Once again researchers have found evidence of the critical role quality sleep plays on our overall health. And addressing the common causes of excessive daytime sleepiness (EDS) could have huge implications for the prevention of Alzheimer’s disease.
From sleep apnea which, left untreated, can lead to high blood pressure, heart disease, stroke, depression, diabetes and other ailments, to Alzheimer’s disease, researchers continue to discover why we need to sleep. Now investigators from the Intramural Research Program (IRP) of the National Institute on Aging (NIA) are saying feeling excessively sleepy during the day could be a sign of increased risk for the brain pathology of Alzheimer’s disease.
According to a new study published in the September 25, 2018 issue of the journal Sleep, older adults who felt sleepy during the day when they wanted to be awake were almost three times more likely to have deposits of beta-amyloid—the protein that clumps in the brain as part of Alzheimer’s pathology. The research team was led by Dr. Adam Spira of Johns Hopkins University and included Dr. Murat Bilgel, Dr. Luigi Ferrucci, Dr. Susan Resnick and Dr. Eleanor Simonsick of NIA’s Intramural Research Program.
Using Neuroimaging Substudy data from the Baltimore Longitudinal Study of Aging (BLSA), researchers looked at the reported daytime sleepiness levels and napping habits of 124 cognitively healthy men and women and then matched that information with PET and MRI scan results from an average of 16 years later. The BLSA is America’s longest-running study of human aging.
Between 1991 and 2000, BLSA participants were asked “Do you often become drowsy or fall asleep during the daytime when you wish to be awake? (e.g. falling asleep watching TV or reading).” They also were asked, “Do you nap?”
Overall, 50% of BLSA participants were women and 21% were non-white. About 24% had EDS and 29% were nappers. Those with EDS were older than those without EDS, and compared with non-nappers, nappers were older, more likely to be male and had slightly more education.
“They found that people who said they often felt sleepy during the day were nearly three times more likely to have deposits of beta-amyloid, the protein that clumps in the brain as part of Alzheimer’s disease pathology, than their peers who didn’t report daytime sleepiness,” researchers reported. “While not a direct correlation, the researchers see the results as further evidence that sleep problems and Alzheimer’s pathology may be connected. The exact mechanism that connects disturbed sleep with beta-amyloid buildup is unclear, but multiple studies have shown that people with dementia often experience sleep disturbances, and other studies have shown buildups of beta-amyloid in the brains of animals whose sleep was disturbed.” Napping habits were not significantly connected to beta-amyloid deposits, the team reported.
Researchers concluded common causes of excessive daytime sleepiness (EDS) (e.g., sleep-disordered breathing, insufficient sleep) being associated with biomarkers for Alzheimer’s disease could help identify those with elevated dementia risk and have important implications for prevention of the disease.
Disturbed sleep has emerged as a candidate risk factor for Alzheimer’s disease, multiple studies link poor sleep to cognitive impairment and decline, and more recent studies link sleep disturbance to biomarkers for Alzheimer’s disease, study authors wrote. Researchers showed that shorter sleep duration and poorer sleep quality were associated with greater beta-amyloid buildup as shown on positron emission tomography (PET) scans. They noted another study had linked poorer sleep and reports of frequent napping with cerebrospinal fluid (CSF) measures of beta-amyloid deposition. The authors said that numerous studies have linked sleep-disordered breathing (SDB) to poor cognitive outcomes, and more recent studies have tied SDB to Alzheimer’s disease.
Study authors said their results could support at least four possibilities:
- Excessive daytime sleepiness may have resulted directly from disturbed sleep that itself promotes beta-amyloid deposition.
- Beta-Amyloid deposition may promote EDS by limiting sleep duration or quality. “The current consensus is that a feed-forward system exists in which disturbed sleep increases beta-amyloid deposition, which disturbs sleep, etc.,” authors wrote. “Although there is not yet evidence that interrupting this cycle by treating disturbed sleep resulting from beta-amyloid deposition slows Alzheimer’s disease progression, this is an important area for investigation.”
- Rather than being a marker of risk for beta-amyloid deposition, EDS actually promotes beta-amyloid clustering. (However, no pathway has been identified by which EDS itself might increase beta-amyloid aggregation, making this a less plausible explanation, authors noted.)
- The fourth possibility is that alterations in circadian rhythms may have played a role in all of the above scenarios. “Circadian rest/activity rhythm alterations have been tied to an increased risk of mild cognitive impairment or dementia diagnosis and preclinical amyloid deposition in humans…Several other factors, including medications, psychopathology, narcolepsy and insufficient sleep can result in EDS…If they are also found to promote beta-amyloid deposition, targeting them directly may help prevent Alzheimer’s disease in addition to relieving EDS and enhancing daytime function.”
According to its authors, the study’s strengths are its large sample of cognitively normal adults with Pittsburgh compound B (PiB) PET data, and the substantial interval between EDS and napping assessment and subsequent PiB imaging. “To the best of our knowledge, this is the first study with these characteristics.”
Authors noted the study’s primary limitations as well, including its observational design and the absence of a baseline beta amyloid measure, which they say limited them from drawing firm causal inferences.
In the end, researchers said their findings provide further support for the literature on sleep disturbance as a risk factor for Alzheimer’s disease. “Screening for EDS could help identify those at elevated AD risk, and further support for a causal role of sleep disturbance would recommend that sleep-related interventions be included in AD prevention efforts.”
While healthy diet and mental and physical exercise habits have been pushed as smart strategies for reducing dementia risk, getting the right quantity and quality of sleep hasn’t been emphasized enough, say the researchers. “The study showed that a simple yes or no question on if people felt drowsy or fell asleep in the daytime when they wanted to be awake was effective to screen those at risk for having beta-amyloid deposits in their brains. While not everyone who has Alzheimer’s disease pathology goes on to develop cognitive problems, adding this question to routine clinical screenings could help identify people who should consider follow-up testing for Alzheimer’s and related dementias risk.”
According to the NIA, future steps for this research include examining if sleep apnea and similar disorders, medications or other health conditions that often affect sleep quality in older adults may be a factor in beta-amyloid accumulation.