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Original Investigation |

Effect of 1 Night of Total Sleep Deprivation on Cerebrospinal Fluid β-Amyloid 42 in Healthy Middle-Aged Men:  A Randomized Clinical Trial

Sharon Ooms, MSc1,2,3; Sebastiaan Overeem, MD1,4; Kees Besse, MD5; Marcel Olde Rikkert, MD, PhD1,2,3; Marcel Verbeek, MSc, PhD1,2,4,6; Jurgen A. H. R. Claassen, MD, PhD1,2,3
[+] Author Affiliations
1Donders Institute for Brain, Cognition, and Behaviour, Radboud University Medical Center, Nijmegen, the Netherlands
2Radboud Alzheimer Center, Radboud University Medical Center, Nijmegen, the Netherlands
3Department of Geriatric Medicine, Radboud University Medical Center, Nijmegen, the Netherlands
4Department of Neurology, Radboud University Medical Center, Nijmegen, the Netherlands
5Department of Anaesthesiology, Radboud University Medical Center, Nijmegen, the Netherlands
6Department of Laboratory Medicine, Radboud University Medical Center, Nijmegen, the Netherlands
JAMA Neurol. 2014;71(8):971-977. doi:10.1001/jamaneurol.2014.1173.
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Importance  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.

Design, Setting, and Participants  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.

Interventions  Participants were randomized to 1 night with unrestricted sleep (n = 13) or 1 night of total sleep deprivation (24 hours of wakefulness) (n = 13).

Main Outcomes and Measures  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 and Relevance  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.

Trial Registration  clinicaltrials.gov Identifier: NCT01194713

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Figure 1.
CONSORT Flow Diagram
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Figure 2.
Individual Cerebrospinal Fluid β-Amyloid 42 (Aβ42) Concentrations

Mean individual cerebrospinal fluid Aβ42 concentrations of both the sleep deprivation and unrestricted sleep groups in comparison with individual cerebrospinal fluid Aβ42 concentrations of healthy elderly patients and patients with Alzheimer disease in a previous serial sampling study. Dotted line indicates the cutoff value of 192 pg/mL; solid lines, mean cerebrospinal fluid concentration of Aβ42.

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Figure 3.
Cerebrospinal Fluid (CSF) β-Amyloid 42 (Aβ42) and Total Protein Concentrations Over Time

Mean CSF concentrations of Aβ42 (A) and total protein (B) over time in the unrestricted sleep group and in the sleep deprivation group. Shaded areas indicate the time the light was turned off in the unrestricted sleep group. Standard errors are indicated by vertical lines; error bars, standard error.aIndividual trajectories of the CSF Aβ42 samples differed between the groups (P = .04).

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Figure 4.
Relationship Between Total Sleep Time and Reduction in β-Amyloid 42 (Aβ42)

Relationship between the reduction in cerebrospinal fluid Aβ42 in between 5 pm and 10 am and the total sleep time in minutes (r = −0.50, P = .04).

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Figure 5.
Cerebrospinal Fluid (CSF) β-Amyloid 40 (Aβ40) and Tau Concentrations Over Time

Mean CSF concentrations of Aβ40 (A), phosphorylated tau (P-tau) (B), and total tau (T-tau) (C) over time in the unrestricted sleep group and in the sleep deprivation group. Shaded areas indicate the time the light was turned off in the unrestricted sleep group; error bars, standard error.

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