Active Lifestyle Lowers Risk of Neuropsychiatric Disease

A RECENT study, presented at the American Academy of Neurology Annual Meeting 2025, aimed to examine the associations between accelerometer-measured physical activity and sedentary behaviour with neuropsychiatric diseases, while also investigating the neurobiological mechanisms underpinning these relationships.

Physical activity and sedentary behaviour are known to be linked with neuropsychiatric conditions, yet prior research has largely depended on self-reported data, which has shown inconsistencies when compared with objective measurements.

Using a large-scale prospective design, this study analysed accelerometer data from 73,411 participants collected between 2013–2015, focusing on energy expenditure and time allocation. The study population had a mean age of 56.08 years (± 7.82), with 55.72% being women and 96.40% identifying as white. Results demonstrated that moderate to vigorous physical activity energy expenditure exhibited a strong protective effect against neuropsychiatric diseases, with hazard ratios ranging from 0.60 to 0.86 (all FDR-Q<0.001). Conversely, increased sedentary time was identified as a risk factor, with hazard ratios between 1.05 and 1.54 (FDR-Q<0.05). Further analyses using restricted cubic splines revealed an L-shaped association between physical activity and neuropsychiatric diseases, while an inverted L-shaped relationship was observed between sedentary behaviour and dementia.

Linear regression models indicated strong links between physical activity, sedentary behaviour, and brain functions, with key brain regions implicated including the lateral occipital cortex, cuneus, pallidum, and accumbens. Proteomic and metabolic analyses further identified the significant role of ITGAV protein and high-intensity lipoproteins in these associations. Structural equation modelling provided evidence that inflammation and metabolism serve as mediators in the relationships between physical activity, sedentary behaviour, and neuropsychiatric diseases.

In conclusion, the findings emphasised the protective role of increased physical activity energy expenditure and reduced sedentary behaviour in lowering the risk of five neuropsychiatric diseases, independent of activity intensity. Moreover, the study identified neurobiological mechanisms linking these behaviours to brain functions, structures, and peripheral biomarkers, while also highlighting the mediating influence of inflammatory and metabolic factors. These insights have important implications for identifying risk factors and shaping preventive interventions for neuropsychiatric conditions, reinforcing the necessity of promoting physical activity and minimising sedentary behaviour as part of public health strategies.

Katie Wright, EMJ

Reference

Wu JY, Jin-Tai Yu JT. Accelerometer-Measured Physical Activity, Sedentary Behavior, and Incident Neuropsychiatric Diseases: A Large Prospective Cohort Study of 73,411 Participants. 2025. Available at: https://aanfiles.blob.core.windows.net/aanfiles/56bf3add-5deb-4b9e-ad6f-3193bdafe3ba/2025%20AAN%20Annual%20Meeting%20Abstract%20-%20Physical%20Activity%20and%20Neuropsychiatric%20Diseases. Last accessed: 12 March 2025.