Aging clocks derived from a database of age-related changes in specific biological data must be validated for any specific use. The construction of the clock grants no insight into how its component measures relate to any specific aspect of aging, or to any specific age-related condition. Even conceptually similar clocks might exhibit quite different relationships with a given age-related condition, a point that is illustrated by the results of this study: some epigenetic clocks show very poor correlation with dementia risk, while others do correlate well enough to provide some insight.
Aging is the strongest risk factor for dementia; however, few studies have examined the association of biological aging with incident dementia. We analyzed 6,069 cognitively unimpaired women (mean age = 70.0 ± 3.8 years) in the Women's Health Initiative Memory Study to examine the association of accelerated biological aging, measured with second and third-generation epigenetic clocks (AgeAccelPheno and AgeAccelGrim2, and DunedinPACE, respectively) with incident mild cognitive impairment (MCI) and probable dementia.
Multivariable Cox proportional hazards models were adjusted for age, education, race, ethnicity, smoking, hormone therapy regimen, physical activity, body mass index, and estimated white blood cell counts. For comparison, we also examined first-generation epigenetic clocks (AgeAccelHorvath; AgeAccelHannum). We evaluated effect modification by age, race/ethnicity, hormone therapy regimen, menopause type (natural vs. surgical), and APOE ε4 carriage.
There were 1,307 incident MCI or probable dementia events over a median follow-up of 9.3 years. The adjusted hazard ratios for incident MCI/probable dementia per one-standard deviation increment were 1.07 for DunedinPACE, 1.11 for AgeAccelGrim2, and 1.01 for AgeAccelPheno. Only AgeAccelGrim2 remained significant under the Bonferroni-corrected threshold for significance. Other epigenetic clocks were not associated with incident MCI/probable dementia. There was no effect modification in most subgroup analyses.
Link: https://doi.org/10.1111/acel.70424
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