Association of DNA methylation age acceleration with digital clock drawing test performance: the Framingham Heart Study
Abstract
BackgroundCognitive function measured by digital clock drawing test (dCDT) has drawn attention for their precision, automation, and reproductivity. However, the relationship between digital cognitive metrics and biological aging is lacking.
MethodsWe conducted association analyses between cognitive function measured by dCDT and biological aging metrics quantified by five DNA methylation (DNAm) age metrics (Horvath, Hannum, GrimAge, PhenoAge, and DunedinPACE) in the Framingham Heart Study (FHS). We conducted linear regression to investigate the association between cognitive functions (global cognitive function and four sub-domain functions) and DNAm age acceleration, adjusting for covariates. We used a false discovery rate (FDR) < 0.05 for significance.
ResultsAmong the 1,798 FHS participants (mean age 65{+/-}13, 53% women), we found that a lower dCDT total score is associated with DNAm age acceleration. Larger magnitudes of associations were observed in older participants ([≥] 65 years). The dCDT total score showed the strongest association with the DundinPACE in the pooled sample (beta = -2.1, FDR = 0.0004), the younger (beta = -1.9, FDR = 0.02), and older age group (beta = -2.2, FDR = 0.01). The dCDT total score was significantly associated with age acceleration estimated by Horvath (beta=-1.9, FDR =0.01) and PhenoAge (beta=-2.5, FDR=0.01) in older participants while not in the pooled sample or younger participants (<65 years). In sub-domain cognitive functions, we found that simple motor function was significantly associated with DunedinPACE (FDR = 0.005) in both age groups and associated with GrimAge (FDR = 0.05 in older age group), indicating the deterioration in various organ systems may particularly impact this domain.
DiscussionOur findings suggest that cognitive function measured by a digital clock drawing test is associated with DNAm age acceleration in middle-aged and older participants in the FHS, potentially shedding light on the epigenetic mechanisms underlying digitally measured cognitive function.
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Research summary
The paper explores the association between cognitive function and DNA methylation age acceleration, which is relevant to understanding biological aging processes. However, the findings are primarily observational and do not address root causes of aging or propose interventions for lifespan extension. The impact is limited as it contributes to existing knowledge without presenting groundbreaking insights or solutions.
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