title: Effect of 1 night of total sleep deprivation on cerebrospinal fluid β-amyloid 42 in healthy middle-aged men: a randomized clinical trial.
abstract: OBJECTIVE
  Increasing evidence suggests a relationship between poor sleep and the risk of developing Alzheimer disease. A previous study found an effect of sleep on β-amyloid (Aβ), which is a key protein in Alzheimer disease pathology.
  
  
  OBJECTIVE
  To determine the effect of 1 night of total sleep deprivation on cerebrospinal fluid Aβ42 protein levels in healthy middle-aged men.
  
  
  METHODS
  The Alzheimer, Wakefulness, and Amyloid Kinetics (AWAKE) study at the Radboud Alzheimer Center, a randomized clinical trial that took place between June 1, 2012, and October 1, 2012. Participants were cognitively normal middle-aged men (40-60 years of age) with normal sleep (n = 26) recruited from the local population.
  
  
  METHODS
  Participants were randomized to 1 night with unrestricted sleep (n = 13) or 1 night of total sleep deprivation (24 hours of wakefulness) (n = 13).
  
  
  METHODS
  Sleep was monitored using continuous polysomnographic recording from 3 pm until 10 am. Cerebrospinal fluid samples were collected using an intrathecal catheter at defined times to compare cerebral Aβ42 concentrations between evening and morning.
  
  
  RESULTS
  A night of unrestricted sleep led to a 6% decrease in Aβ42 levels of 25.3 pg/mL (95% CI [0.94, 49.6], P = .04), whereas sleep deprivation counteracted this decrease. When accounting for the individual trajectories of Aβ42 over time, a difference of 75.8 pg/mL of Aβ42 was shown between the unrestricted sleep and sleep deprivation group (95% CI [3.4, 148.4], P = .04). The individual trajectories of evening and morning Aβ42 concentrations differed between the unrestricted sleep and sleep deprivation groups (P = .04) in contrast to stable Aβ40, tau, and total protein levels.
  
  
  CONCLUSIONS
  Sleep deprivation, or prolonged wakefulness, interferes with a physiological morning decrease in Aβ42. We hypothesize that chronic sleep deprivation increases cerebral Aβ42 levels, which elevates the risk of Alzheimer disease.
  
  
  BACKGROUND
  clinicaltrials.gov Identifier: NCT01194713.
authors.affiliation: Donders Institute for Brain, Cognition, and Behaviour, Radboud University Medical Center, Nijmegen, the Netherlands2Radboud Alzheimer Center, Radboud University Medical Center, Nijmegen, the Netherlands3Department of Geriatric Medicine, Radboud University.
authors.forename: Sharon
authors.initials: S
authors.lastname: Ooms
authors.affiliation: Donders Institute for Brain, Cognition, and Behaviour, Radboud University Medical Center, Nijmegen, the Netherlands4Department of Neurology, Radboud University Medical Center, Nijmegen, the Netherlands.
authors.forename: Sebastiaan
authors.initials: S
authors.lastname: Overeem
authors.affiliation: Department of Anaesthesiology, Radboud University Medical Center, Nijmegen, the Netherlands.
authors.forename: Kees
authors.initials: K
authors.lastname: Besse
authors.affiliation: Donders Institute for Brain, Cognition, and Behaviour, Radboud University Medical Center, Nijmegen, the Netherlands2Radboud Alzheimer Center, Radboud University Medical Center, Nijmegen, the Netherlands3Department of Geriatric Medicine, Radboud University.
authors.forename: Marcel Olde
authors.initials: MO
authors.lastname: Rikkert
authors.affiliation: Donders Institute for Brain, Cognition, and Behaviour, Radboud University Medical Center, Nijmegen, the Netherlands2Radboud Alzheimer Center, Radboud University Medical Center, Nijmegen, the Netherlands4Department of Neurology, Radboud University Medical.
authors.forename: Marcel
authors.initials: M
authors.lastname: Verbeek
authors.affiliation: Donders Institute for Brain, Cognition, and Behaviour, Radboud University Medical Center, Nijmegen, the Netherlands2Radboud Alzheimer Center, Radboud University Medical Center, Nijmegen, the Netherlands3Department of Geriatric Medicine, Radboud University.
authors.forename: Jurgen A H R
authors.initials: JA
authors.lastname: Claassen
mesh_terms: D000328:Adult; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000134:cerebrospinal fluid*; D017286:Polysomnography; D012890:Sleep / Q000502:physiology*; D012892:Sleep Deprivation / Q000134:cerebrospinal fluid*; D013997:Time Factors
chemical_list: D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42)