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Twelve risk factors linked to 40% of world’s dementia cases
according to an update of the Lancet Commission on Dementia Prevention, Intervention, and Care.
The original report, published in 2017, identified nine modifiable risk factors that were estimated to be responsible for one-third of dementia cases. The commission has now added three new modifiable risk factors to the list.
“We reconvened the 2017 Lancet Commission on Dementia Prevention, Intervention, and Care to identify the evidence for advances likely to have the greatest impact since our 2017 paper,” the authors wrote.
The 2020 report was presented at the virtual annual meeting of the Alzheimer’s Association International Conference (AAIC) 2020 and also was published online July 30 in the Lancet.
Alcohol, TBI, air pollution
The three new risk factors that have been added in the latest update are excessive alcohol intake, traumatic brain injury (TBI), and air pollution. The original nine risk factors were not completing secondary education; hypertension; obesity; hearing loss; smoking; depression; physical inactivity; social isolation; and diabetes. Together, these 12 risk factors are estimated to account for 40% of the world’s dementia cases.
“We knew in 2017 when we published our first report with the nine risk factors that they would only be part of the story and that several other factors would likely be involved,” said lead author Gill Livingston, MD, professor, University College London (England). “We now have more published data giving enough evidence” to justify adding the three new factors to the list, she said.
The report includes the following nine recommendations for policymakers and individuals to prevent risk for dementia in the general population:
- Aim to maintain systolic blood pressure of 130 mm Hg or less in midlife from around age 40 years.
- Encourage use of hearing aids for hearing loss, and reduce hearing loss by protecting ears from high noise levels.
- Reduce exposure to air pollution and second-hand tobacco smoke.
- Prevent , particularly by targeting high-risk occupations and transport.
- Prevent alcohol misuse and limit drinking to less than 21 units per week.
- Stop smoking and support individuals to stop smoking, which the authors stress is beneficial at any age.
- Provide all children with primary and secondary education.
- Lead an active life into midlife and possibly later life.
- Reduce obesity and diabetes.
The report also summarizes the evidence supporting the three new risk factors for dementia.
TBI is usually caused by car, motorcycle, and bicycle injuries; military exposures; boxing, horse riding, and other recreational sports; firearms; and falls. The report notes that a single severe TBI is associated in humans and in mouse models with widespread hyperphosphorylated tau pathology. It also cites several nationwide studies that show that TBI is linked with a significantly increased risk for long-term dementia.
“We are not advising against partaking in sports, as playing sports is healthy. But we are urging people to take precautions to protect themselves properly,” Dr. Livingston said.
For excessive alcohol consumption, the report states that an “increasing body of evidence is emerging on alcohol’s complex relationship with cognition and dementia outcomes from a variety of sources including detailed cohorts and large-scale record-based studies.” One French study, which included more than 31 million individuals admitted to the hospital, showed that alcohol use disorders were associated with a threefold increased dementia risk. However, other studies have suggested that moderate drinking may be protective.
“We are not saying it is bad to drink, but we are saying it is bad to drink more than 21 units a week,” Dr. Livingston noted.
On air pollution, the report notes that in animal studies, airborne particulate pollutants have been found to accelerate neurodegenerative processes. Also, high nitrogen dioxide concentrations, fine ambient particulate matter from traffic exhaust, and residential wood burning have been shown in past research to be associated with increased dementia incidence.
“While we need international policy on reducing air pollution, individuals can take some action to reduce their risk,” Dr. Livingston said. For example, she suggested avoiding walking right next to busy roads and instead walking “a few streets back if possible.”
Hearing loss
The researchers assessed how much each risk factor contributes to dementia, expressed as the population-attributable fraction (PAF). Hearing loss had the greatest effect, accounting for an estimated 8.2% of dementia cases. This was followed by lower education levels in young people (7.1%) and smoking (5.2%).
Dr. Livingston noted that the evidence that hearing loss is one of the most important risk factors for dementia is very strong. New studies show that correcting hearing loss with hearing aids negates any increased risk.
Hearing loss “has both a high relative risk for dementia and is a common problem, so it contributes a significant amount to dementia cases. This is really something that we can reduce relatively easily by encouraging use of hearing aids. They need to be made more accessible, more comfortable, and more acceptable,” she said.
“This could make a huge difference in reducing dementia cases in the future,” Dr. Livingston added.
Other risk factors for which the evidence base has strengthened since the 2017 report include systolic blood pressure, social interaction, and early-life education.
Dr. Livingston noted that the SPRINT MIND trial showed that aiming for a target systolic blood pressure of 120 mm Hg reduced risk for future mild cognitive impairment. “Before, we thought under 140 was the target, but now are recommending under 130 to reduce risks of dementia,” she said.
Evidence on social interaction “has been very consistent, and we now have more certainty on this. It is now well established that increased social interaction in midlife reduces dementia in late life,” said Dr. Livingston.
On the benefits of education in the young, she noted that it has been known for some time that education for individuals younger than 11 years is important in reducing later-life dementia. However, it is now thought that education to the age of 20 also makes a difference.
“While keeping the brain active in later years has some positive effects, increasing brain activity in young people seems to be more important. This is probably because of the better plasticity of the brain in the young,” she said.
Sleep and diet
Two risk factors that have not made it onto the list are diet and sleep. “While there has also been a lot more data published on nutrition and sleep with regard to dementia in the last few years, we didn’t think the evidence stacked up enough to include these on the list of modifiable risk factors,” Dr. Livingston said.
The report cites studies that suggest that both more sleep and less sleep are associated with increased risk for dementia, which the authors thought did not make “biological sense.” In addition, other underlying factors involved in sleep, such as depression, apathy, and different sleep patterns, may be symptoms of early dementia.
More data have been published on diet and dementia, “but there isn’t any individual vitamin deficit that is associated with the condition. The evidence is quite clear on that,” Dr. Livingston said. “Global diets, such as the Mediterranean or Nordic diets, can probably make a difference, but there doesn’t seem to be any one particular element that is needed,” she noted.
“We just recommend to eat a healthy diet and stay a healthy weight. Diet is very connected to economic circumstances and so very difficult to separate out as a risk factor. We do think it is linked, but we are not convinced enough to put it in the model,” she added.
Among other key information that has become available since 2017, Dr. Livingston highlighted new data showing that dementia is more common in less privileged populations, including Black and minority ethnic groups and low- and middle-income countries.
Although dementia was traditionally considered a disease of high-income countries, that has now been shown not to be the case. “People in low- and middle-income countries are now living longer and so are developing dementia more, and they have higher rates of many of the risk factors, including smoking and low education levels. There is a huge potential for prevention in these countries,” said Dr. Livingston.
She also highlighted new evidence showing that patients with dementia do not do well when admitted to the hospital. “So we need to do more to keep them well at home,” she said.
COVID-19 advice
The report also has a section on COVID-19. It points out that patients with dementia are particularly vulnerable to the disease because of their age, multimorbidities, and difficulties in maintaining physical distancing. Death certificates from the United Kingdom indicate that dementia and Alzheimer’s disease were the most common underlying conditions (present in 25.6% of all deaths involving COVID-19).
The situation is particularly concerning in care homes. In one U.S. study, nursing home residents living with dementia made up 52% of COVID-19 cases, yet they accounted for 72% of all deaths (increased risk, 1.7), the commission reported.
The authors recommended rigorous public health measures, such as protective equipment and hygiene, not moving staff or residents between care homes, and not admitting new residents when their COVID-19 status is unknown. The report also recommends regular testing of staff in care homes and the provision of oxygen therapy at the home to avoid hospital admission.
It is also important to reduce isolation by providing the necessary equipment to relatives and offering them brief training on how to protect themselves and others from COVID-19 so that they can visit their relatives with dementia in nursing homes safely when it is allowed.
“Most comprehensive overview to date”
Alzheimer’s Research UK welcomed the new report. “This is the most comprehensive overview into dementia risk to date, building on previous work by this commission and moving our understanding forward,” Rosa Sancho, PhD, head of research at the charity, said.
“This report underlines the importance of acting at a personal and policy level to reduce dementia risk. With Alzheimer’s Research UK’s Dementia Attitudes Monitor showing just a third of people think it’s possible to reduce their risk of developing dementia, there’s clearly much to do here to increase people’s awareness of the steps they can take,” Dr. Sancho said.
She added that, although there is “no surefire way of preventing dementia,” the best way to keep a brain healthy as it ages is for an individual to stay physically and mentally active, eat a healthy balanced diet, not smoke, drink only within the recommended limits, and keep weight, cholesterol level, and blood pressure in check. “With no treatments yet able to slow or stop the onset of dementia, taking action to reduce these risks is an important part of our strategy for tackling the condition,” Dr. Sancho said.
The Lancet Commission is partnered by University College London, the Alzheimer’s Society UK, the Economic and Social Research Council, and Alzheimer’s Research UK, which funded fares, accommodation, and food for the commission meeting but had no role in the writing of the manuscript or the decision to submit it for publication.
A version of this article originally appeared on Medscape.com.
according to an update of the Lancet Commission on Dementia Prevention, Intervention, and Care.
The original report, published in 2017, identified nine modifiable risk factors that were estimated to be responsible for one-third of dementia cases. The commission has now added three new modifiable risk factors to the list.
“We reconvened the 2017 Lancet Commission on Dementia Prevention, Intervention, and Care to identify the evidence for advances likely to have the greatest impact since our 2017 paper,” the authors wrote.
The 2020 report was presented at the virtual annual meeting of the Alzheimer’s Association International Conference (AAIC) 2020 and also was published online July 30 in the Lancet.
Alcohol, TBI, air pollution
The three new risk factors that have been added in the latest update are excessive alcohol intake, traumatic brain injury (TBI), and air pollution. The original nine risk factors were not completing secondary education; hypertension; obesity; hearing loss; smoking; depression; physical inactivity; social isolation; and diabetes. Together, these 12 risk factors are estimated to account for 40% of the world’s dementia cases.
“We knew in 2017 when we published our first report with the nine risk factors that they would only be part of the story and that several other factors would likely be involved,” said lead author Gill Livingston, MD, professor, University College London (England). “We now have more published data giving enough evidence” to justify adding the three new factors to the list, she said.
The report includes the following nine recommendations for policymakers and individuals to prevent risk for dementia in the general population:
- Aim to maintain systolic blood pressure of 130 mm Hg or less in midlife from around age 40 years.
- Encourage use of hearing aids for hearing loss, and reduce hearing loss by protecting ears from high noise levels.
- Reduce exposure to air pollution and second-hand tobacco smoke.
- Prevent , particularly by targeting high-risk occupations and transport.
- Prevent alcohol misuse and limit drinking to less than 21 units per week.
- Stop smoking and support individuals to stop smoking, which the authors stress is beneficial at any age.
- Provide all children with primary and secondary education.
- Lead an active life into midlife and possibly later life.
- Reduce obesity and diabetes.
The report also summarizes the evidence supporting the three new risk factors for dementia.
TBI is usually caused by car, motorcycle, and bicycle injuries; military exposures; boxing, horse riding, and other recreational sports; firearms; and falls. The report notes that a single severe TBI is associated in humans and in mouse models with widespread hyperphosphorylated tau pathology. It also cites several nationwide studies that show that TBI is linked with a significantly increased risk for long-term dementia.
“We are not advising against partaking in sports, as playing sports is healthy. But we are urging people to take precautions to protect themselves properly,” Dr. Livingston said.
For excessive alcohol consumption, the report states that an “increasing body of evidence is emerging on alcohol’s complex relationship with cognition and dementia outcomes from a variety of sources including detailed cohorts and large-scale record-based studies.” One French study, which included more than 31 million individuals admitted to the hospital, showed that alcohol use disorders were associated with a threefold increased dementia risk. However, other studies have suggested that moderate drinking may be protective.
“We are not saying it is bad to drink, but we are saying it is bad to drink more than 21 units a week,” Dr. Livingston noted.
On air pollution, the report notes that in animal studies, airborne particulate pollutants have been found to accelerate neurodegenerative processes. Also, high nitrogen dioxide concentrations, fine ambient particulate matter from traffic exhaust, and residential wood burning have been shown in past research to be associated with increased dementia incidence.
“While we need international policy on reducing air pollution, individuals can take some action to reduce their risk,” Dr. Livingston said. For example, she suggested avoiding walking right next to busy roads and instead walking “a few streets back if possible.”
Hearing loss
The researchers assessed how much each risk factor contributes to dementia, expressed as the population-attributable fraction (PAF). Hearing loss had the greatest effect, accounting for an estimated 8.2% of dementia cases. This was followed by lower education levels in young people (7.1%) and smoking (5.2%).
Dr. Livingston noted that the evidence that hearing loss is one of the most important risk factors for dementia is very strong. New studies show that correcting hearing loss with hearing aids negates any increased risk.
Hearing loss “has both a high relative risk for dementia and is a common problem, so it contributes a significant amount to dementia cases. This is really something that we can reduce relatively easily by encouraging use of hearing aids. They need to be made more accessible, more comfortable, and more acceptable,” she said.
“This could make a huge difference in reducing dementia cases in the future,” Dr. Livingston added.
Other risk factors for which the evidence base has strengthened since the 2017 report include systolic blood pressure, social interaction, and early-life education.
Dr. Livingston noted that the SPRINT MIND trial showed that aiming for a target systolic blood pressure of 120 mm Hg reduced risk for future mild cognitive impairment. “Before, we thought under 140 was the target, but now are recommending under 130 to reduce risks of dementia,” she said.
Evidence on social interaction “has been very consistent, and we now have more certainty on this. It is now well established that increased social interaction in midlife reduces dementia in late life,” said Dr. Livingston.
On the benefits of education in the young, she noted that it has been known for some time that education for individuals younger than 11 years is important in reducing later-life dementia. However, it is now thought that education to the age of 20 also makes a difference.
“While keeping the brain active in later years has some positive effects, increasing brain activity in young people seems to be more important. This is probably because of the better plasticity of the brain in the young,” she said.
Sleep and diet
Two risk factors that have not made it onto the list are diet and sleep. “While there has also been a lot more data published on nutrition and sleep with regard to dementia in the last few years, we didn’t think the evidence stacked up enough to include these on the list of modifiable risk factors,” Dr. Livingston said.
The report cites studies that suggest that both more sleep and less sleep are associated with increased risk for dementia, which the authors thought did not make “biological sense.” In addition, other underlying factors involved in sleep, such as depression, apathy, and different sleep patterns, may be symptoms of early dementia.
More data have been published on diet and dementia, “but there isn’t any individual vitamin deficit that is associated with the condition. The evidence is quite clear on that,” Dr. Livingston said. “Global diets, such as the Mediterranean or Nordic diets, can probably make a difference, but there doesn’t seem to be any one particular element that is needed,” she noted.
“We just recommend to eat a healthy diet and stay a healthy weight. Diet is very connected to economic circumstances and so very difficult to separate out as a risk factor. We do think it is linked, but we are not convinced enough to put it in the model,” she added.
Among other key information that has become available since 2017, Dr. Livingston highlighted new data showing that dementia is more common in less privileged populations, including Black and minority ethnic groups and low- and middle-income countries.
Although dementia was traditionally considered a disease of high-income countries, that has now been shown not to be the case. “People in low- and middle-income countries are now living longer and so are developing dementia more, and they have higher rates of many of the risk factors, including smoking and low education levels. There is a huge potential for prevention in these countries,” said Dr. Livingston.
She also highlighted new evidence showing that patients with dementia do not do well when admitted to the hospital. “So we need to do more to keep them well at home,” she said.
COVID-19 advice
The report also has a section on COVID-19. It points out that patients with dementia are particularly vulnerable to the disease because of their age, multimorbidities, and difficulties in maintaining physical distancing. Death certificates from the United Kingdom indicate that dementia and Alzheimer’s disease were the most common underlying conditions (present in 25.6% of all deaths involving COVID-19).
The situation is particularly concerning in care homes. In one U.S. study, nursing home residents living with dementia made up 52% of COVID-19 cases, yet they accounted for 72% of all deaths (increased risk, 1.7), the commission reported.
The authors recommended rigorous public health measures, such as protective equipment and hygiene, not moving staff or residents between care homes, and not admitting new residents when their COVID-19 status is unknown. The report also recommends regular testing of staff in care homes and the provision of oxygen therapy at the home to avoid hospital admission.
It is also important to reduce isolation by providing the necessary equipment to relatives and offering them brief training on how to protect themselves and others from COVID-19 so that they can visit their relatives with dementia in nursing homes safely when it is allowed.
“Most comprehensive overview to date”
Alzheimer’s Research UK welcomed the new report. “This is the most comprehensive overview into dementia risk to date, building on previous work by this commission and moving our understanding forward,” Rosa Sancho, PhD, head of research at the charity, said.
“This report underlines the importance of acting at a personal and policy level to reduce dementia risk. With Alzheimer’s Research UK’s Dementia Attitudes Monitor showing just a third of people think it’s possible to reduce their risk of developing dementia, there’s clearly much to do here to increase people’s awareness of the steps they can take,” Dr. Sancho said.
She added that, although there is “no surefire way of preventing dementia,” the best way to keep a brain healthy as it ages is for an individual to stay physically and mentally active, eat a healthy balanced diet, not smoke, drink only within the recommended limits, and keep weight, cholesterol level, and blood pressure in check. “With no treatments yet able to slow or stop the onset of dementia, taking action to reduce these risks is an important part of our strategy for tackling the condition,” Dr. Sancho said.
The Lancet Commission is partnered by University College London, the Alzheimer’s Society UK, the Economic and Social Research Council, and Alzheimer’s Research UK, which funded fares, accommodation, and food for the commission meeting but had no role in the writing of the manuscript or the decision to submit it for publication.
A version of this article originally appeared on Medscape.com.
according to an update of the Lancet Commission on Dementia Prevention, Intervention, and Care.
The original report, published in 2017, identified nine modifiable risk factors that were estimated to be responsible for one-third of dementia cases. The commission has now added three new modifiable risk factors to the list.
“We reconvened the 2017 Lancet Commission on Dementia Prevention, Intervention, and Care to identify the evidence for advances likely to have the greatest impact since our 2017 paper,” the authors wrote.
The 2020 report was presented at the virtual annual meeting of the Alzheimer’s Association International Conference (AAIC) 2020 and also was published online July 30 in the Lancet.
Alcohol, TBI, air pollution
The three new risk factors that have been added in the latest update are excessive alcohol intake, traumatic brain injury (TBI), and air pollution. The original nine risk factors were not completing secondary education; hypertension; obesity; hearing loss; smoking; depression; physical inactivity; social isolation; and diabetes. Together, these 12 risk factors are estimated to account for 40% of the world’s dementia cases.
“We knew in 2017 when we published our first report with the nine risk factors that they would only be part of the story and that several other factors would likely be involved,” said lead author Gill Livingston, MD, professor, University College London (England). “We now have more published data giving enough evidence” to justify adding the three new factors to the list, she said.
The report includes the following nine recommendations for policymakers and individuals to prevent risk for dementia in the general population:
- Aim to maintain systolic blood pressure of 130 mm Hg or less in midlife from around age 40 years.
- Encourage use of hearing aids for hearing loss, and reduce hearing loss by protecting ears from high noise levels.
- Reduce exposure to air pollution and second-hand tobacco smoke.
- Prevent , particularly by targeting high-risk occupations and transport.
- Prevent alcohol misuse and limit drinking to less than 21 units per week.
- Stop smoking and support individuals to stop smoking, which the authors stress is beneficial at any age.
- Provide all children with primary and secondary education.
- Lead an active life into midlife and possibly later life.
- Reduce obesity and diabetes.
The report also summarizes the evidence supporting the three new risk factors for dementia.
TBI is usually caused by car, motorcycle, and bicycle injuries; military exposures; boxing, horse riding, and other recreational sports; firearms; and falls. The report notes that a single severe TBI is associated in humans and in mouse models with widespread hyperphosphorylated tau pathology. It also cites several nationwide studies that show that TBI is linked with a significantly increased risk for long-term dementia.
“We are not advising against partaking in sports, as playing sports is healthy. But we are urging people to take precautions to protect themselves properly,” Dr. Livingston said.
For excessive alcohol consumption, the report states that an “increasing body of evidence is emerging on alcohol’s complex relationship with cognition and dementia outcomes from a variety of sources including detailed cohorts and large-scale record-based studies.” One French study, which included more than 31 million individuals admitted to the hospital, showed that alcohol use disorders were associated with a threefold increased dementia risk. However, other studies have suggested that moderate drinking may be protective.
“We are not saying it is bad to drink, but we are saying it is bad to drink more than 21 units a week,” Dr. Livingston noted.
On air pollution, the report notes that in animal studies, airborne particulate pollutants have been found to accelerate neurodegenerative processes. Also, high nitrogen dioxide concentrations, fine ambient particulate matter from traffic exhaust, and residential wood burning have been shown in past research to be associated with increased dementia incidence.
“While we need international policy on reducing air pollution, individuals can take some action to reduce their risk,” Dr. Livingston said. For example, she suggested avoiding walking right next to busy roads and instead walking “a few streets back if possible.”
Hearing loss
The researchers assessed how much each risk factor contributes to dementia, expressed as the population-attributable fraction (PAF). Hearing loss had the greatest effect, accounting for an estimated 8.2% of dementia cases. This was followed by lower education levels in young people (7.1%) and smoking (5.2%).
Dr. Livingston noted that the evidence that hearing loss is one of the most important risk factors for dementia is very strong. New studies show that correcting hearing loss with hearing aids negates any increased risk.
Hearing loss “has both a high relative risk for dementia and is a common problem, so it contributes a significant amount to dementia cases. This is really something that we can reduce relatively easily by encouraging use of hearing aids. They need to be made more accessible, more comfortable, and more acceptable,” she said.
“This could make a huge difference in reducing dementia cases in the future,” Dr. Livingston added.
Other risk factors for which the evidence base has strengthened since the 2017 report include systolic blood pressure, social interaction, and early-life education.
Dr. Livingston noted that the SPRINT MIND trial showed that aiming for a target systolic blood pressure of 120 mm Hg reduced risk for future mild cognitive impairment. “Before, we thought under 140 was the target, but now are recommending under 130 to reduce risks of dementia,” she said.
Evidence on social interaction “has been very consistent, and we now have more certainty on this. It is now well established that increased social interaction in midlife reduces dementia in late life,” said Dr. Livingston.
On the benefits of education in the young, she noted that it has been known for some time that education for individuals younger than 11 years is important in reducing later-life dementia. However, it is now thought that education to the age of 20 also makes a difference.
“While keeping the brain active in later years has some positive effects, increasing brain activity in young people seems to be more important. This is probably because of the better plasticity of the brain in the young,” she said.
Sleep and diet
Two risk factors that have not made it onto the list are diet and sleep. “While there has also been a lot more data published on nutrition and sleep with regard to dementia in the last few years, we didn’t think the evidence stacked up enough to include these on the list of modifiable risk factors,” Dr. Livingston said.
The report cites studies that suggest that both more sleep and less sleep are associated with increased risk for dementia, which the authors thought did not make “biological sense.” In addition, other underlying factors involved in sleep, such as depression, apathy, and different sleep patterns, may be symptoms of early dementia.
More data have been published on diet and dementia, “but there isn’t any individual vitamin deficit that is associated with the condition. The evidence is quite clear on that,” Dr. Livingston said. “Global diets, such as the Mediterranean or Nordic diets, can probably make a difference, but there doesn’t seem to be any one particular element that is needed,” she noted.
“We just recommend to eat a healthy diet and stay a healthy weight. Diet is very connected to economic circumstances and so very difficult to separate out as a risk factor. We do think it is linked, but we are not convinced enough to put it in the model,” she added.
Among other key information that has become available since 2017, Dr. Livingston highlighted new data showing that dementia is more common in less privileged populations, including Black and minority ethnic groups and low- and middle-income countries.
Although dementia was traditionally considered a disease of high-income countries, that has now been shown not to be the case. “People in low- and middle-income countries are now living longer and so are developing dementia more, and they have higher rates of many of the risk factors, including smoking and low education levels. There is a huge potential for prevention in these countries,” said Dr. Livingston.
She also highlighted new evidence showing that patients with dementia do not do well when admitted to the hospital. “So we need to do more to keep them well at home,” she said.
COVID-19 advice
The report also has a section on COVID-19. It points out that patients with dementia are particularly vulnerable to the disease because of their age, multimorbidities, and difficulties in maintaining physical distancing. Death certificates from the United Kingdom indicate that dementia and Alzheimer’s disease were the most common underlying conditions (present in 25.6% of all deaths involving COVID-19).
The situation is particularly concerning in care homes. In one U.S. study, nursing home residents living with dementia made up 52% of COVID-19 cases, yet they accounted for 72% of all deaths (increased risk, 1.7), the commission reported.
The authors recommended rigorous public health measures, such as protective equipment and hygiene, not moving staff or residents between care homes, and not admitting new residents when their COVID-19 status is unknown. The report also recommends regular testing of staff in care homes and the provision of oxygen therapy at the home to avoid hospital admission.
It is also important to reduce isolation by providing the necessary equipment to relatives and offering them brief training on how to protect themselves and others from COVID-19 so that they can visit their relatives with dementia in nursing homes safely when it is allowed.
“Most comprehensive overview to date”
Alzheimer’s Research UK welcomed the new report. “This is the most comprehensive overview into dementia risk to date, building on previous work by this commission and moving our understanding forward,” Rosa Sancho, PhD, head of research at the charity, said.
“This report underlines the importance of acting at a personal and policy level to reduce dementia risk. With Alzheimer’s Research UK’s Dementia Attitudes Monitor showing just a third of people think it’s possible to reduce their risk of developing dementia, there’s clearly much to do here to increase people’s awareness of the steps they can take,” Dr. Sancho said.
She added that, although there is “no surefire way of preventing dementia,” the best way to keep a brain healthy as it ages is for an individual to stay physically and mentally active, eat a healthy balanced diet, not smoke, drink only within the recommended limits, and keep weight, cholesterol level, and blood pressure in check. “With no treatments yet able to slow or stop the onset of dementia, taking action to reduce these risks is an important part of our strategy for tackling the condition,” Dr. Sancho said.
The Lancet Commission is partnered by University College London, the Alzheimer’s Society UK, the Economic and Social Research Council, and Alzheimer’s Research UK, which funded fares, accommodation, and food for the commission meeting but had no role in the writing of the manuscript or the decision to submit it for publication.
A version of this article originally appeared on Medscape.com.
From AAIC 2020
Cognitive impairment in 9/11 responders tied to brain atrophy
, suggest results from the first structural neuroimaging study conducted in this population. The study clarifies that a neurodegenerative condition is present in first responders who experience cognitive impairment in midlife, which “is incredibly important to know,” said lead author Sean Clouston, PhD, of Stony Brook (N.Y.) University.
The findings were presented at the virtual annual meeting of the Alzheimer’s Association International Conference and were published online in Alzheimer’s and Dementia: Diagnosis, Assessment and Disease Monitoring.
Brain atrophy in midlife
During the 9/11 attack and in its aftermath, WTC responders were exposed to a range of inhaled neurotoxicants, as well as extreme psychosocial stressors. A growing number of WTC responders who are now in their 50s and early 60s are experiencing early cognitive impairment.
Using MRI, the investigators examined cortical thickness (CTX), a surrogate marker for neurodegeneration, in 99 mostly male WTC responders; 48 had cognitive impairment, and 51 did not. The age range of the participants was 45 to 65 years, a range during which cortical atrophy is uncommon in the general population, the researchers noted.
Compared with cognitively normal responders, those with cognitive impairment were found to have reductions in CTX across the whole brain and across 21 of 34 cortical regions, including frontal, temporal, and occipital lobes.
In both cognitively impaired and cognitively unimpaired WTC responders, CTX was reduced in the entorhinal and temporal cortices compared with normative data, but reductions were greater with cognitive impairment. Posttraumatic distress disorder (PTSD) status was not predictive of a reduction in CTX across groups.
Dr. Clouston said the level of reduction in CTX in many responders is similar to that commonly found in patients with dementia and may reflect early-stage dementia occurring in midlife.
Limitations of the study include the small sample size, the cross-sectional design, the unique nature of the exposure, and a lack of a non-WTC external control group.
‘Illuminating’ study
Keith N. Fargo, PhD, director of scientific engagement for the Alzheimer’s Association, called the findings “interesting and illuminating” but cautioned that it is not possible to show cause and effect with this type of study.
“We also don’t know when cortical thinning might have started or how quickly it might be progressing,” Dr. Fargo said in an interview.
He noted that the pattern of cortical thinning is “somewhat consistent with what we see among people who live with high levels of air pollution, which is an emerging risk factor for Alzheimer’s disease and other dementias.”
The Lancet Commission on Dementia Prevention, Intervention, and Care added air pollution to its list of modifiable risk factors for dementia, which was recently updated.
Clinicians “need to be aware that their middle-aged 9/11 first responders are at a higher risk level for cognitive impairment, as well as PTSD and depression,” Dr. Fargo said.
The study was funded by the Centers for Disease Control and Prevention and the National Institute on Aging. Dr. Clouston and Dr. Fargo have reported no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
, suggest results from the first structural neuroimaging study conducted in this population. The study clarifies that a neurodegenerative condition is present in first responders who experience cognitive impairment in midlife, which “is incredibly important to know,” said lead author Sean Clouston, PhD, of Stony Brook (N.Y.) University.
The findings were presented at the virtual annual meeting of the Alzheimer’s Association International Conference and were published online in Alzheimer’s and Dementia: Diagnosis, Assessment and Disease Monitoring.
Brain atrophy in midlife
During the 9/11 attack and in its aftermath, WTC responders were exposed to a range of inhaled neurotoxicants, as well as extreme psychosocial stressors. A growing number of WTC responders who are now in their 50s and early 60s are experiencing early cognitive impairment.
Using MRI, the investigators examined cortical thickness (CTX), a surrogate marker for neurodegeneration, in 99 mostly male WTC responders; 48 had cognitive impairment, and 51 did not. The age range of the participants was 45 to 65 years, a range during which cortical atrophy is uncommon in the general population, the researchers noted.
Compared with cognitively normal responders, those with cognitive impairment were found to have reductions in CTX across the whole brain and across 21 of 34 cortical regions, including frontal, temporal, and occipital lobes.
In both cognitively impaired and cognitively unimpaired WTC responders, CTX was reduced in the entorhinal and temporal cortices compared with normative data, but reductions were greater with cognitive impairment. Posttraumatic distress disorder (PTSD) status was not predictive of a reduction in CTX across groups.
Dr. Clouston said the level of reduction in CTX in many responders is similar to that commonly found in patients with dementia and may reflect early-stage dementia occurring in midlife.
Limitations of the study include the small sample size, the cross-sectional design, the unique nature of the exposure, and a lack of a non-WTC external control group.
‘Illuminating’ study
Keith N. Fargo, PhD, director of scientific engagement for the Alzheimer’s Association, called the findings “interesting and illuminating” but cautioned that it is not possible to show cause and effect with this type of study.
“We also don’t know when cortical thinning might have started or how quickly it might be progressing,” Dr. Fargo said in an interview.
He noted that the pattern of cortical thinning is “somewhat consistent with what we see among people who live with high levels of air pollution, which is an emerging risk factor for Alzheimer’s disease and other dementias.”
The Lancet Commission on Dementia Prevention, Intervention, and Care added air pollution to its list of modifiable risk factors for dementia, which was recently updated.
Clinicians “need to be aware that their middle-aged 9/11 first responders are at a higher risk level for cognitive impairment, as well as PTSD and depression,” Dr. Fargo said.
The study was funded by the Centers for Disease Control and Prevention and the National Institute on Aging. Dr. Clouston and Dr. Fargo have reported no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
, suggest results from the first structural neuroimaging study conducted in this population. The study clarifies that a neurodegenerative condition is present in first responders who experience cognitive impairment in midlife, which “is incredibly important to know,” said lead author Sean Clouston, PhD, of Stony Brook (N.Y.) University.
The findings were presented at the virtual annual meeting of the Alzheimer’s Association International Conference and were published online in Alzheimer’s and Dementia: Diagnosis, Assessment and Disease Monitoring.
Brain atrophy in midlife
During the 9/11 attack and in its aftermath, WTC responders were exposed to a range of inhaled neurotoxicants, as well as extreme psychosocial stressors. A growing number of WTC responders who are now in their 50s and early 60s are experiencing early cognitive impairment.
Using MRI, the investigators examined cortical thickness (CTX), a surrogate marker for neurodegeneration, in 99 mostly male WTC responders; 48 had cognitive impairment, and 51 did not. The age range of the participants was 45 to 65 years, a range during which cortical atrophy is uncommon in the general population, the researchers noted.
Compared with cognitively normal responders, those with cognitive impairment were found to have reductions in CTX across the whole brain and across 21 of 34 cortical regions, including frontal, temporal, and occipital lobes.
In both cognitively impaired and cognitively unimpaired WTC responders, CTX was reduced in the entorhinal and temporal cortices compared with normative data, but reductions were greater with cognitive impairment. Posttraumatic distress disorder (PTSD) status was not predictive of a reduction in CTX across groups.
Dr. Clouston said the level of reduction in CTX in many responders is similar to that commonly found in patients with dementia and may reflect early-stage dementia occurring in midlife.
Limitations of the study include the small sample size, the cross-sectional design, the unique nature of the exposure, and a lack of a non-WTC external control group.
‘Illuminating’ study
Keith N. Fargo, PhD, director of scientific engagement for the Alzheimer’s Association, called the findings “interesting and illuminating” but cautioned that it is not possible to show cause and effect with this type of study.
“We also don’t know when cortical thinning might have started or how quickly it might be progressing,” Dr. Fargo said in an interview.
He noted that the pattern of cortical thinning is “somewhat consistent with what we see among people who live with high levels of air pollution, which is an emerging risk factor for Alzheimer’s disease and other dementias.”
The Lancet Commission on Dementia Prevention, Intervention, and Care added air pollution to its list of modifiable risk factors for dementia, which was recently updated.
Clinicians “need to be aware that their middle-aged 9/11 first responders are at a higher risk level for cognitive impairment, as well as PTSD and depression,” Dr. Fargo said.
The study was funded by the Centers for Disease Control and Prevention and the National Institute on Aging. Dr. Clouston and Dr. Fargo have reported no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
From AAIC 2020
Plasma exchange is ‘encouraging’ as a novel Alzheimer’s disease treatment
Results from the phase 2b/3 AMBAR study showed that the treatment, which aims to remove amyloid-beta (Abeta) from plasma, was associated with a 60% decrease in functional and cognitive decline in patients with moderate Alzheimer’s disease.
The reduction in cognitive decline uncovered by the study is more striking than that reported for other investigational treatments targeting Abeta, such as monoclonal antibodies, said coinvestigator Antonio Páez, MD, medical director of the AMBAR program, Alzheimer’s Research Group, Grifols, Barcelona.
The results “open a new path for the development of plasma protein replacement therapies not only in Alzheimer’s disease but also in other degenerative diseases that we are planning to investigate,” Dr. Páez said.
The findings were presented at the virtual annual meeting of the Alzheimer’s Association International Conference and were simultaneously published in Alzheimer’s and Dementia.
Removing amyloid
Plasma exchange treatments, which have been available for several decades, are used to treat a range of neurologic, immunologic, and metabolic disorders. The treatment involves plasmapheresis, whereby plasma is separated from blood cells (red blood cells, white blood cells, platelets, etc) and toxic substances are removed. The albumin in plasma, to which plasma Abeta is bound, is replaced with a fresh commercial albumin product made from plasma from healthy donors.
“Our initial hypothesis was that, by removing albumin together with Abeta and substituting it with newer albumin periodically, we may be removing Abeta from the cerebrospinal fluid and eventually from the brain,” Dr. Páez said.
The AMBAR study included 347 men and women aged 55-85 years with probable Alzheimer’s disease dementia who were enrolled at 41 sites in Spain and the United States. All were diagnosed with mild Alzheimer’s disease, as shown by a baseline Mini-Mental State Examination score of 22-26, or moderate Alzheimer’s disease, having a baseline MMSE score of 18-21.
Investigators randomly assigned the participants to four groups; one group received placebo, and each of the other three treatment arms received different doses of albumin and intravenous immunoglobulin (IVIg) replacement.
During the first 6-week study phase, patients received weekly sham or conventional plasma exchange treatments of 2.5-3 liters of plasma, which Dr. Páez referred to as the “intensive-treatment phase to remove as much Abeta as possible.”
This was followed by a 12-month maintenance phase, which involved monthly low-volume (700-800 mL) plasma exchange or sham treatments.
Although the volume of plasma removed was the same in all three active-treatment groups, the amount of albumin and IVIg that was subsequently replaced varied. In one group, the same amount of albumin and IVIg that was removed was replaced; in another, half the amount removed was replaced; and in the third, only albumin was replaced.
The researchers collected cerebrospinal fluid (CSF) samples at baseline and after each treatment period. They assessed Abeta40, Abeta42, total tau, and phosphorylated-tau biomarkers.
The two primary outcomes were change from baseline to 14 months in scores on the Alzheimer’s Disease Cooperative Study–Activities of Daily Living (ADCS-ADL) scale and the Alzheimer’s Disease Assessment Scale–Cognitive Subscale (ADAS-Cog).
Symptom reduction
Results showed a reduction in the progression of symptoms in the plasma exchange–treated patients for both primary endpoints.
The ADCS-ADL showed 52% less decline in the plasma exchange–treated group, compared with the placebo group (P = .03); the ADAS-Cog showed 66% less decline (P = 0.06). In the moderate group, both endpoints showed 61% less decline (P = .002 and .05, respectively).
There were no clear differences between the three active-treatment groups, “suggesting that any of them could be considered for further investigation,” said Dr. Páez.
Differences in baseline demographic characteristics did not appear to have an influence on the outcomes. ADAS-Cog was more than twice as effective as some candidate monoclonal antibodies targeting Abeta that are being investigated for Alzheimer’s disease, Dr. Páez noted.
Although the plasma exchange approach is relatively invasive, so too are monoclonal antibody therapies that are infused intravenously through a pump, he said. In addition, a low-volume plasma exchange maintenance treatment takes less than 2 hours, which is on a par with some monoclonal antibody treatments.
Key secondary outcomes
For both primary outcomes, changes were found in those with moderate but not mild Alzheimer’s disease, possibly because the ADAS-Cog was designed for patients with more severe symptoms and may not be sensitive enough for patients with better cognitive performance, said Dr. Páez.
However, the difference between mild and moderate Alzheimer’s disease did not hold up in post hoc analyses that included additional baseline characteristics, including amyloid and APOE e4 status.
“We observed that both mild and moderate subjects performed better than placebo even in the two coprimary endpoints,” Dr. Páez said. “It suggested that the differences between mild and moderate patients was not so apparent.”
The study’s key secondary outcomes included scores on the Clinical Dementia Rating Sum of Boxes (CDR-sb) and the Alzheimer’s Disease Cooperative Study–Clinical Global Impression of Change (ADCS-CGIC) scales. Treated patients scored better than the placebo group on both the CDR-sb (71% less decline, P = .002) and the ADCS-CGIC (100% less decline, P < .0001) scales.
For disease biomarkers in the moderate Alzheimer’s disease study population, levels of CSF Abeta42 and tau protein remained stable in the treated patients. In the placebo group, Abeta42 was decreased and tau protein increased. Dr. Páez explained that, if amyloid in the brain comes from the CSF, this process may take some time.
The findings suggest that more than one mechanism may be involved in the plasma exchange approach, such as changes in oxidation status and inflammatory mediators, the investigators noted.
Safety profile
About 28% of the participants dropped out of the study, which the researchers note is a rate similar to that reported in studies of solanezumab and other treatments in patients with Alzheimer’s disease. “The high percentage (72%) of patients who completed the study further supports that this procedure is feasible in mild to moderate Alzheimer’s disease,” the investigators wrote.
Overall, adverse events were similar to the known safety profile of plasma exchange procedures for other indications. The two most common adverse events were catheter local reactions and hypotension.
Almost 90% of the apheresis procedures were “uneventful,” the researchers reported. Two patients (0.6%) died during the study, which is similar to the low mortality rates reported elsewhere.
However, the investigators stressed that, because many patients with Alzheimer’s disease are in fragile health, plasma exchange treatments should be undertaken with caution, because of its invasive nature.
Dr. Páez noted that a possible limitation of this treatment approach is the availability of plasma for manufacturing plasma products. In the future, this plasma exchange approach might be combined with current and future Alzheimer’s disease therapies.
They are currently in discussions with the American Society for Apheresis, which develops guidelines for plasma exchange. After additional research, the investigators hope to eventually receive Food and Drug Administration approval of plasma exchange with albumin replacement as a treatment for Alzheimer’s disease.
Speculative, yet reasonable approach
Commenting on the research findings, Pierre N. Tariot, MD, director of Banner Alzheimer’s Institute and research professor of psychiatry at the University of Arizona, both in Phoenix, said the study is “meaningful and large enough” to “come close” to determining whether the therapy is safe and effective. “The fundamental rationale for this experimental approach, while speculative, is reasonable and certainly seems to be worth testing,” said Dr. Tariot, who was not involved with the research.
However, “there’s a decent chance” that not all trial participants had Alzheimer’s disease. Although some CSF amyloid measures suggest levels consistent with AD, “this is not conclusive,” he said.
In addition, “there’s a slightly low rate of apolipoprotein E4 allele carriage [in the current study], compared with most Alzheimer’s disease trials,” Dr. Tariot said.
He also pointed out that the trial failed to show statistical significance on both coprimary outcomes. “It’s unclear what health authorities, if presented with these data, would decide to do with the file.”
Although it was “encouraging” that secondary endpoints were supportive, the fact that they had greater statistical significance than some of the other objective measures “raises at least the potential for partial unblinding as a result of side effects,” said Dr. Tariot. It is also unclear why changes would be more evident in the moderate subpopulation.
The study was funded by Grifols. Dr. Páez is an employee of Grifols. Dr. Tariot reported no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
Results from the phase 2b/3 AMBAR study showed that the treatment, which aims to remove amyloid-beta (Abeta) from plasma, was associated with a 60% decrease in functional and cognitive decline in patients with moderate Alzheimer’s disease.
The reduction in cognitive decline uncovered by the study is more striking than that reported for other investigational treatments targeting Abeta, such as monoclonal antibodies, said coinvestigator Antonio Páez, MD, medical director of the AMBAR program, Alzheimer’s Research Group, Grifols, Barcelona.
The results “open a new path for the development of plasma protein replacement therapies not only in Alzheimer’s disease but also in other degenerative diseases that we are planning to investigate,” Dr. Páez said.
The findings were presented at the virtual annual meeting of the Alzheimer’s Association International Conference and were simultaneously published in Alzheimer’s and Dementia.
Removing amyloid
Plasma exchange treatments, which have been available for several decades, are used to treat a range of neurologic, immunologic, and metabolic disorders. The treatment involves plasmapheresis, whereby plasma is separated from blood cells (red blood cells, white blood cells, platelets, etc) and toxic substances are removed. The albumin in plasma, to which plasma Abeta is bound, is replaced with a fresh commercial albumin product made from plasma from healthy donors.
“Our initial hypothesis was that, by removing albumin together with Abeta and substituting it with newer albumin periodically, we may be removing Abeta from the cerebrospinal fluid and eventually from the brain,” Dr. Páez said.
The AMBAR study included 347 men and women aged 55-85 years with probable Alzheimer’s disease dementia who were enrolled at 41 sites in Spain and the United States. All were diagnosed with mild Alzheimer’s disease, as shown by a baseline Mini-Mental State Examination score of 22-26, or moderate Alzheimer’s disease, having a baseline MMSE score of 18-21.
Investigators randomly assigned the participants to four groups; one group received placebo, and each of the other three treatment arms received different doses of albumin and intravenous immunoglobulin (IVIg) replacement.
During the first 6-week study phase, patients received weekly sham or conventional plasma exchange treatments of 2.5-3 liters of plasma, which Dr. Páez referred to as the “intensive-treatment phase to remove as much Abeta as possible.”
This was followed by a 12-month maintenance phase, which involved monthly low-volume (700-800 mL) plasma exchange or sham treatments.
Although the volume of plasma removed was the same in all three active-treatment groups, the amount of albumin and IVIg that was subsequently replaced varied. In one group, the same amount of albumin and IVIg that was removed was replaced; in another, half the amount removed was replaced; and in the third, only albumin was replaced.
The researchers collected cerebrospinal fluid (CSF) samples at baseline and after each treatment period. They assessed Abeta40, Abeta42, total tau, and phosphorylated-tau biomarkers.
The two primary outcomes were change from baseline to 14 months in scores on the Alzheimer’s Disease Cooperative Study–Activities of Daily Living (ADCS-ADL) scale and the Alzheimer’s Disease Assessment Scale–Cognitive Subscale (ADAS-Cog).
Symptom reduction
Results showed a reduction in the progression of symptoms in the plasma exchange–treated patients for both primary endpoints.
The ADCS-ADL showed 52% less decline in the plasma exchange–treated group, compared with the placebo group (P = .03); the ADAS-Cog showed 66% less decline (P = 0.06). In the moderate group, both endpoints showed 61% less decline (P = .002 and .05, respectively).
There were no clear differences between the three active-treatment groups, “suggesting that any of them could be considered for further investigation,” said Dr. Páez.
Differences in baseline demographic characteristics did not appear to have an influence on the outcomes. ADAS-Cog was more than twice as effective as some candidate monoclonal antibodies targeting Abeta that are being investigated for Alzheimer’s disease, Dr. Páez noted.
Although the plasma exchange approach is relatively invasive, so too are monoclonal antibody therapies that are infused intravenously through a pump, he said. In addition, a low-volume plasma exchange maintenance treatment takes less than 2 hours, which is on a par with some monoclonal antibody treatments.
Key secondary outcomes
For both primary outcomes, changes were found in those with moderate but not mild Alzheimer’s disease, possibly because the ADAS-Cog was designed for patients with more severe symptoms and may not be sensitive enough for patients with better cognitive performance, said Dr. Páez.
However, the difference between mild and moderate Alzheimer’s disease did not hold up in post hoc analyses that included additional baseline characteristics, including amyloid and APOE e4 status.
“We observed that both mild and moderate subjects performed better than placebo even in the two coprimary endpoints,” Dr. Páez said. “It suggested that the differences between mild and moderate patients was not so apparent.”
The study’s key secondary outcomes included scores on the Clinical Dementia Rating Sum of Boxes (CDR-sb) and the Alzheimer’s Disease Cooperative Study–Clinical Global Impression of Change (ADCS-CGIC) scales. Treated patients scored better than the placebo group on both the CDR-sb (71% less decline, P = .002) and the ADCS-CGIC (100% less decline, P < .0001) scales.
For disease biomarkers in the moderate Alzheimer’s disease study population, levels of CSF Abeta42 and tau protein remained stable in the treated patients. In the placebo group, Abeta42 was decreased and tau protein increased. Dr. Páez explained that, if amyloid in the brain comes from the CSF, this process may take some time.
The findings suggest that more than one mechanism may be involved in the plasma exchange approach, such as changes in oxidation status and inflammatory mediators, the investigators noted.
Safety profile
About 28% of the participants dropped out of the study, which the researchers note is a rate similar to that reported in studies of solanezumab and other treatments in patients with Alzheimer’s disease. “The high percentage (72%) of patients who completed the study further supports that this procedure is feasible in mild to moderate Alzheimer’s disease,” the investigators wrote.
Overall, adverse events were similar to the known safety profile of plasma exchange procedures for other indications. The two most common adverse events were catheter local reactions and hypotension.
Almost 90% of the apheresis procedures were “uneventful,” the researchers reported. Two patients (0.6%) died during the study, which is similar to the low mortality rates reported elsewhere.
However, the investigators stressed that, because many patients with Alzheimer’s disease are in fragile health, plasma exchange treatments should be undertaken with caution, because of its invasive nature.
Dr. Páez noted that a possible limitation of this treatment approach is the availability of plasma for manufacturing plasma products. In the future, this plasma exchange approach might be combined with current and future Alzheimer’s disease therapies.
They are currently in discussions with the American Society for Apheresis, which develops guidelines for plasma exchange. After additional research, the investigators hope to eventually receive Food and Drug Administration approval of plasma exchange with albumin replacement as a treatment for Alzheimer’s disease.
Speculative, yet reasonable approach
Commenting on the research findings, Pierre N. Tariot, MD, director of Banner Alzheimer’s Institute and research professor of psychiatry at the University of Arizona, both in Phoenix, said the study is “meaningful and large enough” to “come close” to determining whether the therapy is safe and effective. “The fundamental rationale for this experimental approach, while speculative, is reasonable and certainly seems to be worth testing,” said Dr. Tariot, who was not involved with the research.
However, “there’s a decent chance” that not all trial participants had Alzheimer’s disease. Although some CSF amyloid measures suggest levels consistent with AD, “this is not conclusive,” he said.
In addition, “there’s a slightly low rate of apolipoprotein E4 allele carriage [in the current study], compared with most Alzheimer’s disease trials,” Dr. Tariot said.
He also pointed out that the trial failed to show statistical significance on both coprimary outcomes. “It’s unclear what health authorities, if presented with these data, would decide to do with the file.”
Although it was “encouraging” that secondary endpoints were supportive, the fact that they had greater statistical significance than some of the other objective measures “raises at least the potential for partial unblinding as a result of side effects,” said Dr. Tariot. It is also unclear why changes would be more evident in the moderate subpopulation.
The study was funded by Grifols. Dr. Páez is an employee of Grifols. Dr. Tariot reported no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
Results from the phase 2b/3 AMBAR study showed that the treatment, which aims to remove amyloid-beta (Abeta) from plasma, was associated with a 60% decrease in functional and cognitive decline in patients with moderate Alzheimer’s disease.
The reduction in cognitive decline uncovered by the study is more striking than that reported for other investigational treatments targeting Abeta, such as monoclonal antibodies, said coinvestigator Antonio Páez, MD, medical director of the AMBAR program, Alzheimer’s Research Group, Grifols, Barcelona.
The results “open a new path for the development of plasma protein replacement therapies not only in Alzheimer’s disease but also in other degenerative diseases that we are planning to investigate,” Dr. Páez said.
The findings were presented at the virtual annual meeting of the Alzheimer’s Association International Conference and were simultaneously published in Alzheimer’s and Dementia.
Removing amyloid
Plasma exchange treatments, which have been available for several decades, are used to treat a range of neurologic, immunologic, and metabolic disorders. The treatment involves plasmapheresis, whereby plasma is separated from blood cells (red blood cells, white blood cells, platelets, etc) and toxic substances are removed. The albumin in plasma, to which plasma Abeta is bound, is replaced with a fresh commercial albumin product made from plasma from healthy donors.
“Our initial hypothesis was that, by removing albumin together with Abeta and substituting it with newer albumin periodically, we may be removing Abeta from the cerebrospinal fluid and eventually from the brain,” Dr. Páez said.
The AMBAR study included 347 men and women aged 55-85 years with probable Alzheimer’s disease dementia who were enrolled at 41 sites in Spain and the United States. All were diagnosed with mild Alzheimer’s disease, as shown by a baseline Mini-Mental State Examination score of 22-26, or moderate Alzheimer’s disease, having a baseline MMSE score of 18-21.
Investigators randomly assigned the participants to four groups; one group received placebo, and each of the other three treatment arms received different doses of albumin and intravenous immunoglobulin (IVIg) replacement.
During the first 6-week study phase, patients received weekly sham or conventional plasma exchange treatments of 2.5-3 liters of plasma, which Dr. Páez referred to as the “intensive-treatment phase to remove as much Abeta as possible.”
This was followed by a 12-month maintenance phase, which involved monthly low-volume (700-800 mL) plasma exchange or sham treatments.
Although the volume of plasma removed was the same in all three active-treatment groups, the amount of albumin and IVIg that was subsequently replaced varied. In one group, the same amount of albumin and IVIg that was removed was replaced; in another, half the amount removed was replaced; and in the third, only albumin was replaced.
The researchers collected cerebrospinal fluid (CSF) samples at baseline and after each treatment period. They assessed Abeta40, Abeta42, total tau, and phosphorylated-tau biomarkers.
The two primary outcomes were change from baseline to 14 months in scores on the Alzheimer’s Disease Cooperative Study–Activities of Daily Living (ADCS-ADL) scale and the Alzheimer’s Disease Assessment Scale–Cognitive Subscale (ADAS-Cog).
Symptom reduction
Results showed a reduction in the progression of symptoms in the plasma exchange–treated patients for both primary endpoints.
The ADCS-ADL showed 52% less decline in the plasma exchange–treated group, compared with the placebo group (P = .03); the ADAS-Cog showed 66% less decline (P = 0.06). In the moderate group, both endpoints showed 61% less decline (P = .002 and .05, respectively).
There were no clear differences between the three active-treatment groups, “suggesting that any of them could be considered for further investigation,” said Dr. Páez.
Differences in baseline demographic characteristics did not appear to have an influence on the outcomes. ADAS-Cog was more than twice as effective as some candidate monoclonal antibodies targeting Abeta that are being investigated for Alzheimer’s disease, Dr. Páez noted.
Although the plasma exchange approach is relatively invasive, so too are monoclonal antibody therapies that are infused intravenously through a pump, he said. In addition, a low-volume plasma exchange maintenance treatment takes less than 2 hours, which is on a par with some monoclonal antibody treatments.
Key secondary outcomes
For both primary outcomes, changes were found in those with moderate but not mild Alzheimer’s disease, possibly because the ADAS-Cog was designed for patients with more severe symptoms and may not be sensitive enough for patients with better cognitive performance, said Dr. Páez.
However, the difference between mild and moderate Alzheimer’s disease did not hold up in post hoc analyses that included additional baseline characteristics, including amyloid and APOE e4 status.
“We observed that both mild and moderate subjects performed better than placebo even in the two coprimary endpoints,” Dr. Páez said. “It suggested that the differences between mild and moderate patients was not so apparent.”
The study’s key secondary outcomes included scores on the Clinical Dementia Rating Sum of Boxes (CDR-sb) and the Alzheimer’s Disease Cooperative Study–Clinical Global Impression of Change (ADCS-CGIC) scales. Treated patients scored better than the placebo group on both the CDR-sb (71% less decline, P = .002) and the ADCS-CGIC (100% less decline, P < .0001) scales.
For disease biomarkers in the moderate Alzheimer’s disease study population, levels of CSF Abeta42 and tau protein remained stable in the treated patients. In the placebo group, Abeta42 was decreased and tau protein increased. Dr. Páez explained that, if amyloid in the brain comes from the CSF, this process may take some time.
The findings suggest that more than one mechanism may be involved in the plasma exchange approach, such as changes in oxidation status and inflammatory mediators, the investigators noted.
Safety profile
About 28% of the participants dropped out of the study, which the researchers note is a rate similar to that reported in studies of solanezumab and other treatments in patients with Alzheimer’s disease. “The high percentage (72%) of patients who completed the study further supports that this procedure is feasible in mild to moderate Alzheimer’s disease,” the investigators wrote.
Overall, adverse events were similar to the known safety profile of plasma exchange procedures for other indications. The two most common adverse events were catheter local reactions and hypotension.
Almost 90% of the apheresis procedures were “uneventful,” the researchers reported. Two patients (0.6%) died during the study, which is similar to the low mortality rates reported elsewhere.
However, the investigators stressed that, because many patients with Alzheimer’s disease are in fragile health, plasma exchange treatments should be undertaken with caution, because of its invasive nature.
Dr. Páez noted that a possible limitation of this treatment approach is the availability of plasma for manufacturing plasma products. In the future, this plasma exchange approach might be combined with current and future Alzheimer’s disease therapies.
They are currently in discussions with the American Society for Apheresis, which develops guidelines for plasma exchange. After additional research, the investigators hope to eventually receive Food and Drug Administration approval of plasma exchange with albumin replacement as a treatment for Alzheimer’s disease.
Speculative, yet reasonable approach
Commenting on the research findings, Pierre N. Tariot, MD, director of Banner Alzheimer’s Institute and research professor of psychiatry at the University of Arizona, both in Phoenix, said the study is “meaningful and large enough” to “come close” to determining whether the therapy is safe and effective. “The fundamental rationale for this experimental approach, while speculative, is reasonable and certainly seems to be worth testing,” said Dr. Tariot, who was not involved with the research.
However, “there’s a decent chance” that not all trial participants had Alzheimer’s disease. Although some CSF amyloid measures suggest levels consistent with AD, “this is not conclusive,” he said.
In addition, “there’s a slightly low rate of apolipoprotein E4 allele carriage [in the current study], compared with most Alzheimer’s disease trials,” Dr. Tariot said.
He also pointed out that the trial failed to show statistical significance on both coprimary outcomes. “It’s unclear what health authorities, if presented with these data, would decide to do with the file.”
Although it was “encouraging” that secondary endpoints were supportive, the fact that they had greater statistical significance than some of the other objective measures “raises at least the potential for partial unblinding as a result of side effects,” said Dr. Tariot. It is also unclear why changes would be more evident in the moderate subpopulation.
The study was funded by Grifols. Dr. Páez is an employee of Grifols. Dr. Tariot reported no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
FROM AAIC 2020
Global study to track COVID-19’s impact on the brain
At its annual meeting, the Alzheimer’s Association announced the launch of a global study to examine the impact of COVID-19 on the brain, as well as policy recommendations to better address the COVID-19 crisis in long-term care facilities. The study will be led by researchers at the Alzheimer’s Association and the University of Texas Health, San Antonio, with participation from more than 30 countries and technical guidance from the World Health Organization.
The target sample size is 20,000-40,000 total participants.
Maria C. Carrillo, PhD, chief science officer for the Alzheimer’s Association, announced the study’s launch during a COVID-19–focused panel discussion at the virtual annual meeting of the Alzheimer’s Association International Conference 2020.
“To build a strong foundation for this research, we will align with existing studies, such as the Framingham Heart Study, and clinicians from around the world on how the data are going to be collected, obtained, and shared. We are going to have cross-study collaborations to understand the impact of the virus on the brain directly,” said Dr. Carrillo. “We will have some very good data to present next year at AAIC.”
‘Frightening’ headlines
As previously reported, mounting evidence suggests that SARS-CoV-2 invades the central nervous system, causing a wide range of neurologic and neuropsychiatric complications, including stroke, psychosis, altered mental state, and dementia-like syndrome. It’s likely that “dementia does not increase the risk for COVID-19, just like dementia does not increase risk for the flu. But increased age, being in a long-term care setting, and common health conditions that often accompany dementia may increase the risk,” Dr. Carrillo said.
Panel member Beth Kallmyer, MSW, vice president of care and support at the Alzheimer’s Association, spoke about the ongoing challenges long-term care facilities are facing during the pandemic. “You’ve all seen the headlines, and they’re frightening, frankly,” she said. An estimated 59,000 residents and employees of long-term care have died as a result of COVID-19, which is 42% of all U.S. deaths.
The long-term care community is being impacted at “significantly greater rates than the rest of society and yet we don’t have things in place to protect them. We also know that individuals living with dementia make up a large percentage of those that are living in long-term care,” Ms. Kallmyer said.
She noted that infection control is always a challenge in long-term care settings, but infection control during a pandemic “takes it to a whole other level.” Quarantining is hard for anyone, “but when you layer dementia on top of that we have a real challenge.” One long-term care provider told Ms. Kallmyer that “we might be saving them from COVID, but we’re losing them to social isolation and cognitive decline.”
New recommendations
Ms. Kallmyer outlined new policy recommendations from the Alzheimer’s Association to address the COVID-19 crisis in long-term and community-based care settings. They include:
- Testing every resident, employee, and visitor each time they leave and come back, so residents would not need to be confined to their own rooms
- Having a single portal that is easy and efficient for reporting cases
- Developing “surge activation” protocols to respond to hot spots, including the possibility of “strike teams” that go in and help during an outbreak
- Making sure all long-term care providers have full access to all needed personal protective equipment (PPE)
“Five months in and long-term care providers still don’t have adequate PPE. This is unacceptable,” said Ms. Kallmyer. “We have to be able to provide them with PPE.”
Panel member Gregory A. Jicha, MD, PhD, Sanders-Brown Center on Aging, University of Kentucky, Lexington, spoke about the critical need to continue Alzheimer’s disease research during the pandemic, noting that the number of promising targets for Alzheimer’s disease and related dementias has “never been higher or more comprehensive.”
Measures to ensure safety of researchers and participants include screening for symptoms (50% effective), social distancing (93% effective), minimizing exposure time (50% effective), limiting staff to 50% (50% effective), cloth/paper masks (80% effective), and testing (99.25% effective), Dr. Jicha noted.
With no safety measures in place, the risk of getting COVID-19 from a research visit is 1 in 20; when all these safety measures are combined, the risk is 1 in over 1.5 million, so “we can essentially eradicate or minimize the risks for COVID to less that of a lightning strike,” he said.
Dr. Carrillo, Ms. Kallmyer, and Dr. Jicha disclosed no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
At its annual meeting, the Alzheimer’s Association announced the launch of a global study to examine the impact of COVID-19 on the brain, as well as policy recommendations to better address the COVID-19 crisis in long-term care facilities. The study will be led by researchers at the Alzheimer’s Association and the University of Texas Health, San Antonio, with participation from more than 30 countries and technical guidance from the World Health Organization.
The target sample size is 20,000-40,000 total participants.
Maria C. Carrillo, PhD, chief science officer for the Alzheimer’s Association, announced the study’s launch during a COVID-19–focused panel discussion at the virtual annual meeting of the Alzheimer’s Association International Conference 2020.
“To build a strong foundation for this research, we will align with existing studies, such as the Framingham Heart Study, and clinicians from around the world on how the data are going to be collected, obtained, and shared. We are going to have cross-study collaborations to understand the impact of the virus on the brain directly,” said Dr. Carrillo. “We will have some very good data to present next year at AAIC.”
‘Frightening’ headlines
As previously reported, mounting evidence suggests that SARS-CoV-2 invades the central nervous system, causing a wide range of neurologic and neuropsychiatric complications, including stroke, psychosis, altered mental state, and dementia-like syndrome. It’s likely that “dementia does not increase the risk for COVID-19, just like dementia does not increase risk for the flu. But increased age, being in a long-term care setting, and common health conditions that often accompany dementia may increase the risk,” Dr. Carrillo said.
Panel member Beth Kallmyer, MSW, vice president of care and support at the Alzheimer’s Association, spoke about the ongoing challenges long-term care facilities are facing during the pandemic. “You’ve all seen the headlines, and they’re frightening, frankly,” she said. An estimated 59,000 residents and employees of long-term care have died as a result of COVID-19, which is 42% of all U.S. deaths.
The long-term care community is being impacted at “significantly greater rates than the rest of society and yet we don’t have things in place to protect them. We also know that individuals living with dementia make up a large percentage of those that are living in long-term care,” Ms. Kallmyer said.
She noted that infection control is always a challenge in long-term care settings, but infection control during a pandemic “takes it to a whole other level.” Quarantining is hard for anyone, “but when you layer dementia on top of that we have a real challenge.” One long-term care provider told Ms. Kallmyer that “we might be saving them from COVID, but we’re losing them to social isolation and cognitive decline.”
New recommendations
Ms. Kallmyer outlined new policy recommendations from the Alzheimer’s Association to address the COVID-19 crisis in long-term and community-based care settings. They include:
- Testing every resident, employee, and visitor each time they leave and come back, so residents would not need to be confined to their own rooms
- Having a single portal that is easy and efficient for reporting cases
- Developing “surge activation” protocols to respond to hot spots, including the possibility of “strike teams” that go in and help during an outbreak
- Making sure all long-term care providers have full access to all needed personal protective equipment (PPE)
“Five months in and long-term care providers still don’t have adequate PPE. This is unacceptable,” said Ms. Kallmyer. “We have to be able to provide them with PPE.”
Panel member Gregory A. Jicha, MD, PhD, Sanders-Brown Center on Aging, University of Kentucky, Lexington, spoke about the critical need to continue Alzheimer’s disease research during the pandemic, noting that the number of promising targets for Alzheimer’s disease and related dementias has “never been higher or more comprehensive.”
Measures to ensure safety of researchers and participants include screening for symptoms (50% effective), social distancing (93% effective), minimizing exposure time (50% effective), limiting staff to 50% (50% effective), cloth/paper masks (80% effective), and testing (99.25% effective), Dr. Jicha noted.
With no safety measures in place, the risk of getting COVID-19 from a research visit is 1 in 20; when all these safety measures are combined, the risk is 1 in over 1.5 million, so “we can essentially eradicate or minimize the risks for COVID to less that of a lightning strike,” he said.
Dr. Carrillo, Ms. Kallmyer, and Dr. Jicha disclosed no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
At its annual meeting, the Alzheimer’s Association announced the launch of a global study to examine the impact of COVID-19 on the brain, as well as policy recommendations to better address the COVID-19 crisis in long-term care facilities. The study will be led by researchers at the Alzheimer’s Association and the University of Texas Health, San Antonio, with participation from more than 30 countries and technical guidance from the World Health Organization.
The target sample size is 20,000-40,000 total participants.
Maria C. Carrillo, PhD, chief science officer for the Alzheimer’s Association, announced the study’s launch during a COVID-19–focused panel discussion at the virtual annual meeting of the Alzheimer’s Association International Conference 2020.
“To build a strong foundation for this research, we will align with existing studies, such as the Framingham Heart Study, and clinicians from around the world on how the data are going to be collected, obtained, and shared. We are going to have cross-study collaborations to understand the impact of the virus on the brain directly,” said Dr. Carrillo. “We will have some very good data to present next year at AAIC.”
‘Frightening’ headlines
As previously reported, mounting evidence suggests that SARS-CoV-2 invades the central nervous system, causing a wide range of neurologic and neuropsychiatric complications, including stroke, psychosis, altered mental state, and dementia-like syndrome. It’s likely that “dementia does not increase the risk for COVID-19, just like dementia does not increase risk for the flu. But increased age, being in a long-term care setting, and common health conditions that often accompany dementia may increase the risk,” Dr. Carrillo said.
Panel member Beth Kallmyer, MSW, vice president of care and support at the Alzheimer’s Association, spoke about the ongoing challenges long-term care facilities are facing during the pandemic. “You’ve all seen the headlines, and they’re frightening, frankly,” she said. An estimated 59,000 residents and employees of long-term care have died as a result of COVID-19, which is 42% of all U.S. deaths.
The long-term care community is being impacted at “significantly greater rates than the rest of society and yet we don’t have things in place to protect them. We also know that individuals living with dementia make up a large percentage of those that are living in long-term care,” Ms. Kallmyer said.
She noted that infection control is always a challenge in long-term care settings, but infection control during a pandemic “takes it to a whole other level.” Quarantining is hard for anyone, “but when you layer dementia on top of that we have a real challenge.” One long-term care provider told Ms. Kallmyer that “we might be saving them from COVID, but we’re losing them to social isolation and cognitive decline.”
New recommendations
Ms. Kallmyer outlined new policy recommendations from the Alzheimer’s Association to address the COVID-19 crisis in long-term and community-based care settings. They include:
- Testing every resident, employee, and visitor each time they leave and come back, so residents would not need to be confined to their own rooms
- Having a single portal that is easy and efficient for reporting cases
- Developing “surge activation” protocols to respond to hot spots, including the possibility of “strike teams” that go in and help during an outbreak
- Making sure all long-term care providers have full access to all needed personal protective equipment (PPE)
“Five months in and long-term care providers still don’t have adequate PPE. This is unacceptable,” said Ms. Kallmyer. “We have to be able to provide them with PPE.”
Panel member Gregory A. Jicha, MD, PhD, Sanders-Brown Center on Aging, University of Kentucky, Lexington, spoke about the critical need to continue Alzheimer’s disease research during the pandemic, noting that the number of promising targets for Alzheimer’s disease and related dementias has “never been higher or more comprehensive.”
Measures to ensure safety of researchers and participants include screening for symptoms (50% effective), social distancing (93% effective), minimizing exposure time (50% effective), limiting staff to 50% (50% effective), cloth/paper masks (80% effective), and testing (99.25% effective), Dr. Jicha noted.
With no safety measures in place, the risk of getting COVID-19 from a research visit is 1 in 20; when all these safety measures are combined, the risk is 1 in over 1.5 million, so “we can essentially eradicate or minimize the risks for COVID to less that of a lightning strike,” he said.
Dr. Carrillo, Ms. Kallmyer, and Dr. Jicha disclosed no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
FROM AAIC 2020
‘Long sleep’ or apnea in middle age double risk for Alzheimer’s disease
new research suggests. A U.K. Biobank study of more than 500,000 individuals also showed that excessive daytime sleepiness was associated with increased risk for Alzheimer’s disease.
“Addressing sleep problems in middle-age may play a role in improving brain health,” said lead author Lei Gao, MD, assistant professor of anesthesia at Harvard Medical School and associate scientist in the division of sleep and circadian disorders at Brigham and Women’s Hospital, both in Boston.
The findings were presented at the virtual annual meeting of the Alzheimer’s Association International Conference 2020.
Intricately linked
Sleep disturbances are common and on the rise around the world. In recent years, researchers have become increasingly aware of the intricate link between sleep health and brain health, Dr. Gao noted.
The current study included 502,538 individuals from the U.K. Biobank (mean age, 57 years) who were free from Alzheimer’s disease at baseline. They were followed for up to 12 years. The participants self-reported sleep traits, including hours of nighttime sleep, daytime sleepiness, sleep apnea diagnosis, snoring, and napping. Researchers determined Alzheimer’s disease diagnoses from hospital admissions and from death registries.
In addition to adjusting for age, sex, education, and ethnicity, the full model adjusted for socioeconomic status, body mass index, physical activity, smoking and alcohol use, cardiovascular diseases and risk factors, neurological diseases, respiratory diseases, depression/anxiety, and medication use. Over the course of a mean follow-up of 6.4 years, 932 participants developed Alzheimer’s disease.
Complex disorder
Compared with those who got an average of 6-9 hours of sleep per night, those getting more than 9 hours had a higher risk for Alzheimer’s disease (hazard ratio, 2.04; 95% confidence interval, 1.56-2.67; P < .001). Having sleep apnea also raised the risk significantly (HR, 2.05; 95% CI, 1.23-3.42; P = .006), as did daytime sleepiness (HR, 1.56; 95% CI, 1.18-2.03; P = .001).
Dr. Gao noted that daytime sleepiness and sleep apnea remained predictive after controlling for sleep duration. “In fact, all three sleep traits remained associated with Alzheimer’s disease within the same model, suggesting some degree of independence.”
Interestingly, snoring, which is a common symptom of sleep apnea, was not linked to Alzheimer’s disease risk. The “vast majority” of people who snore don’t meet criteria for a diagnosis of sleep apnea, which was particularly true for this large cohort of relatively healthy study participants, Dr. Gao noted.
“Sleep apnea is a complex, multisystemic sleep disorder associated with obesity, high blood pressure, and often other heart problems,” he said.
He added that, as an anesthesiologist, he is particularly wary if patients have this condition, “given their increased risk for airway difficulties, adverse cardiac events, postoperative respiratory complications, and confusion or delirium, which is also associated with higher risk for eventual Alzheimer’s disease and death.”
These multisystemic factors may be driving the link to Alzheimer’s disease. “We certainly need to address this better as the population ages and obesity rates rise,” Dr. Gao said.
No association with napping
Unlike another of Dr. Gao’s studies that was conducted in a much older population, napping was not a risk factor for Alzheimer’s disease in the current study’s younger participants. It could be that the impacts of different sleep traits on health outcome change with age, Dr. Gao said, or this could represent a limitation of using self-reported sleep measures as opposed to objective and/or quantitative measures, such as actigraphy. The reasons for napping, which differ around the world with the habit being common in certain parts, may also help explain differences in observed associations.
Although the investigators tried to control for comorbidities and medication use, there “most certainly” could be a reverse causation at work. For example, sleeping too much could be both a cause and a symptom of dementia. Dr. Gao noted that sleep disturbances often become more prevalent with dementia, and sleeping too much or complaining of daytime sleepiness may be a result of preclinical Alzheimer’s disease. Even if there is a reverse causation, however, the average time to Alzheimer’s disease diagnosis was over 6 years in this study. “This may be a significant window of time to intervene,” he said.
To improve sleep health, he recommends going to bed and waking at similar times every day, avoiding caffeine or alcohol close to bedtime, limiting screen time before bed, dimming lights, and reducing noise.
It’s also important to have sleep apnea treated. “While more studies are needed, it’s generally believed that addressing the pauses in breathing, the apnea episodes, will help reduce cardiovascular health risks such as obesity, high blood pressure and heart failure. All are known to be strongly linked to dementia risk,” Dr. Gao said.
Results from an assessment of 100,000 actigraphy records from a subset of the same population are expected soon and will add objective confirmation of these self-reported results, he added.
Unique, powerful
Commenting on the findings, Alberto Ramos, MD, associate professor of clinical neurology and research director of the sleep medicine program at the University of Miami, called the study “unique” and “powerful” because of its prospective design and large sample size.
“Another strength of the study was that it included a population-based sample as opposed to one from a memory or sleep clinic where people already have symptoms or are already sick,” said Dr. Ramos, who was not involved with the research.
In addition, while most studies that have linked sleep disturbances with dementia risk have been in older adults, this study’s population was middle-aged to start out, he noted.
Dr. Gao and Dr. Ramos reported no relevant financial relationships. Although Dr. Gao’s lab receives funding from the National Institutes of Health, the BrightFocus Foundation, the University of Manchester, the Medical Biodynamics Program, Brigham and Women’s Hospital, and the Broad Institute, the study itself does not have its own specific funding.
A version of this article originally appeared on Medscape.com.
new research suggests. A U.K. Biobank study of more than 500,000 individuals also showed that excessive daytime sleepiness was associated with increased risk for Alzheimer’s disease.
“Addressing sleep problems in middle-age may play a role in improving brain health,” said lead author Lei Gao, MD, assistant professor of anesthesia at Harvard Medical School and associate scientist in the division of sleep and circadian disorders at Brigham and Women’s Hospital, both in Boston.
The findings were presented at the virtual annual meeting of the Alzheimer’s Association International Conference 2020.
Intricately linked
Sleep disturbances are common and on the rise around the world. In recent years, researchers have become increasingly aware of the intricate link between sleep health and brain health, Dr. Gao noted.
The current study included 502,538 individuals from the U.K. Biobank (mean age, 57 years) who were free from Alzheimer’s disease at baseline. They were followed for up to 12 years. The participants self-reported sleep traits, including hours of nighttime sleep, daytime sleepiness, sleep apnea diagnosis, snoring, and napping. Researchers determined Alzheimer’s disease diagnoses from hospital admissions and from death registries.
In addition to adjusting for age, sex, education, and ethnicity, the full model adjusted for socioeconomic status, body mass index, physical activity, smoking and alcohol use, cardiovascular diseases and risk factors, neurological diseases, respiratory diseases, depression/anxiety, and medication use. Over the course of a mean follow-up of 6.4 years, 932 participants developed Alzheimer’s disease.
Complex disorder
Compared with those who got an average of 6-9 hours of sleep per night, those getting more than 9 hours had a higher risk for Alzheimer’s disease (hazard ratio, 2.04; 95% confidence interval, 1.56-2.67; P < .001). Having sleep apnea also raised the risk significantly (HR, 2.05; 95% CI, 1.23-3.42; P = .006), as did daytime sleepiness (HR, 1.56; 95% CI, 1.18-2.03; P = .001).
Dr. Gao noted that daytime sleepiness and sleep apnea remained predictive after controlling for sleep duration. “In fact, all three sleep traits remained associated with Alzheimer’s disease within the same model, suggesting some degree of independence.”
Interestingly, snoring, which is a common symptom of sleep apnea, was not linked to Alzheimer’s disease risk. The “vast majority” of people who snore don’t meet criteria for a diagnosis of sleep apnea, which was particularly true for this large cohort of relatively healthy study participants, Dr. Gao noted.
“Sleep apnea is a complex, multisystemic sleep disorder associated with obesity, high blood pressure, and often other heart problems,” he said.
He added that, as an anesthesiologist, he is particularly wary if patients have this condition, “given their increased risk for airway difficulties, adverse cardiac events, postoperative respiratory complications, and confusion or delirium, which is also associated with higher risk for eventual Alzheimer’s disease and death.”
These multisystemic factors may be driving the link to Alzheimer’s disease. “We certainly need to address this better as the population ages and obesity rates rise,” Dr. Gao said.
No association with napping
Unlike another of Dr. Gao’s studies that was conducted in a much older population, napping was not a risk factor for Alzheimer’s disease in the current study’s younger participants. It could be that the impacts of different sleep traits on health outcome change with age, Dr. Gao said, or this could represent a limitation of using self-reported sleep measures as opposed to objective and/or quantitative measures, such as actigraphy. The reasons for napping, which differ around the world with the habit being common in certain parts, may also help explain differences in observed associations.
Although the investigators tried to control for comorbidities and medication use, there “most certainly” could be a reverse causation at work. For example, sleeping too much could be both a cause and a symptom of dementia. Dr. Gao noted that sleep disturbances often become more prevalent with dementia, and sleeping too much or complaining of daytime sleepiness may be a result of preclinical Alzheimer’s disease. Even if there is a reverse causation, however, the average time to Alzheimer’s disease diagnosis was over 6 years in this study. “This may be a significant window of time to intervene,” he said.
To improve sleep health, he recommends going to bed and waking at similar times every day, avoiding caffeine or alcohol close to bedtime, limiting screen time before bed, dimming lights, and reducing noise.
It’s also important to have sleep apnea treated. “While more studies are needed, it’s generally believed that addressing the pauses in breathing, the apnea episodes, will help reduce cardiovascular health risks such as obesity, high blood pressure and heart failure. All are known to be strongly linked to dementia risk,” Dr. Gao said.
Results from an assessment of 100,000 actigraphy records from a subset of the same population are expected soon and will add objective confirmation of these self-reported results, he added.
Unique, powerful
Commenting on the findings, Alberto Ramos, MD, associate professor of clinical neurology and research director of the sleep medicine program at the University of Miami, called the study “unique” and “powerful” because of its prospective design and large sample size.
“Another strength of the study was that it included a population-based sample as opposed to one from a memory or sleep clinic where people already have symptoms or are already sick,” said Dr. Ramos, who was not involved with the research.
In addition, while most studies that have linked sleep disturbances with dementia risk have been in older adults, this study’s population was middle-aged to start out, he noted.
Dr. Gao and Dr. Ramos reported no relevant financial relationships. Although Dr. Gao’s lab receives funding from the National Institutes of Health, the BrightFocus Foundation, the University of Manchester, the Medical Biodynamics Program, Brigham and Women’s Hospital, and the Broad Institute, the study itself does not have its own specific funding.
A version of this article originally appeared on Medscape.com.
new research suggests. A U.K. Biobank study of more than 500,000 individuals also showed that excessive daytime sleepiness was associated with increased risk for Alzheimer’s disease.
“Addressing sleep problems in middle-age may play a role in improving brain health,” said lead author Lei Gao, MD, assistant professor of anesthesia at Harvard Medical School and associate scientist in the division of sleep and circadian disorders at Brigham and Women’s Hospital, both in Boston.
The findings were presented at the virtual annual meeting of the Alzheimer’s Association International Conference 2020.
Intricately linked
Sleep disturbances are common and on the rise around the world. In recent years, researchers have become increasingly aware of the intricate link between sleep health and brain health, Dr. Gao noted.
The current study included 502,538 individuals from the U.K. Biobank (mean age, 57 years) who were free from Alzheimer’s disease at baseline. They were followed for up to 12 years. The participants self-reported sleep traits, including hours of nighttime sleep, daytime sleepiness, sleep apnea diagnosis, snoring, and napping. Researchers determined Alzheimer’s disease diagnoses from hospital admissions and from death registries.
In addition to adjusting for age, sex, education, and ethnicity, the full model adjusted for socioeconomic status, body mass index, physical activity, smoking and alcohol use, cardiovascular diseases and risk factors, neurological diseases, respiratory diseases, depression/anxiety, and medication use. Over the course of a mean follow-up of 6.4 years, 932 participants developed Alzheimer’s disease.
Complex disorder
Compared with those who got an average of 6-9 hours of sleep per night, those getting more than 9 hours had a higher risk for Alzheimer’s disease (hazard ratio, 2.04; 95% confidence interval, 1.56-2.67; P < .001). Having sleep apnea also raised the risk significantly (HR, 2.05; 95% CI, 1.23-3.42; P = .006), as did daytime sleepiness (HR, 1.56; 95% CI, 1.18-2.03; P = .001).
Dr. Gao noted that daytime sleepiness and sleep apnea remained predictive after controlling for sleep duration. “In fact, all three sleep traits remained associated with Alzheimer’s disease within the same model, suggesting some degree of independence.”
Interestingly, snoring, which is a common symptom of sleep apnea, was not linked to Alzheimer’s disease risk. The “vast majority” of people who snore don’t meet criteria for a diagnosis of sleep apnea, which was particularly true for this large cohort of relatively healthy study participants, Dr. Gao noted.
“Sleep apnea is a complex, multisystemic sleep disorder associated with obesity, high blood pressure, and often other heart problems,” he said.
He added that, as an anesthesiologist, he is particularly wary if patients have this condition, “given their increased risk for airway difficulties, adverse cardiac events, postoperative respiratory complications, and confusion or delirium, which is also associated with higher risk for eventual Alzheimer’s disease and death.”
These multisystemic factors may be driving the link to Alzheimer’s disease. “We certainly need to address this better as the population ages and obesity rates rise,” Dr. Gao said.
No association with napping
Unlike another of Dr. Gao’s studies that was conducted in a much older population, napping was not a risk factor for Alzheimer’s disease in the current study’s younger participants. It could be that the impacts of different sleep traits on health outcome change with age, Dr. Gao said, or this could represent a limitation of using self-reported sleep measures as opposed to objective and/or quantitative measures, such as actigraphy. The reasons for napping, which differ around the world with the habit being common in certain parts, may also help explain differences in observed associations.
Although the investigators tried to control for comorbidities and medication use, there “most certainly” could be a reverse causation at work. For example, sleeping too much could be both a cause and a symptom of dementia. Dr. Gao noted that sleep disturbances often become more prevalent with dementia, and sleeping too much or complaining of daytime sleepiness may be a result of preclinical Alzheimer’s disease. Even if there is a reverse causation, however, the average time to Alzheimer’s disease diagnosis was over 6 years in this study. “This may be a significant window of time to intervene,” he said.
To improve sleep health, he recommends going to bed and waking at similar times every day, avoiding caffeine or alcohol close to bedtime, limiting screen time before bed, dimming lights, and reducing noise.
It’s also important to have sleep apnea treated. “While more studies are needed, it’s generally believed that addressing the pauses in breathing, the apnea episodes, will help reduce cardiovascular health risks such as obesity, high blood pressure and heart failure. All are known to be strongly linked to dementia risk,” Dr. Gao said.
Results from an assessment of 100,000 actigraphy records from a subset of the same population are expected soon and will add objective confirmation of these self-reported results, he added.
Unique, powerful
Commenting on the findings, Alberto Ramos, MD, associate professor of clinical neurology and research director of the sleep medicine program at the University of Miami, called the study “unique” and “powerful” because of its prospective design and large sample size.
“Another strength of the study was that it included a population-based sample as opposed to one from a memory or sleep clinic where people already have symptoms or are already sick,” said Dr. Ramos, who was not involved with the research.
In addition, while most studies that have linked sleep disturbances with dementia risk have been in older adults, this study’s population was middle-aged to start out, he noted.
Dr. Gao and Dr. Ramos reported no relevant financial relationships. Although Dr. Gao’s lab receives funding from the National Institutes of Health, the BrightFocus Foundation, the University of Manchester, the Medical Biodynamics Program, Brigham and Women’s Hospital, and the Broad Institute, the study itself does not have its own specific funding.
A version of this article originally appeared on Medscape.com.
FROM AAIC 2020
Infection ups mortality risk in patients with dementia
Infection increases mortality risk among patients with dementia, new research suggests. A large, registry-based cohort study showed that
“This is the first study to our knowledge to show that increased mortality is observed across all infection types in people with dementia and that increased mortality is seen both short and long term,” said coinvestigator Janet Janbek, a PhD student at the Danish Dementia Research Center, Rigshospitalet, University of Copenhagen.
The findings were presented at the virtual annual meeting of the Alzheimer’s Association International Conference.
Large Danish cohort
The investigators analyzed data from Danish national health registries for nearly 1.5 million individuals aged 65 years and older who had visited the hospital with an infection. There were 575,260 deaths during more than 12.7 million person-years of follow-up.
Patients with dementia who also had a hospital visit for infection died at a 6.5 times higher rate than participants without dementia or an infection. Those with either dementia alone or infection-related contacts alone had a threefold increased rate of death.
The mortality rate was highest within the first 30 days following the hospital visit for infection. However, the rate remained elevated for 10 years after the initial infection-related hospital visit.
Mortality rates from all infections, including major infections, such as sepsis, down to minor ear infections were elevated in patients with dementia, compared with people who did not have dementia or an infection-related hospital visit.
Ms. Janbek said there are several possible explanations for the association of infection and increased mortality risk in those with dementia. “After a hospital contact with a severe infection, people with dementia may become more reliant on external care, become more frail, and have declined functional levels, which might explain the observed association.”
It might also be that patients with dementia have more severe infections than those without dementia at the time of hospital contact, possibly because of delayed diagnosis, which could explain the higher mortality rates, said Ms. Janbek.
“It is also plausible that infections play a role in worsening dementia and subsequently lead to increased mortality,” she noted.
“Clinicians and health care personnel need to pay closer attention to infections of all types in people with dementia, and steps toward better clinical management and improved posthospital care need to be explored and undertaken. We need to identify possible preventive measures and targeted interventions in people with dementia and infections,” Ms. Janbek said.
‘Interesting observation’
Commenting on the study, Rebecca M. Edelmayer, PhD, director of scientific engagement for the Alzheimer’s Association, said it presents “an interesting observation.” However, “we can’t make any direct assumptions from this research per se about infections and dementia and whether they are causative in any way,” noted Dr. Edelmayer, who was not involved with the study.
Instead, the study highlighted the importance of “taking care of our overall health and making sure that individuals that might be vulnerable to infection, like those who are already living with dementia, are getting the best care possible,” she said.
Ms. Janbek and Dr. Edelmayer have reported no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
Infection increases mortality risk among patients with dementia, new research suggests. A large, registry-based cohort study showed that
“This is the first study to our knowledge to show that increased mortality is observed across all infection types in people with dementia and that increased mortality is seen both short and long term,” said coinvestigator Janet Janbek, a PhD student at the Danish Dementia Research Center, Rigshospitalet, University of Copenhagen.
The findings were presented at the virtual annual meeting of the Alzheimer’s Association International Conference.
Large Danish cohort
The investigators analyzed data from Danish national health registries for nearly 1.5 million individuals aged 65 years and older who had visited the hospital with an infection. There were 575,260 deaths during more than 12.7 million person-years of follow-up.
Patients with dementia who also had a hospital visit for infection died at a 6.5 times higher rate than participants without dementia or an infection. Those with either dementia alone or infection-related contacts alone had a threefold increased rate of death.
The mortality rate was highest within the first 30 days following the hospital visit for infection. However, the rate remained elevated for 10 years after the initial infection-related hospital visit.
Mortality rates from all infections, including major infections, such as sepsis, down to minor ear infections were elevated in patients with dementia, compared with people who did not have dementia or an infection-related hospital visit.
Ms. Janbek said there are several possible explanations for the association of infection and increased mortality risk in those with dementia. “After a hospital contact with a severe infection, people with dementia may become more reliant on external care, become more frail, and have declined functional levels, which might explain the observed association.”
It might also be that patients with dementia have more severe infections than those without dementia at the time of hospital contact, possibly because of delayed diagnosis, which could explain the higher mortality rates, said Ms. Janbek.
“It is also plausible that infections play a role in worsening dementia and subsequently lead to increased mortality,” she noted.
“Clinicians and health care personnel need to pay closer attention to infections of all types in people with dementia, and steps toward better clinical management and improved posthospital care need to be explored and undertaken. We need to identify possible preventive measures and targeted interventions in people with dementia and infections,” Ms. Janbek said.
‘Interesting observation’
Commenting on the study, Rebecca M. Edelmayer, PhD, director of scientific engagement for the Alzheimer’s Association, said it presents “an interesting observation.” However, “we can’t make any direct assumptions from this research per se about infections and dementia and whether they are causative in any way,” noted Dr. Edelmayer, who was not involved with the study.
Instead, the study highlighted the importance of “taking care of our overall health and making sure that individuals that might be vulnerable to infection, like those who are already living with dementia, are getting the best care possible,” she said.
Ms. Janbek and Dr. Edelmayer have reported no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
Infection increases mortality risk among patients with dementia, new research suggests. A large, registry-based cohort study showed that
“This is the first study to our knowledge to show that increased mortality is observed across all infection types in people with dementia and that increased mortality is seen both short and long term,” said coinvestigator Janet Janbek, a PhD student at the Danish Dementia Research Center, Rigshospitalet, University of Copenhagen.
The findings were presented at the virtual annual meeting of the Alzheimer’s Association International Conference.
Large Danish cohort
The investigators analyzed data from Danish national health registries for nearly 1.5 million individuals aged 65 years and older who had visited the hospital with an infection. There were 575,260 deaths during more than 12.7 million person-years of follow-up.
Patients with dementia who also had a hospital visit for infection died at a 6.5 times higher rate than participants without dementia or an infection. Those with either dementia alone or infection-related contacts alone had a threefold increased rate of death.
The mortality rate was highest within the first 30 days following the hospital visit for infection. However, the rate remained elevated for 10 years after the initial infection-related hospital visit.
Mortality rates from all infections, including major infections, such as sepsis, down to minor ear infections were elevated in patients with dementia, compared with people who did not have dementia or an infection-related hospital visit.
Ms. Janbek said there are several possible explanations for the association of infection and increased mortality risk in those with dementia. “After a hospital contact with a severe infection, people with dementia may become more reliant on external care, become more frail, and have declined functional levels, which might explain the observed association.”
It might also be that patients with dementia have more severe infections than those without dementia at the time of hospital contact, possibly because of delayed diagnosis, which could explain the higher mortality rates, said Ms. Janbek.
“It is also plausible that infections play a role in worsening dementia and subsequently lead to increased mortality,” she noted.
“Clinicians and health care personnel need to pay closer attention to infections of all types in people with dementia, and steps toward better clinical management and improved posthospital care need to be explored and undertaken. We need to identify possible preventive measures and targeted interventions in people with dementia and infections,” Ms. Janbek said.
‘Interesting observation’
Commenting on the study, Rebecca M. Edelmayer, PhD, director of scientific engagement for the Alzheimer’s Association, said it presents “an interesting observation.” However, “we can’t make any direct assumptions from this research per se about infections and dementia and whether they are causative in any way,” noted Dr. Edelmayer, who was not involved with the study.
Instead, the study highlighted the importance of “taking care of our overall health and making sure that individuals that might be vulnerable to infection, like those who are already living with dementia, are getting the best care possible,” she said.
Ms. Janbek and Dr. Edelmayer have reported no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
FROM AAIC 2020
P-tau217 differentiates Alzheimer’s disease from other neurodegenerative conditions
new research suggests.
Results from a large multinational study showed that the level of P-tau217 in blood collected during life was an accurate predictor of tau brain changes seen in brain tissue after death. In addition, increasing blood P-tau217 levels can be detected in some individuals up to 20 years before the average age of onset of the early cognitive decline that signals Alzheimer’s disease, researchers reported.
“While there is still more work to be done, this biomarker has the potential to have a transformational impact on research, treatment, prevention, and therapy development, and in the clinical setting,” said senior author Eric M. Reiman, MD, executive director of Banner Alzheimer’s Institute in Phoenix.
The findings were presented at the virtual annual meeting of the Alzheimer’s Association International Conference and simultaneously published online July 28 in JAMA.
Three cohorts
The international team of researchers evaluated the P-tau217 blood test in 1,402 adults from three cohorts. The first cohort was made up of 81 individuals in the Arizona (Banner Sun Health Research Institute) Brain Donation program and included clinical, blood, and neuropathologic data. The second cohort included 699 individuals in the Swedish BioFINDER-2 study and provided clinical, brain imaging, cerebrospinal fluid (CSF), and blood data. The third cohort was made up of 522 participants from the Columbian autosomal-dominant Alzheimer’s disease kindred, including 365 PSEN1 E280A mutation carriers and 257 mutation noncarriers.
In the Arizona cohort, plasma P-tau217 discriminated neuropathologically defined Alzheimer’s disease from non-Alzheimer’s disease (area under the curve, 0.89; 95% CI, 0.81-0.97) with significantly higher accuracy than plasma P-tau181 and neurofilament light chain (NfL) (AUC range, 0.50-0.72; P < .05).
In the Swedish BioFINDER-2 cohort, the discriminative accuracy of plasma P-tau217 for clinical Alzheimer’s disease dementia versus other neurodegenerative diseases was 96% (AUC, 0.96; 95% CI, 0.93-0.98).
This was significantly higher than plasma P-tau181, plasma NfL, and MRI measures (AUC range, 0.50-0.81; P < .001), but was not significantly different than CSF P-tau217, CSF P-tau181, and tau-PET (AUC range, 0.90-0.99; P > .15).
In the Colombian cohort, plasma P-tau217 levels were significantly greater among PSEN1 mutation carriers than noncarriers starting at around age 25 years, which is 20 years prior to the estimated onset of mild cognitive impairment among mutation carriers.
Additionally, plasma P-tau217 levels correlated with cerebral tau tangles, and discriminated abnormal versus normal tau-PET scans with significantly higher accuracy than plasma P-tau181, plasma NfL, CSF P-tau181, CSF Abeta42:Abeta40 ratio, and MRI measures.
The blood test “opens the possibility of early diagnosis of Alzheimer’s disease before the dementia stage, which is very important for clinical trials evaluating novel therapies that might stop or slow down the disease process,” presenting author Oskar Hansson, MD, PhD, of Lund (Sweden) University, said in a statement.
Further research is now needed to optimize the P-tau217 blood test, validate the findings in unselected and diverse populations, and determine its potential role in the clinic, the investigators noted.
Potential game changer?
Commenting on the study, Howard Fillit, MD, founding executive director and chief science officer of the Alzheimer’s Drug Discovery Foundation, noted his enthusiasm for the test. “This tau blood test will be a real game changer, advancing clinical care and research,” said Dr. Fillit, who was not involved in the research.
“This is a real breakthrough: a simple and accessible blood test that can diagnose Alzheimer’s disease better than the more costly and invasive methods currently available like PET scans and cerebrospinal fluid biomarkers,” he said.
The P-tau217 blood test “is like the equivalent of the cholesterol test for heart disease, but for Alzheimer’s disease,” Dr. Fillit added.
As previously reported, another study presented at AAIC 2020 compared P-tau217 with P-tau181 to determine which could best identify individuals with Alzheimer’s disease. Results showed that, although the two biomarkers were similar overall, P-tau217 had a slight edge in terms of accuracy.
The study by Reiman et al. was funded by the Swedish Research Council, the Knut and Alice Wallenberg Foundation, and the Swedish Alzheimer Foundation. Dr. Hansson reported receiving grants from Roche, Biogen, and Pfizer, and receiving nonfinancial support from GE Healthcare, AVID Radiopharmaceuticals, and Euroimmun. Dr. Reiman has received grants from Roche/Roche Diagnostics and received personal fees from Alkahest, Alzheon, Aural Analytics, Denali, Green Valley, MagQ, Takeda/Zinfandel, and United Neuroscience. He is also a cofounder of AlzPath, which aims to further develop P-tau217 and fluid biomarkers; holds a patent owned by Banner Health for a strategy to use biomarkers to accelerate evaluation of Alzheimer prevention therapies; and is a principal investigator of prevention trials that include research agreements with Genentech/Roche and Novartis/Amgen, PET studies that include research agreements with Avid/Lilly, and several National Institute of Health–supported research studies. Dr. Fillit reported no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
new research suggests.
Results from a large multinational study showed that the level of P-tau217 in blood collected during life was an accurate predictor of tau brain changes seen in brain tissue after death. In addition, increasing blood P-tau217 levels can be detected in some individuals up to 20 years before the average age of onset of the early cognitive decline that signals Alzheimer’s disease, researchers reported.
“While there is still more work to be done, this biomarker has the potential to have a transformational impact on research, treatment, prevention, and therapy development, and in the clinical setting,” said senior author Eric M. Reiman, MD, executive director of Banner Alzheimer’s Institute in Phoenix.
The findings were presented at the virtual annual meeting of the Alzheimer’s Association International Conference and simultaneously published online July 28 in JAMA.
Three cohorts
The international team of researchers evaluated the P-tau217 blood test in 1,402 adults from three cohorts. The first cohort was made up of 81 individuals in the Arizona (Banner Sun Health Research Institute) Brain Donation program and included clinical, blood, and neuropathologic data. The second cohort included 699 individuals in the Swedish BioFINDER-2 study and provided clinical, brain imaging, cerebrospinal fluid (CSF), and blood data. The third cohort was made up of 522 participants from the Columbian autosomal-dominant Alzheimer’s disease kindred, including 365 PSEN1 E280A mutation carriers and 257 mutation noncarriers.
In the Arizona cohort, plasma P-tau217 discriminated neuropathologically defined Alzheimer’s disease from non-Alzheimer’s disease (area under the curve, 0.89; 95% CI, 0.81-0.97) with significantly higher accuracy than plasma P-tau181 and neurofilament light chain (NfL) (AUC range, 0.50-0.72; P < .05).
In the Swedish BioFINDER-2 cohort, the discriminative accuracy of plasma P-tau217 for clinical Alzheimer’s disease dementia versus other neurodegenerative diseases was 96% (AUC, 0.96; 95% CI, 0.93-0.98).
This was significantly higher than plasma P-tau181, plasma NfL, and MRI measures (AUC range, 0.50-0.81; P < .001), but was not significantly different than CSF P-tau217, CSF P-tau181, and tau-PET (AUC range, 0.90-0.99; P > .15).
In the Colombian cohort, plasma P-tau217 levels were significantly greater among PSEN1 mutation carriers than noncarriers starting at around age 25 years, which is 20 years prior to the estimated onset of mild cognitive impairment among mutation carriers.
Additionally, plasma P-tau217 levels correlated with cerebral tau tangles, and discriminated abnormal versus normal tau-PET scans with significantly higher accuracy than plasma P-tau181, plasma NfL, CSF P-tau181, CSF Abeta42:Abeta40 ratio, and MRI measures.
The blood test “opens the possibility of early diagnosis of Alzheimer’s disease before the dementia stage, which is very important for clinical trials evaluating novel therapies that might stop or slow down the disease process,” presenting author Oskar Hansson, MD, PhD, of Lund (Sweden) University, said in a statement.
Further research is now needed to optimize the P-tau217 blood test, validate the findings in unselected and diverse populations, and determine its potential role in the clinic, the investigators noted.
Potential game changer?
Commenting on the study, Howard Fillit, MD, founding executive director and chief science officer of the Alzheimer’s Drug Discovery Foundation, noted his enthusiasm for the test. “This tau blood test will be a real game changer, advancing clinical care and research,” said Dr. Fillit, who was not involved in the research.
“This is a real breakthrough: a simple and accessible blood test that can diagnose Alzheimer’s disease better than the more costly and invasive methods currently available like PET scans and cerebrospinal fluid biomarkers,” he said.
The P-tau217 blood test “is like the equivalent of the cholesterol test for heart disease, but for Alzheimer’s disease,” Dr. Fillit added.
As previously reported, another study presented at AAIC 2020 compared P-tau217 with P-tau181 to determine which could best identify individuals with Alzheimer’s disease. Results showed that, although the two biomarkers were similar overall, P-tau217 had a slight edge in terms of accuracy.
The study by Reiman et al. was funded by the Swedish Research Council, the Knut and Alice Wallenberg Foundation, and the Swedish Alzheimer Foundation. Dr. Hansson reported receiving grants from Roche, Biogen, and Pfizer, and receiving nonfinancial support from GE Healthcare, AVID Radiopharmaceuticals, and Euroimmun. Dr. Reiman has received grants from Roche/Roche Diagnostics and received personal fees from Alkahest, Alzheon, Aural Analytics, Denali, Green Valley, MagQ, Takeda/Zinfandel, and United Neuroscience. He is also a cofounder of AlzPath, which aims to further develop P-tau217 and fluid biomarkers; holds a patent owned by Banner Health for a strategy to use biomarkers to accelerate evaluation of Alzheimer prevention therapies; and is a principal investigator of prevention trials that include research agreements with Genentech/Roche and Novartis/Amgen, PET studies that include research agreements with Avid/Lilly, and several National Institute of Health–supported research studies. Dr. Fillit reported no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
new research suggests.
Results from a large multinational study showed that the level of P-tau217 in blood collected during life was an accurate predictor of tau brain changes seen in brain tissue after death. In addition, increasing blood P-tau217 levels can be detected in some individuals up to 20 years before the average age of onset of the early cognitive decline that signals Alzheimer’s disease, researchers reported.
“While there is still more work to be done, this biomarker has the potential to have a transformational impact on research, treatment, prevention, and therapy development, and in the clinical setting,” said senior author Eric M. Reiman, MD, executive director of Banner Alzheimer’s Institute in Phoenix.
The findings were presented at the virtual annual meeting of the Alzheimer’s Association International Conference and simultaneously published online July 28 in JAMA.
Three cohorts
The international team of researchers evaluated the P-tau217 blood test in 1,402 adults from three cohorts. The first cohort was made up of 81 individuals in the Arizona (Banner Sun Health Research Institute) Brain Donation program and included clinical, blood, and neuropathologic data. The second cohort included 699 individuals in the Swedish BioFINDER-2 study and provided clinical, brain imaging, cerebrospinal fluid (CSF), and blood data. The third cohort was made up of 522 participants from the Columbian autosomal-dominant Alzheimer’s disease kindred, including 365 PSEN1 E280A mutation carriers and 257 mutation noncarriers.
In the Arizona cohort, plasma P-tau217 discriminated neuropathologically defined Alzheimer’s disease from non-Alzheimer’s disease (area under the curve, 0.89; 95% CI, 0.81-0.97) with significantly higher accuracy than plasma P-tau181 and neurofilament light chain (NfL) (AUC range, 0.50-0.72; P < .05).
In the Swedish BioFINDER-2 cohort, the discriminative accuracy of plasma P-tau217 for clinical Alzheimer’s disease dementia versus other neurodegenerative diseases was 96% (AUC, 0.96; 95% CI, 0.93-0.98).
This was significantly higher than plasma P-tau181, plasma NfL, and MRI measures (AUC range, 0.50-0.81; P < .001), but was not significantly different than CSF P-tau217, CSF P-tau181, and tau-PET (AUC range, 0.90-0.99; P > .15).
In the Colombian cohort, plasma P-tau217 levels were significantly greater among PSEN1 mutation carriers than noncarriers starting at around age 25 years, which is 20 years prior to the estimated onset of mild cognitive impairment among mutation carriers.
Additionally, plasma P-tau217 levels correlated with cerebral tau tangles, and discriminated abnormal versus normal tau-PET scans with significantly higher accuracy than plasma P-tau181, plasma NfL, CSF P-tau181, CSF Abeta42:Abeta40 ratio, and MRI measures.
The blood test “opens the possibility of early diagnosis of Alzheimer’s disease before the dementia stage, which is very important for clinical trials evaluating novel therapies that might stop or slow down the disease process,” presenting author Oskar Hansson, MD, PhD, of Lund (Sweden) University, said in a statement.
Further research is now needed to optimize the P-tau217 blood test, validate the findings in unselected and diverse populations, and determine its potential role in the clinic, the investigators noted.
Potential game changer?
Commenting on the study, Howard Fillit, MD, founding executive director and chief science officer of the Alzheimer’s Drug Discovery Foundation, noted his enthusiasm for the test. “This tau blood test will be a real game changer, advancing clinical care and research,” said Dr. Fillit, who was not involved in the research.
“This is a real breakthrough: a simple and accessible blood test that can diagnose Alzheimer’s disease better than the more costly and invasive methods currently available like PET scans and cerebrospinal fluid biomarkers,” he said.
The P-tau217 blood test “is like the equivalent of the cholesterol test for heart disease, but for Alzheimer’s disease,” Dr. Fillit added.
As previously reported, another study presented at AAIC 2020 compared P-tau217 with P-tau181 to determine which could best identify individuals with Alzheimer’s disease. Results showed that, although the two biomarkers were similar overall, P-tau217 had a slight edge in terms of accuracy.
The study by Reiman et al. was funded by the Swedish Research Council, the Knut and Alice Wallenberg Foundation, and the Swedish Alzheimer Foundation. Dr. Hansson reported receiving grants from Roche, Biogen, and Pfizer, and receiving nonfinancial support from GE Healthcare, AVID Radiopharmaceuticals, and Euroimmun. Dr. Reiman has received grants from Roche/Roche Diagnostics and received personal fees from Alkahest, Alzheon, Aural Analytics, Denali, Green Valley, MagQ, Takeda/Zinfandel, and United Neuroscience. He is also a cofounder of AlzPath, which aims to further develop P-tau217 and fluid biomarkers; holds a patent owned by Banner Health for a strategy to use biomarkers to accelerate evaluation of Alzheimer prevention therapies; and is a principal investigator of prevention trials that include research agreements with Genentech/Roche and Novartis/Amgen, PET studies that include research agreements with Avid/Lilly, and several National Institute of Health–supported research studies. Dr. Fillit reported no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
FROM AAIC 2020
A better tau blood test for diagnosing Alzheimer’s disease?
.
In one new development, experts at the University of California, San Francisco (UCSF) compared phosphorylated-tau181 (P-tau181) to a related form of tau called P-tau217 to determine which can best identify individuals with Alzheimer’s disease.
Results showed that the two biomarkers were similar overall, but P-tau 217 had a slight edge in terms of accuracy. Importantly, both tau isoforms distinguished frontotemporal lobar degeneration (FTLD).
“These new blood tests for P-tau are going to be really exciting because they will improve our ability to simply and inexpensively assess whether someone is at high risk for having Alzheimer’s disease,” said study author Adam L. Boxer, MD, PhD, professor in UCSF’s department of neurology.
With the approval of the first disease-modifying therapy for Alzheimer’s disease possibly around the corner, developing an accurate diagnostic blood test for this condition is even more urgent, added Dr. Boxer, who is also director of UCSF’s Neurosciences Clinical Research Unit and AD and FTD Clinical Trials Program.
The findings were presented at the virtual annual meeting of the Alzheimer’s Association International Conference.
Important implications
Currently, the only approved Alzheimer’s disease biomarkers are expensive positron emission tomography (PET) scans using agents that detect tau or amyloid, another hallmark Alzheimer’s disease protein, and cerebrospinal fluid levels of amyloid and tau, the measurement of which entails invasive lumbar puncture procedures. This limits the ability to easily confirm the underlying cause of dementia or cognitive impairment, which “obviously has important prognostic and therapeutic implications,” said Dr. Boxer.
Having a plasma biomarker, especially for tau, would be extremely useful. Patients with increased tau in the brain tend to exhibit Alzheimer’s disease symptoms while those with amyloid plaques do not always have clear signs, at least not immediately. “We think that P-tau is probably a better measure because it is much more closely related to symptoms of disease,” said Dr. Boxer.
Earlier this year, he and colleagues published a study in Nature Medicine showing that P-tau181 is more than three times as high in individuals with Alzheimer’s disease compared with healthy elderly people. It also differentiated Alzheimer’s disease from frontotemporal dementia (FTD). “We found that P-tau 181 was almost as good as a PET scan or lumbar puncture at identifying individuals with Alzheimer’s disease pathology in the brain,” said Dr. Boxer.
They next wanted to assess how well P-tau 217 held up as a possible biomarker.
The new retrospective study was composed of 210 participants: 37 who acted as healthy controls, 99 who had FTLD, 39 who had Alzheimer’s disease, and 35 who had mild cognitive impairment.
More accurate test
Results showed that plasma P-tau217 was increased 5.7-fold in the participants with Alzheimer’s disease compared with the healthy controls group, and increased fivefold compared with those who had FTLD (both comparisons, P < .001).
The increase in plasma P-tau181 was lower. It was increased only 4.5-times in participants with Alzheimer’s disease compared with the healthy controls and 3.8-times relative to those with FTLD (both, P < .001). In addition, P-tau217 was potentially superior in predicting whether a person had a tau positive FTP-PET brain scan.
“This newer P-tau 217 test produces very similar results to the previous test we published [on P-tau181], but might be incrementally better or slightly more accurate, and even more closely related to the signal you get with a tau PET scan,” Dr. Boxer said.
The researchers are now examining these issues in a larger group of participants (N = 617). Results for those analyses are expected to be published soon. In addition to tau and amyloid markers, the researchers are examining another potential biomarker of neurodegeneration: the triple protein neurofilament light chain.
It’s too early to say which biomarker or biomarkers will prove to be the most useful in diagnosing Alzheimer’s disease, Dr. Boxer noted. “It’s an open question whether it will be necessary to measure multiple P-taus plus beta amyloid plus neurofilament, or maybe just measuring one P-tau level will be sufficient,” he said.
Upcoming therapy?
Having a test that verifies Alzheimer’s disease is becoming all the more important now that a therapy might soon be available. Massachusetts-based biotech company Biogen has submitted aducanumab, a monoclonal antibody that targets amyloid-beta (Abeta), to the Food and Drug Administration for approval. Should that move forward, aducanumab would be the first disease-modifying therapy for Alzheimer’s disease.
“If that’s the case, it will be even more important to have simple ways to screen people, to see if they might eventually be eligible for treatment,” said Dr. Boxer. Even if the drug isn’t approved, many patients simply want to know what is causing their cognitive problems, he added. Knowing they have Alzheimer’s disease might impact their life planning. If they have mild symptoms, interventions such as exercise and reducing cardiovascular risk could improve their overall health and quality of life, he said.
If individuals have another type of dementia, such as FTLD, that, too, might determine a different approach. Some forms of FTLD are caused by “completely different biological processes,” which are now being studied, Dr. Boxer said. So knowing that patients have this condition would allow them to participate in relevant clinical trials.
Exciting aspect
Having a tau blood test will also help those in underserviced and minority communities who can’t easily access memory specialists, Dr. Boxer noted. “It might allow them to access care, and get help much more easily, and that is a really exciting aspect of this new technology,” he said. It’s not clear when such blood tests will be on the market, although many companies are “scrambling” to make them available, said Dr. Boxer.
P-tau217 also holds promise as a marker for early Alzheimer’s disease pathology, according to another study presented at AAIC 2020. A Swedish research team measured P-tau217 in more than 1,000 participants, including those who were unimpaired and those with mild cognitive impairment, Alzheimer’s disease dementia, or non-Alzheimer’s disease neurodegenerative diseases.
Results showed that plasma P-tau217 levels increase in early stages of Alzheimer’s disease when insoluble tau aggregates are not yet detectable with PET. They also predict subsequent increases in tau-PET, as well as conversion to Alzheimer’s disease dementia.
‘Incredible breakthrough’
Commenting on the research, Howard Fillit, MD, founding executive director and chief science officer of the Alzheimer’s Drug Discovery Foundation, called the study amazing and “an incredible breakthrough.
“Researchers are able to detect disease up to 20 years before symptoms. The blood test has very good characteristics in terms of sensitivity and specificity. It correlates with the spinal fluid, it’s better than the PET imaging, it correlates with the amyloid test, and the results are being confirmed in many different cohorts,” said Dr. Fillit, who was not involved with the research.
A tau blood test, especially for P-tau 217, has the potential to be as important to determining dementia risk as cholesterol is to gauging heart disease risk, he added.
Having a tau blood test will “make our clinical trials much more precise and more efficient and reduce costs tremendously,” Dr. Fillit said, adding that he thinks tau blood tests might come to market as early as within a year.
Also commenting on the research, Rebecca M. Edelmayer, PhD, director of scientific engagement for the Alzheimer’s Association, said the new studies illustrate the rapid progress being made “in the blood biomarker space.”
Even 5 years ago, researchers would “never have thought” that blood biomarkers could be used as a tool to detect brain changes related to Alzheimer’s disease, said Dr. Edelmayer.
These new studies are “filling a gap in our understanding around tau” in Alzheimer’s disease and other neurodegenerative diseases, she said. “Being able to distinguish between diseases is going to be very, very crucial for clinicians in the future,” she added.
Dr. Edelmayer foresees that in the future there will be a panel of blood biomarkers in addition to imaging tests to help clinicians make an accurate diagnosis.
The study was supported by the National Institutes of Health and the Tau Research Consortium. Dr. Boxer disclosed that the blood p-tau test was done as part of a research collaboration between UCSF and Eli Lilly. Dr. Fillit and Dr. Edelmayer have disclosed no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
.
In one new development, experts at the University of California, San Francisco (UCSF) compared phosphorylated-tau181 (P-tau181) to a related form of tau called P-tau217 to determine which can best identify individuals with Alzheimer’s disease.
Results showed that the two biomarkers were similar overall, but P-tau 217 had a slight edge in terms of accuracy. Importantly, both tau isoforms distinguished frontotemporal lobar degeneration (FTLD).
“These new blood tests for P-tau are going to be really exciting because they will improve our ability to simply and inexpensively assess whether someone is at high risk for having Alzheimer’s disease,” said study author Adam L. Boxer, MD, PhD, professor in UCSF’s department of neurology.
With the approval of the first disease-modifying therapy for Alzheimer’s disease possibly around the corner, developing an accurate diagnostic blood test for this condition is even more urgent, added Dr. Boxer, who is also director of UCSF’s Neurosciences Clinical Research Unit and AD and FTD Clinical Trials Program.
The findings were presented at the virtual annual meeting of the Alzheimer’s Association International Conference.
Important implications
Currently, the only approved Alzheimer’s disease biomarkers are expensive positron emission tomography (PET) scans using agents that detect tau or amyloid, another hallmark Alzheimer’s disease protein, and cerebrospinal fluid levels of amyloid and tau, the measurement of which entails invasive lumbar puncture procedures. This limits the ability to easily confirm the underlying cause of dementia or cognitive impairment, which “obviously has important prognostic and therapeutic implications,” said Dr. Boxer.
Having a plasma biomarker, especially for tau, would be extremely useful. Patients with increased tau in the brain tend to exhibit Alzheimer’s disease symptoms while those with amyloid plaques do not always have clear signs, at least not immediately. “We think that P-tau is probably a better measure because it is much more closely related to symptoms of disease,” said Dr. Boxer.
Earlier this year, he and colleagues published a study in Nature Medicine showing that P-tau181 is more than three times as high in individuals with Alzheimer’s disease compared with healthy elderly people. It also differentiated Alzheimer’s disease from frontotemporal dementia (FTD). “We found that P-tau 181 was almost as good as a PET scan or lumbar puncture at identifying individuals with Alzheimer’s disease pathology in the brain,” said Dr. Boxer.
They next wanted to assess how well P-tau 217 held up as a possible biomarker.
The new retrospective study was composed of 210 participants: 37 who acted as healthy controls, 99 who had FTLD, 39 who had Alzheimer’s disease, and 35 who had mild cognitive impairment.
More accurate test
Results showed that plasma P-tau217 was increased 5.7-fold in the participants with Alzheimer’s disease compared with the healthy controls group, and increased fivefold compared with those who had FTLD (both comparisons, P < .001).
The increase in plasma P-tau181 was lower. It was increased only 4.5-times in participants with Alzheimer’s disease compared with the healthy controls and 3.8-times relative to those with FTLD (both, P < .001). In addition, P-tau217 was potentially superior in predicting whether a person had a tau positive FTP-PET brain scan.
“This newer P-tau 217 test produces very similar results to the previous test we published [on P-tau181], but might be incrementally better or slightly more accurate, and even more closely related to the signal you get with a tau PET scan,” Dr. Boxer said.
The researchers are now examining these issues in a larger group of participants (N = 617). Results for those analyses are expected to be published soon. In addition to tau and amyloid markers, the researchers are examining another potential biomarker of neurodegeneration: the triple protein neurofilament light chain.
It’s too early to say which biomarker or biomarkers will prove to be the most useful in diagnosing Alzheimer’s disease, Dr. Boxer noted. “It’s an open question whether it will be necessary to measure multiple P-taus plus beta amyloid plus neurofilament, or maybe just measuring one P-tau level will be sufficient,” he said.
Upcoming therapy?
Having a test that verifies Alzheimer’s disease is becoming all the more important now that a therapy might soon be available. Massachusetts-based biotech company Biogen has submitted aducanumab, a monoclonal antibody that targets amyloid-beta (Abeta), to the Food and Drug Administration for approval. Should that move forward, aducanumab would be the first disease-modifying therapy for Alzheimer’s disease.
“If that’s the case, it will be even more important to have simple ways to screen people, to see if they might eventually be eligible for treatment,” said Dr. Boxer. Even if the drug isn’t approved, many patients simply want to know what is causing their cognitive problems, he added. Knowing they have Alzheimer’s disease might impact their life planning. If they have mild symptoms, interventions such as exercise and reducing cardiovascular risk could improve their overall health and quality of life, he said.
If individuals have another type of dementia, such as FTLD, that, too, might determine a different approach. Some forms of FTLD are caused by “completely different biological processes,” which are now being studied, Dr. Boxer said. So knowing that patients have this condition would allow them to participate in relevant clinical trials.
Exciting aspect
Having a tau blood test will also help those in underserviced and minority communities who can’t easily access memory specialists, Dr. Boxer noted. “It might allow them to access care, and get help much more easily, and that is a really exciting aspect of this new technology,” he said. It’s not clear when such blood tests will be on the market, although many companies are “scrambling” to make them available, said Dr. Boxer.
P-tau217 also holds promise as a marker for early Alzheimer’s disease pathology, according to another study presented at AAIC 2020. A Swedish research team measured P-tau217 in more than 1,000 participants, including those who were unimpaired and those with mild cognitive impairment, Alzheimer’s disease dementia, or non-Alzheimer’s disease neurodegenerative diseases.
Results showed that plasma P-tau217 levels increase in early stages of Alzheimer’s disease when insoluble tau aggregates are not yet detectable with PET. They also predict subsequent increases in tau-PET, as well as conversion to Alzheimer’s disease dementia.
‘Incredible breakthrough’
Commenting on the research, Howard Fillit, MD, founding executive director and chief science officer of the Alzheimer’s Drug Discovery Foundation, called the study amazing and “an incredible breakthrough.
“Researchers are able to detect disease up to 20 years before symptoms. The blood test has very good characteristics in terms of sensitivity and specificity. It correlates with the spinal fluid, it’s better than the PET imaging, it correlates with the amyloid test, and the results are being confirmed in many different cohorts,” said Dr. Fillit, who was not involved with the research.
A tau blood test, especially for P-tau 217, has the potential to be as important to determining dementia risk as cholesterol is to gauging heart disease risk, he added.
Having a tau blood test will “make our clinical trials much more precise and more efficient and reduce costs tremendously,” Dr. Fillit said, adding that he thinks tau blood tests might come to market as early as within a year.
Also commenting on the research, Rebecca M. Edelmayer, PhD, director of scientific engagement for the Alzheimer’s Association, said the new studies illustrate the rapid progress being made “in the blood biomarker space.”
Even 5 years ago, researchers would “never have thought” that blood biomarkers could be used as a tool to detect brain changes related to Alzheimer’s disease, said Dr. Edelmayer.
These new studies are “filling a gap in our understanding around tau” in Alzheimer’s disease and other neurodegenerative diseases, she said. “Being able to distinguish between diseases is going to be very, very crucial for clinicians in the future,” she added.
Dr. Edelmayer foresees that in the future there will be a panel of blood biomarkers in addition to imaging tests to help clinicians make an accurate diagnosis.
The study was supported by the National Institutes of Health and the Tau Research Consortium. Dr. Boxer disclosed that the blood p-tau test was done as part of a research collaboration between UCSF and Eli Lilly. Dr. Fillit and Dr. Edelmayer have disclosed no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
.
In one new development, experts at the University of California, San Francisco (UCSF) compared phosphorylated-tau181 (P-tau181) to a related form of tau called P-tau217 to determine which can best identify individuals with Alzheimer’s disease.
Results showed that the two biomarkers were similar overall, but P-tau 217 had a slight edge in terms of accuracy. Importantly, both tau isoforms distinguished frontotemporal lobar degeneration (FTLD).
“These new blood tests for P-tau are going to be really exciting because they will improve our ability to simply and inexpensively assess whether someone is at high risk for having Alzheimer’s disease,” said study author Adam L. Boxer, MD, PhD, professor in UCSF’s department of neurology.
With the approval of the first disease-modifying therapy for Alzheimer’s disease possibly around the corner, developing an accurate diagnostic blood test for this condition is even more urgent, added Dr. Boxer, who is also director of UCSF’s Neurosciences Clinical Research Unit and AD and FTD Clinical Trials Program.
The findings were presented at the virtual annual meeting of the Alzheimer’s Association International Conference.
Important implications
Currently, the only approved Alzheimer’s disease biomarkers are expensive positron emission tomography (PET) scans using agents that detect tau or amyloid, another hallmark Alzheimer’s disease protein, and cerebrospinal fluid levels of amyloid and tau, the measurement of which entails invasive lumbar puncture procedures. This limits the ability to easily confirm the underlying cause of dementia or cognitive impairment, which “obviously has important prognostic and therapeutic implications,” said Dr. Boxer.
Having a plasma biomarker, especially for tau, would be extremely useful. Patients with increased tau in the brain tend to exhibit Alzheimer’s disease symptoms while those with amyloid plaques do not always have clear signs, at least not immediately. “We think that P-tau is probably a better measure because it is much more closely related to symptoms of disease,” said Dr. Boxer.
Earlier this year, he and colleagues published a study in Nature Medicine showing that P-tau181 is more than three times as high in individuals with Alzheimer’s disease compared with healthy elderly people. It also differentiated Alzheimer’s disease from frontotemporal dementia (FTD). “We found that P-tau 181 was almost as good as a PET scan or lumbar puncture at identifying individuals with Alzheimer’s disease pathology in the brain,” said Dr. Boxer.
They next wanted to assess how well P-tau 217 held up as a possible biomarker.
The new retrospective study was composed of 210 participants: 37 who acted as healthy controls, 99 who had FTLD, 39 who had Alzheimer’s disease, and 35 who had mild cognitive impairment.
More accurate test
Results showed that plasma P-tau217 was increased 5.7-fold in the participants with Alzheimer’s disease compared with the healthy controls group, and increased fivefold compared with those who had FTLD (both comparisons, P < .001).
The increase in plasma P-tau181 was lower. It was increased only 4.5-times in participants with Alzheimer’s disease compared with the healthy controls and 3.8-times relative to those with FTLD (both, P < .001). In addition, P-tau217 was potentially superior in predicting whether a person had a tau positive FTP-PET brain scan.
“This newer P-tau 217 test produces very similar results to the previous test we published [on P-tau181], but might be incrementally better or slightly more accurate, and even more closely related to the signal you get with a tau PET scan,” Dr. Boxer said.
The researchers are now examining these issues in a larger group of participants (N = 617). Results for those analyses are expected to be published soon. In addition to tau and amyloid markers, the researchers are examining another potential biomarker of neurodegeneration: the triple protein neurofilament light chain.
It’s too early to say which biomarker or biomarkers will prove to be the most useful in diagnosing Alzheimer’s disease, Dr. Boxer noted. “It’s an open question whether it will be necessary to measure multiple P-taus plus beta amyloid plus neurofilament, or maybe just measuring one P-tau level will be sufficient,” he said.
Upcoming therapy?
Having a test that verifies Alzheimer’s disease is becoming all the more important now that a therapy might soon be available. Massachusetts-based biotech company Biogen has submitted aducanumab, a monoclonal antibody that targets amyloid-beta (Abeta), to the Food and Drug Administration for approval. Should that move forward, aducanumab would be the first disease-modifying therapy for Alzheimer’s disease.
“If that’s the case, it will be even more important to have simple ways to screen people, to see if they might eventually be eligible for treatment,” said Dr. Boxer. Even if the drug isn’t approved, many patients simply want to know what is causing their cognitive problems, he added. Knowing they have Alzheimer’s disease might impact their life planning. If they have mild symptoms, interventions such as exercise and reducing cardiovascular risk could improve their overall health and quality of life, he said.
If individuals have another type of dementia, such as FTLD, that, too, might determine a different approach. Some forms of FTLD are caused by “completely different biological processes,” which are now being studied, Dr. Boxer said. So knowing that patients have this condition would allow them to participate in relevant clinical trials.
Exciting aspect
Having a tau blood test will also help those in underserviced and minority communities who can’t easily access memory specialists, Dr. Boxer noted. “It might allow them to access care, and get help much more easily, and that is a really exciting aspect of this new technology,” he said. It’s not clear when such blood tests will be on the market, although many companies are “scrambling” to make them available, said Dr. Boxer.
P-tau217 also holds promise as a marker for early Alzheimer’s disease pathology, according to another study presented at AAIC 2020. A Swedish research team measured P-tau217 in more than 1,000 participants, including those who were unimpaired and those with mild cognitive impairment, Alzheimer’s disease dementia, or non-Alzheimer’s disease neurodegenerative diseases.
Results showed that plasma P-tau217 levels increase in early stages of Alzheimer’s disease when insoluble tau aggregates are not yet detectable with PET. They also predict subsequent increases in tau-PET, as well as conversion to Alzheimer’s disease dementia.
‘Incredible breakthrough’
Commenting on the research, Howard Fillit, MD, founding executive director and chief science officer of the Alzheimer’s Drug Discovery Foundation, called the study amazing and “an incredible breakthrough.
“Researchers are able to detect disease up to 20 years before symptoms. The blood test has very good characteristics in terms of sensitivity and specificity. It correlates with the spinal fluid, it’s better than the PET imaging, it correlates with the amyloid test, and the results are being confirmed in many different cohorts,” said Dr. Fillit, who was not involved with the research.
A tau blood test, especially for P-tau 217, has the potential to be as important to determining dementia risk as cholesterol is to gauging heart disease risk, he added.
Having a tau blood test will “make our clinical trials much more precise and more efficient and reduce costs tremendously,” Dr. Fillit said, adding that he thinks tau blood tests might come to market as early as within a year.
Also commenting on the research, Rebecca M. Edelmayer, PhD, director of scientific engagement for the Alzheimer’s Association, said the new studies illustrate the rapid progress being made “in the blood biomarker space.”
Even 5 years ago, researchers would “never have thought” that blood biomarkers could be used as a tool to detect brain changes related to Alzheimer’s disease, said Dr. Edelmayer.
These new studies are “filling a gap in our understanding around tau” in Alzheimer’s disease and other neurodegenerative diseases, she said. “Being able to distinguish between diseases is going to be very, very crucial for clinicians in the future,” she added.
Dr. Edelmayer foresees that in the future there will be a panel of blood biomarkers in addition to imaging tests to help clinicians make an accurate diagnosis.
The study was supported by the National Institutes of Health and the Tau Research Consortium. Dr. Boxer disclosed that the blood p-tau test was done as part of a research collaboration between UCSF and Eli Lilly. Dr. Fillit and Dr. Edelmayer have disclosed no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
FROM AAIC 2020
Flu and pneumonia vaccination tied to lower dementia risk
In a cohort study of more than 9,000 older adults, receiving a single influenza vaccination was associated with a 17% lower prevalence of Alzheimer’s disease compared with not receiving the vaccine. In addition, for those who were vaccinated more than once over the years, there was an additional 13% reduction in Alzheimer’s disease incidence.
In another study, which included more than 5,000 older participants, being vaccinated against pneumonia between the ages of 65 and 75 reduced the risk of developing Alzheimer’s disease by 30%.
The subject of vaccines “is obviously very topical with the COVID-19 pandemic,” said Rebecca M. Edelmayer, PhD, director of scientific engagement for the Alzheimer’s Association. “While these are very preliminary data, these studies do suggest that with vaccination against both respiratory illnesses, there is the potential to lower risk for developing cognitive decline and dementia,” said Dr. Edelmayer, who was not involved in the research.
The findings of both studies were presented at the virtual annual meeting of the Alzheimer’s Association International Conference.
Lower Alzheimer’s disease prevalence
The influenza vaccine study was presented by Albert Amran, a fourth-year medical student at McGovern Medical School at the University of Texas Health Science Center at Houston. The researchers used electronic health record data to create a propensity-matched cohort of 9,066 vaccinated and unvaccinated adults ages 60 and older.
Influenza vaccination, increased frequency of administration, and younger age at time of vaccination were all associated with reduced incidence of Alzheimer’s disease, Mr. Amran reported.
Being vaccinated for influenza was significantly linked to a lower prevalence of Alzheimer’s disease (odds ratio [OR], 0.83; P < .0001) in comparison with not being vaccinated. Receiving more than one vaccination over the years was associated with an additional reduction in AD incidence (OR, 0.87; P = .0342). The protection appeared to be strongest for those who received their first vaccination at a younger age, for example, at age 60 versus 70.
Mr. Amran and research colleagues have two theories as to why influenza vaccination may protect the brain.
One is that vaccination may aid the immune system as people age. “As people get older, their immune systems become less able to control infection. We’ve seen this with the ongoing pandemic, with older people at much higher risk for dying. Giving people the vaccine once a year may help keep the immune system in shape,” Mr. Amran said.
Another theory is that the prevention of influenza itself may be relevant. “Flu infections can be extremely deadly in older patients. Maybe the results of our study will give another reason for people to get vaccinated,” Mr. Amran said.
Pneumonia vaccine
The other study was presented by Svetlana Ukraintseva, PhD, of Duke University, Durham, N.C.
Dr. Ukraintseva and colleagues investigated associations between pneumococcal vaccine, with and without an accompanying influenza vaccine, and the risk for Alzheimer’s disease among 5,146 participants in the Cardiovascular Health Study. Covariates included sex, race, birth cohort, education, smoking, and a known genetic risk factor for Alzheimer’s disease: the rs2075650 G allele in the TOMM40 gene.
In a logistic model with all covariates, vaccination against pneumonia between ages 65 and 75 was significantly associated with reduced risk of developing AD (OR, 0.70; P < .04). The largest reduction in Alzheimer’s disease risk (OR, 0.62; P < .04) was among those vaccinated against pneumonia who were noncarriers of the rs2075650 G allele.
Total number of vaccinations against pneumonia and influenza between ages 65 and 75 was also associated with a lower risk for Alzheimer’s disease (OR, 0.88; P < .01). However, the effect was not evident for the influenza vaccination alone.
“The fact that very different pathogens – viral, bacterial, fungal – have been linked to Alzheimer’s disease indicates a possibility that compromised host immunity may play a role in Alzheimer’s disease through increasing overall brain’s vulnerability to various microbes,” said Dr. Ukraintseva.
The current findings support further investigation of pneumococcal vaccine as a “reasonable candidate for repurposing in personalized AD prevention,” she noted. “These results also support the important role of boosting overall immune robustness/resilience in preventing Alzheimer’s disease,” Dr. Ukraintseva added.
Her group is currently working on confirming the findings in another population.
Brain protective?
“Neither study can prove that the benefit is directly related to the vaccine itself, but what they can indicate is that potentially, vaccines are a way to protect your health and brain,” Dr. Edelmayer said.
In a statement, Maria Carrillo, PhD, chief science officer for the Alzheimer’s Association, noted that more research is needed.
The new data call “for further studies in large, diverse clinical trials to inform whether vaccinations as a public health strategy decrease our risk for developing dementia as we age,” Dr. Carillo said.
Funding for the influenza vaccine study was provided by the Christopher Sarofim Family Professorship in Biomedical Informatics and Bioengineering, a UT STARs Award, the Cancer Prevention and Research Institute of Texas, and the National Institutes of Health. Funding for the pneumonia study was provided by the National Institute on Aging. Dr. Amran, Dr. Ukraintseva, Dr. Edelmayer, and Dr. Carrillo have reported no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
In a cohort study of more than 9,000 older adults, receiving a single influenza vaccination was associated with a 17% lower prevalence of Alzheimer’s disease compared with not receiving the vaccine. In addition, for those who were vaccinated more than once over the years, there was an additional 13% reduction in Alzheimer’s disease incidence.
In another study, which included more than 5,000 older participants, being vaccinated against pneumonia between the ages of 65 and 75 reduced the risk of developing Alzheimer’s disease by 30%.
The subject of vaccines “is obviously very topical with the COVID-19 pandemic,” said Rebecca M. Edelmayer, PhD, director of scientific engagement for the Alzheimer’s Association. “While these are very preliminary data, these studies do suggest that with vaccination against both respiratory illnesses, there is the potential to lower risk for developing cognitive decline and dementia,” said Dr. Edelmayer, who was not involved in the research.
The findings of both studies were presented at the virtual annual meeting of the Alzheimer’s Association International Conference.
Lower Alzheimer’s disease prevalence
The influenza vaccine study was presented by Albert Amran, a fourth-year medical student at McGovern Medical School at the University of Texas Health Science Center at Houston. The researchers used electronic health record data to create a propensity-matched cohort of 9,066 vaccinated and unvaccinated adults ages 60 and older.
Influenza vaccination, increased frequency of administration, and younger age at time of vaccination were all associated with reduced incidence of Alzheimer’s disease, Mr. Amran reported.
Being vaccinated for influenza was significantly linked to a lower prevalence of Alzheimer’s disease (odds ratio [OR], 0.83; P < .0001) in comparison with not being vaccinated. Receiving more than one vaccination over the years was associated with an additional reduction in AD incidence (OR, 0.87; P = .0342). The protection appeared to be strongest for those who received their first vaccination at a younger age, for example, at age 60 versus 70.
Mr. Amran and research colleagues have two theories as to why influenza vaccination may protect the brain.
One is that vaccination may aid the immune system as people age. “As people get older, their immune systems become less able to control infection. We’ve seen this with the ongoing pandemic, with older people at much higher risk for dying. Giving people the vaccine once a year may help keep the immune system in shape,” Mr. Amran said.
Another theory is that the prevention of influenza itself may be relevant. “Flu infections can be extremely deadly in older patients. Maybe the results of our study will give another reason for people to get vaccinated,” Mr. Amran said.
Pneumonia vaccine
The other study was presented by Svetlana Ukraintseva, PhD, of Duke University, Durham, N.C.
Dr. Ukraintseva and colleagues investigated associations between pneumococcal vaccine, with and without an accompanying influenza vaccine, and the risk for Alzheimer’s disease among 5,146 participants in the Cardiovascular Health Study. Covariates included sex, race, birth cohort, education, smoking, and a known genetic risk factor for Alzheimer’s disease: the rs2075650 G allele in the TOMM40 gene.
In a logistic model with all covariates, vaccination against pneumonia between ages 65 and 75 was significantly associated with reduced risk of developing AD (OR, 0.70; P < .04). The largest reduction in Alzheimer’s disease risk (OR, 0.62; P < .04) was among those vaccinated against pneumonia who were noncarriers of the rs2075650 G allele.
Total number of vaccinations against pneumonia and influenza between ages 65 and 75 was also associated with a lower risk for Alzheimer’s disease (OR, 0.88; P < .01). However, the effect was not evident for the influenza vaccination alone.
“The fact that very different pathogens – viral, bacterial, fungal – have been linked to Alzheimer’s disease indicates a possibility that compromised host immunity may play a role in Alzheimer’s disease through increasing overall brain’s vulnerability to various microbes,” said Dr. Ukraintseva.
The current findings support further investigation of pneumococcal vaccine as a “reasonable candidate for repurposing in personalized AD prevention,” she noted. “These results also support the important role of boosting overall immune robustness/resilience in preventing Alzheimer’s disease,” Dr. Ukraintseva added.
Her group is currently working on confirming the findings in another population.
Brain protective?
“Neither study can prove that the benefit is directly related to the vaccine itself, but what they can indicate is that potentially, vaccines are a way to protect your health and brain,” Dr. Edelmayer said.
In a statement, Maria Carrillo, PhD, chief science officer for the Alzheimer’s Association, noted that more research is needed.
The new data call “for further studies in large, diverse clinical trials to inform whether vaccinations as a public health strategy decrease our risk for developing dementia as we age,” Dr. Carillo said.
Funding for the influenza vaccine study was provided by the Christopher Sarofim Family Professorship in Biomedical Informatics and Bioengineering, a UT STARs Award, the Cancer Prevention and Research Institute of Texas, and the National Institutes of Health. Funding for the pneumonia study was provided by the National Institute on Aging. Dr. Amran, Dr. Ukraintseva, Dr. Edelmayer, and Dr. Carrillo have reported no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
In a cohort study of more than 9,000 older adults, receiving a single influenza vaccination was associated with a 17% lower prevalence of Alzheimer’s disease compared with not receiving the vaccine. In addition, for those who were vaccinated more than once over the years, there was an additional 13% reduction in Alzheimer’s disease incidence.
In another study, which included more than 5,000 older participants, being vaccinated against pneumonia between the ages of 65 and 75 reduced the risk of developing Alzheimer’s disease by 30%.
The subject of vaccines “is obviously very topical with the COVID-19 pandemic,” said Rebecca M. Edelmayer, PhD, director of scientific engagement for the Alzheimer’s Association. “While these are very preliminary data, these studies do suggest that with vaccination against both respiratory illnesses, there is the potential to lower risk for developing cognitive decline and dementia,” said Dr. Edelmayer, who was not involved in the research.
The findings of both studies were presented at the virtual annual meeting of the Alzheimer’s Association International Conference.
Lower Alzheimer’s disease prevalence
The influenza vaccine study was presented by Albert Amran, a fourth-year medical student at McGovern Medical School at the University of Texas Health Science Center at Houston. The researchers used electronic health record data to create a propensity-matched cohort of 9,066 vaccinated and unvaccinated adults ages 60 and older.
Influenza vaccination, increased frequency of administration, and younger age at time of vaccination were all associated with reduced incidence of Alzheimer’s disease, Mr. Amran reported.
Being vaccinated for influenza was significantly linked to a lower prevalence of Alzheimer’s disease (odds ratio [OR], 0.83; P < .0001) in comparison with not being vaccinated. Receiving more than one vaccination over the years was associated with an additional reduction in AD incidence (OR, 0.87; P = .0342). The protection appeared to be strongest for those who received their first vaccination at a younger age, for example, at age 60 versus 70.
Mr. Amran and research colleagues have two theories as to why influenza vaccination may protect the brain.
One is that vaccination may aid the immune system as people age. “As people get older, their immune systems become less able to control infection. We’ve seen this with the ongoing pandemic, with older people at much higher risk for dying. Giving people the vaccine once a year may help keep the immune system in shape,” Mr. Amran said.
Another theory is that the prevention of influenza itself may be relevant. “Flu infections can be extremely deadly in older patients. Maybe the results of our study will give another reason for people to get vaccinated,” Mr. Amran said.
Pneumonia vaccine
The other study was presented by Svetlana Ukraintseva, PhD, of Duke University, Durham, N.C.
Dr. Ukraintseva and colleagues investigated associations between pneumococcal vaccine, with and without an accompanying influenza vaccine, and the risk for Alzheimer’s disease among 5,146 participants in the Cardiovascular Health Study. Covariates included sex, race, birth cohort, education, smoking, and a known genetic risk factor for Alzheimer’s disease: the rs2075650 G allele in the TOMM40 gene.
In a logistic model with all covariates, vaccination against pneumonia between ages 65 and 75 was significantly associated with reduced risk of developing AD (OR, 0.70; P < .04). The largest reduction in Alzheimer’s disease risk (OR, 0.62; P < .04) was among those vaccinated against pneumonia who were noncarriers of the rs2075650 G allele.
Total number of vaccinations against pneumonia and influenza between ages 65 and 75 was also associated with a lower risk for Alzheimer’s disease (OR, 0.88; P < .01). However, the effect was not evident for the influenza vaccination alone.
“The fact that very different pathogens – viral, bacterial, fungal – have been linked to Alzheimer’s disease indicates a possibility that compromised host immunity may play a role in Alzheimer’s disease through increasing overall brain’s vulnerability to various microbes,” said Dr. Ukraintseva.
The current findings support further investigation of pneumococcal vaccine as a “reasonable candidate for repurposing in personalized AD prevention,” she noted. “These results also support the important role of boosting overall immune robustness/resilience in preventing Alzheimer’s disease,” Dr. Ukraintseva added.
Her group is currently working on confirming the findings in another population.
Brain protective?
“Neither study can prove that the benefit is directly related to the vaccine itself, but what they can indicate is that potentially, vaccines are a way to protect your health and brain,” Dr. Edelmayer said.
In a statement, Maria Carrillo, PhD, chief science officer for the Alzheimer’s Association, noted that more research is needed.
The new data call “for further studies in large, diverse clinical trials to inform whether vaccinations as a public health strategy decrease our risk for developing dementia as we age,” Dr. Carillo said.
Funding for the influenza vaccine study was provided by the Christopher Sarofim Family Professorship in Biomedical Informatics and Bioengineering, a UT STARs Award, the Cancer Prevention and Research Institute of Texas, and the National Institutes of Health. Funding for the pneumonia study was provided by the National Institute on Aging. Dr. Amran, Dr. Ukraintseva, Dr. Edelmayer, and Dr. Carrillo have reported no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
FROM AAIC 2020