Associations of childhood, adolescence, and midlife cognitive function with DNA methylation age acceleration in midlife

Prior studies showed increased age acceleration (AgeAccel) is associated with worse cognitive function among old adults. We examine the associations of childhood, adolescence and midlife cognition with AgeAccel based on DNA methylation (DNAm) in midlife. Data are from 359 participants who had cognition measured in childhood and adolescence in the Child Health and Development study, and had cognition, blood based DNAm measured during midlife in the Disparities study. Childhood cognition was measured by Raven's Progressive Matrices and Peabody Picture Vocabulary Test (PPVT). Adolescent cognition was measured only by PPVT. Midlife cognition included Wechsler Test of Adult Reading (WTAR), Verbal Fluency (VF), Digit Symbol (DS). AgeAccel measures including Horvath, Hannum, PhenoAge, GrimAge and DunedinPACE were calculated from DNAm. Linear regressions adjusted for potential confounders were utilized to examine the association between each cognitive measure in relation to each AgeAccel. There are no significant associations between childhood cognition and midlife AgeAccel. A 1-unit increase in adolescent PPVT, which measures crystalized intelligence, is associated with 0.048-year decrease of aging measured by GrimAge and this association is attenuated after adjustment for adult socioeconomic status. Midlife crystalized intelligence measure WTAR is negatively associated with PhenoAge and DunedinPACE, and midlife fluid intelligence measure (DS) is negatively associated with GrimAge, PhenoAge and DunedinPACE. AgeAccel is not associated with VF in midlife. In conclusion, our study showed the potential role of cognitive functions at younger ages in the process of biological aging. We also showed a potential relationship of both crystalized and fluid intelligence with aging acceleration.