Cited by 110Gut microbiota and healthDementia and Cognitive Impairment ResearchNutritional Studies and Diet

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Association of the Gut Microbiota With Cognitive Function in Midlife

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Meyer, Katie, Lulla, Anju, Debroy, Kunal, Shikany, James M., Yaffe, Kristine, Meirelles, Osorio, Launer, Lenore J.·2022·JAMA Network Open

DOI 10.1001/jamanetworkopen.2021.43941PMC PMC8826173

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Abstract

Importance: Animal experiments and small clinical studies support a role for the gut microbiota in cognitive functioning. Few studies have investigated gut microbiota and cognition in large community samples. Objective: To examine associations of gut microbial composition with measures of cognition in an established population-based study of middle-aged adults. Design, Setting, and Participants: This cross-sectional study analyzed data from the prospective Coronary Artery Risk Development in Young Adults (CARDIA) cohort in 4 US metropolitan centers between 2015 and 2016. Data were analyzed in 2019 and 2020. Exposures: Stool DNA were sequenced, and the following gut microbial measures were gathered: (1) β-diversity (between-person) derived with multivariate principal coordinates analysis; (2) α-diversity (within-person), defined as richness (genera count) and the Shannon index (integrative measure of genera richness and evenness); and (3) taxonomy (107 genera, after filtering). Main Outcomes and Measures: Cognitive status was assessed using 6 clinic-administered cognitive tests: Montreal Cognitive Assessment (MoCA), Digit Symbol Substitution Test (DSST), Rey-Auditory Verbal Learning Test (RAVLT), Stroop, category fluency, and letter fluency. A global score measure derived using principal components analysis was also assessed; the first principal component explained 56% of variability. Results: Microbiome data were available on 597 CARDIA participants; mean (SD) age was 55.2 (3.5) years, 268 participants (44.7%) were men, and 270 (45.2%) were Black. In multivariable-adjusted principal coordinates analysis, permutational multivariate analysis of variance tests for β-diversity were statistically significant for all cognition measures (principal component analysis, P = .001; MoCA, P = .001; DSST, P = .001; RAVLT, P = .001; Stroop, P = .007; category fluency, P = .001) with the exception of letter fluency (P = .07). After adjusting for sociodemographic variables (age, race, sex, education), health behaviors (physical activity, diet, smoking, medication use), and clinical covariates (body mass index, diabetes, hypertension), Barnesiella was positively associated with the first principal component (β, 0.16; 95% CI, 0.08-0.24), DSST (β, 1.18; 95% CI, 0.35-2.00), and category fluency (β, 0.59; 95% CI, 0.31-0.87); Lachnospiraceae FCS020 group was positively associated with DSST (β, 2.67; 95% CI, 1.10-4.23), and Sutterella was negatively associated with MoCA (β, -0.27; 95% CI, -0.44 to -0.11). Conclusions and Relevance: In this cross-sectional study, microbial community composition, based on β-diversity, was associated with all cognitive measures in multivariable-adjusted analysis. These data contribute to a growing body of literature suggesting that the gut microbiota may be associated with cognitive aging, but must be replicated in larger samples and further researched to identify relevant pathways.

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Figure. Multivariable-Adjusted Associations Between Specific Genera and Measures of Cognitive Function Genera are restricted to those associated with at least 1 cognitive measure with an FDR-adjusted P < .20. Colors reflect direction of β coefficients (blue indicates positive; orange, negative). Stroop is on its natural scale, with lower values reflecting higher cognitive scores. Patterning indicates the highest level of multivariable adjustment for which results were statistically significant, as follows: solid indicates results were significant after adjustment for sequencing batch, age, race, sex, study center; dotted, results remained significant after additional adjustment for education; horizontal lines, results were significant after further adjustment for physical activity, diet, smoking, medication use, body mass index, diabetes, and hypertension.CC BY · PubMed Central

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The Role of Gut Microbiota in Cognitive Impairment
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Authors: Meyer, K., Lulla, A., Debroy, K., Shikany, J. M., Yaffe, K., Meirelles, O., & Launer, L. J.
Affiliations: University of North Carolina at Chapel Hill (US)
National Institutes of Health (US)
University of Alabama at Birmingham (US)
University of California, San Francisco (US)
Corresponding author: Meyer, Katie
ORCID: Meyer, Katie
Shikany, James M.
Yaffe, Kristine
Meirelles, Osorio
Launer, Lenore J.
Venue: JAMA Network Open
Publisher: American Medical Association (AMA)
Published: 2022-02-08
Volume: 5
Issue: 2
Pages: e2143941
ISSN: 2574-3805 (ISSN-L)
DOI: 10.1001/jamanetworkopen.2021.43941
PMC: PMC8826173
OpenAlex: W4210905338
Cited by: 110
References: 43
Citations by year: 2026: 15 · 2025: 22 · 2024: 35 · 2023: 25 · 2022: 13
FWCI: 7.75
Type: journal article
Language: en
Open access: gold
doi.org
Licence: cc-by
Locations: JAMA Network Open (publishedVersion, cc-by)
PubMed Central (publishedVersion, cc-by)
PubMed (publishedVersion)
Funders: National Institute on Aging (R01AG063887, R35AG071916)
National Heart, Lung, and Blood Institute (K01HL127159)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Nutritional Studies and Diet
Keywords: gut microbiota, cognitive function, middle-aged adults, beta diversity, alpha diversity, Barnesiella, Prevotella, executive function, memory, CARDIA cohort, health behavior, sociodemographic factors, racial and ethnic differences, sex differences, physical activity, diet, smoking, body mass index, diabetes mellitus, hypertension
MeSH terms: Gastrointestinal Microbiome, Race Factors, Age Factors, Aging, Alabama, Black or African American, California, Chicago, Cognition, Cross-Sectional Studies, Female, Humans, Longitudinal Studies, Male, Middle Aged, Minnesota, Prospective Studies, Risk Factors, Socioeconomic Factors, Cohort Studies, White People

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