MONDAY, July 10, 2023 (HealthDay News) — High levels of genetically proxied appendicular lean mass are associated with reduction in the risk of Alzheimer disease, according to a study published online June 29 in BMJ Medicine.
Iyas Daghlas, M.D., from the University of California San Francisco, and colleagues conducted a Mendelian randomization study to examine whether genetically proxied lean mass is associated with Alzheimer disease. Summary level genetic data were included from 450,243 U.K. Biobank participants; an independent sample of 21,982 patients with and 41,944 controls without Alzheimer disease; a replication sample of 7,329 patients with Alzheimer disease and 252,879 controls; and 269,867 individuals participating in a genome-wide association study of cognitive performance.
The researchers found that a 1 standard deviation increase in genetically proxied appendicular lean mass was associated with a reduction in Alzheimer disease risk (odds ratio [OR], 0.88). This finding was replicated in an independent cohort of Alzheimer disease patients (OR, 0.91) and was consistent in sensitivity analyses more robust to inclusion of pleiotropic variants. Higher genetically proxied appendicular lean mass was also associated with increased cognitive performance (standard deviation increase in cognitive performance for each standard deviation increase in appendicular lean mass, 0.09). The association between appendicular lean mass and risk of Alzheimer disease was not reduced after adjustment for potential mediation through genetically proxied cognitive performance.
“We identified genetic support for a protective effect of lean mass on the risk of Alzheimer’s disease and on higher cognitive performance,” the authors write. “Further investigation is warranted to understand the clinical and public health implications of these findings.”
One author disclosed ties to Novo Nordisk.
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