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Sarcopenia and Risk of Cognitive Impairment: Cohort Study and Mendelian Randomization Analysis

Ting-Ting Sha, Yuqing Zhang, Jie Wei, Changjun Li, Chao Zeng, G. Lei, Yi-Lun Wang

JMIR Aging, 2025

34,457 participants · 11 citations

Abstract

Abstract Background Over half the people over 60 years of age experience cognitive impairment, with limited treatment options, making it crucial to identify risk factors. Studies have examined the association between sarcopenia and cognitive impairment; however, the evidence is inconclusive and cannot be used to make causal inferences. Objective This study aims to appraise the causal association of sarcopenia with cognitive impairment by triangulating the data from a cohort study and Mendelian randomization (MR) analysis. Methods Using UK Biobank data, we first examined the associations of sarcopenia and its indices (appendicular lean mass [ALM], handgrip strength, and gait speed) with cognitive function (fluid intelligence and prospective memory) by using mixed-effects regression models. Then, we explored the causal associations of genetically predicted sarcopenic indices with cognitive function through a 2-sample MR, and examined potential mediation by omega-3 fatty acids, vitamin D levels, physical inactivity, falls, frailty, sleep disorders, anxiety, depression, stroke, metabolic syndrome, and type 2 diabetes. Results A total of 34,457 participants, with a mean age of 56.4 (SD 7.6) years, 51.1% (n=17,620) of which were female, completed baseline cognitive tests between 2006 and 2010 and attended at least 1 follow-up visit in 2012, 2014, or 2019, and were included in the observational analysis. The cohort study revealed that sarcopenia was significantly associated with…

How strong is the evidence?

Evidence Hub reads this as a cohort study, done in people. Its evidence level is 3 of 5 (Moderate · trial / cohort / secondary analysis). Trials without a large randomized design, cohorts and secondary analyses give moderate evidence. Reported size: 34,457 participants or records.

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