DNA methylation age acceleration as a potential biomarker for early onset of REM sleep behavior disorder.

REM sleep behavior disorder (RBD) is the strongest prodromal marker for α-synucleinopathies. The Horvath DNA-methylation-age (DNAm-age) is an epigenetic clock reflecting biological aging. We found an association of DNAm-age-acceleration with RBD age-at-onset at baseline (N=162; B=-0.68; SE=0.12; P=2.59e-08) and follow-up (N=45; B=-1.07; SE=0.21; P=9.73e-06). The result remains similar after accounting for genetic risk-factors (e.g., RBD polygenic risk score). On average, RBD patients with faster vs slow/normal epigenetic aging had a 5.2-year earlier phenoconversion, and the cox-regression analysis revealed a trend towards significance (N=53; HR=1.05 (0.99-1.11); P=0.06). Our findings suggest that DNAm-age-acceleration is a potential biomarker for earlier RBD onset. This article is protected by copyright. All rights reserved.