Some Epigenetic Clocks Correlate with Risk of Dementia
Analysis of 6,069 cognitively unimpaired women in the Women's Health Initiative Memory Study (mean age 70) linked epigenetic clocks to incident mild cognitive impairment (MCI) or probable dementia over a median 9.3-year follow-up. Second- and third-generation clocks showed heterogeneous results: AgeAccelGrim2 had an adjusted hazard ratio of 1.11 per SD and remained significant after Bonferroni correction, DunedinPACE had HR 1.07, AgeAccelPheno 1.01, while first-generation clocks (Horvath, Hannum) showed no association. Subgroup analyses found no consistent effect modification by age, race/ethnicity, hormone therapy, menopause type, or APOE ε4 carriage.
Why it mattersAgeAccelGrim2 associated with incident MCI/probable dementia in WHIMS; validate it before using for dementia risk stratification.