Reduced Slow-Wave Sleep Is Associated with High Cerebrospinal Fluid Aβ42 Levels in Cognitively Normal Elderly.

Publication Type Academic Article
Authors Varga A, Wohlleber M, Giménez S, Romero S, Alonso J, Ducca E, Kam K, Lewis C, Tanzi E, Tweardy S, Kishi A, Parekh A, Fischer E, Gumb T, Alcolea D, Fortea J, Lleó A, Blennow K, Zetterberg H, Mosconi L, Glodzik L, Pirraglia E, Burschtin O, de Leon M, Rapoport D, Lu S, Ayappa I, Osorio R
Journal Sleep
Volume 39
Issue 11
Pagination 2041-2048
Date Published 11/01/2016
ISSN 1550-9109
Keywords Amyloid beta-Peptides, Peptide Fragments, Sleep Stages
Abstract STUDY OBJECTIVES: Emerging evidence suggests a role for sleep in contributing to the progression of Alzheimer disease (AD). Slow wave sleep (SWS) is the stage during which synaptic activity is minimal and clearance of neuronal metabolites is high, making it an ideal state to regulate levels of amyloid beta (Aβ). We thus aimed to examine relationships between concentrations of Aβ42 in the cerebrospinal fluid (CSF) and measures of SWS in cognitively normal elderly subjects. METHODS: Thirty-six subjects underwent a clinical and cognitive assessment, a structural MRI, a morning to early afternoon lumbar puncture, and nocturnal polysomnography. Correlations and linear regression analyses were used to assess for associations between CSF Aβ42 levels and measures of SWS controlling for potential confounders. Resulting models were compared to each other using ordinary least squared linear regression analysis. Additionally, the participant sample was dichotomized into "high" and "low" Aβ42 groups to compare SWS bout length using survival analyses. RESULTS: A significant inverse correlation was found between CSF Aβ42 levels, SWS duration and other SWS characteristics. Collectively, total SWA in the frontal lead was the best predictor of reduced CSF Aβ42 levels when controlling for age and ApoE status. Total sleep time, time spent in NREM1, NREM2, or REM sleep were not correlated with CSF Aβ42. CONCLUSIONS: In cognitively normal elderly, reduced and fragmented SWS is associated with increases in CSF Aβ42, suggesting that disturbed sleep might drive an increase in soluble brain Aβ levels prior to amyloid deposition.
DOI 10.5665/sleep.6240
PubMed ID 27568802
PubMed Central ID PMC5070758
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