A comparison of cognitive performances based on differing rates of DNA methylation GrimAge acceleration among older men and women

O’Shea, Deirdre; Alaimo, Hannah; Davis, Jennifer; Galvin, James E.; Tremont, Geoffrey

doi:10.1016/j.neurobiolaging.2022.12.011

Cited by 3 publications

(1 citation statement)

References 58 publications

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“…Many studies have demonstrated the role of epigenetic modifications in cognitive aging at old age [ 5 , 20 , 21 , 24 ]. Others have suggested DNAm age acceleration is a mediator for sex differences in verbal memory and processing speed [ 25 , 26 ]. Thus, we hypothesized that the DNAm age acceleration influenced by cognitive skills at early age could in turn affect one’s cognition in later life and examined the cross-sectional associations of DNAm age acceleration and cognitive measures in midlife.…”

Section: Introductionmentioning

confidence: 99%

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

Chen,

Moubadder,

Clausing

et al. 2024

Aging

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Section: Introductionmentioning

confidence: 99%

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

Chen,

Moubadder,

Clausing

et al. 2024

Aging

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DNA Methylation Mediates the Association Between Cardiometabolic Risk Factors and Cognition: Findings From the Health and Retirement Study

Wan,

Chibnik,

Valeri

et al. 2024

The Journals of Gerontology, Series A: Biological Sciences and Medical Sciences

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The association between cardiometabolic risk factors and cognitive function has been well documented, but the underlying mechanisms are not fully understood. This longitudinal study aimed to investigate the potential mediating role of DNA methylation in this association. We conducted the analyses in 3708 participants (mean [SD] age: 67.3 [9.49], women: 57.9%) from the Health and Retirement Study who were assessed in the 2014 to 2020 waves, had Infinium Methylation EPIC BeadChip methylation assays from the 2016 Venous Blood Study, and had cognitive assessment between 2016-2020. Causal mediation analyses were used to test the mediation role of DNA methylation in the associations between cardiometabolic risk factors and cognition, adjusting for demographic, socioeconomic, and lifestyle factors. Hypertension (-0.061 in composite cognitive z-score; 95% CI: (-0.119, -0.004)) and diabetes (-0.134; 95% CI: (-0.198, -0.071)) were significantly associated with worse cognitive function while abnormal BMI and hypercholesterolemia were not. An increased number of cardiometabolic risk factors was associated with worse cognitive function (P=0.002). DNA methylation significantly mediated the association of hypertension (mediated effect on composite cognitive z-score: -0.023; 95% CI: (-0.033, -0.014)), diabetes (-0.022; 95% CI: (-0.032, -0.014)), and obesity (-0.021; 95% CI: (-0.033, -0.011)) with cognitive function, while the mediation effect was not observed for having hypercholesterolemia. The estimated proportions mediated were 37.4% for hypertension and 16.7% for diabetes. DNA methylation may be an important mediator linking cardiometabolic risk factors to worse cognition and might even provide a potential target for dementia prevention.

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Pilot Study of Second-Generation DNA Methylation Epigenetic Markers in Relation to Cognitive and Neuropsychiatric Symptoms in Older Adults

Vyas

Sadreyev

Gatchel

et al. 2023

JAD

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Background: Associations between epigenetic aging with cognitive aging and neuropsychiatric measures are not well-understood. Objective: 1) To assess cross-sectional correlations between second-generation DNA methylation (DNAm)-based clocks of healthspan and lifespan (i.e., GrimAge, PhenoAge, and DNAm-based estimator of telomere length [DNAmTL]) and cognitive and neuropsychiatric measures; 2) To examine longitudinal associations between change in DNAm markers and change in cognition over 2 years. Methods: Participants were members of VITAL-DEP (VITamin D and OmegA-3 TriaL- Depression Endpoint Prevention) study. From previously ascertained cognitive groups (i.e., cognitively normal and mild cognitive impairment), we randomly selected 45 participants, aged≥60 years, who completed in-person neuropsychiatric assessments at baseline and 2 years. The primary outcome was global cognitive score (averaging z-scores of 9 tests). Neuropsychiatric Inventory severity scores were mapped from neuropsychiatric symptoms (NPS) from psychological scales and structured diagnostic interviews. DNAm was assayed using Illumina MethylationEPIC 850K BeadChip at baseline and 2 years. We calculated baseline partial Spearman\hfilneg correlations between DNAm markers and cognitive and NPS measures. We constructed multivariable linear regression models to examine longitudinal relations between DNAm markers and cognition. Results: At baseline, we observed a suggestive negative correlation between GrimAge clock markers and global cognition but no signal between DNAm markers and NPS measures. Over 2 years: each 1-year increase in DNAmGrimAge was significantly associated with faster declines in global cognition; each 100-base pair increase in DNAmTL was significantly associated with better global cognition. Conclusion: We found preliminary evidence of cross-sectional and longitudinal associations between DNAm markers and global cognition.

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A comparison of cognitive performances based on differing rates of DNA methylation GrimAge acceleration among older men and women

Cited by 3 publications

References 58 publications

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

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

DNA Methylation Mediates the Association Between Cardiometabolic Risk Factors and Cognition: Findings From the Health and Retirement Study

Pilot Study of Second-Generation DNA Methylation Epigenetic Markers in Relation to Cognitive and Neuropsychiatric Symptoms in Older Adults

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