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.

The authors have declared no competing interest.

This work was supported by the G. Harris Sheppard Fund for Research in Parkinson′s and other Neurodegenerative Diseases (ER), Canadian Consortium on Neurodegeneration in Aging (ER, ZGO), the Blidner Family Foundation (NPV), and the McLaughlin Accelerator Grants in Genomic Medicine (ER, ZGO, AEL, RP). ZGO is supported by the Fonds de recherche du Quebec - Sante (FRQS) Chercheurs-boursiers award, in collaboration with Parkinson Quebec, and is a William Dawson Scholar. KS is supported by a post-doctoral fellowship from the Canada First Research Excellence Fund (CFREF), awarded to McGill University for the Healthy Brains for Healthy Lives initiative (HBHL), FRQS post-doctoral fellowship and McKerracher Award.

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