A new research paper has been published in Volume 18. Aging-United States April 7, 2026, titled “The association between MRI biomarkers of aging and Alzheimer’s disease neurodegeneration and epigenetic aging acceleration.”
The study was led by lead and corresponding author Linda K. McEvoy of the Kaiser Permanente Washington Health Research Institute, who collaborated with an interdisciplinary team of researchers from leading institutions in the United States and Europe.
In this study, researchers investigated whether epigenetic measures of biological aging are associated with structural brain changes associated with aging and Alzheimer’s disease. Using data from 1,196 older women enrolled in the Women’s Health Initiative’s memory study, they analyzed five widely used epigenetic clocks and compared them to MRI-derived measurements taken about eight years later.
The results revealed that different aspects of aging are clearly distinct. None of the epigenetic clocks was associated with accelerated brain aging, as measured by the SPARE-BA index, a composite MRI marker of brain age. However, one particular clock, AgeAccelGrim2, was significantly associated with Alzheimer’s disease pattern similarity score (AD-PS), a validated imaging biomarker associated with increased risk of dementia.
Further analysis suggested that this association was primarily driven by epigenetic features related to smoking exposure. In particular, DNA methylation markers reflecting cumulative smoking history were associated with decreased volume in the frontal and temporal lobes, which are commonly affected in age-related neurodegeneration. Of note, no significant association was observed with the volume of the hippocampus or entorhinal cortex, regions more directly involved in early Alzheimer’s disease pathology.
”Taken together with previous findings, these results suggest that measurements of epigenetic brain age acceleration capture multiple aspects of biological aging and that AgeAccelGrim2 can predict smoking-related neurodegenerative changes that increase the risk of dementia..”
This study highlights the complexity of biological aging and emphasizes that not all aging biomarkers reflect the same underlying processes. Epigenetic clocks are increasingly used to estimate biological age, but their relationship with brain structure appears to depend on the specific pathways they capture, particularly those influenced by environmental exposures such as smoking.
Collectively, these findings provide important insights into how molecular measures of aging relate to neuroimaging markers of brain health. By distinguishing between general brain aging and disease-related neurodegeneration, this study may help refine the use of epigenetic biomarkers in aging research and aid future efforts to identify individuals at risk of cognitive decline.
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Reference magazines:
McEvoy, L.K. Others. (2026). Association of epigenetic age acceleration with MRI biomarkers of aging and Alzheimer’s disease neurodegeneration. aging. DOI: 10.18632/Aging.206369. https://www.aging-us.com/article/206369/text
