Evidence map›Paper›PMID 41646682›Full record

ArticlemedRxiv : the preprint server for health sciences2026

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

Linda K McEvoy, Bowei Zhang, Steve Nguyen, Adam X Maihofer, Caroline M Nievergelt, Ramon Casanova, Steve Horvath, Ake T Lu, Christos Davatzikos, Guray Erus and 7 more

Abstract readPreprint
In one paragraph

Article in medRxiv : the preprint server for health sciences, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

17 authors.

Linda K McEvoyKaiser Permanente Washington Health Research Institute, Seattle, WA, USA.
Bowei ZhangHerbert Wertheim School of Public Health and Human Longevity Science, University of California San Diego, La Jolla, CA, USA.ORCID 0009-0000-9686-0897
Steve NguyenHerbert Wertheim School of Public Health and Human Longevity Science, University of California San Diego, La Jolla, CA, USA.ORCID 0000-0002-5193-7042
Adam X MaihoferDepartment of Psychiatry, School of Medicine, University of California San Diego, La Jolla, CA, USA.
Caroline M NievergeltDepartment of Psychiatry, School of Medicine, University of California San Diego, La Jolla, CA, USA.
Ramon CasanovaDepartment of Biostatistics and Data Science, Wake University School of Medicine, Winston-Salem, NC.
Steve HorvathAltos Labs Cambridge Institute of Science, Cambridge, UK.ORCID 0000-0002-4110-3589
Ake T LuAltos Labs, San Diego, CA.
Christos DavatzikosDepartment of Radiology, University of Pennsylvania School of Medicine, Philadelphia, PA.
Guray ErusDepartment of Radiology, University of Pennsylvania School of Medicine, Philadelphia, PA.ORCID 0000-0001-6633-4861
Susan M ResnickLaboratory of Behavioral Neuroscience, National Institute on Aging, National Institutes of Health, Baltimore, MD, USA.
Mark A EspelandDivision of Gerontology and Geriatric Medicine, School of Medicine, Wake Forest University School of Medicine, Winston-Salem, NC, USA.
Stephen R RappDepartment of Psychiatry and Behavioral Medicine, Wake Forest University School of Medicine, Winston-Salem, NC, USA.
Kenneth BeckmanGenomics Center, University of Minnesota, Minneapolis, MN, USA.
Luigi FerrucciLongitudinal Studies Section, Translational Gerontology Branch, National Institute on Aging, Baltimore, MD.
Andrea Z LacroixHerbert Wertheim School of Public Health and Human Longevity Science, University of California San Diego, La Jolla, CA, USA.
Aladdin H ShadyabHerbert Wertheim School of Public Health and Human Longevity Science, University of California San Diego, La Jolla, CA, USA.

Funding

WOMEN'S HEALTH INITIATIVE - CLINICAL COORDINATING CENTER: TASK AREA B - LONG LIFE STUDY VISIT 2 LIMITED HOME VISIT75N92021D00001 · NHLBI · FRED HUTCHINSON CANCER RESEARCH CENTER · PI ANDERSON, GARNET L. · 2021 to 2025
$52.0M
Sedentary Behaviour Interrupted: Acute, medium and long-term effects on biomarkers of healthy aging, physical function and mortalityP01AG052352 · NIA · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI LACROIX, ANDREA Z. · 2017 to 2022
$9.0M
WOMEN'S HEALTH INITIATIVE (WHI) REGIONAL CENTER (RC): TASK AREA A AND A275N92021D00002 · NHLBI · STATE UNIVERSITY OF NEW YORK AT BUFFALO · PI WACTAWSKI-WENDE, JEAN · 2021 to 2025
$6.9M
WOMEN'S HEALTH INITIATIVE (WHI) REGIONAL CENTER (RC) - TO EXERCISE OPTION PERIOD ONE (1) AND REVISE CONTRACT ARTICLES.75N92021D00004 · NHLBI · STANFORD UNIVERSITY · PI STEFANICK, MARCIA · 2021 to 2025
$6.5M
WOMEN'S HEALTH INITIATIVE (WHI) REGIONAL CENTER (RC) - TO EXERCISE OPTION PERIOD ONE (1) AND REVISE CONTRACT ARTICLES.75N92021D00003 · NHLBI · OHIO STATE UNIVERSITY · PI JACKSON, REBECCA · 2021 to 2025
$5.0M
WOMEN'S HEALTH INITIATIVE (WHI) REGIONAL CENTER (RC) - TO EXERCISE OPTION PERIOD ONE (1) AND REVISE CONTRACT ARTICLES.75N92021D00005 · NHLBI · WAKE FOREST UNIVERSITY HEALTH SCIENCES · PI VITOLINS, MARA · 2021 to 2025
$4.2M
Epigenetic Aging Biomarkers of Mild Cognitive Impairment, Alzheimer's Disease and Related Dementias, and Brain AgingR01AG074345 · NIA · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI SHADYAB, ALADDIN · 2024 to 2025
$1.1M
Plasma proteomic signatures of physical activity and Alzheimer's disease and related dementiasK99AG082863 · NIA · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI NGUYEN, STEVE · 2023 to 2024
$206k
BLRD VA IK2 BX006536NHLBI NIH HHS 75N92021D00001NHLBI NIH HHS 75N92021D00002NIA NIH HHS K99 AG082863NIA NIH HHS P01 AG052352NIA NIH HHS R01 AG074345WHI NIH HHS 75N92021D00003WHI NIH HHS 75N92021D00004WHI NIH HHS 75N92021D00005
6 · The paper itself

Abstract

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.

Indexed as

biological agingbrain ageepigenetic clocksfrontal lobesmoking

Identifiers

PMID41646682
PMCPMC12870710

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.