Evidence map›Paper›PMID 41358508›Full record

ArticleEpigenomics2025

DNA methylation age acceleration mediates the relationship between systemic inflammation and cognitive impairment.

César Higgins Tejera, Peiyao Zhu, Erin B Ware, Margaret T Hicken, Matthew Zawistowski, Lindsay C Kobayashi, Dominika Seblova, Jennifer Manly, Bhramar Mukherjee, Kelly M Bakulski

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Epigenomics, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing 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

4 citing papers in PubMed.

  1. Article
  2. Article
  3. Article
  4. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

10 authors.

César Higgins TejeraSchool of Public Health, University of Michigan, Ann Arbor, MI, USA.ORCID 0000-0001-5999-3607
Peiyao ZhuSchool of Public Health, University of Michigan, Ann Arbor, MI, USA.ORCID 0009-0004-5266-5570
Erin B WareInstitute for Social Research, University of Michigan, Ann Arbor, MI, USA.ORCID 0000-0003-4731-8158
Margaret T HickenInstitute for Social Research, University of Michigan, Ann Arbor, MI, USA.ORCID 0000-0001-6443-2249
Matthew ZawistowskiSchool of Public Health, University of Michigan, Ann Arbor, MI, USA.ORCID 0000-0002-3005-083X
Lindsay C KobayashiSchool of Public Health, University of Michigan, Ann Arbor, MI, USA.ORCID 0000-0003-2725-3107
Dominika SeblovaDepartment of Public Health, Second Faculty of Medicine, Charles University, Prague.ORCID 0000-0001-6147-6895
Jennifer ManlyDepartments of Epidemiology and Sociomedical Sciences, Mailman School of Public Health, Columbia University, New York, NY, USA.ORCID 0000-0002-9481-7497
Bhramar MukherjeeSchool of Public Health, University of Michigan, Ann Arbor, MI, USA.ORCID 0000-0003-0118-4561
Kelly M BakulskiSchool of Public Health, University of Michigan, Ann Arbor, MI, USA.ORCID 0000-0002-9605-6337

Funding

HRS Yrs29-34: Y33 SSA CoFundingU01AG009740 · NIA · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Jessica Faul, KENNETH M LANGA · 1990 to 2026
$555.8M
Research Education ComponentP30AG072931 · NIA · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Henry L Paulson · 2021 to 2026
$26.5M
DNA Methylation, Genetics, and Modifiable Risk Factors of Dementia in a Nationally Representative, Multi-Ethnic Cohort - Diversity SupplementR01AG067592 · NIA · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI BAKULSKI, KELLY, WARE, ERIN BAKSHIS · 2020 to 2025
$3.8M
DNA methylation in context: Racial inequities in social adversity and vulnerability to the health impact of air pollution - Diversity Supplement (Fike)R01AG074887 · NIA · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI HICKEN, MARGARET TAKAKO · 2021 to 2025
$3.4M
Characterizing disparities in late-onset Alzheimer's disease risk through polygenic risk and epidemiologic factors in the Health and Retirement SurveyR01AG055406 · NIA · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI BAKULSKI, KELLY, WARE, ERIN BAKSHIS · 2017 to 2020
$1.7M
NIA NIH HHS P30 AG072931NIA NIH HHS R01 AG055406NIA NIH HHS R01 AG067592NIA NIH HHS R01 AG074887NIA NIH HHS U01 AG009740
6 · The paper itself

Abstract

backgroundChronic inflammation and DNA methylation are potential mechanisms in dementia etiology. The linkage between inflammation and DNA methylation age acceleration in shaping dementia risk remains understudied. We explored the association of inflammatory cytokines with cognitive impairment and whether DNA methylation age acceleration mediates this relationship. RESEARCH DESIGN AND

methodsUsing data from the 2016 Health and Retirement Study (

resultsCognitive impairment prevalence was 16%. A doubling of IL-6 was associated with a 12% higher odds of cognitive impairment (OR = 1.12, 95% CI: 1.02-1.22), and 0.77 years of GrimAge acceleration (95% CI: 0.64-0.90). Similar associations were found for CRP and IGF-1. Mediation analysis indicated that 17.7% (95% CI: 7.0-50.9%) of the IL-6-cognitive impairment association was mediated by the GrimAge acceleration. Comparable mediated estimates were found for CRP and IGF-1.

conclusionsSystemic inflammation is associated with cognitive impairment, with suggestive evidence that this relationship is partially mediated through DNA methylation age acceleration.

Indexed as

AgingCognitive DysfunctionDNA MethylationInflammationAgedAged, 80 and overC-Reactive ProteinFemaleHumansInsulin-Like Growth Factor IInterleukin-6MaleMiddle AgedC-Reactive ProteinIL6 protein, humanInsulin-Like Growth Factor IInterleukin-6cognitionCytokinesdementiaDNA methylationepigenetic clocksGrimAgeinflammation

Identifiers

PMID41358508
PMCPMC12826733

What OpenQuestion holds

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LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

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.