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Sleepiness, Brain Proteins, and Fitness in Older Adults
Mark L. Fuerst
Hot off the press: Three new studies, including one that reports middle-age physically fit women are nearly 90% less likely to develop dementia decades later.
Three studies highlight sleepiness, brain proteins, and fitness: older adults without dementia who have excessive daytime sleepiness may be at greater risk for Alzheimer disease (AD); people with more amyloid in their brains also produce more tau, linking two key AD proteins; and middle-age physically fit women are nearly 90% less likely to develop dementia decades later. Scroll through the slides for summaries and links to sources.
Excessive daytime sleepiness in older adults without dementia appears to increase accumulation of the brain protein β-amyloid, which is an important biomarker for Alzheimer disease. A cohort study of 283 participants, age 70 or older without dementia, had participants complete surveys assessing sleepiness at baseline. The participants had at least two consecutive imaging scans of their brains from 2009 to 2016. About one-quarter (22.3%) of participants self-reported excessive daytime sleepiness at baseline. This was associated with increased β-amyloid accumulation in susceptible regions of the brain.
Clinical Implications: Sleepiness may be a simple clinical tool in assessing AD risk, although further work is needed to elucidate whether excessive daytime sleepiness is a clinical marker of greater sleep instability, synaptic or network overload, or neurodegeneration of wakefulness-promoting centers. “Early identification of patients with excessive daytime sleepiness and treatment of underlying sleep disorders could reduce β-amyloid accumulation in this vulnerable group,” stated the researchers, led by Diego Z. Carvalho, MD, of the Mayo Clinic in Rochester, MN.
Source: Carvalho DZ, et al. Association of Excessive Daytime Sleepiness With Longitudinal β-Amyloid Accumulation in Elderly Persons Without Dementia. JAMA Neurol. 2018 Mar 12.
The presence of amyloid protein in the brain increases the production of tau, which in turn may increase the development of AD. A study using stable isotope labeling and mass spectrometry approaches measured the kinetics of multiple isoforms and fragments of tau in the human central nervous system (CNS) of 24 people, some of whom exhibited amyloid plaques and mild AD symptoms. In both cognitively normal and AD participants, the production rate of tau positively correlated with the amount of amyloid plaques, indicating a biological link between amyloid plaques and tau physiology.
Clinical Implications: “We think this discovery is going to lead to more specific therapies targeting the disease process,” said senior author Randall Bateman, MD, Professor of Neurology at Washington University School of Medicine in St. Louis, MO. Blocking tau production could be considered as a target for treatment for the disease, the researchers stated.
Source: C Sato et al. Tau Kinetics in Neurons and the Human Central Nervous System. Neuron. 2018;97:1284-1298.e7.
Physically fit women in midlife have a dramatically decreased risk of subsequent dementia. In a population-based study of 1462 women, aged 38 to 60 years, a subset of 191 women completed a stepwise-increased maximal ergometer cycling test to evaluate their cardiovascular fitness. Over the following 44 years they had 6 examinations of dementia incidence. Women with high fitness showed a delayed age at dementia onset by 9.5 years and time to dementia onset by 5 years compared with those with medium fitness. The highly fit women were 88% less likely to develop dementia than the moderately fit women.
Clinical Implications: “These findings are exciting because it’s possible that improving people’s cardiovascular fitness in middle age could delay or even prevent them from developing dementia,” said lead author Helena Hörder, PhD, of the University of Gothenburg in Gothenburg, Sweden. She noted the study only shows an association between cardiovascular fitness and dementia. “More research is needed to see if improved fitness could have a positive effect on the risk of dementia and also to look at when during a lifetime a high fitness level is most important,” she said.
Source: Hörder H, Johansson L, Guo X, et al. Midlife cardiovascular fitness and dementia: A 44-year longitudinal population study in women. Neurology. 2018;90:e1298-e1305.