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Genetic predisposition to hand grip strength predicts cognitive decline
Rachel Bercovitch1, Earvin S Tio1, Rajith Wickramatunga2
1The Krembil Centre for Neuroinformatics, Centre for Addiction and Mental Health, 250 College St., Toronto, ON M5T 1R8, Canada; Institute of Medical Science, University of Toronto, 6 Queen's Park Crescent, Suit 119, Toronto, ON M5S 3H2, Canada.
Abstract:
Hand grip strength (HGS) is a predictor of cognitive decline in aging. To understand the direct and indirect mechanisms underlying this association, we performed integrative analyses of genetic, cognitive, and autopsy data. A polygenic risk score for HGS (PRSHGS) was calculated in two independent studies of aging (total n = 25,227). Cross-sectional and longitudinal modeling, including mediation with physical activity, assessed the effects of PRSHGS on cognitive performance and postmortem neuropathology. In both cohorts, higher PRSHGS predicted better global cognitive performance (p = 7.77 × 10-4 and p = 0.025) and improved the predictive performance of an Alzheimer's disease PRS (likelihood ratio test p = 2.5 × 10-5 and p = 0.007). PRSHGS was not associated with levels of any postmortem neuropathology. PRSHGS effects on cognition were only partially and inconsistently mediated by physical activity. Genetic predisposition for greater HGS predicts better cognitive performance in late life, independent from Alzheimer's disease-related neuropathology.
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