deliver supportive services to people living with dementia and provide access to a care navigator to help patients and caregivers access services and support.
“There is growing momentum in this country to enhance dementia care navigation,” Dr. Fazio said in the release. “Dementia care navigation programs have shown they can be a huge benefit to people living with dementia and their caregivers.”
These programs are unfortunately not widespread across the country, but the Alzheimer’s Association hopes this report “will be a catalyst for change,” Dr. Fazio added.
A separate survey of dementia caregivers found they would overwhelmingly welcome navigator support. The vast majority (97%) said they would find navigation services helpful.
Such services may also go a long way to alleviating stresses involved in dementia caregiving, a top stressor being care coordination, the report noted. Seven in 10 caregiver survey respondents (70%) reported coordinating care is stressful. More than half (53%) said navigating healthcare is difficult, and two-thirds (66%) said they have difficulty finding resources and supports.
Around-the-clock support in addition to care coordination and help understanding their care recipient’s condition are among the top services dementia caregiver respondents cited as being most helpful.
Dr. Knopman reported no relevant conflicts of interest.
A version of this article appeared on Medscape.com.
An estimated 6.9 million older adults are living with Alzheimer’s disease (AD) in the United States, and another 200,000 people under age 65 have younger-onset AD, new data showed.
The report also included sobering statistics on AD-related mortality — which increased 141% between 2001 and 2021 — and described “dementia neurology deserts” that will leave some states with less than 10 neurologists per 10,000 people with dementia as early as 2025. The shortages extend to other specialties, clinical professionals, and direct care workers, the report authors wrote.
“Dementia healthcare is a complex maze composed of primary care providers, specialists, social services, medication management, and caregiver support,” Sam Fazio, PhD, senior director, psychosocial research and quality care, Alzheimer’s Association, said in a press release.
“As the number of individuals living with Alzheimer’s continues to grow, ensuring patients, their caregivers, and families have a clear understanding of how to navigate dementia care resources is critical to improving health outcomes,” Dr. Fazio added.
The “2024 Alzheimer’s Disease Facts and Figures” study and accompanying report “Mapping a Better Future for Dementia Care Navigation” were published online on March 20 by the Alzheimer’s Association and will appear in the May issue of Alzheimer’s & Dementia.
Significant Increase in Mortality
The number of people over 65 with AD rose slightly in 2024 to 6.9 million from 6.7 million in 2023. The number of younger-onset AD cases remained roughly the same.
States and counties in the eastern and southeastern United States have the highest percentage of people over 65 with AD, with the District of Columbia reporting 16.8% and New York, Florida, and Mississippi between 12.5% and 12.7%. Alaska has the lowest with 8.8%.
Based on an analysis of death certificate data, the number of deaths from AD increased 141% between 2000 and 2021, while deaths from heart disease — the number-one cause of death — decreased 2.1%. Among people aged 70, 61% of those with AD are expected to die before age 80 compared with 30% of those without AD.
The cost of health and long-term care for people with AD has also risen, the data suggested, with a projected total for 2024 of $360 billion, a $15 billion increase since 2023. That figure does not include unpaid caregiving by family and friends, which the report valued at nearly $350 billion.
With the prevalence of AD expected to rise — the report projected 11.2 million by 2040 and 12.7 million by 2050 — mortality, morbidity, and healthcare costs will only continue to go up. Without new treatments and advancements in care, study authors estimated the cost will reach $1 trillion in 2050.
The report also waded into the issue of workforce deficits. Between 2012 and 2022, the number of direct care workers in the United States increased from 3.2 million to 4.8 million. Study authors estimated more than 1 million additional direct care workers will be needed before 2031.
There is a shortage of clinicians as well, especially for geriatricians, specially trained family physicians, or board-certified internists who can screen for, detect, and diagnose possible dementia. The National Center for Health Workforce Analysis (NCHWA) determined shortages in that specialty began a decade ago, and the projected need for geriatricians is expected to far exceed the supply in every region of the United States by 2050.
The NCHWA also projected a shortfall of neurologists by 2025. The report listed 20 US states as “dementia neurology deserts,” meaning they’re projected to have fewer than 10 neurologists per 10,000 people with dementia in 2025.
Several factors may contribute to the scarcity of specialists. In addition to an aging population, contributors include lower pay for geriatricians and neurologists compared with other specialists, an inadequate number of clinician educators with relevant specialties on faculties of health professional schools, and limited incentives to choose these specialties.
Underestimating a ‘Serious Problem’
The report “probably underestimates” the “serious problem with dementia specialty care in the United States,” David S. Knopman, MD, professor of neurology, Mayo Clinic, Rochester, Minnesota, told this news organization.
Given the complexity of managing treatments for AD, such as the monoclonal antibody lecanemab, or those for dementia with Lewy bodies, “my sense is that very few geriatricians are likely to take an active role in dementia care,” said Dr. Knopman.
Very few neurologists have specialty training in dementia diagnosis and care, he added, and neurologists who do specialize in dementia are generally located exclusively in tertiary medical centers.
“While neurologists are more likely to be able to diagnose dementia subtypes compared to geriatricians or general internists or family physicians, non-specialty neurologists are also unlikely to have the expertise to manage lecanemab therapy or to deal with diagnosis and management of dementia subtypes,” Dr. Knopman said.
“Filling the pipeline with new trainees is going to take a long, long time,” he added.
As it stands, most dementia diagnoses are not made by specialists. The report cited a study of Medicare beneficiaries that found 85% of people living with dementia were diagnosed by providers such as primary care physicians (PCPs).
Barriers to Care
Although screening is now a reimbursable service by Medicare, PCPs experience numerous barriers to detecting cognitive impairment and diagnosing dementia. Routinely used cognitive assessments are time-consuming and labor-intensive, making them challenging to use in a busy clinical setting.
“Even if dementia is diagnosed, providers sometimes wait to disclose this information to the patient due to diagnostic uncertainty, time constraints, stigma, and fear of causing emotional distress,” the authors wrote.
A previous survey by the Alzheimer’s Association uncovered a high degree of uncertainty and discomfort among PCPs in making a dementia diagnosis. While almost a third reported referring patients to specialists, 55% said there were not enough geriatricians and other specialists in their area to meet the demand.
In tackling the theme of dementia care navigation, the report included a survey of 1204 nonphysician healthcare workers, including nurses, physician assistants, and social workers.
About 60% believed the US healthcare system isn’t effectively helping patients and families navigate the system and that training in dementia care navigation is lacking and not standardized. Respondents also said nonmedical professionals are best suited to help people with dementia and their caregivers navigate care.
Respondents identified a range of barriers that make navigating dementia care difficult for patients and families. More than three in four (77%) identified a lack of community-based resources as a barrier. And 70% called out restrictions in current payment models as a barrier, with 41% saying this was the greatest barrier.
Alternative Model
In July, the Centers for Medicare & Medicaid Services will launch a pilot model in dementia care management, the Guiding an Improved Dementia Experience. The program will test a monthly per-patient payment model as a fee-for-service replacement.
Healthcare providers who participate in the program will deliver supportive services to people living with dementia and provide access to a care navigator to help patients and caregivers access services and support.
“There is growing momentum in this country to enhance dementia care navigation,” Dr. Fazio said in the release. “Dementia care navigation programs have shown they can be a huge benefit to people living with dementia and their caregivers.”
These programs are unfortunately not widespread across the country, but the Alzheimer’s Association hopes this report “will be a catalyst for change,” Dr. Fazio added.
A separate survey of dementia caregivers found they would overwhelmingly welcome navigator support. The vast majority (97%) said they would find navigation services helpful.
Such services may also go a long way to alleviating stresses involved in dementia caregiving, a top stressor being care coordination, the report noted. Seven in 10 caregiver survey respondents (70%) reported coordinating care is stressful. More than half (53%) said navigating healthcare is difficult, and two-thirds (66%) said they have difficulty finding resources and supports.
Around-the-clock support in addition to care coordination and help understanding their care recipient’s condition are among the top services dementia caregiver respondents cited as being most helpful.
Dr. Knopman reported no relevant conflicts of interest.
A version of this article appeared on Medscape.com.
An estimated 6.9 million older adults are living with Alzheimer’s disease (AD) in the United States, and another 200,000 people under age 65 have younger-onset AD, new data showed.
The report also included sobering statistics on AD-related mortality — which increased 141% between 2001 and 2021 — and described “dementia neurology deserts” that will leave some states with less than 10 neurologists per 10,000 people with dementia as early as 2025. The shortages extend to other specialties, clinical professionals, and direct care workers, the report authors wrote.
“Dementia healthcare is a complex maze composed of primary care providers, specialists, social services, medication management, and caregiver support,” Sam Fazio, PhD, senior director, psychosocial research and quality care, Alzheimer’s Association, said in a press release.
“As the number of individuals living with Alzheimer’s continues to grow, ensuring patients, their caregivers, and families have a clear understanding of how to navigate dementia care resources is critical to improving health outcomes,” Dr. Fazio added.
The “2024 Alzheimer’s Disease Facts and Figures” study and accompanying report “Mapping a Better Future for Dementia Care Navigation” were published online on March 20 by the Alzheimer’s Association and will appear in the May issue of Alzheimer’s & Dementia.
Significant Increase in Mortality
The number of people over 65 with AD rose slightly in 2024 to 6.9 million from 6.7 million in 2023. The number of younger-onset AD cases remained roughly the same.
States and counties in the eastern and southeastern United States have the highest percentage of people over 65 with AD, with the District of Columbia reporting 16.8% and New York, Florida, and Mississippi between 12.5% and 12.7%. Alaska has the lowest with 8.8%.
Based on an analysis of death certificate data, the number of deaths from AD increased 141% between 2000 and 2021, while deaths from heart disease — the number-one cause of death — decreased 2.1%. Among people aged 70, 61% of those with AD are expected to die before age 80 compared with 30% of those without AD.
The cost of health and long-term care for people with AD has also risen, the data suggested, with a projected total for 2024 of $360 billion, a $15 billion increase since 2023. That figure does not include unpaid caregiving by family and friends, which the report valued at nearly $350 billion.
With the prevalence of AD expected to rise — the report projected 11.2 million by 2040 and 12.7 million by 2050 — mortality, morbidity, and healthcare costs will only continue to go up. Without new treatments and advancements in care, study authors estimated the cost will reach $1 trillion in 2050.
The report also waded into the issue of workforce deficits. Between 2012 and 2022, the number of direct care workers in the United States increased from 3.2 million to 4.8 million. Study authors estimated more than 1 million additional direct care workers will be needed before 2031.
There is a shortage of clinicians as well, especially for geriatricians, specially trained family physicians, or board-certified internists who can screen for, detect, and diagnose possible dementia. The National Center for Health Workforce Analysis (NCHWA) determined shortages in that specialty began a decade ago, and the projected need for geriatricians is expected to far exceed the supply in every region of the United States by 2050.
The NCHWA also projected a shortfall of neurologists by 2025. The report listed 20 US states as “dementia neurology deserts,” meaning they’re projected to have fewer than 10 neurologists per 10,000 people with dementia in 2025.
Several factors may contribute to the scarcity of specialists. In addition to an aging population, contributors include lower pay for geriatricians and neurologists compared with other specialists, an inadequate number of clinician educators with relevant specialties on faculties of health professional schools, and limited incentives to choose these specialties.
Underestimating a ‘Serious Problem’
The report “probably underestimates” the “serious problem with dementia specialty care in the United States,” David S. Knopman, MD, professor of neurology, Mayo Clinic, Rochester, Minnesota, told this news organization.
Given the complexity of managing treatments for AD, such as the monoclonal antibody lecanemab, or those for dementia with Lewy bodies, “my sense is that very few geriatricians are likely to take an active role in dementia care,” said Dr. Knopman.
Very few neurologists have specialty training in dementia diagnosis and care, he added, and neurologists who do specialize in dementia are generally located exclusively in tertiary medical centers.
“While neurologists are more likely to be able to diagnose dementia subtypes compared to geriatricians or general internists or family physicians, non-specialty neurologists are also unlikely to have the expertise to manage lecanemab therapy or to deal with diagnosis and management of dementia subtypes,” Dr. Knopman said.
“Filling the pipeline with new trainees is going to take a long, long time,” he added.
As it stands, most dementia diagnoses are not made by specialists. The report cited a study of Medicare beneficiaries that found 85% of people living with dementia were diagnosed by providers such as primary care physicians (PCPs).
Barriers to Care
Although screening is now a reimbursable service by Medicare, PCPs experience numerous barriers to detecting cognitive impairment and diagnosing dementia. Routinely used cognitive assessments are time-consuming and labor-intensive, making them challenging to use in a busy clinical setting.
“Even if dementia is diagnosed, providers sometimes wait to disclose this information to the patient due to diagnostic uncertainty, time constraints, stigma, and fear of causing emotional distress,” the authors wrote.
A previous survey by the Alzheimer’s Association uncovered a high degree of uncertainty and discomfort among PCPs in making a dementia diagnosis. While almost a third reported referring patients to specialists, 55% said there were not enough geriatricians and other specialists in their area to meet the demand.
In tackling the theme of dementia care navigation, the report included a survey of 1204 nonphysician healthcare workers, including nurses, physician assistants, and social workers.
About 60% believed the US healthcare system isn’t effectively helping patients and families navigate the system and that training in dementia care navigation is lacking and not standardized. Respondents also said nonmedical professionals are best suited to help people with dementia and their caregivers navigate care.
Respondents identified a range of barriers that make navigating dementia care difficult for patients and families. More than three in four (77%) identified a lack of community-based resources as a barrier. And 70% called out restrictions in current payment models as a barrier, with 41% saying this was the greatest barrier.
Alternative Model
In July, the Centers for Medicare & Medicaid Services will launch a pilot model in dementia care management, the Guiding an Improved Dementia Experience. The program will test a monthly per-patient payment model as a fee-for-service replacement.
Healthcare providers who participate in the program will deliver supportive services to people living with dementia and provide access to a care navigator to help patients and caregivers access services and support.
“There is growing momentum in this country to enhance dementia care navigation,” Dr. Fazio said in the release. “Dementia care navigation programs have shown they can be a huge benefit to people living with dementia and their caregivers.”
These programs are unfortunately not widespread across the country, but the Alzheimer’s Association hopes this report “will be a catalyst for change,” Dr. Fazio added.
A separate survey of dementia caregivers found they would overwhelmingly welcome navigator support. The vast majority (97%) said they would find navigation services helpful.
Such services may also go a long way to alleviating stresses involved in dementia caregiving, a top stressor being care coordination, the report noted. Seven in 10 caregiver survey respondents (70%) reported coordinating care is stressful. More than half (53%) said navigating healthcare is difficult, and two-thirds (66%) said they have difficulty finding resources and supports.
Around-the-clock support in addition to care coordination and help understanding their care recipient’s condition are among the top services dementia caregiver respondents cited as being most helpful.
Dr. Knopman reported no relevant conflicts of interest.
A version of this article appeared on Medscape.com.