Extended Data Fig. 2: Interactive association between baseline physical activity and Aβ burden on initial ITC tau burden.

Linear regression model revealed a significant interaction between baseline physical activity and Aβ burden on initial inferior temporal cortex (ITC) tau burden (Physical activity*Aβ: β = -0.19 [-0.30 to -0.08], p = 0.001), adjusting for age, sex, years of education, and time interval between study baseline and first tau scan. There was no significant independent effect of physical activity on tau (Physical activity: β = -0.06 [-0.18 to 0.05], p = 0.28). Statistical significance was assessed using two-tailed t-tests, with p < 0.05 considered statistically significant without adjustment for multiple comparisons. Physical activity (mean steps per day) was square-root transformed prior to model entry to account for skewness with improvement in model fit (reduced BIC by 2.2). Non-transformed mean steps per day was used to plot the model result to enhance interpretability. Baseline Aβ burden was modeled as a continuous variable. To visualize the model results, the estimated ITC tau burden across the range of baseline physical activity at representative levels of low versus high baseline Aβ burden are presented. Error bands represent the 95% confidence intervals for the estimated tau burden. Low and high Aβ are represented, for illustration purposes, by the mean Aβ burden of Aβ-negative (PiB PVC-DVR 1.17) and Aβ-positive (PiB PVC-DVR 1.85) participants respectively. Aβ = beta-amyloid; DVR = distribution volume ratio; ITC = inferior temporal cortex; PVC = partial volume correction; SUVR = standardized uptake value ratio.