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

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 reflecting biological aging. We found an association of DNAm‐age acceleration with RBD age at onset at baseline (N = 162, B = −0.68, standard error [SE] = 0.12, p = 2.59e‐08) and follow‐up (n = 45, B = −1.07, SE = 0.21, p = 9.73e‐06). The result remained similar after accounting for genetic risk factors (eg, RBD polygenic risk score). On average, RBD patients with faster versus slow/normal epigenetic aging had a 5.2‐year earlier phenoconversion, and the Cox regression analysis revealed a trend toward significance (n = 53, hazard ratio = 1.05, 95% confidence interval = 0.99–1.11, p = 0.06). Our findings suggest that DNAm‐age acceleration is a potential biomarker for earlier RBD onset. ANN NEUROL 2023