Elderly individuals who have excessive daytime sleepiness may be more susceptible to accumulation of an Alzheimer’s disease biomarker, according to a study published online ahead of print March 12 in JAMA Neurology.
Excessive daytime sleepiness (EDS) was associated with increased accumulation of beta-amyloid, an important biomarker of Alzheimer’s disease that manifests in early preclinical stages, said Diego Z. Carvalho, MD, a senior neurology resident at the Mayo Clinic in Rochester, Minnesota, and colleagues.
This finding corroborates previous studies showing that EDS is a risk factor for dementia or cognitive decline, the authors noted.
“It remains unclear whether EDS is a result of greater sleep instability, synaptic or network overload, or neurodegeneration of wakefulness-promoting centers,” said Dr. Carvalho and colleagues. “However, participants with EDS were more vulnerable to Alzheimer’s disease pathologic processes.”
The researchers conducted a prospective, longitudinal cohort analysis that included 283 participants age 70 or older without a diagnosis of dementia who filled out a sleepiness assessment survey and underwent baseline and follow-up imaging studies as part of the Mayo Clinic Study of Aging. All participants included in the analysis underwent at least two consecutive carbon 11–labeled Pittsburgh compound B PET (PiB-PET) scans.
EDS, defined as a score of at least 10 on the Epworth Sleepiness Scale (ESS), was observed in 63 participants (22.3%). At baseline, EDS was significantly associated with increased beta-amyloid accumulation in the anterior cingulate, posterior cingulate-precuneus, and parietal regions. The association between EDS and longitudinal beta-amyloid accumulation was most pronounced in participants who had global PiB positivity at baseline in anterior cingulate and cingulate-precuneus regions. Findings of the study are consistent with a previous investigation of middle-aged participants without dementia, said Dr. Carvalho and colleagues. In that study, increased daytime somnolence was associated with increased beta-amyloid burden in regions including the precuneus and anterior cingulate. Daytime sleepiness in that study was measured using the Sleep Scale.
Further investigation of the link between EDS and beta-amyloid accumulation is warranted. In particular, the researchers suggested that future studies might evaluate whether amyloid accumulation can be avoided through early recognition of EDS and subsequent treatment of underlying sleep disorders.
Poor Sleep Quality May Be an Early Warning Sign of Alzheimer’s Disease
The study advances the understanding of sleep disturbance as a risk factor for Alzheimer’s disease, said Joseph R. Winer, of the Department of Psychology at the University of California, Berkeley, and Bryce A. Mander, PhD, Assistant Professor of Psychiatry and Human Behavior at the University of California, Irvine School of Medicine, in an accompanying editorial.
Findings from the study suggest that poor sleep quality may be an early warning sign of Alzheimer’s disease-related processes. The results should be interpreted with caution, however, because daytime sleepiness was assessed subjectively using the Epworth Sleepiness Scale (ESS), they said. ESS score may reflect declining sleep quality, but it is not necessarily a warning sign for impending amyloidosis because of the low specificity of subjective sleepiness and the many underlying causes that could contribute to ESS scores.
The results suggest that in the future sleep dysfunction might be managed with sleep-based interventions at the optimal time to intervene in the beta-amyloid cascade, Mr. Winer and Dr. Mander said.
Future studies would ideally include other markers of Alzheimer’s disease progression, such as cortical atrophy, tau deposition, or cardiovascular changes, and better explain a physiologic link between subjective daytime sleepiness and longitudinal change in beta-amyloid, said Mr. Winer and Dr. Mander.
—Andrew D. Bowser
Suggested Reading
Carvalho DZ, St Louis EK, Knopman DS, et al. Association of excessive daytime sleepiness with β-amyloid accumulation in elderly persons without dementia. JAMA Neurol. 2018 March 12 [Epub ahead of print].
Winer JR, Mander BA. Waking up to the importance of sleep in the pathogenesis of Alzheimer disease. JAMA Neurol. 2018 Mar 12 [Epub ahead of print].