Excessive Sleepiness Associated With Increased Aβ Accumulation in Elderly Without Dementia

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Higher levels of EDS at baseline were associated with significantly greater accumulation of Aβ in the anterior cingulate, posterior cingulate-precuneus, and parietal regions.
Higher levels of EDS at baseline were associated with significantly greater accumulation of Aβ in the anterior cingulate, posterior cingulate-precuneus, and parietal regions.

Excessive daytime sleepiness (EDS) is associated with long-term accumulation of β-amyloid (Aβ) and an increased risk for Alzheimer disease among elderly individuals without dementia, according to prospective findings published in JAMA Neurology.

A total of 283 elderly participants (mean [standard deviation] age, 77.1 [4.8] years) without dementia who were enrolled in the Mayo Clinic Study of Aging were included in this analysis. Of the participants, 63 (22.3%) had EDS at enrollment. Participants had undergone ≥2 consecutive carbon 11-labeled Pittsburgh compound B positron emission tomography (PiB-PET) scans between 2009 and 2016 and had been surveyed on their baseline sleepiness. A score of ≥10 on the Epworth Sleepiness Scale defined EDS in this study.

Higher levels of EDS at baseline were associated with significantly greater accumulation of Aβ in the anterior cingulate (B coefficient = 0.031; 95% CI, 0.001-0.061; P =.04), posterior cingulate-precuneus (B coefficient = 0.038; 95% CI, 0.006-0.069; P =.02), and parietal (B coefficient = 0.033; 95% CI, 0.001-0.065; P =.04) regions. The strongest associations between baseline EDS and long-term accumulation of Aβ were observed in participants with baseline global PiB positivity in the anterior cingulate (B coefficient = 0.065; 95% CI, 0.010-0.118; P =.02) and cingulate-precuneus (B coefficient = 0.068; 95% CI, 0.009-0.126; P =.02) regions of the brain.

Associations between baseline EDS and long-term differences in Aβ levels between the 2 consecutive scans were sustained following adjustment for sex, hypertension, diabetes, depression, baseline age, interval between scans, baseline PiB uptake, and presence of apolipoprotein E ε4 allele in the anterior cingulate (B coefficient = 0.056; 95% CI, 0.006-0.106) and cingulate precuneus (B coefficient = 0.064; 95% CI, 0.010-0.118) regions of participants with PiB positivity.

This study predominantly relied on a subjective patient reporting system to assess sleep disturbances, which may have limited the findings. Additionally, the investigators did not measure participants' sleep time, which may have limited the observed associations between reported EDS and accumulation of Aβ.

According to the investigators, the data are “unclear whether EDS is a result of greater sleep instability, synaptic or network overload, or neurodegeneration of wakefulness promoting centers.”

Reference

Carvalho DZ, St Louis EK, Knopman DS, et al. Association of excessive daytime sleepiness with longitudinal β-amyloid accumulation in elderly persons without dementia [published online March 12, 2018]. JAMA Neurol. doi: 10.1001/jamaneurol.2018.0049

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