Sleep/wake cycle alterations as a cause of neurodegenerative diseases: a mendelian randomization study

Sleep and/or wake cycle alterations are common in neurodegenerative diseases (ND). Our aim was to determine whether there is a causal relationship between sleep and/or wake cycle patterns and ND (Parkinson's disease (PD) age at onset (AAO), Alzheimer's disease (AD), and amyotrophic lateral sclerosis (ALS)) using two-sample Mendelian Randomization (MR). We selected 12 sleep traits with available GenomeWide Association Study (GWAS) to evaluate their causal relationship with the ND risk through InverseVariance Weighted regression as main analysis. We used as outcome the latest ND GWAS with available summary-statistics: PD-AAO (N = 17,996), AD (N = 21,235) and ALS (N = 40,136). MR results pointed to a causal effect of subjective and objective-measured morning chronotype on later PD-AAO (95%CI:0.33-1.81, p = 8.47x10(-09) and 95%CI:-7.28 to -4.44, p = 5.87x10(-16), respectively). Sleep efficiency was causally associated with a decreased AD risk (95%CI:-20.408 to -0.66, p = 0.04) and daytime sleepiness with an increased ALS risk (95%CI:0.15 to 1.61, p = 0.01). Our study suggests that sleep and/or wake patterns have causal relationship with ND. Given that sleep and/or wake patterns are modifiable risk factors, sleep interventions should be investigated as a potential treatment in PD-AAO, AD and ALS. (C) 2021 The Author(s). Published by Elsevier Inc.

Automated summary

The study suggests a causal relationship between sleep and/or wake patterns and neurodegenerative diseases, such as Parkinson's disease, Alzheimer's disease, and amyotrophic lateral sclerosis. Morning chronotype, sleep efficiency, and daytime sleepiness were found to be associated with different risks of these diseases, highlighting the potential importance of sleep interventions as a treatment approach.