Evidence map›Paper›PMID 39007867›Full record

ArticleThe journals of gerontology. Series A, Biological sciences and medical sciences2024

Joint and Individual Mitochondrial DNA Variation and Cognitive Outcomes in Black and White Older Adults.

Michelle C Odden, Yongmei Li, Vasantha Jotwani, Sylvie Dobrota, Annabel X Tan, Steven R Cummings, Michael G Shlipak, Rebecca Scherzer, Joachim H Ix, Marion S Buckwalter and 1 more

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Article in The journals of gerontology. Series A, Biological sciences and medical sciences, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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1 · What the graph read from it

What it found

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2 · The registry

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3 · Its place in the literature

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4 · The record

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5 · Who and what money

Authors and funding

11 authors.

Michelle C OddenDepartment of Epidemiology and Population Health, Stanford School of Medicine, Stanford, California, USA.ORCID 0000-0002-5974-3648
Yongmei LiDepartment of Epidemiology and Population Health, Stanford School of Medicine, Stanford, California, USA.
Vasantha JotwaniKidney Health Research Collaborative, Department of Medicine, San Francisco Veterans Affairs Health Care System, San Francisco, California, USA.
Sylvie DobrotaDepartment of Epidemiology and Population Health, Stanford School of Medicine, Stanford, California, USA.ORCID 0000-0001-5134-2105
Annabel X TanDepartment of Epidemiology and Population Health, Stanford School of Medicine, Stanford, California, USA.
Steven R CummingsCalifornia Pacific Medical Center Research Institute, San Francisco, California, USA.
Michael G ShlipakKidney Health Research Collaborative, Department of Medicine, San Francisco Veterans Affairs Health Care System, San Francisco, California, USA.
Rebecca ScherzerKidney Health Research Collaborative, Department of Medicine, San Francisco Veterans Affairs Health Care System, San Francisco, California, USA.
Joachim H IxDivision of Nephrology-Hypertension, Department of Medicine, University of California San Diego, San Diego, California, USA.
Marion S BuckwalterDepartment of Neurology and Neurological Sciences, Stanford School of Medicine, Stanford, California, USA.
Gregory J TranahCalifornia Pacific Medical Center Research Institute, San Francisco, California, USA.

Funding

Peripheral Nerve Function Decline in an Aged CohortR01AG028050 · NIA · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI STROTMEYER, ELSA S. · 2007 to 2015
$3.5M
Mitochondrial health, cardiovascular risk, and blood pressure targets in hypertensive adultsR01HL151564 · NHLBI · NORTHERN CALIFORNIA INSTITUTE/RES/EDU · PI JOTWANI, VASANTHA KOLAVENNU, ODDEN, MICHELLE CHRISTINA · 2021 to 2024
$3.2M
BBB Dysfunction in Post-Stroke DementiaR01NS124927 · NINDS · STANFORD UNIVERSITY · PI MARION S BUCKWALTER · 2022 to 2026
$3.2M
End of Life in the Very OldR01NR012459 · NINR · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI ALBERT, STEVEN M, LUNNEY, JUNE R · 2011 to 2015
$2.7M
NHLBI NIH HHS R01 HL151564NIA NIH HHS R01 AG028050NIA NIH HHS R01-AG028050NIHNINDS NIH HHS R01 NS124927NINR NIH HHS R01 NR012459Stanford Knight Initiative for Brain Resilience
6 · The paper itself

Abstract

backgroundMitochondrial dysfunction manifests in neurodegenerative diseases and other age-associated disorders. In this study, we examined variation in inherited mitochondrial DNA (mtDNA) sequences in Black and White participants from 2 large aging studies to identify variants related to cognitive function.

methodsParticipants included self-reported Black and White adults aged ≥70 years in the Lifestyle Interventions and Independence for Elders (LIFE; N = 1 319) and Health Aging and Body Composition (Health ABC; N = 788) studies. Cognitive function was measured by the Digit-Symbol Substitution Test (DSST), and the Modified Mini-Mental State Examination (3MSE) at baseline and over follow-up in LIFE (3.6 years) and Health ABC (10 years). We examined the joint effects of multiple variants across 16 functional mitochondrial regions with cognitive function using a sequence kernel association test. Based on these results, we prioritized meta-analysis of common variants in Black and White participants using mixed effects models. A Bonferroni-adjusted p value of <.05 was considered statistically significant.

resultsJoint variation in subunits ND1, ND2, and ND5 of Complex I, 12S RNA, and hypervariable region (HVR) were significantly associated with DSST and 3MSE at baseline. In meta-analyses among Black participants, variant m.4216T>C, ND1 was associated with a faster decline in 3MSE, and variant m.462C>T in the HVR was associated with a slower decline in DSST. Variant m.5460G>C, ND2 was associated with slower and m.182C>T in the HVR was associated with faster decline in 3MSE in White participants.

conclusionsAmong Black and White adults, oxidative phosphorylation Complex I variants were associated with cognitive function.

Indexed as

CognitionDNA, MitochondrialAgedAged, 80 and overAgingBlack or African AmericanFemaleGenetic VariationHumansMaleWhiteDNA, MitochondrialCognitive functionGeneticsMitochondria

Identifiers

PMID39007867
PMCPMC11345514

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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.