Greater Physical Activity May Lower Risk for Neuropsychiatric Diseases

Greater physical activity levels and less sedentary behavior protect against the risk of developing neuropsychiatric diseases, according to study results presented at the 2025 American Academy of Neurology (AAN) annual meeting, held from April 5 to 9, 2025, in San Diego, California.

Previous studies examining the association between physical activity and neuropsychiatric diseases have mostly depended on self-reported data instead of objective metrics.

In a large-scale, prospective study, researchers from China collected accelerometer data on energy expenditure and time allocation from 73,411 participants (mean age, 56 years; women, 55.72%; White, 96.40%) between 2013 and 2015.

Based on this objective, accelerometer-measured data, energy expenditure corresponding to moderate to vigorous physical activity had the strongest protective effects against developing neuropsychiatric diseases (hazard ratios [HRs], 0.60-0.86). Similarly, more time spent being sedentary increased the risk of developing neuropsychiatric conditions (HRs, 1.05-1.54), especially dementia.

The researchers investigated potential mechanisms underlying this association, analyzing specific brain structures and functions and peripheral biomarkers that were significantly influenced by physical activity levels. Key brain structures associated with physical activity and sedentary behaviors included the lateral occipital cortex, pallidum, accumbens, and cuneus. 

Proteomic and metabolic analyses confirmed the significant effect of physical activity on the peripheral biomarkers, high-density lipoproteins (HDL) and integrin alpha V (ITGAV) proteins. Inflammation and metabolic processes were shown to mediate the relationship between physical activity and risk of neuropsychiatric diseases. 

“We underscored the protective role of higher physical activity energy expenditure, increased engagement with physical activity, and reduced sedentary behavior in mitigating the risk of [5] neuropsychiatric diseases, regardless of activity intensity,” the researchers stated. “These findings have significant implications for assessing risk factors and developing preventive interventions for neuropsychiatric diseases.”