Association of moderate to vigorous physical activity with cognitive performance and risk of cognitive impairment: A cross-sectional study and Mendelian randomization analysis

Abstract

Background: Cognitive performance and cognitive impairment are critical indicators of brain health in older adults, with moderate-to-vigorous physical activity (MVPA) suggested as protective, though its causal relationship remains unclear. Methods: Using data from the National Health and Nutrition Examination Survey (NHANES), weighted linear and logistic regression assessed associations between MVPA, cognitive performance, and cognitive impairment risk. Restricted cubic spline and subgroup analyses examined dose–response and robustness. Additionally, genome-wide association study (GWAS) data were used for two-sample Mendelian randomization to explore causality. Results: Cross-sectional analysis showed that moderate MVPA was associated with better cognitive performance (β = 0.35, p = 0.015) and exhibited a nonlinear trend. High levels of MVPA were significantly associated with a reduced risk of cognitive impairment (OR = 0.44, p = 0.009). Subgroup analysis indicated consistent associations between physical activity and cognitive outcomes across different populations without significant interactions. The MR analysis demonstrated a negative effect of MVPA on cognitive performance (β = −0.54, p < 0.001). However, no significant causal relationship was found between MVPA and the risk of cognitive impairment. Conclusion: MVPA was associated with better cognitive performance and a lower risk of cognitive impairment in cross-sectional analyses, but MR findings did not support a protective causal effect and indicated a potential negative association with cognitive performance. These mixed results suggest that the causal impact of MVPA on cognitive health in later life remains uncertain, and that the potential benefits and optimal dose of MVPA should be clarified in future large-scale longitudinal and intervention studies using objective and age appropriate assessments of activity.