Epigenetic clock acceleration is linked to earlier onset and phenoconversion age in REM sleep behavior disorder

Abstract Rapid-eye movement sleep behavior disorder (RBD) is the strongest prodromal marker for α-synucleinopathies. The Horvath DNA-methylation-age (DNAm-age) is an epigenetic clock that could reflect biological aging. We evaluated whether RBD age-at-onset/phenoconversion are associated with DNAm-age-acceleration in 162 RBD patients. We found an association of DNAm-age-acceleration with RBD age-at-onset at baseline (P=2.59e-08) and at follow-up (N=45; P=9.73e-06). RBD patients with faster aging had 4.6 years earlier onset than patients with slow/normal aging. Similarly, earlier age-at-phenoconversion was associated with DNAm-age-acceleration (N=53; P=1.26e-04). We demonstrated that epigenetic clock acceleration is linked with an earlier RBD age-at-onset and, hence with earlier phenoconversion.