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

Senkevich, K.; Pelletier, A.; Sato, C.; Keil, A.; Gan-Or, Z.; Lang, A. E.; Postuma, R.; Rogaeva, E.

2023-03-27 neurology
10.1101/2023.03.24.23287635 medRxiv
Show abstract

Rapid-eye movement sleep behavior disorder (RBD) is the strongest prodromal marker for -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.

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