Causal relationship between hand grip strength and cognition/dementia risk: a Mendelian randomization study

Muscle strength positively correlates with cognitive function, with the bidirectional causal link between hand grip strength and cognition posing a significant but incompletely understood public health challenge. This study aimed to explore the causal relationship between hand grip strength and cognition and its effect on dementia.

A two-sample Mendelian randomization analysis used genome-wide significant single nucleotide polymorphisms (SNPs) (P < 5×10^-8, at least P < 5×10^-6) linked to hand grip strength (right or left), cognition/dementia risk from the IEU Open GWAS project with 42,484 GWAS summary data sets. The primary analysis employed the inverse variance weighted method, while sensitivity analyses were conducted using the weighted mode and MR-Egger. These analyses aimed to assess the causal relationships between hand grip strength and cognition/dementia risk.

The inverse variance weighted (IVW) analysis indicated a directional positive causal effects of hand grip strength on cognition (Left-hand grip strength on cognitive function (OR (95% Cl): 1.23 (1.02-1.48), P = 0.026)/performance (OR (95% Cl): 1.16 (1.04-1.30), P = 0.009); Right-hand grip strength on cognitive function (OR (95% Cl): 1.23 (1.02-1.48), P = 0.031)/performance (OR (95% Cl): 1.10 (1.02-1.19), P = 0.018), with almost no reverse causality between cognitive function/performance and hand grip strength. Based on the results above, we then researched the directional causal effects of hand grip strength on neurodegenerative diseases (like dementia) with cognitive decline as the main clinical manifestation. However, the IVW methods yielded no evidence to support a causal effect of left-hand grip strength on dementia (P > 0.05).

This MR study indicates a positive directional causal relationship between hand grip strength and cognition, with no observed causal link to dementia. These results hold implications for the development of public health measures and strategies for preventing cognitive decline.