Evidence map›Paper›PMID 41152152›Full record

ArticleAlzheimer's & dementia : the journal of the Alzheimer's Association2025

Mitochondrial haplogroups, but not heteroplasmy, are associated with midlife cognitive function.

Nien Yeh Daphne Yu, Shea J Andrews, Lifang Hou, Myriam Fornage, Kristine Yaffe

Abstract read
In one paragraph

Article in Alzheimer's & dementia : the journal of the Alzheimer's Association, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing 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

2 citing papers in PubMed.

  1. Review
  2. Mitochondrial haplogroups, but not heteroplasmy, are associated with midlife cognitive function.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025
    Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

5 authors.

Nien Yeh Daphne YuDepartment of Epidemiology and Biostatistics, University of California, San Francisco, California, USA.ORCID 0009-0008-6674-0227
Shea J AndrewsDepartment of Psychiatry and Behavioral Sciences, University of California, San Francisco, California, USA.
Lifang HouDepartment of Preventive Medicine, Northwestern University Feinberg School of Medicine, Evanston, Illinois, USA.
Myriam FornageInstitute of Molecular Medicine, Health Science Center at Houston, University of Texas, Houston, Texas, USA.
Kristine YaffeDepartment of Epidemiology and Biostatistics, University of California, San Francisco, California, USA.

Funding

CORONARY ARTERY RISK DEVELOPMENT IN YOUNG ADULTS (CARDIA) STUDY - COORDINATING CENTER (CC)75N92023D00002 · NHLBI · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI LI, JING · 2023 to 2025
$6.8M
Blood mitochondrial DNA biomarkers of midlife cognitive decline and adverse brain imaging changes - A longitudinal investigation in the CARDIA population‐based cohort studyR01AG069120 · NIA · NORTHWESTERN UNIVERSITY AT CHICAGO · PI HOU, LIFANG, YAFFE, KRISTINE · 2020 to 2024
$4.0M
Population Based Research for Alzheimer's Innovation (POP BRAIN)R35AG071916 · NIA · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI YAFFE, KRISTINE · 2021 to 2024
$3.8M
Lifecourse CVD Risk and Midlife Cognitive Trajectories and Brain Aging: Implications for Alzheimer's and Dementia PreventionR01AG063887 · NIA · NORTHERN CALIFORNIA INSTITUTE/RES/EDU · PI YAFFE, KRISTINE · 2019 to 2022
$3.0M
Lifecourse Predictors and Mechanisms of Early Clinical ADRD among Black and White Adults in their SixtiesR01AG091431 · NIA · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Kristine Yaffe · 2025 to 2026
$2.6M
CORONARY ARTERY RISK DEVELOPMENT IN YOUNG ADULTS (CARDIA) STUDY - OAKLAND FIELD CENTER75N92023D00003 · NHLBI · KAISER FOUNDATION RESEARCH INSTITUTE · PI BHATT, ANKEET S. · 2023 to 2025
$2.2M
CORONARY ARTERY RISK DEVELOPMENT IN YOUNG ADULTS (CARDIA) STUDY - BIRMINGHAM FIELD CENTER75N92023D00005 · NHLBI · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI LEWIS, CORA · 2023 to 2025
$2.2M
CORONARY ARTERY RISK DEVELOPMENT IN YOUNG ADULTS (CARDIA) STUDY - CHICAGO FIELD CENTERDIVERSITY SUPPLEMENT FOR MORGANN WEST75N92023D00004 · NHLBI · NORTHWESTERN UNIVERSITY · PI CARNETHON, MERCEDES · 2023 to 2025
$2.1M
CORONARY ARTERY RISK DEVELOPMENT IN YOUNG ADULTS (CARDIA) STUDY - UNIVERSITY OF MINNESOTA FIELD CENTER.75N92023D00006 · NHLBI · UNIVERSITY OF MINNESOTA · PI SCHREINER, PAMELA J · 2023 to 2025
$1.7M
NHLBI NIH HHS 75N92023D00002NHLBI NIH HHS 75N92023D00003NHLBI NIH HHS 75N92023D00004NHLBI NIH HHS 75N92023D00005NHLBI NIH HHS 75N92023D00006NIA NIH HHS R01 AG063887NIA NIH HHS R01AG063887NIA NIH HHS R01 AG069120NIA NIH HHS R01 AG091431NIA NIH HHS R01AG091431NIA NIH HHS R35 AG071916NIA NIH HHS R35AG071916
6 · The paper itself

Abstract

introductionMitochondrial DNA (mtDNA) variation may influence cognitive performance, but prior findings are inconsistent.

methodsWe analyzed data from 2308 participants in the Coronary Artery Risk Development in Young Adults (CARDIA) study, assessing heteroplasmy (mtHz) burden and haplogroups (mtHg) from blood-derived mtDNA at three timepoints and cognitive function across multiple domains. Multivariate linear regression models and multivariate linear mixed models adjusted for age, sex, education, and race.

resultsMtDNA heteroplasmy burden and count were not associated with cognitive performance. However, mtHgs in macro-mtHg L were linked to poorer cognitive outcomes, particularly in processing speed and global cognition in cross-sectional and longitudinal analyses. Associations remained significant after adjusting for social determinants of health (SDOH) or APOE ε4, comorbidities, and lifestyle variables. DISCUSSION: The mtDNA variation, especially mtHgs, may play a role in influencing cognitive trajectories, warranting further research on its role in cognitive aging. HIGHLIGHTS: Heteroplasmy burden was not associated with cognitive performance at midlife. Haplogroups were associated with cognitive outcomes at midlife. Longitudinal analysis revealed that haplogroups are associated with cognitive trajectories.

Indexed as

CognitionCognitive DysfunctionDNA, MitochondrialHaplotypesMitochondriaAdultCross-Sectional StudiesFemaleHumansLongitudinal StudiesMaleMiddle AgedNeuropsychological TestsDNA, Mitochondrialcognitive functionmidlifemitochondriamitochondrial DNAmitochondrial haplogroupmitochondrial heteroplasmy

Identifiers

PMID41152152
PMCPMC12567638

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
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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 Socratic graph.