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Updated: Nov 16, 2025

Generalized Psychophysiological Interaction PPI Analysis of Memory Related Connectivity in Individuals at Genetic Risk for Alzheimer's Disease
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Epigenetic Age Acceleration and Cognitive Decline: A Twin Study.

Viola Vaccarino1,2, Minxuan Huang1, Zeyuan Wang1

  • 1Department of Epidemiology, Emory University Rollins School of Public Health, Atlanta, Georgia, US.

The Journals of Gerontology. Series A, Biological Sciences and Medical Sciences
|February 19, 2021
PubMed
Summary

Epigenetic age acceleration, measured by DNA methylation (DNAm), is linked to cognitive decline in middle-aged men. Older epigenetic age predicts faster declines in executive function and memory over time.

Keywords:
BiomarkersCognitive agingEpidemiologyEpigeneticsTwin studies

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Area of Science:

  • Epigenetics
  • Neuroscience
  • Gerontology

Background:

  • The role of DNA methylation (DNAm) epigenetic age acceleration in cognitive decline is not well understood.
  • This study investigates the association between DNAm age acceleration and longitudinal cognitive decline in individuals without dementia.

Purpose of the Study:

  • To examine if DNAm age acceleration predicts cognitive decline in middle-aged men.
  • To assess the relationship between epigenetic aging and executive function and memory over time.

Main Methods:

  • A longitudinal twin study included 266 male twins (133 pairs), with 114 twins followed up over 11.5 years.
  • Epigenome-wide DNAm data yielded 6 indices of DNAm age acceleration.
  • Cognitive function was assessed using executive function and memory composite scores.

Main Results:

  • No cross-sectional association was found at baseline.
  • Longitudinally, each year of accelerated epigenetic age correlated with a 3% decline in executive function and a 2.5% decline in memory.
  • These associations remained significant after adjusting for covariates.

Conclusions:

  • Older epigenetic age relative to chronological age is associated with accelerated cognitive decline.
  • Epigenetic modifications play a role in cognitive aging processes.