Aging clocksHumans

Epigenetic age links to higher dementia risk in older adults

In 2,606 participants, higher DunedinPACE was associated with increased risks of mild cognitive impairment (hazard ratio 1.16) and all-cause dementia (hazard ratio 1.30).

Neurology Open Access

In 2,606 Framingham Heart Study Offspring cohort participants (mean age 66 years), researchers examined how three DNA methylation measures—DunedinPACE, PCPhenoAge, and PCGrimAge—linked to cognitive performance, brain measures, and dementia risk. They also assessed whether total cerebral brain volume or plasma total tau moderated these relationships.

All three epigenetic age measures associated with worse baseline executive function. Higher PCPhenoAge was also associated with poorer baseline memory and language. Over follow-up, faster aging measured by DunedinPACE was associated with time to mild cognitive impairment (hazard ratio 1.16) and all-cause dementia (hazard ratio 1.30). However, epigenetic age measures were not associated with the rate of longitudinal cognitive decline. The associations remained consistent after adjusting for total cerebral brain volume and plasma total tau.

Why it matters

The findings show that epigenetic age marks cognitive resilience through brain reserve independently of brain volume and tau. This supports the potential use of epigenetic clocks to track interventions aimed at preserving cognitive reserve.

Caveats

The observational study cannot establish causal mechanisms, and the epigenetic clocks did not predict the longitudinal rate of cognitive decline.

The paper

Epigenetic Age and Resilience in the Framingham Heart Study

Dacey R, Durape S, Wang M et al.

Neurology Open Access · 8 Jun 2026

doi.org/10.1212/wn9.0000000000000081 PubMed

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