Evidence map›Paper›PMID 42015047›Full record

ArticleBMC neurology2026

Blood mitochondrial heteroplasmic variants and cognitive performance in late midlife: REGARDS study.

Diddier Prada, Eva Morava-Kozicz, Aravind Lathika Rajendrakumar, Allison Kupsco, Corina Lesseur, Haritz Irizar, David Cantú-de-Leon, Claudia García-Cuellar, Andrea Ramírez, Jonathan González-Ruíz and 7 more

Abstract read
In one paragraph

Article in BMC neurology, 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

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

17 authors.

Diddier PradaInstitute for Health Equity Research, Icahn School of Medicine at Mount Sinai, New York City, NY, USA. diddier.prada@mountsinai.org.
Eva Morava-KoziczDepartment of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York City, NY, USA.
Aravind Lathika RajendrakumarInstitute for Health Equity Research, Icahn School of Medicine at Mount Sinai, New York City, NY, USA.
Allison KupscoDepartment of Environmental Health Sciences, Mailman School of Public Health, New York City, NY, USA.
Corina LesseurDepartment of Environmental Medicine, Icahn School of Medicine at Mount Sinai, New York City, NY, USA.
Haritz IrizarDepartment of Population Health Science and Policy, Icahn School of Medicine at Mount Sinai, New York City, NY, USA.
David Cantú-de-LeonInstituto Nacional de Cancerología - Mexico, Mexico City, Mexico.
Claudia García-CuellarInstituto Nacional de Cancerología - Mexico, Mexico City, Mexico.
Andrea RamírezInstituto Nacional de Cancerología - Mexico, Mexico City, Mexico.
Jonathan González-RuízInstituto Nacional de Cancerología - Mexico, Mexico City, Mexico.
Carol R HorowitzInstitute for Health Equity Research, Icahn School of Medicine at Mount Sinai, New York City, NY, USA.
Mary CushmanLarner College of Medicine, The University of Vermont, Burlington, VT, USA.
Jennifer ManlyDepartment of Neurology, Vagelos College of Physicians and Surgeons, Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University, New York City, NY, USA.
Suzanne JuddSchool of Public Health, University of Alabama at Birmingham, Birmingham, AL, USA.
Emilia BagiellaDepartment of Population Health Science and Policy, Icahn School of Medicine at Mount Sinai, New York City, NY, USA.
Andrea BaccarelliHarvard T.H. Chan School of Public Health, Harvard University, Boston, USA.
Robbie ParksDepartment of Environmental Health Sciences, Mailman School of Public Health, New York City, NY, USA. robbie.parks@columbia.edu.

Funding

VCID and Stroke in a Bi-racial National CohortU01NS041588 · NINDS · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI CUSHMAN, MARY, HOWARD, GEORGE · 2002 to 2022
$96.0M
NIH FIRST Cohort Cluster Hiring Initiative at Icahn School of Medicine at Mount SinaiU54CA267776 · NCI · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI Nihal Mohamed · 2021 to 2026
$17.4M
Impact of environmental toxicants on AD and ADRD risk in the Diabetes Prevention Program Outcomes study AD/ADRD projectU01AG088684 · NIA · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI Andres Cardenas, Abby Fleisch · 2024 to 2026
$5.0M
NCI NIH HHS U54CA267776NIA NIH HHS U01AG088684NIA NIH HHS U01 NS041588NINDS NIH HHS U01 NS041588
6 · The paper itself

Abstract

backgroundStudies linking mitochondrial DNA (mtDNA) variants to cognition yielded inconsistent findings, and the underlying mechanisms remain unclear. We investigated whether mtDNA heteroplasmic variants were associated with cognitive outcomes, including the Montreal Cognitive Assessment (MoCA), in 197 late midlife adults from the Reasons for Geographic and Racial Differences in Stroke (REGARDS) cohort with complete data.

methodsMtDNA was sequenced from blood using targeted deep sequencing. Adjusted linear and mixed-effects models examined the associations by functional regions, genes, total variant burden, nonsynonymous variants, and control regions.

resultsHeteroplasmic variants in the control region (β = -0.44, 95% CI: -0.83, -0.05, p = 0.027) and transfer RNA (tRNA) genes (β = -1.34, 95% CI: -2.58, -0.11, p = 0.034) were associated with MoCA baseline scores. Individual variants in cytochrome c oxidase subunit 1 (CO1) (β = -1.51, 95% CI: -2.54, -0.47, p = 0.005), NADH dehydrogenase subunit 1 (ND1) (β = -2.63, 95% CI: -4.56, -0.70, p = 0.008), and Displacement Loop (D-LOOP2) (β = -2.25, 95% CI: -4.20, -0.30, p = 0.025) was associated with reduced baseline MoCA scores. The ND6 (β = −1.23, 95% CI: −2.09, − 0.37, p = 0.006), ND4 (β = −1.11, 95% CI: −2.02, − 0.20, p = 0.018), ATP Synthase Membrane Subunit 8 (ATP8; β = −1.38, 95% CI: −2.63, − 0.13, p = 0.031), and D-LOOP1 (β = −0.61, 95% CI: −1.20, − 0.01, p = 0.045) genes suggested a potential association with executive function. Longitudinal Animal Fluency Test (AFT) scores were inversely associated with heteroplasmic variants in coding regions (β = -0.10, 95% CI: -0.19, -0.006, p = 0.049), the total number of variants (β = -0.06, 95% CI: -0.11, -0.003, p = 0.037) and total nonsynonymous variants (β = -0.11, 95% CI: -0.21, -0.01, p = 0.040). Variants in the control region were associated with the greatest decline in verbal fluency (β = −0.20, 95% CI: −0.39 to − 0.002, p = 0.049). No associations were observed between mitochondrial variants and verbal memory performance or the MoCA composite scores.

conclusionsOur study indicates that mitochondrial variants measured in blood may provide insight into cognitive function during midlife. However, additional studies are needed to validate these associations and to address potential power limitations in our study.

Indexed as

CognitionDNA, MitochondrialHeteroplasmyAgedCohort StudiesFemaleGenetic VariationHumansMaleMental Status and Dementia TestsMiddle AgedDNA, MitochondrialAge-related neurodegenerationAlzheimer’s diseaseDementiaHeteroplasmyMoCAmtDNA

Identifiers

PMID42015047
PMCPMC13101111

What Socratic holds

Textmetadata
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 Socratic graph.