Title | Reduced Slow-Wave Sleep Is Associated with High Cerebrospinal Fluid Aβ42 Levels in Cognitively Normal Elderly. |
Publication Type | Journal Article |
Year of Publication | 2016 |
Authors | Varga AW, Wohlleber ME, Giménez S, Romero S, Alonso JF, Ducca EL, Kam K, Lewis C, Tanzi EB, 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 OE, de Leon MJ, Rapoport DM, Lu S-E, Ayappa I, Osorio RS |
Journal | Sleep |
Volume | 39 |
Issue | 11 |
Pagination | 2041-2048 |
Date Published | 2016 Nov 01 |
ISSN | 1550-9109 |
Keywords | Aged, Aged, 80 and over, Alzheimer Disease, Amyloid beta-Peptides, Biomarkers, Cognition, Female, Humans, Linear Models, Longitudinal Studies, Magnetic Resonance Imaging, Male, Peptide Fragments, Polysomnography, 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 |
Alternate Journal | Sleep |
PubMed ID | 27568802 |
PubMed Central ID | PMC5070758 |
Grant List | R01 AG022374 / AG / NIA NIH HHS / United States R01 HL111724 / HL / NHLBI NIH HHS / United States R01 AG035137 / AG / NIA NIH HHS / United States R01 AG013616 / AG / NIA NIH HHS / United States R21 AG032554 / AG / NIA NIH HHS / United States R01 HL118624 / HL / NHLBI NIH HHS / United States P30 AG008051 / AG / NIA NIH HHS / United States K24 HL109156 / HL / NHLBI NIH HHS / United States R21 AG049348 / AG / NIA NIH HHS / United States R01 AG012101 / AG / NIA NIH HHS / United States UL1 TR000038 / TR / NCATS NIH HHS / United States |
Related Institute:
Brain Health Imaging Institute (BHII)