Abstract
BACKGROUND: The protective effect of physical activity on dementia risk is well established, yet the magnitude of effect remains highly inconsistent, possibly due to various approaches to physical activity measurement and potential moderating effects of environmental factors such as air pollution. OBJECTIVE: To evaluate the independent and interaction effects of air pollution and accelerometer-based physical activity on incident risks of dementia subtypes. METHODS: This study included 96,661 participants from the UK Biobank study with accelerometer-derived physical activity measures. Dementia diagnosis was algorithmically defined based on self-reports, primary care, hospital, and mortality records. We assessed five air pollutants, including particulate matters (PM(2.5), PM(2.5-10), PM(10)), nitrogen dioxide (NO(2)), and nitrous oxides (NO(x)). Multivariable-adjusted Cox proportional hazard models were employed to estimate the associations between physical activity, air pollution, and the risks of Alzheimer's Disease (AD) and Vascular Dementia (VaD). Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated. Several sensitivity analyses were conducted to assess the robustness of the results. RESULTS: A one-IQR (10.13 milli-gravity) higher level of physical activity was significantly associated with a 30% lower risk of AD (HR = 0.7, 95% CI: 0.57-0.86, p < 0.001) and a 32% lower risk of VaD (HR = 0.68, 95% CI: 0.5-0.91, p < 0.05). Exposure to NO(2) was significantly associated with an increased incident risk of AD, while exposure to PM(2.5), PM(2.5-10), PM(10), and NO(2) was associated with an increased risk of VaD. Results from models with interaction terms indicate that the protective effect of physical activity against AD was attenuated among individuals exposed to higher levels of PM(2.5) and NO(2,) and that the effect of physical activity against VaD was attenuated by higher PM(2.5-10) exposure. SIGNIFICANCE: This study provides new evidence on the independent and interactive effects of objectively measured physical activity and air pollution on the risks of dementia subtypes, thereby improving the biological specificity of these associations.