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COVID-19 tied to acceleration of Alzheimer’s disease pathology
, a new study shows.
These results suggest that COVID-19 may accelerate Alzheimer’s disease symptoms and pathology, said study investigator Thomas Wisniewski, MD, professor of neurology, pathology, and psychiatry at New York University.
The findings were presented here at the Alzheimer’s Association International Conference (AAIC) 2021.
Strong correlation
There’s a clear association between SARS-CoV-2 infection and Alzheimer’s disease-related dementia. Patients with Alzheimer’s disease are at threefold higher risk for the infection and have a twofold higher risk for death, Dr. Wisniewski told meeting delegates.
He and his colleagues conducted a prospective study of patients who had tested positive for SARS-CoV-2 and who experienced neurologic sequelae and SARS-CoV-2 patients who were without neurologic sequelae. All patients were hospitalized from March 10 to May 20, 2020. This was during a period when New York City was overwhelmed by COVID: About 35% of hospitalized patients had COVID.
Of those who experienced neurologic events, the most common “by far and away” (51%) was toxic metabolic encephalopathy (TME), said Dr. Wisniewski. Other associations included seizures, hypoxic/anoxic injury, and ischemic stroke.
The most common TMEs were septic and hypoxic ischemia. In most patients (78%), TME had more than one cause.
Researchers followed 196 patients with COVID and neurologic complications (case patients) and 186 matched control patients who had no neurologic complications over a period of 6 months.
“Unfortunately, both groups had poor outcomes,” said Dr. Wisniewski. About 50% had impaired cognition, and 56% experienced limitations in activities of daily living.
However, those patients with COVID-19 who had neurologic sequelae “fared even worse,” said Dr. Wisniewski. Compared with control patients, they had twofold worse Modified Rankin Scale scores and worse scores on activity of daily living, and they were much less likely to return to work.
Mechanisms by which COVID-19 affects longer-term cognitive dysfunction are unclear, but inflammation likely plays a role.
The research team compared a number of Alzheimer’s disease plasma biomarkers in 158 patients with COVID-19 who had neurologic symptoms and 152 COVID patients with COVID but no neurologic symptoms. They found marked elevations of neurofilament light, a marker of neuronal injury, in those with symptoms (P = .0003) as well as increased glial fibrillary acid protein, a marker of neuroinflammation (P = .0098).
Ubiquitin carboxyl-terminal hydrolase L1, another marker of neuronal injury, was also elevated in those with neurologic symptoms. Regarding Alzheimer’s disease pathology, total tau (t-tau) and phosphorylated tau “also tracked with neurological sequelae,” said Dr. Wisniewski.
There was no difference in levels of amyloid beta 40 (A beta 40) between groups. However, A beta 42 plasma levels were significantly lower in those with neurologic effects, suggesting higher levels in the brain. In addition, the ratio of t-tau to A beta 42 “clearly differentiated the two groups,” he said.
“Serum biomarkers of neuroinflammation and neuronal injury and Alzheimer’s disease correlate strongly, perhaps suggesting that folks with COVID infection and neurological sequelae may have an acceleration of Alzheimer’s disease symptoms and pathology,” he said. “That’s something that needs longer follow-up.”
Important differentiation
Commenting on the research, Rebecca Edelmayer, PhD, senior director of scientific engagement, Alzheimer’s Association, said the study provides important information. The inclusion of plasma biomarkers in this research is “really critical to tease out what’s the impact of COVID itself on the brain,” said Dr. Edelmayer.
“We’re in an era of biomarkers when it comes to Alzheimer’s disease and other dementias, and being able to define those changes that are happening in the brain over time is going to be really critical and aid in early detection and accurate diagnoses,” she said.
What is still to be learned is what these biomarkers reveal long term, said Dr. Edelmayer. “Do those biological markers change? Do they go back to normal? A lot of that is still unknown,” she said.
She noted that many diseases that are linked to inflammation produce similar biomarkers in the brain – for example, neurofilament light.
With other viral infections, such as severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS), similar associations between the infection and cognition have been reported, said Dr. Edelmayer.
“But there are still a lot of questions around cause and effect. Is it really a direct effect of the virus on the brain itself? Is it an effect of having an enormous amount of inflammation going on in the body? A lot of that still needs to be teased out,” she commented.
The study was supported by the National Institutes of Health, the Alzheimer’s Association, and the State of New York. Dr. Wisniewski has consulted for Grifols, Amylon Pharmaceuticals, and Alzamed Neuro; 30 NYU patents are related to AD therapeutics.
A version of this article first appeared on Medscape.com.
, a new study shows.
These results suggest that COVID-19 may accelerate Alzheimer’s disease symptoms and pathology, said study investigator Thomas Wisniewski, MD, professor of neurology, pathology, and psychiatry at New York University.
The findings were presented here at the Alzheimer’s Association International Conference (AAIC) 2021.
Strong correlation
There’s a clear association between SARS-CoV-2 infection and Alzheimer’s disease-related dementia. Patients with Alzheimer’s disease are at threefold higher risk for the infection and have a twofold higher risk for death, Dr. Wisniewski told meeting delegates.
He and his colleagues conducted a prospective study of patients who had tested positive for SARS-CoV-2 and who experienced neurologic sequelae and SARS-CoV-2 patients who were without neurologic sequelae. All patients were hospitalized from March 10 to May 20, 2020. This was during a period when New York City was overwhelmed by COVID: About 35% of hospitalized patients had COVID.
Of those who experienced neurologic events, the most common “by far and away” (51%) was toxic metabolic encephalopathy (TME), said Dr. Wisniewski. Other associations included seizures, hypoxic/anoxic injury, and ischemic stroke.
The most common TMEs were septic and hypoxic ischemia. In most patients (78%), TME had more than one cause.
Researchers followed 196 patients with COVID and neurologic complications (case patients) and 186 matched control patients who had no neurologic complications over a period of 6 months.
“Unfortunately, both groups had poor outcomes,” said Dr. Wisniewski. About 50% had impaired cognition, and 56% experienced limitations in activities of daily living.
However, those patients with COVID-19 who had neurologic sequelae “fared even worse,” said Dr. Wisniewski. Compared with control patients, they had twofold worse Modified Rankin Scale scores and worse scores on activity of daily living, and they were much less likely to return to work.
Mechanisms by which COVID-19 affects longer-term cognitive dysfunction are unclear, but inflammation likely plays a role.
The research team compared a number of Alzheimer’s disease plasma biomarkers in 158 patients with COVID-19 who had neurologic symptoms and 152 COVID patients with COVID but no neurologic symptoms. They found marked elevations of neurofilament light, a marker of neuronal injury, in those with symptoms (P = .0003) as well as increased glial fibrillary acid protein, a marker of neuroinflammation (P = .0098).
Ubiquitin carboxyl-terminal hydrolase L1, another marker of neuronal injury, was also elevated in those with neurologic symptoms. Regarding Alzheimer’s disease pathology, total tau (t-tau) and phosphorylated tau “also tracked with neurological sequelae,” said Dr. Wisniewski.
There was no difference in levels of amyloid beta 40 (A beta 40) between groups. However, A beta 42 plasma levels were significantly lower in those with neurologic effects, suggesting higher levels in the brain. In addition, the ratio of t-tau to A beta 42 “clearly differentiated the two groups,” he said.
“Serum biomarkers of neuroinflammation and neuronal injury and Alzheimer’s disease correlate strongly, perhaps suggesting that folks with COVID infection and neurological sequelae may have an acceleration of Alzheimer’s disease symptoms and pathology,” he said. “That’s something that needs longer follow-up.”
Important differentiation
Commenting on the research, Rebecca Edelmayer, PhD, senior director of scientific engagement, Alzheimer’s Association, said the study provides important information. The inclusion of plasma biomarkers in this research is “really critical to tease out what’s the impact of COVID itself on the brain,” said Dr. Edelmayer.
“We’re in an era of biomarkers when it comes to Alzheimer’s disease and other dementias, and being able to define those changes that are happening in the brain over time is going to be really critical and aid in early detection and accurate diagnoses,” she said.
What is still to be learned is what these biomarkers reveal long term, said Dr. Edelmayer. “Do those biological markers change? Do they go back to normal? A lot of that is still unknown,” she said.
She noted that many diseases that are linked to inflammation produce similar biomarkers in the brain – for example, neurofilament light.
With other viral infections, such as severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS), similar associations between the infection and cognition have been reported, said Dr. Edelmayer.
“But there are still a lot of questions around cause and effect. Is it really a direct effect of the virus on the brain itself? Is it an effect of having an enormous amount of inflammation going on in the body? A lot of that still needs to be teased out,” she commented.
The study was supported by the National Institutes of Health, the Alzheimer’s Association, and the State of New York. Dr. Wisniewski has consulted for Grifols, Amylon Pharmaceuticals, and Alzamed Neuro; 30 NYU patents are related to AD therapeutics.
A version of this article first appeared on Medscape.com.
, a new study shows.
These results suggest that COVID-19 may accelerate Alzheimer’s disease symptoms and pathology, said study investigator Thomas Wisniewski, MD, professor of neurology, pathology, and psychiatry at New York University.
The findings were presented here at the Alzheimer’s Association International Conference (AAIC) 2021.
Strong correlation
There’s a clear association between SARS-CoV-2 infection and Alzheimer’s disease-related dementia. Patients with Alzheimer’s disease are at threefold higher risk for the infection and have a twofold higher risk for death, Dr. Wisniewski told meeting delegates.
He and his colleagues conducted a prospective study of patients who had tested positive for SARS-CoV-2 and who experienced neurologic sequelae and SARS-CoV-2 patients who were without neurologic sequelae. All patients were hospitalized from March 10 to May 20, 2020. This was during a period when New York City was overwhelmed by COVID: About 35% of hospitalized patients had COVID.
Of those who experienced neurologic events, the most common “by far and away” (51%) was toxic metabolic encephalopathy (TME), said Dr. Wisniewski. Other associations included seizures, hypoxic/anoxic injury, and ischemic stroke.
The most common TMEs were septic and hypoxic ischemia. In most patients (78%), TME had more than one cause.
Researchers followed 196 patients with COVID and neurologic complications (case patients) and 186 matched control patients who had no neurologic complications over a period of 6 months.
“Unfortunately, both groups had poor outcomes,” said Dr. Wisniewski. About 50% had impaired cognition, and 56% experienced limitations in activities of daily living.
However, those patients with COVID-19 who had neurologic sequelae “fared even worse,” said Dr. Wisniewski. Compared with control patients, they had twofold worse Modified Rankin Scale scores and worse scores on activity of daily living, and they were much less likely to return to work.
Mechanisms by which COVID-19 affects longer-term cognitive dysfunction are unclear, but inflammation likely plays a role.
The research team compared a number of Alzheimer’s disease plasma biomarkers in 158 patients with COVID-19 who had neurologic symptoms and 152 COVID patients with COVID but no neurologic symptoms. They found marked elevations of neurofilament light, a marker of neuronal injury, in those with symptoms (P = .0003) as well as increased glial fibrillary acid protein, a marker of neuroinflammation (P = .0098).
Ubiquitin carboxyl-terminal hydrolase L1, another marker of neuronal injury, was also elevated in those with neurologic symptoms. Regarding Alzheimer’s disease pathology, total tau (t-tau) and phosphorylated tau “also tracked with neurological sequelae,” said Dr. Wisniewski.
There was no difference in levels of amyloid beta 40 (A beta 40) between groups. However, A beta 42 plasma levels were significantly lower in those with neurologic effects, suggesting higher levels in the brain. In addition, the ratio of t-tau to A beta 42 “clearly differentiated the two groups,” he said.
“Serum biomarkers of neuroinflammation and neuronal injury and Alzheimer’s disease correlate strongly, perhaps suggesting that folks with COVID infection and neurological sequelae may have an acceleration of Alzheimer’s disease symptoms and pathology,” he said. “That’s something that needs longer follow-up.”
Important differentiation
Commenting on the research, Rebecca Edelmayer, PhD, senior director of scientific engagement, Alzheimer’s Association, said the study provides important information. The inclusion of plasma biomarkers in this research is “really critical to tease out what’s the impact of COVID itself on the brain,” said Dr. Edelmayer.
“We’re in an era of biomarkers when it comes to Alzheimer’s disease and other dementias, and being able to define those changes that are happening in the brain over time is going to be really critical and aid in early detection and accurate diagnoses,” she said.
What is still to be learned is what these biomarkers reveal long term, said Dr. Edelmayer. “Do those biological markers change? Do they go back to normal? A lot of that is still unknown,” she said.
She noted that many diseases that are linked to inflammation produce similar biomarkers in the brain – for example, neurofilament light.
With other viral infections, such as severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS), similar associations between the infection and cognition have been reported, said Dr. Edelmayer.
“But there are still a lot of questions around cause and effect. Is it really a direct effect of the virus on the brain itself? Is it an effect of having an enormous amount of inflammation going on in the body? A lot of that still needs to be teased out,” she commented.
The study was supported by the National Institutes of Health, the Alzheimer’s Association, and the State of New York. Dr. Wisniewski has consulted for Grifols, Amylon Pharmaceuticals, and Alzamed Neuro; 30 NYU patents are related to AD therapeutics.
A version of this article first appeared on Medscape.com.
From AAIC 2021
‘Alarming’ data on early cognitive decline in transgender adults
, new research shows.
Investigators found transgender adults – individuals who identify with a gender different than the one assigned to them at birth – were nearly twice as likely to report subjective cognitive decline and more than twice as likely to report SCD-related functional limitations – such as reduced ability to work, volunteer, or be social – than cisgender adults.
“Trans populations are disproportionately impacted by health disparities and also risk factors for dementia. Putting these pieces together, I wasn’t surprised by their greater risk of cognitive decline,” said study investigator Ethan Cicero, PhD, RN, an assistant professor at Emory University, Atlanta.
The findings were presented at the 2021 Alzheimer’s Association International Conference.
‘Alarming’ finding
SCD is a self-reported experience of worsening memory or thinking and is one of the first clinical manifestations of Alzheimer’s disease and related dementia (ADRD). Yet there is limited research into cognitive impairment among transgender adults.
The researchers examined SCD and associated functional limitations among transgender and cisgender adults older than age 45 years who provided health and health behavior data as part of the Behavioral Risk Factor Surveillance System (BRFSS) surveys (2015-2019).
The sample included 386,529 adults of whom 1,302 identified as transgender and 385,227 as cisgender.
Roughly 17% of transgender adults reported SCD, which is significantly higher than the 10.6% rate for cisgender adults (P < .001).
Compared with cisgender adults reporting SCD, transgender adults reporting SCD were younger (mean age 61.9 vs. 65.2 years, P = .0005), more likely to be in a racial/ethnic minority group (37.3% vs. 19.5%, P < .0001), have a high school degree or less (59.6% vs. 43.4%, P = .0003), be uninsured (17% vs. 5.5%, P = .0007) and have a depressive disorder (58.8% vs. 45.7%, P = .0028).
The fact that transgender people who reported SCD were about 3 years younger than cisgender people who reported SCD is “somewhat alarming and a red flag to ask middle-aged trans adults about their brain health and not just older or elderly trans adults,” said Dr. Cicero.
The study also showed that transgender adults reporting SCD were 2.3 times more likely to report related social and self-care limitations when compared with cisgender adults reporting SCD.
The findings align with a study reported at AAIC 2019, which showed that sexual or gender minorities (SGM) are almost 30% more likely to report subjective cognitive decline compared with the non-SGM population.
Cause unclear
“We are not certain what may be causing the elevated subjective cognitive decline rates among transgender adults. We postulate that it may be in part due to anti-transgender stigma and prejudice that expose transgender people to high rates of mistreatment and discrimination where they live, work, learn, seek health care, and age,” Dr. Cicero said.
“More research is needed to identify and target preventive intervention strategies, develop culturally relevant screenings, and shape policies to improve the health and well-being of the transgender population,” he added.
Weighing in on the study, Rebecca Edelmayer, PhD, senior director of scientific engagement at the Alzheimer’s Association, said “researchers have only just started to explore the experiences of dementia within the lesbian, gay, and bisexual community, but this is the first time we are seeing some specific research that’s looking at cognition in transgender individuals and gender nonbinary individuals.”
“We don’t know exactly why transgender and gender nonbinary individuals experience greater rates of subjective cognitive decline, but we do know that they have greater rates of health disparities that are considered risk factors for dementia, including higher rates of cardiovascular disease, depression, diabetes, tobacco and alcohol use, and obesity,” Dr. Edelmayer said.
“Alzheimer’s and dementia do not discriminate. Neither can we,” Maria C. Carrillo, PhD, chief science officer for the Alzheimer’s Association, said in a statement.
“The Alzheimer’s Association advocates for more research to better understand the cognitive and emotional needs of transgender and nonbinary individuals so that our nation’s health care providers can offer them culturally sensitive care,” said Dr. Carrillo.
The study had no specific funding. Dr. Cicero, Dr. Carrillo, and Dr. Edelmayer have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
, new research shows.
Investigators found transgender adults – individuals who identify with a gender different than the one assigned to them at birth – were nearly twice as likely to report subjective cognitive decline and more than twice as likely to report SCD-related functional limitations – such as reduced ability to work, volunteer, or be social – than cisgender adults.
“Trans populations are disproportionately impacted by health disparities and also risk factors for dementia. Putting these pieces together, I wasn’t surprised by their greater risk of cognitive decline,” said study investigator Ethan Cicero, PhD, RN, an assistant professor at Emory University, Atlanta.
The findings were presented at the 2021 Alzheimer’s Association International Conference.
‘Alarming’ finding
SCD is a self-reported experience of worsening memory or thinking and is one of the first clinical manifestations of Alzheimer’s disease and related dementia (ADRD). Yet there is limited research into cognitive impairment among transgender adults.
The researchers examined SCD and associated functional limitations among transgender and cisgender adults older than age 45 years who provided health and health behavior data as part of the Behavioral Risk Factor Surveillance System (BRFSS) surveys (2015-2019).
The sample included 386,529 adults of whom 1,302 identified as transgender and 385,227 as cisgender.
Roughly 17% of transgender adults reported SCD, which is significantly higher than the 10.6% rate for cisgender adults (P < .001).
Compared with cisgender adults reporting SCD, transgender adults reporting SCD were younger (mean age 61.9 vs. 65.2 years, P = .0005), more likely to be in a racial/ethnic minority group (37.3% vs. 19.5%, P < .0001), have a high school degree or less (59.6% vs. 43.4%, P = .0003), be uninsured (17% vs. 5.5%, P = .0007) and have a depressive disorder (58.8% vs. 45.7%, P = .0028).
The fact that transgender people who reported SCD were about 3 years younger than cisgender people who reported SCD is “somewhat alarming and a red flag to ask middle-aged trans adults about their brain health and not just older or elderly trans adults,” said Dr. Cicero.
The study also showed that transgender adults reporting SCD were 2.3 times more likely to report related social and self-care limitations when compared with cisgender adults reporting SCD.
The findings align with a study reported at AAIC 2019, which showed that sexual or gender minorities (SGM) are almost 30% more likely to report subjective cognitive decline compared with the non-SGM population.
Cause unclear
“We are not certain what may be causing the elevated subjective cognitive decline rates among transgender adults. We postulate that it may be in part due to anti-transgender stigma and prejudice that expose transgender people to high rates of mistreatment and discrimination where they live, work, learn, seek health care, and age,” Dr. Cicero said.
“More research is needed to identify and target preventive intervention strategies, develop culturally relevant screenings, and shape policies to improve the health and well-being of the transgender population,” he added.
Weighing in on the study, Rebecca Edelmayer, PhD, senior director of scientific engagement at the Alzheimer’s Association, said “researchers have only just started to explore the experiences of dementia within the lesbian, gay, and bisexual community, but this is the first time we are seeing some specific research that’s looking at cognition in transgender individuals and gender nonbinary individuals.”
“We don’t know exactly why transgender and gender nonbinary individuals experience greater rates of subjective cognitive decline, but we do know that they have greater rates of health disparities that are considered risk factors for dementia, including higher rates of cardiovascular disease, depression, diabetes, tobacco and alcohol use, and obesity,” Dr. Edelmayer said.
“Alzheimer’s and dementia do not discriminate. Neither can we,” Maria C. Carrillo, PhD, chief science officer for the Alzheimer’s Association, said in a statement.
“The Alzheimer’s Association advocates for more research to better understand the cognitive and emotional needs of transgender and nonbinary individuals so that our nation’s health care providers can offer them culturally sensitive care,” said Dr. Carrillo.
The study had no specific funding. Dr. Cicero, Dr. Carrillo, and Dr. Edelmayer have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
, new research shows.
Investigators found transgender adults – individuals who identify with a gender different than the one assigned to them at birth – were nearly twice as likely to report subjective cognitive decline and more than twice as likely to report SCD-related functional limitations – such as reduced ability to work, volunteer, or be social – than cisgender adults.
“Trans populations are disproportionately impacted by health disparities and also risk factors for dementia. Putting these pieces together, I wasn’t surprised by their greater risk of cognitive decline,” said study investigator Ethan Cicero, PhD, RN, an assistant professor at Emory University, Atlanta.
The findings were presented at the 2021 Alzheimer’s Association International Conference.
‘Alarming’ finding
SCD is a self-reported experience of worsening memory or thinking and is one of the first clinical manifestations of Alzheimer’s disease and related dementia (ADRD). Yet there is limited research into cognitive impairment among transgender adults.
The researchers examined SCD and associated functional limitations among transgender and cisgender adults older than age 45 years who provided health and health behavior data as part of the Behavioral Risk Factor Surveillance System (BRFSS) surveys (2015-2019).
The sample included 386,529 adults of whom 1,302 identified as transgender and 385,227 as cisgender.
Roughly 17% of transgender adults reported SCD, which is significantly higher than the 10.6% rate for cisgender adults (P < .001).
Compared with cisgender adults reporting SCD, transgender adults reporting SCD were younger (mean age 61.9 vs. 65.2 years, P = .0005), more likely to be in a racial/ethnic minority group (37.3% vs. 19.5%, P < .0001), have a high school degree or less (59.6% vs. 43.4%, P = .0003), be uninsured (17% vs. 5.5%, P = .0007) and have a depressive disorder (58.8% vs. 45.7%, P = .0028).
The fact that transgender people who reported SCD were about 3 years younger than cisgender people who reported SCD is “somewhat alarming and a red flag to ask middle-aged trans adults about their brain health and not just older or elderly trans adults,” said Dr. Cicero.
The study also showed that transgender adults reporting SCD were 2.3 times more likely to report related social and self-care limitations when compared with cisgender adults reporting SCD.
The findings align with a study reported at AAIC 2019, which showed that sexual or gender minorities (SGM) are almost 30% more likely to report subjective cognitive decline compared with the non-SGM population.
Cause unclear
“We are not certain what may be causing the elevated subjective cognitive decline rates among transgender adults. We postulate that it may be in part due to anti-transgender stigma and prejudice that expose transgender people to high rates of mistreatment and discrimination where they live, work, learn, seek health care, and age,” Dr. Cicero said.
“More research is needed to identify and target preventive intervention strategies, develop culturally relevant screenings, and shape policies to improve the health and well-being of the transgender population,” he added.
Weighing in on the study, Rebecca Edelmayer, PhD, senior director of scientific engagement at the Alzheimer’s Association, said “researchers have only just started to explore the experiences of dementia within the lesbian, gay, and bisexual community, but this is the first time we are seeing some specific research that’s looking at cognition in transgender individuals and gender nonbinary individuals.”
“We don’t know exactly why transgender and gender nonbinary individuals experience greater rates of subjective cognitive decline, but we do know that they have greater rates of health disparities that are considered risk factors for dementia, including higher rates of cardiovascular disease, depression, diabetes, tobacco and alcohol use, and obesity,” Dr. Edelmayer said.
“Alzheimer’s and dementia do not discriminate. Neither can we,” Maria C. Carrillo, PhD, chief science officer for the Alzheimer’s Association, said in a statement.
“The Alzheimer’s Association advocates for more research to better understand the cognitive and emotional needs of transgender and nonbinary individuals so that our nation’s health care providers can offer them culturally sensitive care,” said Dr. Carrillo.
The study had no specific funding. Dr. Cicero, Dr. Carrillo, and Dr. Edelmayer have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
From AAIC 2021
Low-dose aspirin linked to lower dementia risk in some
, according to a retrospective analysis of two large cohorts. The association with all-cause dementia was weak, but much more pronounced in subjects with coronary heart disease.
The results underscore that individuals with cardiovascular disease risk factors should be prescribed LDASA, and they should be encouraged to be compliant. The study differed from previous observational and randomized, controlled trials, which yielded mixed results. Many looked at individuals older than age 65. The pathological changes associated with dementia may occur up to 2 decades before symptom onset, and it appears that LDASA cannot counter cognitive decline after a diagnosis is made. “The use of LDASA at this age may be already too late,” said Thi Ngoc Mai Nguyen, a PhD student at Network Aging Research, Heidelberg University, Germany. She presented the results at the 2021 Alzheimer’s Association International Conference.
Previous studies also included individuals using LDASA to prevent cardiovascular disease, and they didn’t always adjust for these risk factors. The current work used two large databases, UK Biobank and ESTHER, with a follow-up time of over 10 years for both. “We were able to balance out the distribution of measured baseline covariates (to be) similar between LDASA users and nonusers, and thus, we were able to adjust for confounders more comprehensively,” said Ms. Nguyen.
Not yet a definitive answer
Although the findings are promising, Ms. Nguyen noted that the study is not the final word. “Residual confounding is possible, and causation cannot be tested. The only way to answer this is to have clinical trials with at least 10 years of follow-up,” said Ms. Nguyen. She plans to conduct similar studies in non-White populations, and also to examine whether LDASA can help preserve cognitive function in middle-age adults.
The study is interesting, said Claire Sexton, DPhil, who was asked to comment, but she suggested that it is not practice changing. “There is not evidence from the dementia science perspective that should go against whatever the recommendations are for cardiovascular risk,” said Dr. Sexton, director of scientific programs and outreach at the Alzheimer’s Association. “I don’t think this study alone can provide a definitive answer on low-dose aspirin and its association with dementia and Alzheimer’s disease, but it’s an important addition to the literature,” she added.
Meta-analysis data
The researchers examined two prospective cohort studies, and combined them into a meta-analysis. It included the ESTHER cohort from Saarland, Germany, with 5,258 individuals and 14.3 years of follow-up, and the UK Biobank cohort, with 305,394 individuals and 11.6 years of follow-up. Subjects selected for analysis were 55 years old or older.
The meta-analysis showed no significant association between LDASA use and reduced risk of Alzheimer’s disease, but there was an association between LDASA use and all-cause dementia (hazard ratio [HR], 0.96; 95% confidence interval [CI], 0.93-0.99).
There were no sex differences with respect to Alzheimer’s dementia, but in males, LDASA was associated with lower risk of vascular dementia (HR, 0.85; 95% CI, 0.79-0.93) and all-cause dementia (HR, 0.87; 95% CI, 0.83-0.92). However, in females, LDASA was tied to greater risk of both vascular dementia (HR, 1.13; 95% CI, 1.02-1.24) and all-cause dementia (HR, 1.07; 95% CI, 1.02-1.13).
The strongest association between LDASA and reduced dementia risk was found in subjects with coronary heart disease (HR, 0.69; 95% CI, 0.59-0.80).
The researchers also used UK Biobank primary care data to analyze associations between longer use of LDASA and reduced dementia risk. Those who used LDASA for 0-5 years were at a higher than average risk of all-cause dementia (HR, 2.80; 95% CI, 2.48-3.16), Alzheimer’s disease (HR, 2.26; 95% CI, 1.84-2.77), and vascular dementia (HR, 3.79; 95% CI, 3.17-4.53). Long-term LDASA users, defined as 10 years or longer, had a lower risk of all-cause dementia (HR, 0.51; 95% CI, 0.47-0.56), Alzheimer’s disease (HR, 0.58; 95% CI, 0.51-0.68), and vascular dementia (HR, 0.48; 95% CI, 0.42-0.56).
Dr. Nguyen and Dr. Sexton have no relevant financial disclosures.
, according to a retrospective analysis of two large cohorts. The association with all-cause dementia was weak, but much more pronounced in subjects with coronary heart disease.
The results underscore that individuals with cardiovascular disease risk factors should be prescribed LDASA, and they should be encouraged to be compliant. The study differed from previous observational and randomized, controlled trials, which yielded mixed results. Many looked at individuals older than age 65. The pathological changes associated with dementia may occur up to 2 decades before symptom onset, and it appears that LDASA cannot counter cognitive decline after a diagnosis is made. “The use of LDASA at this age may be already too late,” said Thi Ngoc Mai Nguyen, a PhD student at Network Aging Research, Heidelberg University, Germany. She presented the results at the 2021 Alzheimer’s Association International Conference.
Previous studies also included individuals using LDASA to prevent cardiovascular disease, and they didn’t always adjust for these risk factors. The current work used two large databases, UK Biobank and ESTHER, with a follow-up time of over 10 years for both. “We were able to balance out the distribution of measured baseline covariates (to be) similar between LDASA users and nonusers, and thus, we were able to adjust for confounders more comprehensively,” said Ms. Nguyen.
Not yet a definitive answer
Although the findings are promising, Ms. Nguyen noted that the study is not the final word. “Residual confounding is possible, and causation cannot be tested. The only way to answer this is to have clinical trials with at least 10 years of follow-up,” said Ms. Nguyen. She plans to conduct similar studies in non-White populations, and also to examine whether LDASA can help preserve cognitive function in middle-age adults.
The study is interesting, said Claire Sexton, DPhil, who was asked to comment, but she suggested that it is not practice changing. “There is not evidence from the dementia science perspective that should go against whatever the recommendations are for cardiovascular risk,” said Dr. Sexton, director of scientific programs and outreach at the Alzheimer’s Association. “I don’t think this study alone can provide a definitive answer on low-dose aspirin and its association with dementia and Alzheimer’s disease, but it’s an important addition to the literature,” she added.
Meta-analysis data
The researchers examined two prospective cohort studies, and combined them into a meta-analysis. It included the ESTHER cohort from Saarland, Germany, with 5,258 individuals and 14.3 years of follow-up, and the UK Biobank cohort, with 305,394 individuals and 11.6 years of follow-up. Subjects selected for analysis were 55 years old or older.
The meta-analysis showed no significant association between LDASA use and reduced risk of Alzheimer’s disease, but there was an association between LDASA use and all-cause dementia (hazard ratio [HR], 0.96; 95% confidence interval [CI], 0.93-0.99).
There were no sex differences with respect to Alzheimer’s dementia, but in males, LDASA was associated with lower risk of vascular dementia (HR, 0.85; 95% CI, 0.79-0.93) and all-cause dementia (HR, 0.87; 95% CI, 0.83-0.92). However, in females, LDASA was tied to greater risk of both vascular dementia (HR, 1.13; 95% CI, 1.02-1.24) and all-cause dementia (HR, 1.07; 95% CI, 1.02-1.13).
The strongest association between LDASA and reduced dementia risk was found in subjects with coronary heart disease (HR, 0.69; 95% CI, 0.59-0.80).
The researchers also used UK Biobank primary care data to analyze associations between longer use of LDASA and reduced dementia risk. Those who used LDASA for 0-5 years were at a higher than average risk of all-cause dementia (HR, 2.80; 95% CI, 2.48-3.16), Alzheimer’s disease (HR, 2.26; 95% CI, 1.84-2.77), and vascular dementia (HR, 3.79; 95% CI, 3.17-4.53). Long-term LDASA users, defined as 10 years or longer, had a lower risk of all-cause dementia (HR, 0.51; 95% CI, 0.47-0.56), Alzheimer’s disease (HR, 0.58; 95% CI, 0.51-0.68), and vascular dementia (HR, 0.48; 95% CI, 0.42-0.56).
Dr. Nguyen and Dr. Sexton have no relevant financial disclosures.
, according to a retrospective analysis of two large cohorts. The association with all-cause dementia was weak, but much more pronounced in subjects with coronary heart disease.
The results underscore that individuals with cardiovascular disease risk factors should be prescribed LDASA, and they should be encouraged to be compliant. The study differed from previous observational and randomized, controlled trials, which yielded mixed results. Many looked at individuals older than age 65. The pathological changes associated with dementia may occur up to 2 decades before symptom onset, and it appears that LDASA cannot counter cognitive decline after a diagnosis is made. “The use of LDASA at this age may be already too late,” said Thi Ngoc Mai Nguyen, a PhD student at Network Aging Research, Heidelberg University, Germany. She presented the results at the 2021 Alzheimer’s Association International Conference.
Previous studies also included individuals using LDASA to prevent cardiovascular disease, and they didn’t always adjust for these risk factors. The current work used two large databases, UK Biobank and ESTHER, with a follow-up time of over 10 years for both. “We were able to balance out the distribution of measured baseline covariates (to be) similar between LDASA users and nonusers, and thus, we were able to adjust for confounders more comprehensively,” said Ms. Nguyen.
Not yet a definitive answer
Although the findings are promising, Ms. Nguyen noted that the study is not the final word. “Residual confounding is possible, and causation cannot be tested. The only way to answer this is to have clinical trials with at least 10 years of follow-up,” said Ms. Nguyen. She plans to conduct similar studies in non-White populations, and also to examine whether LDASA can help preserve cognitive function in middle-age adults.
The study is interesting, said Claire Sexton, DPhil, who was asked to comment, but she suggested that it is not practice changing. “There is not evidence from the dementia science perspective that should go against whatever the recommendations are for cardiovascular risk,” said Dr. Sexton, director of scientific programs and outreach at the Alzheimer’s Association. “I don’t think this study alone can provide a definitive answer on low-dose aspirin and its association with dementia and Alzheimer’s disease, but it’s an important addition to the literature,” she added.
Meta-analysis data
The researchers examined two prospective cohort studies, and combined them into a meta-analysis. It included the ESTHER cohort from Saarland, Germany, with 5,258 individuals and 14.3 years of follow-up, and the UK Biobank cohort, with 305,394 individuals and 11.6 years of follow-up. Subjects selected for analysis were 55 years old or older.
The meta-analysis showed no significant association between LDASA use and reduced risk of Alzheimer’s disease, but there was an association between LDASA use and all-cause dementia (hazard ratio [HR], 0.96; 95% confidence interval [CI], 0.93-0.99).
There were no sex differences with respect to Alzheimer’s dementia, but in males, LDASA was associated with lower risk of vascular dementia (HR, 0.85; 95% CI, 0.79-0.93) and all-cause dementia (HR, 0.87; 95% CI, 0.83-0.92). However, in females, LDASA was tied to greater risk of both vascular dementia (HR, 1.13; 95% CI, 1.02-1.24) and all-cause dementia (HR, 1.07; 95% CI, 1.02-1.13).
The strongest association between LDASA and reduced dementia risk was found in subjects with coronary heart disease (HR, 0.69; 95% CI, 0.59-0.80).
The researchers also used UK Biobank primary care data to analyze associations between longer use of LDASA and reduced dementia risk. Those who used LDASA for 0-5 years were at a higher than average risk of all-cause dementia (HR, 2.80; 95% CI, 2.48-3.16), Alzheimer’s disease (HR, 2.26; 95% CI, 1.84-2.77), and vascular dementia (HR, 3.79; 95% CI, 3.17-4.53). Long-term LDASA users, defined as 10 years or longer, had a lower risk of all-cause dementia (HR, 0.51; 95% CI, 0.47-0.56), Alzheimer’s disease (HR, 0.58; 95% CI, 0.51-0.68), and vascular dementia (HR, 0.48; 95% CI, 0.42-0.56).
Dr. Nguyen and Dr. Sexton have no relevant financial disclosures.
FROM AAIC 2021
Short sleep is linked to future dementia
, according to a new analysis of data from the Whitehall II cohort study.
Previous work had identified links between short sleep duration and dementia risk, but few studies examined sleep habits long before onset of dementia. Those that did produced inconsistent results, according to Séverine Sabia, PhD, who is a research associate at Inserm (France) and the University College London.
“One potential reason for these inconstancies is the large range of ages of the study populations, and the small number of participants within each sleep duration group. The novelty of our study is to examine this association among almost 8,000 participants with a follow-up of 30 years, using repeated measures of sleep duration starting in midlife to consider sleep duration at specific ages,” Dr. Sabia said in an interview. She presented the research at the 2021 Alzheimer’s Association International Conference.
Those previous studies found a U-shaped association between sleep duration and dementia risk, with lowest risk associated with 7-8 hours of sleep, but greater risk for shorter and longer durations. However, because the studies had follow-up periods shorter than 10 years, they are at greater risk of reverse causation bias. Longer follow-up studies tended to have small sample sizes or to focus on older adults.
The longer follow-up in the current study makes for a more compelling case, said Claire Sexton, DPhil, director of Scientific Programs & Outreach for the Alzheimer’s Association. Observations of short or long sleep closer to the onset of symptoms could just be a warning sign of dementia. “But looking at age 50, age 60 ... if you’re seeing those relationships, then it’s less likely that it is just purely prodromal,” said Dr. Sexton. But it still doesn’t necessarily confirm causation. “It could also be a risk factor,” Dr. Sexton added.
Multifactorial risk
Dr. Sabia also noted that the magnitude of risk was similar to that seen with smoking or obesity, and many factors play a role in dementia risk. “Even if the risk of dementia was 30% higher in those with persistent short sleep duration, in absolute terms, the percentage of those with persistent short duration who developed dementia was 8%, and 6% in those with persistent sleep duration of 7 hours. Dementia is a multifactorial disease, which means that several factors are likely to influence its onset. Sleep duration is one of them, but if a person has poor sleep and does not manage to increase it, there are other important prevention measures. It is important to keep a healthy lifestyle and cardiometabolic measures in the normal range. All together it is likely to be beneficial for brain health in later life,” she said.
Dr. Sexton agreed. “With sleep we’re still trying to tease apart what aspect of sleep is important. Is it the sleep duration? Is it the quality of sleep? Is it certain sleep stages?” she said.
Regardless of sleep’s potential influence on dementia risk, both Dr. Sexton and Dr. Sabia noted the importance of sleep for general health. “These types of problems are very prevalent, so it’s good for people to be aware of them. And then if they notice any problems with their sleep, or any changes, to go and see their health care provider, and to be discussing them, and then to be investigating the cause, and to see whether changes in sleep hygiene and treatments for insomnia could address these sleep problems,” said Dr. Sexton.
Decades of data
During the Whitehall II study, researchers assessed average sleep duration (“How many hours of sleep do you have on an average weeknight?”) six times over 30 years of follow-up. Dr. Sabia’s group extracted self-reported sleep duration data at ages 50, 60, and 70. Short sleep duration was defined as fewer than 5 hours, or 6 hours. Normal sleep duration was defined as 7 hours. Long duration was defined as 8 hours or more.
A questioner during the Q&A period noted that this grouping is a little unusual. Many studies define 7-8 hours as normal. Dr. Sabia answered that they were unable to examine periods of 9 hours or more due to the nature of the data, and the lowest associated risk was found at 7 hours.
The researchers analyzed data from 7,959 participants (33.0% women). At age 50, compared with 7 hours of sleep, 6 or few hours of sleep was associated with a higher risk of dementia over the ensuing 25 years of follow-up (hazard ratio [HR], 1.22; 95% confidence interval [CI], 1.01-1.48). The same was true at age 60 (15 years of follow-up HR, 1.37; 95% CI, 1.10-1.72). There was a trend at age 70 (8 years follow-up; HR, 1.24; 95% CI, 0.98-1.57). For 8 or more hours of sleep, there were trends toward increased risk at age 50 (HR, 1.25; 95% CI, 0.98-1.60). Long sleep at age 60 and 70 was associated with heightened risk, but the confidence intervals were well outside statistical significance.
Twenty percent of participants had persistent short sleep over the course of follow-up, 37% had persistent normal sleep, and 7% had persistent long sleep. Seven percent of participants experienced a change from normal sleep to short sleep, 16% had a change from short sleep to normal sleep, and 13% had a change from normal sleep to long sleep.
Persistent short sleep between age 50 and 70 was associated with a 30% increased risk of dementia (HR, 1.30; 95% CI, 1.00-1.69). There were no statistically significant associations between dementia risk and any of the changing sleep pattern groups.
Dr. Sabia and Dr. Sexton have no relevant financial disclosures.
, according to a new analysis of data from the Whitehall II cohort study.
Previous work had identified links between short sleep duration and dementia risk, but few studies examined sleep habits long before onset of dementia. Those that did produced inconsistent results, according to Séverine Sabia, PhD, who is a research associate at Inserm (France) and the University College London.
“One potential reason for these inconstancies is the large range of ages of the study populations, and the small number of participants within each sleep duration group. The novelty of our study is to examine this association among almost 8,000 participants with a follow-up of 30 years, using repeated measures of sleep duration starting in midlife to consider sleep duration at specific ages,” Dr. Sabia said in an interview. She presented the research at the 2021 Alzheimer’s Association International Conference.
Those previous studies found a U-shaped association between sleep duration and dementia risk, with lowest risk associated with 7-8 hours of sleep, but greater risk for shorter and longer durations. However, because the studies had follow-up periods shorter than 10 years, they are at greater risk of reverse causation bias. Longer follow-up studies tended to have small sample sizes or to focus on older adults.
The longer follow-up in the current study makes for a more compelling case, said Claire Sexton, DPhil, director of Scientific Programs & Outreach for the Alzheimer’s Association. Observations of short or long sleep closer to the onset of symptoms could just be a warning sign of dementia. “But looking at age 50, age 60 ... if you’re seeing those relationships, then it’s less likely that it is just purely prodromal,” said Dr. Sexton. But it still doesn’t necessarily confirm causation. “It could also be a risk factor,” Dr. Sexton added.
Multifactorial risk
Dr. Sabia also noted that the magnitude of risk was similar to that seen with smoking or obesity, and many factors play a role in dementia risk. “Even if the risk of dementia was 30% higher in those with persistent short sleep duration, in absolute terms, the percentage of those with persistent short duration who developed dementia was 8%, and 6% in those with persistent sleep duration of 7 hours. Dementia is a multifactorial disease, which means that several factors are likely to influence its onset. Sleep duration is one of them, but if a person has poor sleep and does not manage to increase it, there are other important prevention measures. It is important to keep a healthy lifestyle and cardiometabolic measures in the normal range. All together it is likely to be beneficial for brain health in later life,” she said.
Dr. Sexton agreed. “With sleep we’re still trying to tease apart what aspect of sleep is important. Is it the sleep duration? Is it the quality of sleep? Is it certain sleep stages?” she said.
Regardless of sleep’s potential influence on dementia risk, both Dr. Sexton and Dr. Sabia noted the importance of sleep for general health. “These types of problems are very prevalent, so it’s good for people to be aware of them. And then if they notice any problems with their sleep, or any changes, to go and see their health care provider, and to be discussing them, and then to be investigating the cause, and to see whether changes in sleep hygiene and treatments for insomnia could address these sleep problems,” said Dr. Sexton.
Decades of data
During the Whitehall II study, researchers assessed average sleep duration (“How many hours of sleep do you have on an average weeknight?”) six times over 30 years of follow-up. Dr. Sabia’s group extracted self-reported sleep duration data at ages 50, 60, and 70. Short sleep duration was defined as fewer than 5 hours, or 6 hours. Normal sleep duration was defined as 7 hours. Long duration was defined as 8 hours or more.
A questioner during the Q&A period noted that this grouping is a little unusual. Many studies define 7-8 hours as normal. Dr. Sabia answered that they were unable to examine periods of 9 hours or more due to the nature of the data, and the lowest associated risk was found at 7 hours.
The researchers analyzed data from 7,959 participants (33.0% women). At age 50, compared with 7 hours of sleep, 6 or few hours of sleep was associated with a higher risk of dementia over the ensuing 25 years of follow-up (hazard ratio [HR], 1.22; 95% confidence interval [CI], 1.01-1.48). The same was true at age 60 (15 years of follow-up HR, 1.37; 95% CI, 1.10-1.72). There was a trend at age 70 (8 years follow-up; HR, 1.24; 95% CI, 0.98-1.57). For 8 or more hours of sleep, there were trends toward increased risk at age 50 (HR, 1.25; 95% CI, 0.98-1.60). Long sleep at age 60 and 70 was associated with heightened risk, but the confidence intervals were well outside statistical significance.
Twenty percent of participants had persistent short sleep over the course of follow-up, 37% had persistent normal sleep, and 7% had persistent long sleep. Seven percent of participants experienced a change from normal sleep to short sleep, 16% had a change from short sleep to normal sleep, and 13% had a change from normal sleep to long sleep.
Persistent short sleep between age 50 and 70 was associated with a 30% increased risk of dementia (HR, 1.30; 95% CI, 1.00-1.69). There were no statistically significant associations between dementia risk and any of the changing sleep pattern groups.
Dr. Sabia and Dr. Sexton have no relevant financial disclosures.
, according to a new analysis of data from the Whitehall II cohort study.
Previous work had identified links between short sleep duration and dementia risk, but few studies examined sleep habits long before onset of dementia. Those that did produced inconsistent results, according to Séverine Sabia, PhD, who is a research associate at Inserm (France) and the University College London.
“One potential reason for these inconstancies is the large range of ages of the study populations, and the small number of participants within each sleep duration group. The novelty of our study is to examine this association among almost 8,000 participants with a follow-up of 30 years, using repeated measures of sleep duration starting in midlife to consider sleep duration at specific ages,” Dr. Sabia said in an interview. She presented the research at the 2021 Alzheimer’s Association International Conference.
Those previous studies found a U-shaped association between sleep duration and dementia risk, with lowest risk associated with 7-8 hours of sleep, but greater risk for shorter and longer durations. However, because the studies had follow-up periods shorter than 10 years, they are at greater risk of reverse causation bias. Longer follow-up studies tended to have small sample sizes or to focus on older adults.
The longer follow-up in the current study makes for a more compelling case, said Claire Sexton, DPhil, director of Scientific Programs & Outreach for the Alzheimer’s Association. Observations of short or long sleep closer to the onset of symptoms could just be a warning sign of dementia. “But looking at age 50, age 60 ... if you’re seeing those relationships, then it’s less likely that it is just purely prodromal,” said Dr. Sexton. But it still doesn’t necessarily confirm causation. “It could also be a risk factor,” Dr. Sexton added.
Multifactorial risk
Dr. Sabia also noted that the magnitude of risk was similar to that seen with smoking or obesity, and many factors play a role in dementia risk. “Even if the risk of dementia was 30% higher in those with persistent short sleep duration, in absolute terms, the percentage of those with persistent short duration who developed dementia was 8%, and 6% in those with persistent sleep duration of 7 hours. Dementia is a multifactorial disease, which means that several factors are likely to influence its onset. Sleep duration is one of them, but if a person has poor sleep and does not manage to increase it, there are other important prevention measures. It is important to keep a healthy lifestyle and cardiometabolic measures in the normal range. All together it is likely to be beneficial for brain health in later life,” she said.
Dr. Sexton agreed. “With sleep we’re still trying to tease apart what aspect of sleep is important. Is it the sleep duration? Is it the quality of sleep? Is it certain sleep stages?” she said.
Regardless of sleep’s potential influence on dementia risk, both Dr. Sexton and Dr. Sabia noted the importance of sleep for general health. “These types of problems are very prevalent, so it’s good for people to be aware of them. And then if they notice any problems with their sleep, or any changes, to go and see their health care provider, and to be discussing them, and then to be investigating the cause, and to see whether changes in sleep hygiene and treatments for insomnia could address these sleep problems,” said Dr. Sexton.
Decades of data
During the Whitehall II study, researchers assessed average sleep duration (“How many hours of sleep do you have on an average weeknight?”) six times over 30 years of follow-up. Dr. Sabia’s group extracted self-reported sleep duration data at ages 50, 60, and 70. Short sleep duration was defined as fewer than 5 hours, or 6 hours. Normal sleep duration was defined as 7 hours. Long duration was defined as 8 hours or more.
A questioner during the Q&A period noted that this grouping is a little unusual. Many studies define 7-8 hours as normal. Dr. Sabia answered that they were unable to examine periods of 9 hours or more due to the nature of the data, and the lowest associated risk was found at 7 hours.
The researchers analyzed data from 7,959 participants (33.0% women). At age 50, compared with 7 hours of sleep, 6 or few hours of sleep was associated with a higher risk of dementia over the ensuing 25 years of follow-up (hazard ratio [HR], 1.22; 95% confidence interval [CI], 1.01-1.48). The same was true at age 60 (15 years of follow-up HR, 1.37; 95% CI, 1.10-1.72). There was a trend at age 70 (8 years follow-up; HR, 1.24; 95% CI, 0.98-1.57). For 8 or more hours of sleep, there were trends toward increased risk at age 50 (HR, 1.25; 95% CI, 0.98-1.60). Long sleep at age 60 and 70 was associated with heightened risk, but the confidence intervals were well outside statistical significance.
Twenty percent of participants had persistent short sleep over the course of follow-up, 37% had persistent normal sleep, and 7% had persistent long sleep. Seven percent of participants experienced a change from normal sleep to short sleep, 16% had a change from short sleep to normal sleep, and 13% had a change from normal sleep to long sleep.
Persistent short sleep between age 50 and 70 was associated with a 30% increased risk of dementia (HR, 1.30; 95% CI, 1.00-1.69). There were no statistically significant associations between dementia risk and any of the changing sleep pattern groups.
Dr. Sabia and Dr. Sexton have no relevant financial disclosures.
FROM AAIC 2021
Inflammatory diet is linked to dementia
according to a new analysis of longitudinal data from the Framingham Heart Study Offspring Cohort.
The lack of an association with Alzheimer’s disease was a surprise because amyloid-beta prompts microglia and astrocytes to release markers of systemic inflammation, according to Debora Melo van Lent, PhD, who is a postdoctoral fellow at the University of Texas Health San Antonio – Glenn Biggs Institute for Alzheimer’s and Neurodegenerative Diseases. “We expected to see a relationship between higher DII scores and an increased risk for incident Alzheimer’s disease,” said Dr. Melo van Lent, who presented the findings at the 2021 Alzheimer’s Association International Conference.
Dr. Melo van Lent added that the most likely explanation is that the study was underpowered to produce a positive association, and the team is conducting further study in a larger population.
A modifiable risk factor
The study is the first to look at all-cause dementia and Alzheimer’s disease dementia and their association with DII, Dr. Melo van Lent said.
“As diet is a modifiable risk factor, we can actually do something about it. If we take a closer look at five components of the DII which are most anti-inflammatory, these components are present in green leafy vegetables, vegetables, fruit, soy, whole grains, and green and black tea. Most of these components are included in the Mediterranean diet. When we look at the three most proinflammatory components, they are present in high caloric products; such as butter or margarine, pastries and sweets, fried snacks, and red or processed meat. These components are present in ‘Western diets,’ which are discouraged,” said Dr. Melo van Lent.
The researchers analyzed data from 1,486 participants who were free of dementia, stroke, or other neurologic diseases at baseline. They analyzed DII scores both in a continuous range and divided into quartiles, using the first quartile as a reference.
The mean age of participants was 69 years, and 53% were women. During follow-up, 11.3% developed AD dementia, and 14.8% developed non-AD dementia.
In the continuous model, DII was associated with increased risk of all-cause dementia after adjusting for age, sex, APOE E4 status, body mass index, smoking, physical activity index score, total energy intake, lipid-lowering medications, and total cholesterol to HDL cholesterol ratio (hazard ratio, 1.18; P =.001). In the quartile analysis, after adjustments, compared with quartile 1, there was an increased risk of all-cause dementia for those in quartile 3 (HR, 1.69; P =.020) and quartile 4 (HR, 1.84; P =.013).
In the continuous analysis, after adjustments, there was an association between DII score and Alzheimer’s dementia (HR, 1.15; P =.020). In the quartile analysis, no associations were significant, though there was a trend of quartile 4 versus quartile 1 (HR, 1.65; P =.077).
The researchers found no significant interactions between higher DII scores and sex, the APOE E4 allele, or physical activity with respect to all-cause dementia or Alzheimer’s dementia.
Intertwined variables
The results were interesting, but cause and effect relationships can be difficult to tease out from such a study, according to Claire Sexton, DPhil, director of scientific programs and outreach at the Alzheimer’s Association, who was asked to comment on the study. Dr. Sexton noted that individuals who eat well are more likely to have energy to exercise, which could in turn help them to sleep better, and all of those factors could be involved in reducing dementia risk. “They’re all kind of intertwined. So in this study, they were taking into account physical activity, but they can’t take into account every single variable. It’s important for them to be followed up by randomized control trials.”
Dr. Sexton also referenced the U.S. Pointer study being conducted by the Alzheimer’s Association, which is examining various interventions related to diet, physical activity, and cognitive stimulation. “Whether intervening and improving people’s health behaviors then goes on to reduce their risk for dementia is a key question. We still need more results from studies to be reporting out before we get definitive answers,” she said.
The study was funded by the ASPEN Rhoads Research Foundation. Dr. Melo van Lent and Dr. Sexton have no relevant financial disclosures.
according to a new analysis of longitudinal data from the Framingham Heart Study Offspring Cohort.
The lack of an association with Alzheimer’s disease was a surprise because amyloid-beta prompts microglia and astrocytes to release markers of systemic inflammation, according to Debora Melo van Lent, PhD, who is a postdoctoral fellow at the University of Texas Health San Antonio – Glenn Biggs Institute for Alzheimer’s and Neurodegenerative Diseases. “We expected to see a relationship between higher DII scores and an increased risk for incident Alzheimer’s disease,” said Dr. Melo van Lent, who presented the findings at the 2021 Alzheimer’s Association International Conference.
Dr. Melo van Lent added that the most likely explanation is that the study was underpowered to produce a positive association, and the team is conducting further study in a larger population.
A modifiable risk factor
The study is the first to look at all-cause dementia and Alzheimer’s disease dementia and their association with DII, Dr. Melo van Lent said.
“As diet is a modifiable risk factor, we can actually do something about it. If we take a closer look at five components of the DII which are most anti-inflammatory, these components are present in green leafy vegetables, vegetables, fruit, soy, whole grains, and green and black tea. Most of these components are included in the Mediterranean diet. When we look at the three most proinflammatory components, they are present in high caloric products; such as butter or margarine, pastries and sweets, fried snacks, and red or processed meat. These components are present in ‘Western diets,’ which are discouraged,” said Dr. Melo van Lent.
The researchers analyzed data from 1,486 participants who were free of dementia, stroke, or other neurologic diseases at baseline. They analyzed DII scores both in a continuous range and divided into quartiles, using the first quartile as a reference.
The mean age of participants was 69 years, and 53% were women. During follow-up, 11.3% developed AD dementia, and 14.8% developed non-AD dementia.
In the continuous model, DII was associated with increased risk of all-cause dementia after adjusting for age, sex, APOE E4 status, body mass index, smoking, physical activity index score, total energy intake, lipid-lowering medications, and total cholesterol to HDL cholesterol ratio (hazard ratio, 1.18; P =.001). In the quartile analysis, after adjustments, compared with quartile 1, there was an increased risk of all-cause dementia for those in quartile 3 (HR, 1.69; P =.020) and quartile 4 (HR, 1.84; P =.013).
In the continuous analysis, after adjustments, there was an association between DII score and Alzheimer’s dementia (HR, 1.15; P =.020). In the quartile analysis, no associations were significant, though there was a trend of quartile 4 versus quartile 1 (HR, 1.65; P =.077).
The researchers found no significant interactions between higher DII scores and sex, the APOE E4 allele, or physical activity with respect to all-cause dementia or Alzheimer’s dementia.
Intertwined variables
The results were interesting, but cause and effect relationships can be difficult to tease out from such a study, according to Claire Sexton, DPhil, director of scientific programs and outreach at the Alzheimer’s Association, who was asked to comment on the study. Dr. Sexton noted that individuals who eat well are more likely to have energy to exercise, which could in turn help them to sleep better, and all of those factors could be involved in reducing dementia risk. “They’re all kind of intertwined. So in this study, they were taking into account physical activity, but they can’t take into account every single variable. It’s important for them to be followed up by randomized control trials.”
Dr. Sexton also referenced the U.S. Pointer study being conducted by the Alzheimer’s Association, which is examining various interventions related to diet, physical activity, and cognitive stimulation. “Whether intervening and improving people’s health behaviors then goes on to reduce their risk for dementia is a key question. We still need more results from studies to be reporting out before we get definitive answers,” she said.
The study was funded by the ASPEN Rhoads Research Foundation. Dr. Melo van Lent and Dr. Sexton have no relevant financial disclosures.
according to a new analysis of longitudinal data from the Framingham Heart Study Offspring Cohort.
The lack of an association with Alzheimer’s disease was a surprise because amyloid-beta prompts microglia and astrocytes to release markers of systemic inflammation, according to Debora Melo van Lent, PhD, who is a postdoctoral fellow at the University of Texas Health San Antonio – Glenn Biggs Institute for Alzheimer’s and Neurodegenerative Diseases. “We expected to see a relationship between higher DII scores and an increased risk for incident Alzheimer’s disease,” said Dr. Melo van Lent, who presented the findings at the 2021 Alzheimer’s Association International Conference.
Dr. Melo van Lent added that the most likely explanation is that the study was underpowered to produce a positive association, and the team is conducting further study in a larger population.
A modifiable risk factor
The study is the first to look at all-cause dementia and Alzheimer’s disease dementia and their association with DII, Dr. Melo van Lent said.
“As diet is a modifiable risk factor, we can actually do something about it. If we take a closer look at five components of the DII which are most anti-inflammatory, these components are present in green leafy vegetables, vegetables, fruit, soy, whole grains, and green and black tea. Most of these components are included in the Mediterranean diet. When we look at the three most proinflammatory components, they are present in high caloric products; such as butter or margarine, pastries and sweets, fried snacks, and red or processed meat. These components are present in ‘Western diets,’ which are discouraged,” said Dr. Melo van Lent.
The researchers analyzed data from 1,486 participants who were free of dementia, stroke, or other neurologic diseases at baseline. They analyzed DII scores both in a continuous range and divided into quartiles, using the first quartile as a reference.
The mean age of participants was 69 years, and 53% were women. During follow-up, 11.3% developed AD dementia, and 14.8% developed non-AD dementia.
In the continuous model, DII was associated with increased risk of all-cause dementia after adjusting for age, sex, APOE E4 status, body mass index, smoking, physical activity index score, total energy intake, lipid-lowering medications, and total cholesterol to HDL cholesterol ratio (hazard ratio, 1.18; P =.001). In the quartile analysis, after adjustments, compared with quartile 1, there was an increased risk of all-cause dementia for those in quartile 3 (HR, 1.69; P =.020) and quartile 4 (HR, 1.84; P =.013).
In the continuous analysis, after adjustments, there was an association between DII score and Alzheimer’s dementia (HR, 1.15; P =.020). In the quartile analysis, no associations were significant, though there was a trend of quartile 4 versus quartile 1 (HR, 1.65; P =.077).
The researchers found no significant interactions between higher DII scores and sex, the APOE E4 allele, or physical activity with respect to all-cause dementia or Alzheimer’s dementia.
Intertwined variables
The results were interesting, but cause and effect relationships can be difficult to tease out from such a study, according to Claire Sexton, DPhil, director of scientific programs and outreach at the Alzheimer’s Association, who was asked to comment on the study. Dr. Sexton noted that individuals who eat well are more likely to have energy to exercise, which could in turn help them to sleep better, and all of those factors could be involved in reducing dementia risk. “They’re all kind of intertwined. So in this study, they were taking into account physical activity, but they can’t take into account every single variable. It’s important for them to be followed up by randomized control trials.”
Dr. Sexton also referenced the U.S. Pointer study being conducted by the Alzheimer’s Association, which is examining various interventions related to diet, physical activity, and cognitive stimulation. “Whether intervening and improving people’s health behaviors then goes on to reduce their risk for dementia is a key question. We still need more results from studies to be reporting out before we get definitive answers,” she said.
The study was funded by the ASPEN Rhoads Research Foundation. Dr. Melo van Lent and Dr. Sexton have no relevant financial disclosures.
FROM AAIC 2021
Prevalence of dementia before age 65 much higher than expected
Results of a large meta-analysis show that currently 3.9 million individuals are living with young-onset dementia. Among these patients, symptoms of the disease start before age 65.
Recent global young-onset dementia estimates have ranged from 42.3 to 54.0 per 100,000 population, the researchers noted. However, the new study, which included 74 global studies with 2.7 million participants, shows that the global age-standardized prevalence of young-onset dementia is 119.00 per 100,000 among individuals aged 30-64 years; there was little difference in prevalence between men and women. On the basis of the latest population estimates, these new prevalence data imply that there are approximately 175,000 persons with young-onset dementia in the United States.
Although the new global estimate of young-onset dementia is higher than previously thought, “it is still probably an underestimation owing to lack of high-quality data. This should raise awareness for policy makers and health care professionals to organize more and better care for this subgroup of individuals with dementia,” wrote the investigators, with first author Stevie Hendriks, MSc, Maastricht (the Netherlands) University, and the Young-Onset Dementia Epidemiology Study Group.
The study was published online July 19, 2021, in JAMA Neurology.
‘Essential’ data
Young-onset dementia is exceedingly rare in those aged 30-63 years (1.1 per 100,000) but is more prevalent at age 60-64 years (77.4 per 100,000). “Our findings fit the general observation that prevalence of dementia increases exponentially from 60 years of age onward,” they wrote.
The prevalence of young-onset dementia was similar in men and women, lower in the United States than in Europe, highest in upper- to middle-income countries, and highest for Alzheimer’s disease, followed by vascular dementia and frontotemporal dementia.
Monitoring the prevalence of young-onset dementia is “essential” to adequately plan and organize health services, the investigators noted.
To ensure more accurate prevalence estimates in the future, “efforts should be made to conduct more cohort studies and to standardize procedures and reporting of prevalence studies. In addition, more data are needed from low-income countries as well as studies that include younger age ranges,” they said.
New insights
In an accompanying editorial, David S. Knopman, MD, department of neurology, Mayo Clinic, Rochester, Minn., noted that the study provides new insights into an “underappreciated problem.”.
Young-onset dementia is a “particularly disheartening diagnosis because it affects individuals in their prime years, in the midst of their careers, and while raising families,” Dr. Knopman wrote.
“Most dementia care is geared for older patients, and as a consequence, services are rarely available to address the needs of someone diagnosed with dementia in their 50s who has dependent children at home and a spouse who must continue working. Understanding the prevalence and incidence of young-onset dementia is a first step in addressing this challenge,” Dr. Knopman wrote.
He noted that the authors of this analysis have “done a service to the dementia community by collecting and analyzing the dozens of individual studies of young-onset dementia.
“The product, a rationally derived estimate of dementia prevalence across the population aged 30-64 years, provides a basis for initiating more efforts to improve methods for timely diagnosis and to address the unique needs of patients with young-onset dementia,” Dr. Knopman concluded.
A version of this article first appeared on Medscape.com.
Results of a large meta-analysis show that currently 3.9 million individuals are living with young-onset dementia. Among these patients, symptoms of the disease start before age 65.
Recent global young-onset dementia estimates have ranged from 42.3 to 54.0 per 100,000 population, the researchers noted. However, the new study, which included 74 global studies with 2.7 million participants, shows that the global age-standardized prevalence of young-onset dementia is 119.00 per 100,000 among individuals aged 30-64 years; there was little difference in prevalence between men and women. On the basis of the latest population estimates, these new prevalence data imply that there are approximately 175,000 persons with young-onset dementia in the United States.
Although the new global estimate of young-onset dementia is higher than previously thought, “it is still probably an underestimation owing to lack of high-quality data. This should raise awareness for policy makers and health care professionals to organize more and better care for this subgroup of individuals with dementia,” wrote the investigators, with first author Stevie Hendriks, MSc, Maastricht (the Netherlands) University, and the Young-Onset Dementia Epidemiology Study Group.
The study was published online July 19, 2021, in JAMA Neurology.
‘Essential’ data
Young-onset dementia is exceedingly rare in those aged 30-63 years (1.1 per 100,000) but is more prevalent at age 60-64 years (77.4 per 100,000). “Our findings fit the general observation that prevalence of dementia increases exponentially from 60 years of age onward,” they wrote.
The prevalence of young-onset dementia was similar in men and women, lower in the United States than in Europe, highest in upper- to middle-income countries, and highest for Alzheimer’s disease, followed by vascular dementia and frontotemporal dementia.
Monitoring the prevalence of young-onset dementia is “essential” to adequately plan and organize health services, the investigators noted.
To ensure more accurate prevalence estimates in the future, “efforts should be made to conduct more cohort studies and to standardize procedures and reporting of prevalence studies. In addition, more data are needed from low-income countries as well as studies that include younger age ranges,” they said.
New insights
In an accompanying editorial, David S. Knopman, MD, department of neurology, Mayo Clinic, Rochester, Minn., noted that the study provides new insights into an “underappreciated problem.”.
Young-onset dementia is a “particularly disheartening diagnosis because it affects individuals in their prime years, in the midst of their careers, and while raising families,” Dr. Knopman wrote.
“Most dementia care is geared for older patients, and as a consequence, services are rarely available to address the needs of someone diagnosed with dementia in their 50s who has dependent children at home and a spouse who must continue working. Understanding the prevalence and incidence of young-onset dementia is a first step in addressing this challenge,” Dr. Knopman wrote.
He noted that the authors of this analysis have “done a service to the dementia community by collecting and analyzing the dozens of individual studies of young-onset dementia.
“The product, a rationally derived estimate of dementia prevalence across the population aged 30-64 years, provides a basis for initiating more efforts to improve methods for timely diagnosis and to address the unique needs of patients with young-onset dementia,” Dr. Knopman concluded.
A version of this article first appeared on Medscape.com.
Results of a large meta-analysis show that currently 3.9 million individuals are living with young-onset dementia. Among these patients, symptoms of the disease start before age 65.
Recent global young-onset dementia estimates have ranged from 42.3 to 54.0 per 100,000 population, the researchers noted. However, the new study, which included 74 global studies with 2.7 million participants, shows that the global age-standardized prevalence of young-onset dementia is 119.00 per 100,000 among individuals aged 30-64 years; there was little difference in prevalence between men and women. On the basis of the latest population estimates, these new prevalence data imply that there are approximately 175,000 persons with young-onset dementia in the United States.
Although the new global estimate of young-onset dementia is higher than previously thought, “it is still probably an underestimation owing to lack of high-quality data. This should raise awareness for policy makers and health care professionals to organize more and better care for this subgroup of individuals with dementia,” wrote the investigators, with first author Stevie Hendriks, MSc, Maastricht (the Netherlands) University, and the Young-Onset Dementia Epidemiology Study Group.
The study was published online July 19, 2021, in JAMA Neurology.
‘Essential’ data
Young-onset dementia is exceedingly rare in those aged 30-63 years (1.1 per 100,000) but is more prevalent at age 60-64 years (77.4 per 100,000). “Our findings fit the general observation that prevalence of dementia increases exponentially from 60 years of age onward,” they wrote.
The prevalence of young-onset dementia was similar in men and women, lower in the United States than in Europe, highest in upper- to middle-income countries, and highest for Alzheimer’s disease, followed by vascular dementia and frontotemporal dementia.
Monitoring the prevalence of young-onset dementia is “essential” to adequately plan and organize health services, the investigators noted.
To ensure more accurate prevalence estimates in the future, “efforts should be made to conduct more cohort studies and to standardize procedures and reporting of prevalence studies. In addition, more data are needed from low-income countries as well as studies that include younger age ranges,” they said.
New insights
In an accompanying editorial, David S. Knopman, MD, department of neurology, Mayo Clinic, Rochester, Minn., noted that the study provides new insights into an “underappreciated problem.”.
Young-onset dementia is a “particularly disheartening diagnosis because it affects individuals in their prime years, in the midst of their careers, and while raising families,” Dr. Knopman wrote.
“Most dementia care is geared for older patients, and as a consequence, services are rarely available to address the needs of someone diagnosed with dementia in their 50s who has dependent children at home and a spouse who must continue working. Understanding the prevalence and incidence of young-onset dementia is a first step in addressing this challenge,” Dr. Knopman wrote.
He noted that the authors of this analysis have “done a service to the dementia community by collecting and analyzing the dozens of individual studies of young-onset dementia.
“The product, a rationally derived estimate of dementia prevalence across the population aged 30-64 years, provides a basis for initiating more efforts to improve methods for timely diagnosis and to address the unique needs of patients with young-onset dementia,” Dr. Knopman concluded.
A version of this article first appeared on Medscape.com.
FROM JAMA NEUROLOGY
Alzheimer’s disease plasma biomarkers may be nuanced
Such tests are likely to be widely available in the near future.
But work remains to be done to translate findings from academic studies to the more general population. A key consideration is that plasma levels of these biomarkers could be affected by other conditions, which could in turn skew test results, according to Michelle Mielke, PhD, who spoke on the topic at the 2021 Alzheimer’s Association International Conference.
“The markers, which we’ve published on as well, look really promising. But they have primarily been looked at in more specialty clinics or memory clinics, and have not been examined in the general community. The goal of this presentation was really just to take a look at this in the community, in older individuals that have multiple comorbidities, and to understand what factors might affect the levels of these markers. Because as we do go forward and develop cut points, we are going to have to consider these aspects,” said Dr. Mielke in an interview. She is a professor of epidemiology and neurology at the Mayo Clinic in Rochester, Minn.
Case in point
To illustrate the point, Dr. Mielke presented data from her group, which analyzed P-tau 181 and P-tau 217 data from 1,329 Mayo clinic patients. Of that total, 1,161 were cognitively unimpaired (CU), 153 had mild cognitive impairment (MCI), and 15 had dementia. The median age was 67, 55% were male, and 26% had the APOE e4 allele.
After adjustment for age and sex, there were statistically significantly elevated levels of both biomarkers among patients who had tested positive for amyloid and patients who had had a stroke or myocardial infarction, and in the presence of chronic kidney disease (CKD). There also was a trend towards an increase of biomarker levels with increasing body mass index. The differences remained even after the analysis was restricted to individuals who were amyloid negative.
The researchers then looked more closely at the impact of CKD, stroke, and MI on P-tau cut points and the ability to predict abnormal amyloid positron emission tomography (PET) scans. They defined an abnormal range as 1.96 standard deviation units beyond the mean among amyloid-negative individuals who are cognitively impaired. They excluded subjects with those risk factors and then established new cut points in the absence of the factors. The approach led to a significant change for the cutoff of P-tau 181 values, from 1.57 pg/mL or greater for individuals without stroke, MI, or CKD, and 1.75 pg/mL or greater for individuals with one such factor. There was little difference in the cutoff value for P-tau 217, from 0.25 pg/mL to 0.26 pg/mL.
Among people without a history of stroke, MI, or CKD, a P-tau 181 cutoff of 1.57 pg/mL or greater had an area under the receiving operating characteristic (AUROC) value of 0.717 (95% confidence interval, 0.691-0.744), compared with an AUROC of 0.687 (95% CI, 0.662-0.712) at a cutoff of 1.75 pg/mL or greater among people with those conditions. For P-tau 217, the values were 0.737 pg/mL (95% CI, 0.712-0.762) and 0.724 pg/mL (95% CI, 0.699-0.748), respectively.
“The sensitivity was better when they excluded those individuals with these conditions. Specificity was slightly, but not significantly, lower,” said Dr. Mielke during her talk.
Other considerations
Dr. Mielke added that it will be important to account for these and other factors when applying biomarkers in community settings, but they should also be considered in the context of health care disparities. Stroke, MI, and CKD are more common in African Americans, for example, suggesting that there could be racial differences in biomarker levels, though she said the difference in biomarker levels would be more likely attributable to the underlying comorbidities than race per se. “As shown, these factors can affect the consideration of an accuracy of cut points for clinical use. So I think future discussions will be needed as to how best to determine the cut points, and how to base them off of (different) populations,” said Dr. Mielke.
These sorts of refinements are important, according to Christopher Weber, PhD, who was asked for comment. “We have learned the importance of an early and accurate diagnosis. The blood test is a biomarker that does detect the hallmarks of Alzheimer’s disease sometimes up to decades before symptoms even appear,” said Dr. Weber, who is director of Global Science Initiatives at the Alzheimer’s Association.
But “there’s a lot more that we need to learn regarding when exactly to use them, who they’re appropriate for. And I think validation is the key to these blood biomarkers,” Dr. Weber added.
Dr. Mielke has been a consultant with the Brain Protection Company and Biogen. Dr. Weber has no relevant financial disclosures.
Such tests are likely to be widely available in the near future.
But work remains to be done to translate findings from academic studies to the more general population. A key consideration is that plasma levels of these biomarkers could be affected by other conditions, which could in turn skew test results, according to Michelle Mielke, PhD, who spoke on the topic at the 2021 Alzheimer’s Association International Conference.
“The markers, which we’ve published on as well, look really promising. But they have primarily been looked at in more specialty clinics or memory clinics, and have not been examined in the general community. The goal of this presentation was really just to take a look at this in the community, in older individuals that have multiple comorbidities, and to understand what factors might affect the levels of these markers. Because as we do go forward and develop cut points, we are going to have to consider these aspects,” said Dr. Mielke in an interview. She is a professor of epidemiology and neurology at the Mayo Clinic in Rochester, Minn.
Case in point
To illustrate the point, Dr. Mielke presented data from her group, which analyzed P-tau 181 and P-tau 217 data from 1,329 Mayo clinic patients. Of that total, 1,161 were cognitively unimpaired (CU), 153 had mild cognitive impairment (MCI), and 15 had dementia. The median age was 67, 55% were male, and 26% had the APOE e4 allele.
After adjustment for age and sex, there were statistically significantly elevated levels of both biomarkers among patients who had tested positive for amyloid and patients who had had a stroke or myocardial infarction, and in the presence of chronic kidney disease (CKD). There also was a trend towards an increase of biomarker levels with increasing body mass index. The differences remained even after the analysis was restricted to individuals who were amyloid negative.
The researchers then looked more closely at the impact of CKD, stroke, and MI on P-tau cut points and the ability to predict abnormal amyloid positron emission tomography (PET) scans. They defined an abnormal range as 1.96 standard deviation units beyond the mean among amyloid-negative individuals who are cognitively impaired. They excluded subjects with those risk factors and then established new cut points in the absence of the factors. The approach led to a significant change for the cutoff of P-tau 181 values, from 1.57 pg/mL or greater for individuals without stroke, MI, or CKD, and 1.75 pg/mL or greater for individuals with one such factor. There was little difference in the cutoff value for P-tau 217, from 0.25 pg/mL to 0.26 pg/mL.
Among people without a history of stroke, MI, or CKD, a P-tau 181 cutoff of 1.57 pg/mL or greater had an area under the receiving operating characteristic (AUROC) value of 0.717 (95% confidence interval, 0.691-0.744), compared with an AUROC of 0.687 (95% CI, 0.662-0.712) at a cutoff of 1.75 pg/mL or greater among people with those conditions. For P-tau 217, the values were 0.737 pg/mL (95% CI, 0.712-0.762) and 0.724 pg/mL (95% CI, 0.699-0.748), respectively.
“The sensitivity was better when they excluded those individuals with these conditions. Specificity was slightly, but not significantly, lower,” said Dr. Mielke during her talk.
Other considerations
Dr. Mielke added that it will be important to account for these and other factors when applying biomarkers in community settings, but they should also be considered in the context of health care disparities. Stroke, MI, and CKD are more common in African Americans, for example, suggesting that there could be racial differences in biomarker levels, though she said the difference in biomarker levels would be more likely attributable to the underlying comorbidities than race per se. “As shown, these factors can affect the consideration of an accuracy of cut points for clinical use. So I think future discussions will be needed as to how best to determine the cut points, and how to base them off of (different) populations,” said Dr. Mielke.
These sorts of refinements are important, according to Christopher Weber, PhD, who was asked for comment. “We have learned the importance of an early and accurate diagnosis. The blood test is a biomarker that does detect the hallmarks of Alzheimer’s disease sometimes up to decades before symptoms even appear,” said Dr. Weber, who is director of Global Science Initiatives at the Alzheimer’s Association.
But “there’s a lot more that we need to learn regarding when exactly to use them, who they’re appropriate for. And I think validation is the key to these blood biomarkers,” Dr. Weber added.
Dr. Mielke has been a consultant with the Brain Protection Company and Biogen. Dr. Weber has no relevant financial disclosures.
Such tests are likely to be widely available in the near future.
But work remains to be done to translate findings from academic studies to the more general population. A key consideration is that plasma levels of these biomarkers could be affected by other conditions, which could in turn skew test results, according to Michelle Mielke, PhD, who spoke on the topic at the 2021 Alzheimer’s Association International Conference.
“The markers, which we’ve published on as well, look really promising. But they have primarily been looked at in more specialty clinics or memory clinics, and have not been examined in the general community. The goal of this presentation was really just to take a look at this in the community, in older individuals that have multiple comorbidities, and to understand what factors might affect the levels of these markers. Because as we do go forward and develop cut points, we are going to have to consider these aspects,” said Dr. Mielke in an interview. She is a professor of epidemiology and neurology at the Mayo Clinic in Rochester, Minn.
Case in point
To illustrate the point, Dr. Mielke presented data from her group, which analyzed P-tau 181 and P-tau 217 data from 1,329 Mayo clinic patients. Of that total, 1,161 were cognitively unimpaired (CU), 153 had mild cognitive impairment (MCI), and 15 had dementia. The median age was 67, 55% were male, and 26% had the APOE e4 allele.
After adjustment for age and sex, there were statistically significantly elevated levels of both biomarkers among patients who had tested positive for amyloid and patients who had had a stroke or myocardial infarction, and in the presence of chronic kidney disease (CKD). There also was a trend towards an increase of biomarker levels with increasing body mass index. The differences remained even after the analysis was restricted to individuals who were amyloid negative.
The researchers then looked more closely at the impact of CKD, stroke, and MI on P-tau cut points and the ability to predict abnormal amyloid positron emission tomography (PET) scans. They defined an abnormal range as 1.96 standard deviation units beyond the mean among amyloid-negative individuals who are cognitively impaired. They excluded subjects with those risk factors and then established new cut points in the absence of the factors. The approach led to a significant change for the cutoff of P-tau 181 values, from 1.57 pg/mL or greater for individuals without stroke, MI, or CKD, and 1.75 pg/mL or greater for individuals with one such factor. There was little difference in the cutoff value for P-tau 217, from 0.25 pg/mL to 0.26 pg/mL.
Among people without a history of stroke, MI, or CKD, a P-tau 181 cutoff of 1.57 pg/mL or greater had an area under the receiving operating characteristic (AUROC) value of 0.717 (95% confidence interval, 0.691-0.744), compared with an AUROC of 0.687 (95% CI, 0.662-0.712) at a cutoff of 1.75 pg/mL or greater among people with those conditions. For P-tau 217, the values were 0.737 pg/mL (95% CI, 0.712-0.762) and 0.724 pg/mL (95% CI, 0.699-0.748), respectively.
“The sensitivity was better when they excluded those individuals with these conditions. Specificity was slightly, but not significantly, lower,” said Dr. Mielke during her talk.
Other considerations
Dr. Mielke added that it will be important to account for these and other factors when applying biomarkers in community settings, but they should also be considered in the context of health care disparities. Stroke, MI, and CKD are more common in African Americans, for example, suggesting that there could be racial differences in biomarker levels, though she said the difference in biomarker levels would be more likely attributable to the underlying comorbidities than race per se. “As shown, these factors can affect the consideration of an accuracy of cut points for clinical use. So I think future discussions will be needed as to how best to determine the cut points, and how to base them off of (different) populations,” said Dr. Mielke.
These sorts of refinements are important, according to Christopher Weber, PhD, who was asked for comment. “We have learned the importance of an early and accurate diagnosis. The blood test is a biomarker that does detect the hallmarks of Alzheimer’s disease sometimes up to decades before symptoms even appear,” said Dr. Weber, who is director of Global Science Initiatives at the Alzheimer’s Association.
But “there’s a lot more that we need to learn regarding when exactly to use them, who they’re appropriate for. And I think validation is the key to these blood biomarkers,” Dr. Weber added.
Dr. Mielke has been a consultant with the Brain Protection Company and Biogen. Dr. Weber has no relevant financial disclosures.
FROM AAIC 2021
Changes in metabolism tied to risk of subsequent dementia
in new findings that may provide a prevention target.
Investigators found one of the clusters includes small high-density lipoprotein (HDL) metabolites associated with vascular dementia, while another cluster involves ketone bodies and citrate that are primarily associated with Alzheimer’s disease.
Ketone bodies, or ketones, are three related compounds – acetone, acetoacetic acid, and beta-hydroxybutyric acid (BHB) – produced by the liver during fat metabolism. Citrate is a salt or ester of citric acid.
These metabolite clusters are not only linked to the future development of dementia but also correlate with early pathology in those under age 60 years, said study investigator Cornelia M. van Duijn, PhD, professor of epidemiology at Nuffield Department of Population Health, Oxford (England) University.
“These metabolites flag early and late pathology and may be relevant as targets for prevention of dementia,” she noted.
The findings were presented at the 2021 Alzheimer’s Association International Conference.
Weight loss before dementia explained?
For the study, investigators included 125,000 patients from the UK Biobank, which includes 51,031 who were over age 60 at baseline. Of these, 1,188 developed dementia during a follow-up of about 10 years; 553 were diagnosed with Alzheimer’s disease and 298 with vascular dementia.
Researchers used a platform that covers 249 metabolic measures, including small molecules, fatty acids, and lipoprotein lipids.
They estimated risk associated with these metabolites, adjusting for age, sex, body mass index, technical variables, ethnicity, smoking, alcohol, education, metabolic and neuropsychiatric medication, and APOE4 genotypes.
Of the 249 metabolites, 47 (19%) were associated with dementia risk in those over age 60, after adjustment.
The investigators examined effect estimates for associations of metabolites with both Alzheimer’s disease and vascular dementia over age 60 versus hippocampal volume under age 60. They found a “very strong, very significant” association for Alzheimer’s disease, and a “marginally significant” association for vascular dementia, said Dr. van Duijn.
This would be expected, as there is a much stronger correlation between hippocampal and Alzheimer’s disease versus vascular dementia, she added.
“We not only see that the metabolites predict dementia, but also early pathology. This makes these findings rather interesting for targeting prevention,” she said. An analysis of total brain volume showed “very strong, very similar, very significant associations” for both Alzheimer’s disease and vascular dementia,” added Dr. van Duijn.
The researchers found a major shift in various metabolites involved in energy metabolism in the 10-year period before the diagnosis of Alzheimer’s disease. These changes include low levels of branched-chain amino acids and omega-3 fatty acids and high levels of glucose, citrate, acetone, beta-hydroxybutyrate, and acetate. “This finding is in line with that in APOE models that show reduced energy metabolism over age in the brain,” said Dr. van Duijn.
She added that high levels of some of these metabolites are associated with low body weight before dementia onset, which may explain the weight loss seen in patients before developing the disease. “Our hypothesis is that the liver is burning the fat reserves of the patients in order to provide the brain with fuel,” she explained.
Diet a prevention target?
The results also showed ketone bodies increase with age, which may represent the aging brain’s “compensation mechanism” to deal with an energy shortage, said Dr. van Duijn. “Supplementation of ketone bodies, branched-chain amino and omega-3 fatty acids may help support brain function.”
The fact that ketone bodies were positively associated with the risk of dementia is “a very important finding,” she said.
Following this and other presentations, session cochair Rima Kaddurah-Daouk, PhD, professor in psychiatry and behavioral sciences, Institute for Brain Sciences, Duke University, Durham, N.C., noted the research is “an important part of trying to decipher some of the mysteries in Alzheimer’s disease.”
The research contributes to the understanding of how nutrition and diet could influence metabolism and then the brain and is “opening the horizon” for thinking about “strategies for therapeutic interventions,” she said.
The study received funding support from the National Institute on Aging. The investigators have reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
in new findings that may provide a prevention target.
Investigators found one of the clusters includes small high-density lipoprotein (HDL) metabolites associated with vascular dementia, while another cluster involves ketone bodies and citrate that are primarily associated with Alzheimer’s disease.
Ketone bodies, or ketones, are three related compounds – acetone, acetoacetic acid, and beta-hydroxybutyric acid (BHB) – produced by the liver during fat metabolism. Citrate is a salt or ester of citric acid.
These metabolite clusters are not only linked to the future development of dementia but also correlate with early pathology in those under age 60 years, said study investigator Cornelia M. van Duijn, PhD, professor of epidemiology at Nuffield Department of Population Health, Oxford (England) University.
“These metabolites flag early and late pathology and may be relevant as targets for prevention of dementia,” she noted.
The findings were presented at the 2021 Alzheimer’s Association International Conference.
Weight loss before dementia explained?
For the study, investigators included 125,000 patients from the UK Biobank, which includes 51,031 who were over age 60 at baseline. Of these, 1,188 developed dementia during a follow-up of about 10 years; 553 were diagnosed with Alzheimer’s disease and 298 with vascular dementia.
Researchers used a platform that covers 249 metabolic measures, including small molecules, fatty acids, and lipoprotein lipids.
They estimated risk associated with these metabolites, adjusting for age, sex, body mass index, technical variables, ethnicity, smoking, alcohol, education, metabolic and neuropsychiatric medication, and APOE4 genotypes.
Of the 249 metabolites, 47 (19%) were associated with dementia risk in those over age 60, after adjustment.
The investigators examined effect estimates for associations of metabolites with both Alzheimer’s disease and vascular dementia over age 60 versus hippocampal volume under age 60. They found a “very strong, very significant” association for Alzheimer’s disease, and a “marginally significant” association for vascular dementia, said Dr. van Duijn.
This would be expected, as there is a much stronger correlation between hippocampal and Alzheimer’s disease versus vascular dementia, she added.
“We not only see that the metabolites predict dementia, but also early pathology. This makes these findings rather interesting for targeting prevention,” she said. An analysis of total brain volume showed “very strong, very similar, very significant associations” for both Alzheimer’s disease and vascular dementia,” added Dr. van Duijn.
The researchers found a major shift in various metabolites involved in energy metabolism in the 10-year period before the diagnosis of Alzheimer’s disease. These changes include low levels of branched-chain amino acids and omega-3 fatty acids and high levels of glucose, citrate, acetone, beta-hydroxybutyrate, and acetate. “This finding is in line with that in APOE models that show reduced energy metabolism over age in the brain,” said Dr. van Duijn.
She added that high levels of some of these metabolites are associated with low body weight before dementia onset, which may explain the weight loss seen in patients before developing the disease. “Our hypothesis is that the liver is burning the fat reserves of the patients in order to provide the brain with fuel,” she explained.
Diet a prevention target?
The results also showed ketone bodies increase with age, which may represent the aging brain’s “compensation mechanism” to deal with an energy shortage, said Dr. van Duijn. “Supplementation of ketone bodies, branched-chain amino and omega-3 fatty acids may help support brain function.”
The fact that ketone bodies were positively associated with the risk of dementia is “a very important finding,” she said.
Following this and other presentations, session cochair Rima Kaddurah-Daouk, PhD, professor in psychiatry and behavioral sciences, Institute for Brain Sciences, Duke University, Durham, N.C., noted the research is “an important part of trying to decipher some of the mysteries in Alzheimer’s disease.”
The research contributes to the understanding of how nutrition and diet could influence metabolism and then the brain and is “opening the horizon” for thinking about “strategies for therapeutic interventions,” she said.
The study received funding support from the National Institute on Aging. The investigators have reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
in new findings that may provide a prevention target.
Investigators found one of the clusters includes small high-density lipoprotein (HDL) metabolites associated with vascular dementia, while another cluster involves ketone bodies and citrate that are primarily associated with Alzheimer’s disease.
Ketone bodies, or ketones, are three related compounds – acetone, acetoacetic acid, and beta-hydroxybutyric acid (BHB) – produced by the liver during fat metabolism. Citrate is a salt or ester of citric acid.
These metabolite clusters are not only linked to the future development of dementia but also correlate with early pathology in those under age 60 years, said study investigator Cornelia M. van Duijn, PhD, professor of epidemiology at Nuffield Department of Population Health, Oxford (England) University.
“These metabolites flag early and late pathology and may be relevant as targets for prevention of dementia,” she noted.
The findings were presented at the 2021 Alzheimer’s Association International Conference.
Weight loss before dementia explained?
For the study, investigators included 125,000 patients from the UK Biobank, which includes 51,031 who were over age 60 at baseline. Of these, 1,188 developed dementia during a follow-up of about 10 years; 553 were diagnosed with Alzheimer’s disease and 298 with vascular dementia.
Researchers used a platform that covers 249 metabolic measures, including small molecules, fatty acids, and lipoprotein lipids.
They estimated risk associated with these metabolites, adjusting for age, sex, body mass index, technical variables, ethnicity, smoking, alcohol, education, metabolic and neuropsychiatric medication, and APOE4 genotypes.
Of the 249 metabolites, 47 (19%) were associated with dementia risk in those over age 60, after adjustment.
The investigators examined effect estimates for associations of metabolites with both Alzheimer’s disease and vascular dementia over age 60 versus hippocampal volume under age 60. They found a “very strong, very significant” association for Alzheimer’s disease, and a “marginally significant” association for vascular dementia, said Dr. van Duijn.
This would be expected, as there is a much stronger correlation between hippocampal and Alzheimer’s disease versus vascular dementia, she added.
“We not only see that the metabolites predict dementia, but also early pathology. This makes these findings rather interesting for targeting prevention,” she said. An analysis of total brain volume showed “very strong, very similar, very significant associations” for both Alzheimer’s disease and vascular dementia,” added Dr. van Duijn.
The researchers found a major shift in various metabolites involved in energy metabolism in the 10-year period before the diagnosis of Alzheimer’s disease. These changes include low levels of branched-chain amino acids and omega-3 fatty acids and high levels of glucose, citrate, acetone, beta-hydroxybutyrate, and acetate. “This finding is in line with that in APOE models that show reduced energy metabolism over age in the brain,” said Dr. van Duijn.
She added that high levels of some of these metabolites are associated with low body weight before dementia onset, which may explain the weight loss seen in patients before developing the disease. “Our hypothesis is that the liver is burning the fat reserves of the patients in order to provide the brain with fuel,” she explained.
Diet a prevention target?
The results also showed ketone bodies increase with age, which may represent the aging brain’s “compensation mechanism” to deal with an energy shortage, said Dr. van Duijn. “Supplementation of ketone bodies, branched-chain amino and omega-3 fatty acids may help support brain function.”
The fact that ketone bodies were positively associated with the risk of dementia is “a very important finding,” she said.
Following this and other presentations, session cochair Rima Kaddurah-Daouk, PhD, professor in psychiatry and behavioral sciences, Institute for Brain Sciences, Duke University, Durham, N.C., noted the research is “an important part of trying to decipher some of the mysteries in Alzheimer’s disease.”
The research contributes to the understanding of how nutrition and diet could influence metabolism and then the brain and is “opening the horizon” for thinking about “strategies for therapeutic interventions,” she said.
The study received funding support from the National Institute on Aging. The investigators have reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM AAIC 2021
‘Staggering’ increase in global dementia cases predicted by 2050
, new global prevalence data show. “These extreme increases are due largely to demographic trends, including population growth and aging,” said study investigator Emma Nichols, MPH, a researcher at the Institute for Health Metrics and Evaluation at the University of Washington in Seattle.
“Our estimates of expected increases can and should inform policy and planning efforts that will be needed to address the needs of the growing number of individuals with dementia in the future,” Ms. Nichols said.
The latest global prevalence data were reported at the 2021 Alzheimer’s Association International Conference.
“The numbers are staggering: Nearly 153 million cases of dementia are predicted worldwide by the year 2050. To put that in context, that number is equal to approximately half of the U.S. population in 2020,” Heather M. Snyder, PhD, vice president of medical and scientific relations for the Alzheimer’s Association, said in a statement.
Prevalence by country
To more accurately forecast global dementia prevalence and produce country-level estimates, the investigators leveraged data from 1999 to 2019 from the Global Burden of Disease study, a comprehensive set of estimates of worldwide health trends.
These data suggest global dementia cases will increase from 57.4 million (50.4 to 65.1) in 2019 to 152.8 million (130.8 to 175.9) in 2050.
Regions that will experience the worst of the increase are eastern Sub-Saharan Africa, North Africa, and the Middle East.
The researchers also factored into the forecasts expected trends in obesity, diabetes, smoking, and educational attainment.
Increases in better education around the world are projected to decrease dementia prevalence by 6.2 million cases worldwide by 2050. However, anticipated trends in smoking, high body mass index, and diabetes will offset this gain, increasing global dementia cases by 6.8 million cases.
“A reversal of these expected trends in cardiovascular risks would be necessary to alter the anticipated trends,” Ms. Nichols said. “Interventions targeted at modifiable risk factors for dementia represent a viable strategy to help address the anticipated trends in dementia burden,” she added.
Need for effective prevention, treatment
Commenting on the research, Rebecca M. Edelmayer, PhD, senior director of scientific engagement at the Alzheimer’s Association, said the global increase in dementia cases is something the association has been following for many years. “We know that if we do not find effective treatments that are going to stop, slow, or prevent Alzheimer’s disease, this number will continue to grow and it will continue to impact people globally,” Dr. Edelmayer said.
She noted that although there are some positive trends, including the fact that increased education may drive down dementia risk, other factors, such as smoking, high body mass index, and high blood sugar level, are predicted to increase in prevalence.
“Some of these factors are actually counterbalancing each other, and in the end, if we don’t continue to develop culturally tailored interventions or even risk reduction strategies for individuals across the globe, we will continue to see those numbers rise overall,” Dr. Edelmayer said.
A version of this article first appeared on Medscape.com.
, new global prevalence data show. “These extreme increases are due largely to demographic trends, including population growth and aging,” said study investigator Emma Nichols, MPH, a researcher at the Institute for Health Metrics and Evaluation at the University of Washington in Seattle.
“Our estimates of expected increases can and should inform policy and planning efforts that will be needed to address the needs of the growing number of individuals with dementia in the future,” Ms. Nichols said.
The latest global prevalence data were reported at the 2021 Alzheimer’s Association International Conference.
“The numbers are staggering: Nearly 153 million cases of dementia are predicted worldwide by the year 2050. To put that in context, that number is equal to approximately half of the U.S. population in 2020,” Heather M. Snyder, PhD, vice president of medical and scientific relations for the Alzheimer’s Association, said in a statement.
Prevalence by country
To more accurately forecast global dementia prevalence and produce country-level estimates, the investigators leveraged data from 1999 to 2019 from the Global Burden of Disease study, a comprehensive set of estimates of worldwide health trends.
These data suggest global dementia cases will increase from 57.4 million (50.4 to 65.1) in 2019 to 152.8 million (130.8 to 175.9) in 2050.
Regions that will experience the worst of the increase are eastern Sub-Saharan Africa, North Africa, and the Middle East.
The researchers also factored into the forecasts expected trends in obesity, diabetes, smoking, and educational attainment.
Increases in better education around the world are projected to decrease dementia prevalence by 6.2 million cases worldwide by 2050. However, anticipated trends in smoking, high body mass index, and diabetes will offset this gain, increasing global dementia cases by 6.8 million cases.
“A reversal of these expected trends in cardiovascular risks would be necessary to alter the anticipated trends,” Ms. Nichols said. “Interventions targeted at modifiable risk factors for dementia represent a viable strategy to help address the anticipated trends in dementia burden,” she added.
Need for effective prevention, treatment
Commenting on the research, Rebecca M. Edelmayer, PhD, senior director of scientific engagement at the Alzheimer’s Association, said the global increase in dementia cases is something the association has been following for many years. “We know that if we do not find effective treatments that are going to stop, slow, or prevent Alzheimer’s disease, this number will continue to grow and it will continue to impact people globally,” Dr. Edelmayer said.
She noted that although there are some positive trends, including the fact that increased education may drive down dementia risk, other factors, such as smoking, high body mass index, and high blood sugar level, are predicted to increase in prevalence.
“Some of these factors are actually counterbalancing each other, and in the end, if we don’t continue to develop culturally tailored interventions or even risk reduction strategies for individuals across the globe, we will continue to see those numbers rise overall,” Dr. Edelmayer said.
A version of this article first appeared on Medscape.com.
, new global prevalence data show. “These extreme increases are due largely to demographic trends, including population growth and aging,” said study investigator Emma Nichols, MPH, a researcher at the Institute for Health Metrics and Evaluation at the University of Washington in Seattle.
“Our estimates of expected increases can and should inform policy and planning efforts that will be needed to address the needs of the growing number of individuals with dementia in the future,” Ms. Nichols said.
The latest global prevalence data were reported at the 2021 Alzheimer’s Association International Conference.
“The numbers are staggering: Nearly 153 million cases of dementia are predicted worldwide by the year 2050. To put that in context, that number is equal to approximately half of the U.S. population in 2020,” Heather M. Snyder, PhD, vice president of medical and scientific relations for the Alzheimer’s Association, said in a statement.
Prevalence by country
To more accurately forecast global dementia prevalence and produce country-level estimates, the investigators leveraged data from 1999 to 2019 from the Global Burden of Disease study, a comprehensive set of estimates of worldwide health trends.
These data suggest global dementia cases will increase from 57.4 million (50.4 to 65.1) in 2019 to 152.8 million (130.8 to 175.9) in 2050.
Regions that will experience the worst of the increase are eastern Sub-Saharan Africa, North Africa, and the Middle East.
The researchers also factored into the forecasts expected trends in obesity, diabetes, smoking, and educational attainment.
Increases in better education around the world are projected to decrease dementia prevalence by 6.2 million cases worldwide by 2050. However, anticipated trends in smoking, high body mass index, and diabetes will offset this gain, increasing global dementia cases by 6.8 million cases.
“A reversal of these expected trends in cardiovascular risks would be necessary to alter the anticipated trends,” Ms. Nichols said. “Interventions targeted at modifiable risk factors for dementia represent a viable strategy to help address the anticipated trends in dementia burden,” she added.
Need for effective prevention, treatment
Commenting on the research, Rebecca M. Edelmayer, PhD, senior director of scientific engagement at the Alzheimer’s Association, said the global increase in dementia cases is something the association has been following for many years. “We know that if we do not find effective treatments that are going to stop, slow, or prevent Alzheimer’s disease, this number will continue to grow and it will continue to impact people globally,” Dr. Edelmayer said.
She noted that although there are some positive trends, including the fact that increased education may drive down dementia risk, other factors, such as smoking, high body mass index, and high blood sugar level, are predicted to increase in prevalence.
“Some of these factors are actually counterbalancing each other, and in the end, if we don’t continue to develop culturally tailored interventions or even risk reduction strategies for individuals across the globe, we will continue to see those numbers rise overall,” Dr. Edelmayer said.
A version of this article first appeared on Medscape.com.
From AAIC 2021
Coffee and the brain: ‘Concerning’ new data
according to the results of a large study.
“With coffee intake, moderation is the key, and especially high levels of consumption may have adverse long-term effects on the brain,” said study investigator Elina Hypponen, PhD, professor of nutritional and genetic epidemiology and director of the Australian Center for Precision Health at the University of South Australia.
“These new data are concerning, and there is a need to conduct further carefully controlled studies to clarify the effects of coffee on the brain.”
The study was published online June 24 in Nutritional Neuroscience.
Potent stimulant
Coffee is a potent nervous system stimulant and is among the most popular nonalcoholic beverages. Some previous research suggests it benefits the brain, but the investigators noted that other research shows a negative or U-shaped relationship.
To investigate, the researchers examined data from the U.K. Biobank, a long-term prospective epidemiologic study of more than 500,000 participants aged 37-73 years who were recruited in 22 assessment centers in the United Kingdom between March 2006 and October 2010.
During the baseline assessment, information was gathered using touchscreen questionnaires, verbal interviews, and physical examinations that involved collection of blood, urine, and saliva samples. An imaging substudy was incorporated in 2014, the goal of which was to conduct brain, heart, and body MRI imaging for 100,000 participants.
The investigators conducted analyses on disease outcomes for 398,646 participants for whom information on habitual coffee consumption was available. Brain volume analyses were conducted in 17,702 participants for whom valid brain imaging data were available.
Participants reported coffee intake in cups per day. Researchers grouped coffee consumption into seven categories: nondrinkers, decaffeinated coffee drinkers, and caffeinated coffee drinkers who consumed less than 1 cup/d, 1-2 cups/d, 3-4 cups/d, 5-6 cups/d, and more than 6 cups/d.
The reference category was those who consumed 1-2 cups/d, rather than those who abstained from coffee, because persons who abstain are more likely to be at suboptimal health.
“Comparing the health of coffee drinkers to the health of those choosing to abstain from coffee will typically lead to an impression of a health benefit, even if there would not be one,” said Dr. Hypponen.
The researchers obtained total and regional brain volumes from the MRI imaging substudy starting 4-6 years after baseline assessment. They accessed information on incident dementia and stroke using primary care data, hospital admission electronic health records, national death registers, and self-reported medical conditions.
Covariates included socioeconomic, health, and other factors, such as smoking, alcohol and tea consumption, physical activity, stressful life events, and body mass index.
The investigators found that there was a linear inverse association between coffee consumption and total brain volume (fully adjusted beta per cup, –1.42; 95% confidence interval, –1.89 to –0.94), with consistent patterns for gray matter, white matter, and hippocampal volumes.
There was no evidence to support an association with white matter hyperintensity (WMH) volume (beta –0.01; 95% CI, –0.07 to 0.05).
Higher consumption, higher risk
The analysis also revealed a nonlinear association between coffee consumption and the odds of dementia (P nonlinearity = .0001), with slightly higher odds seen with non–coffee drinkers and decaffeinated-coffee drinkers and more notable increases for participants in the highest categories of coffee consumption compared with light coffee drinkers.
After adjustment for all covariates, the odds ratio of dementia among persons in the category of coffee intake was 1.53 (95% CI, 1.28-1.83). After full adjustments, the association with heavy coffee consumption and stroke was not significant, although “we can’t exclude a weak effect,” said Dr. Hypponen.
“For the highest coffee consumption group, the data support an association which may be anywhere from 0% to 37% higher odds of stroke after full adjustment,” she added.
People at risk for hypertension may develop “unpleasant sensations” and stop drinking coffee before a serious adverse event occurs, said Dr. Hypponen. In a previous study, she and her colleagues showed that those who have genetically higher blood pressure tend to drink less coffee than their counterparts without the condition.
“This type of effect might be expected to naturally limit the adverse effects of coffee on the risk of stroke,” said Dr. Hypponen.
The odds remained elevated for participants drinking more than 6 cups/d after the researchers accounted for sleep quality. There were no differences in risk between men and women or by age.
An examination of the consumption of tea, which often contains caffeine, did not show an association with brain volume or the odds of dementia or stroke.
“We don’t know whether the difference between associations seen for coffee and tea intake reflects the difference in related caffeine intake or some other explanation, such as dehydration or effects operating through blood cholesterol,” said Dr. Hypponen.
Although reverse causation is possible, there’s no reason to believe that it is relevant to the study results. Genetic evidence suggests a causal role of higher coffee intake on risk for Alzheimer’s disease. In addition, results of a clinical trial support the association between higher caffeine intake and smaller gray matter volume, said Dr. Hypponen.
The mechanisms linking coffee consumption to brain volumes and dementia are not well established. However, Dr. Hypponen noted that caffeine has been used to induce apoptosis in cancer studies using glial cells.
“Furthermore, adenosine receptors, which mediate many of the effects of caffeine in the brain, have been suggested to influence the release of growth factors, which in turn can have an influence on astrocyte proliferation and angiogenesis in the brain,” she said.
Some types of coffee contain cafestol, which increases blood cholesterol and can have adverse effects though related mechanisms, said Dr. Hypponen.
The mechanism may also involve dehydration, which may have a harmful effect on the brain. The study suggested a correlation between dehydration and high coffee intake. “Of course, if this is the case, it is good news, as then we can do something about it simply by drinking some water every time we have a cup of coffee,” she said.
Misleading conclusions
Coffee contains antioxidants, and although previous studies have suggested it might be beneficial, this hypothesis is “too simplistic,” said Dr. Hypponen. “While coffee is not going to be all ‘bad’ either, there are a lot of controversies and suggestions about beneficial effects of coffee which may not be true, or at least do not reflect the full story.”
If the drinking of coffee is at least partly determined by an individual’s health status, then that would often lead to misleading conclusions in observational studies, said Dr. Hypponen.
“When one uses as a comparison people who already have poor health and who do not drink coffee because of that, coffee intake will by default appear beneficial simply because there are more people with disease among those choosing abstinence,” she said.
Before now, there was “very little evidence about the association between coffee intake and brain morphology,” and the studies that were conducted were relatively small, said Dr. Hypponen.
One of these smaller studies included a group of women aged 13-30 years. It found that coffee consumption was not associated with total brain volumes, but the findings suggested a U-shaped association with hippocampal volume; higher values were seen both for nondrinkers and the groups with higher consumption.
A small study of elderly patients with diabetes showed no evidence of an association with white matter volume, but there was a possible age-dependent association with gray matter volume.
The largest of the earlier studies had results that were very similar to those of the current study, suggesting that increasing coffee intake is associated with smaller hippocampal volumes, said Dr. Hypponen.
One of the study’s limitations included the fact that full dietary information was available only for a subsample and that factors such as dehydration were measured at baseline rather than at the time of brain MRI.
Another possible study limitation was the use of self-reported data and the fact that lifestyle changes may have occurred between baseline and MRI or covariate measurement.
In addition, the study is subject to a healthy-volunteer bias, and its implications are restricted to White British persons. The association needs to be studied in other ethnic populations, the authors noted.
A reason to cut back?
Commenting on the findings, Walter Willett, MD, DrPH, professor of epidemiology and nutrition, Harvard T. H. Chan School of Public Health, Boston, said the study is large and quite well done.
“It does raise questions about an increase in risk of dementia with six or more cups of coffee per day,” said Dr. Willett. “At the same time, it provides reassurance about lack of adverse effects of coffee for those consuming three or four cups per day, and little increase in risk, if any, with five cups per day.”
It’s not entirely clear whether the increase in risk with six or more cups of coffee per day represents a “true effect” of coffee, inasmuch as the study did not seem to adjust fully for dietary factors, high consumption of alcohol, or past smoking, said Dr. Willett.
The findings don’t suggest that coffee lovers should give up their Java. “But six or more cups per day is a lot, and those who drink that much might consider cutting back a bit while research continues,” said Dr. Willett.
The study was supported by the National Health and Medical Research Council.
A version of this article first appeared on Medscape.com.
according to the results of a large study.
“With coffee intake, moderation is the key, and especially high levels of consumption may have adverse long-term effects on the brain,” said study investigator Elina Hypponen, PhD, professor of nutritional and genetic epidemiology and director of the Australian Center for Precision Health at the University of South Australia.
“These new data are concerning, and there is a need to conduct further carefully controlled studies to clarify the effects of coffee on the brain.”
The study was published online June 24 in Nutritional Neuroscience.
Potent stimulant
Coffee is a potent nervous system stimulant and is among the most popular nonalcoholic beverages. Some previous research suggests it benefits the brain, but the investigators noted that other research shows a negative or U-shaped relationship.
To investigate, the researchers examined data from the U.K. Biobank, a long-term prospective epidemiologic study of more than 500,000 participants aged 37-73 years who were recruited in 22 assessment centers in the United Kingdom between March 2006 and October 2010.
During the baseline assessment, information was gathered using touchscreen questionnaires, verbal interviews, and physical examinations that involved collection of blood, urine, and saliva samples. An imaging substudy was incorporated in 2014, the goal of which was to conduct brain, heart, and body MRI imaging for 100,000 participants.
The investigators conducted analyses on disease outcomes for 398,646 participants for whom information on habitual coffee consumption was available. Brain volume analyses were conducted in 17,702 participants for whom valid brain imaging data were available.
Participants reported coffee intake in cups per day. Researchers grouped coffee consumption into seven categories: nondrinkers, decaffeinated coffee drinkers, and caffeinated coffee drinkers who consumed less than 1 cup/d, 1-2 cups/d, 3-4 cups/d, 5-6 cups/d, and more than 6 cups/d.
The reference category was those who consumed 1-2 cups/d, rather than those who abstained from coffee, because persons who abstain are more likely to be at suboptimal health.
“Comparing the health of coffee drinkers to the health of those choosing to abstain from coffee will typically lead to an impression of a health benefit, even if there would not be one,” said Dr. Hypponen.
The researchers obtained total and regional brain volumes from the MRI imaging substudy starting 4-6 years after baseline assessment. They accessed information on incident dementia and stroke using primary care data, hospital admission electronic health records, national death registers, and self-reported medical conditions.
Covariates included socioeconomic, health, and other factors, such as smoking, alcohol and tea consumption, physical activity, stressful life events, and body mass index.
The investigators found that there was a linear inverse association between coffee consumption and total brain volume (fully adjusted beta per cup, –1.42; 95% confidence interval, –1.89 to –0.94), with consistent patterns for gray matter, white matter, and hippocampal volumes.
There was no evidence to support an association with white matter hyperintensity (WMH) volume (beta –0.01; 95% CI, –0.07 to 0.05).
Higher consumption, higher risk
The analysis also revealed a nonlinear association between coffee consumption and the odds of dementia (P nonlinearity = .0001), with slightly higher odds seen with non–coffee drinkers and decaffeinated-coffee drinkers and more notable increases for participants in the highest categories of coffee consumption compared with light coffee drinkers.
After adjustment for all covariates, the odds ratio of dementia among persons in the category of coffee intake was 1.53 (95% CI, 1.28-1.83). After full adjustments, the association with heavy coffee consumption and stroke was not significant, although “we can’t exclude a weak effect,” said Dr. Hypponen.
“For the highest coffee consumption group, the data support an association which may be anywhere from 0% to 37% higher odds of stroke after full adjustment,” she added.
People at risk for hypertension may develop “unpleasant sensations” and stop drinking coffee before a serious adverse event occurs, said Dr. Hypponen. In a previous study, she and her colleagues showed that those who have genetically higher blood pressure tend to drink less coffee than their counterparts without the condition.
“This type of effect might be expected to naturally limit the adverse effects of coffee on the risk of stroke,” said Dr. Hypponen.
The odds remained elevated for participants drinking more than 6 cups/d after the researchers accounted for sleep quality. There were no differences in risk between men and women or by age.
An examination of the consumption of tea, which often contains caffeine, did not show an association with brain volume or the odds of dementia or stroke.
“We don’t know whether the difference between associations seen for coffee and tea intake reflects the difference in related caffeine intake or some other explanation, such as dehydration or effects operating through blood cholesterol,” said Dr. Hypponen.
Although reverse causation is possible, there’s no reason to believe that it is relevant to the study results. Genetic evidence suggests a causal role of higher coffee intake on risk for Alzheimer’s disease. In addition, results of a clinical trial support the association between higher caffeine intake and smaller gray matter volume, said Dr. Hypponen.
The mechanisms linking coffee consumption to brain volumes and dementia are not well established. However, Dr. Hypponen noted that caffeine has been used to induce apoptosis in cancer studies using glial cells.
“Furthermore, adenosine receptors, which mediate many of the effects of caffeine in the brain, have been suggested to influence the release of growth factors, which in turn can have an influence on astrocyte proliferation and angiogenesis in the brain,” she said.
Some types of coffee contain cafestol, which increases blood cholesterol and can have adverse effects though related mechanisms, said Dr. Hypponen.
The mechanism may also involve dehydration, which may have a harmful effect on the brain. The study suggested a correlation between dehydration and high coffee intake. “Of course, if this is the case, it is good news, as then we can do something about it simply by drinking some water every time we have a cup of coffee,” she said.
Misleading conclusions
Coffee contains antioxidants, and although previous studies have suggested it might be beneficial, this hypothesis is “too simplistic,” said Dr. Hypponen. “While coffee is not going to be all ‘bad’ either, there are a lot of controversies and suggestions about beneficial effects of coffee which may not be true, or at least do not reflect the full story.”
If the drinking of coffee is at least partly determined by an individual’s health status, then that would often lead to misleading conclusions in observational studies, said Dr. Hypponen.
“When one uses as a comparison people who already have poor health and who do not drink coffee because of that, coffee intake will by default appear beneficial simply because there are more people with disease among those choosing abstinence,” she said.
Before now, there was “very little evidence about the association between coffee intake and brain morphology,” and the studies that were conducted were relatively small, said Dr. Hypponen.
One of these smaller studies included a group of women aged 13-30 years. It found that coffee consumption was not associated with total brain volumes, but the findings suggested a U-shaped association with hippocampal volume; higher values were seen both for nondrinkers and the groups with higher consumption.
A small study of elderly patients with diabetes showed no evidence of an association with white matter volume, but there was a possible age-dependent association with gray matter volume.
The largest of the earlier studies had results that were very similar to those of the current study, suggesting that increasing coffee intake is associated with smaller hippocampal volumes, said Dr. Hypponen.
One of the study’s limitations included the fact that full dietary information was available only for a subsample and that factors such as dehydration were measured at baseline rather than at the time of brain MRI.
Another possible study limitation was the use of self-reported data and the fact that lifestyle changes may have occurred between baseline and MRI or covariate measurement.
In addition, the study is subject to a healthy-volunteer bias, and its implications are restricted to White British persons. The association needs to be studied in other ethnic populations, the authors noted.
A reason to cut back?
Commenting on the findings, Walter Willett, MD, DrPH, professor of epidemiology and nutrition, Harvard T. H. Chan School of Public Health, Boston, said the study is large and quite well done.
“It does raise questions about an increase in risk of dementia with six or more cups of coffee per day,” said Dr. Willett. “At the same time, it provides reassurance about lack of adverse effects of coffee for those consuming three or four cups per day, and little increase in risk, if any, with five cups per day.”
It’s not entirely clear whether the increase in risk with six or more cups of coffee per day represents a “true effect” of coffee, inasmuch as the study did not seem to adjust fully for dietary factors, high consumption of alcohol, or past smoking, said Dr. Willett.
The findings don’t suggest that coffee lovers should give up their Java. “But six or more cups per day is a lot, and those who drink that much might consider cutting back a bit while research continues,” said Dr. Willett.
The study was supported by the National Health and Medical Research Council.
A version of this article first appeared on Medscape.com.
according to the results of a large study.
“With coffee intake, moderation is the key, and especially high levels of consumption may have adverse long-term effects on the brain,” said study investigator Elina Hypponen, PhD, professor of nutritional and genetic epidemiology and director of the Australian Center for Precision Health at the University of South Australia.
“These new data are concerning, and there is a need to conduct further carefully controlled studies to clarify the effects of coffee on the brain.”
The study was published online June 24 in Nutritional Neuroscience.
Potent stimulant
Coffee is a potent nervous system stimulant and is among the most popular nonalcoholic beverages. Some previous research suggests it benefits the brain, but the investigators noted that other research shows a negative or U-shaped relationship.
To investigate, the researchers examined data from the U.K. Biobank, a long-term prospective epidemiologic study of more than 500,000 participants aged 37-73 years who were recruited in 22 assessment centers in the United Kingdom between March 2006 and October 2010.
During the baseline assessment, information was gathered using touchscreen questionnaires, verbal interviews, and physical examinations that involved collection of blood, urine, and saliva samples. An imaging substudy was incorporated in 2014, the goal of which was to conduct brain, heart, and body MRI imaging for 100,000 participants.
The investigators conducted analyses on disease outcomes for 398,646 participants for whom information on habitual coffee consumption was available. Brain volume analyses were conducted in 17,702 participants for whom valid brain imaging data were available.
Participants reported coffee intake in cups per day. Researchers grouped coffee consumption into seven categories: nondrinkers, decaffeinated coffee drinkers, and caffeinated coffee drinkers who consumed less than 1 cup/d, 1-2 cups/d, 3-4 cups/d, 5-6 cups/d, and more than 6 cups/d.
The reference category was those who consumed 1-2 cups/d, rather than those who abstained from coffee, because persons who abstain are more likely to be at suboptimal health.
“Comparing the health of coffee drinkers to the health of those choosing to abstain from coffee will typically lead to an impression of a health benefit, even if there would not be one,” said Dr. Hypponen.
The researchers obtained total and regional brain volumes from the MRI imaging substudy starting 4-6 years after baseline assessment. They accessed information on incident dementia and stroke using primary care data, hospital admission electronic health records, national death registers, and self-reported medical conditions.
Covariates included socioeconomic, health, and other factors, such as smoking, alcohol and tea consumption, physical activity, stressful life events, and body mass index.
The investigators found that there was a linear inverse association between coffee consumption and total brain volume (fully adjusted beta per cup, –1.42; 95% confidence interval, –1.89 to –0.94), with consistent patterns for gray matter, white matter, and hippocampal volumes.
There was no evidence to support an association with white matter hyperintensity (WMH) volume (beta –0.01; 95% CI, –0.07 to 0.05).
Higher consumption, higher risk
The analysis also revealed a nonlinear association between coffee consumption and the odds of dementia (P nonlinearity = .0001), with slightly higher odds seen with non–coffee drinkers and decaffeinated-coffee drinkers and more notable increases for participants in the highest categories of coffee consumption compared with light coffee drinkers.
After adjustment for all covariates, the odds ratio of dementia among persons in the category of coffee intake was 1.53 (95% CI, 1.28-1.83). After full adjustments, the association with heavy coffee consumption and stroke was not significant, although “we can’t exclude a weak effect,” said Dr. Hypponen.
“For the highest coffee consumption group, the data support an association which may be anywhere from 0% to 37% higher odds of stroke after full adjustment,” she added.
People at risk for hypertension may develop “unpleasant sensations” and stop drinking coffee before a serious adverse event occurs, said Dr. Hypponen. In a previous study, she and her colleagues showed that those who have genetically higher blood pressure tend to drink less coffee than their counterparts without the condition.
“This type of effect might be expected to naturally limit the adverse effects of coffee on the risk of stroke,” said Dr. Hypponen.
The odds remained elevated for participants drinking more than 6 cups/d after the researchers accounted for sleep quality. There were no differences in risk between men and women or by age.
An examination of the consumption of tea, which often contains caffeine, did not show an association with brain volume or the odds of dementia or stroke.
“We don’t know whether the difference between associations seen for coffee and tea intake reflects the difference in related caffeine intake or some other explanation, such as dehydration or effects operating through blood cholesterol,” said Dr. Hypponen.
Although reverse causation is possible, there’s no reason to believe that it is relevant to the study results. Genetic evidence suggests a causal role of higher coffee intake on risk for Alzheimer’s disease. In addition, results of a clinical trial support the association between higher caffeine intake and smaller gray matter volume, said Dr. Hypponen.
The mechanisms linking coffee consumption to brain volumes and dementia are not well established. However, Dr. Hypponen noted that caffeine has been used to induce apoptosis in cancer studies using glial cells.
“Furthermore, adenosine receptors, which mediate many of the effects of caffeine in the brain, have been suggested to influence the release of growth factors, which in turn can have an influence on astrocyte proliferation and angiogenesis in the brain,” she said.
Some types of coffee contain cafestol, which increases blood cholesterol and can have adverse effects though related mechanisms, said Dr. Hypponen.
The mechanism may also involve dehydration, which may have a harmful effect on the brain. The study suggested a correlation between dehydration and high coffee intake. “Of course, if this is the case, it is good news, as then we can do something about it simply by drinking some water every time we have a cup of coffee,” she said.
Misleading conclusions
Coffee contains antioxidants, and although previous studies have suggested it might be beneficial, this hypothesis is “too simplistic,” said Dr. Hypponen. “While coffee is not going to be all ‘bad’ either, there are a lot of controversies and suggestions about beneficial effects of coffee which may not be true, or at least do not reflect the full story.”
If the drinking of coffee is at least partly determined by an individual’s health status, then that would often lead to misleading conclusions in observational studies, said Dr. Hypponen.
“When one uses as a comparison people who already have poor health and who do not drink coffee because of that, coffee intake will by default appear beneficial simply because there are more people with disease among those choosing abstinence,” she said.
Before now, there was “very little evidence about the association between coffee intake and brain morphology,” and the studies that were conducted were relatively small, said Dr. Hypponen.
One of these smaller studies included a group of women aged 13-30 years. It found that coffee consumption was not associated with total brain volumes, but the findings suggested a U-shaped association with hippocampal volume; higher values were seen both for nondrinkers and the groups with higher consumption.
A small study of elderly patients with diabetes showed no evidence of an association with white matter volume, but there was a possible age-dependent association with gray matter volume.
The largest of the earlier studies had results that were very similar to those of the current study, suggesting that increasing coffee intake is associated with smaller hippocampal volumes, said Dr. Hypponen.
One of the study’s limitations included the fact that full dietary information was available only for a subsample and that factors such as dehydration were measured at baseline rather than at the time of brain MRI.
Another possible study limitation was the use of self-reported data and the fact that lifestyle changes may have occurred between baseline and MRI or covariate measurement.
In addition, the study is subject to a healthy-volunteer bias, and its implications are restricted to White British persons. The association needs to be studied in other ethnic populations, the authors noted.
A reason to cut back?
Commenting on the findings, Walter Willett, MD, DrPH, professor of epidemiology and nutrition, Harvard T. H. Chan School of Public Health, Boston, said the study is large and quite well done.
“It does raise questions about an increase in risk of dementia with six or more cups of coffee per day,” said Dr. Willett. “At the same time, it provides reassurance about lack of adverse effects of coffee for those consuming three or four cups per day, and little increase in risk, if any, with five cups per day.”
It’s not entirely clear whether the increase in risk with six or more cups of coffee per day represents a “true effect” of coffee, inasmuch as the study did not seem to adjust fully for dietary factors, high consumption of alcohol, or past smoking, said Dr. Willett.
The findings don’t suggest that coffee lovers should give up their Java. “But six or more cups per day is a lot, and those who drink that much might consider cutting back a bit while research continues,” said Dr. Willett.
The study was supported by the National Health and Medical Research Council.
A version of this article first appeared on Medscape.com.
FROM NUTRITIONAL NEUROSCIENCE