Association of epigenetic age acceleration with MRI biomarkers of aging and Alzheimer’s disease neurodegeneration

Apr 8, 2026Aging

Faster biological aging linked to brain scans of aging and Alzheimer's disease

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Abstract

Among 1,196 older women, AgeAccelGrim2 was significantly associated with the Alzheimer's Disease Pattern Similarity Score (β = 0.015; p = 0.01).

Epigenetic clocks may relate to biological aging, but their connection to brain aging patterns remains unclear.
No associations were found between any epigenetic clock and accelerated brain aging assessed through SPARE-BA.
The association between AgeAccelGrim2 and AD-PS was primarily influenced by a DNA methylation marker linked to smoking history.
AgeAccelGrim2 did not show an association with brain regions typically affected in early Alzheimer's disease.
These findings indicate that different measures of epigenetic and brain age acceleration may represent distinct aspects of biological aging.

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Epigenetic clocks of biological aging have been associated with cognitive impairment and dementia. Less is known about whether they are associated with an older-appearing brain or with an atrophy pattern associated with dementia. We examined associations of five epigenetic clocks measured at baseline with the Spatial Pattern of Atrophy for Recognition of Brain Aging (SPARE-BA) and the Alzheimer's Disease Pattern Similarity Score (AD-PS) derived from structural MRIs obtained an average of 8 years later among 1,196 older women. Using linear regression models adjusting for relevant covariates, we observed no associations between any epigenetic clock and accelerated brain aging based on SPARE-BA. We observed a significant association between AgeAccelGrim2 and AD-PS (β = 0.015; 95% CI 0.004 to 0.027; p = 0.01). This association appeared to be primarily driven by the association of a DNA methylation marker of smoking pack years with frontal and temporal lobe volumes. AgeAccelGrim2 was not associated with volumes in regions implicated in early AD (hippocampus and entorhinal cortex). Taken together with prior findings, these results suggest that measures of epigenetic and brain age acceleration capture different aspects of biological aging, and that AgeAccelGrim2 is predictive of neurodegenerative changes associated with smoking that increase risk of dementia.

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Association of epigenetic age acceleration with MRI biomarkers of aging and Alzheimer’s disease neurodegeneration

Abstract

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