Age-related differences in the association between REM sleep and the polygenic risk for Parkinson’s disease

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Objective Parkinson’s disease (PD) is one of the rare diseases for which sleep alteration is a true marker of disease outcome. Yet, how the association between sleep and PD emerges over the healthy lifetime is not established. We examined association between the polygenic risk score (PRS) for PD and the variability in the electrophysiology of Rapid Eye Movement (REM) sleep in 433 younger (18-31y) and 85 late-midlife (50-69y) healthy individuals. Methods In this prospective cross-sectional study, in-lab EEG recordings of sleep were recorded to extract REM sleep metrics. PRS was computed using SBayesR approach. Results Generalized Additive Model for Location, Scale and Shape (GAMLSS) analysis showed significant association of REM duration ( p corr =0.03) and theta energy in REM ( p corr =0.004 ) with PRS for PD in interaction with age group. In the younger sub-sample, REM duration and theta energy were positively associated with PD PRS. In contrast, in the late-midlife sub-sample, the same associations were negative (though only qualitatively for REM theta energy) and may differ between men and women. Interpretation REM sleep is associated with the PRS for PD in early adulthood, 2 to 5 decades prior to typical symptoms onset. The association changes from positive in younger individuals, presumably free of alpha-synuclein, to negative in late-midlife individuals, possibly because of the progressive presence of alpha-synuclein aggregates or of the repeated increased oxidative metabolism imposed by REM sleep. Our findings may unravel core associations between PD and sleep and may contribute to novel intervention targets to prevent or delay PD.

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