title: Reduced Slow-Wave Sleep Is Associated with High Cerebrospinal Fluid Aβ42 Levels in Cognitively Normal Elderly.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
authors: Division of Pulmonary, Critical Care, and Sleep Medicine, NYU Langone Medical Center, New York, NY.
authors: Andrew W
authors: AW
authors: Varga
authors: Center for Brain Health, Department of Psychiatry, NYU Langone Medical Center, New York, NY.
authors: Margaret E
authors: ME
authors: Wohlleber
authors: Department of Neurology, Hospital de la Santa Creu i Sant Pau-Biomedical Research Institute Sant Pau- Universitat Autònoma de Barcelona, Spain.
authors: Sandra
authors: S
authors: Giménez
authors: Department of Neurology, Hospital de la Santa Creu i Sant Pau-Biomedical Research Institute Sant Pau- Universitat Autònoma de Barcelona, Spain.|Departament d'Enginyeria de Sistemes, Automàtica i Informàtica Industrial, Universitat Politecnica de Catalunya (UPC), Barcelona, Spain.
authors: Sergio
authors: S
authors: Romero
authors: Departament d'Enginyeria de Sistemes, Automàtica i Informàtica Industrial, Universitat Politecnica de Catalunya (UPC), Barcelona, Spain.|Escola Universitària d'Enginyeria Tècnica Industrial de Barcelona, UPC, Barcelona, Spain.|CIBER de Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), Madrid, Spain.
authors: Joan F
authors: JF
authors: Alonso
authors: Division of Pulmonary, Critical Care, and Sleep Medicine, NYU Langone Medical Center, New York, NY.
authors: Emma L
authors: EL
authors: Ducca
authors: The Nathan Kline Institute for Psychiatric Research, Orangeburg, NY.
authors: Korey
authors: K
authors: Kam
authors: Division of Pulmonary, Critical Care, and Sleep Medicine, NYU Langone Medical Center, New York, NY.|Center for Brain Health, Department of Psychiatry, NYU Langone Medical Center, New York, NY.
authors: Clifton
authors: C
authors: Lewis
authors: Center for Brain Health, Department of Psychiatry, NYU Langone Medical Center, New York, NY.
authors: Emily B
authors: EB
authors: Tanzi
authors: Center for Brain Health, Department of Psychiatry, NYU Langone Medical Center, New York, NY.
authors: Samuel
authors: S
authors: Tweardy
authors: Graduate School of Education, The University of Tokyo, Tokyo, Japan.
authors: Akifumi
authors: A
authors: Kishi
authors: NYU Polytechnic School of Engineering, Brooklyn, NY.
authors: Ankit
authors: A
authors: Parekh
authors: Center for Brain Health, Department of Psychiatry, NYU Langone Medical Center, New York, NY.
authors: Esther
authors: E
authors: Fischer
authors: Division of Pulmonary, Critical Care, and Sleep Medicine, NYU Langone Medical Center, New York, NY.|Center for Brain Health, Department of Psychiatry, NYU Langone Medical Center, New York, NY.
authors: Tyler
authors: T
authors: Gumb
authors: Department of Neurology, Hospital de la Santa Creu i Sant Pau-Biomedical Research Institute Sant Pau- Universitat Autònoma de Barcelona, Spain.
authors: Daniel
authors: D
authors: Alcolea
authors: Department of Neurology, Hospital de la Santa Creu i Sant Pau-Biomedical Research Institute Sant Pau- Universitat Autònoma de Barcelona, Spain.|Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas, CIBERNED.
authors: Juan
authors: J
authors: Fortea
authors: Department of Neurology, Hospital de la Santa Creu i Sant Pau-Biomedical Research Institute Sant Pau- Universitat Autònoma de Barcelona, Spain.|Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas, CIBERNED.
authors: Alberto
authors: A
authors: Lleó
authors: Institute of Neuroscience and Psychiatry, Department of Psychiatry and Neurochemistry, the Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden.
authors: Kaj
authors: K
authors: Blennow
authors: Institute of Neuroscience and Psychiatry, Department of Psychiatry and Neurochemistry, the Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden.
authors: Henrik
authors: H
authors: Zetterberg
authors: Center for Brain Health, Department of Psychiatry, NYU Langone Medical Center, New York, NY.
authors: Lisa
authors: L
authors: Mosconi
authors: Center for Brain Health, Department of Psychiatry, NYU Langone Medical Center, New York, NY.
authors: Lidia
authors: L
authors: Glodzik
authors: Center for Brain Health, Department of Psychiatry, NYU Langone Medical Center, New York, NY.
authors: Elizabeth
authors: E
authors: Pirraglia
authors: Division of Pulmonary, Critical Care, and Sleep Medicine, NYU Langone Medical Center, New York, NY.
authors: Omar E
authors: OE
authors: Burschtin
authors: Center for Brain Health, Department of Psychiatry, NYU Langone Medical Center, New York, NY.
authors: Mony J
authors: MJ
authors: de Leon
authors: Division of Pulmonary, Critical Care, and Sleep Medicine, NYU Langone Medical Center, New York, NY.
authors: David M
authors: DM
authors: Rapoport
authors: Department of Biostatistics, Rutgers School of Public Health, Piscataway, NJ.
authors: Shou-En
authors: SE
authors: Lu
authors: Division of Pulmonary, Critical Care, and Sleep Medicine, NYU Langone Medical Center, New York, NY.
authors: Indu
authors: I
authors: Ayappa
authors: Center for Brain Health, Department of Psychiatry, NYU Langone Medical Center, New York, NY.
authors: Ricardo S
authors: RS
authors: Osorio
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000503:physiopathology; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid*; D015415:Biomarkers / Q000134:cerebrospinal fluid; D003071:Cognition / Q000502:physiology; D005260:Female; D006801:Humans; D016014:Linear Models; D008137:Longitudinal Studies; D008279:Magnetic Resonance Imaging; D008297:Male; D010446:Peptide Fragments / Q000134:cerebrospinal fluid*; D017286:Polysomnography; D012894:Sleep Stages / Q000502:physiology*
chemical_list: D016229:Amyloid beta-Peptides; D015415:Biomarkers; D010446:Peptide Fragments
keywords: Alzheimer disease; amyloid beta; elderly; prevention; sleep