Effects of a 24-week resistance exercise program on brain amyloid and Alzheimer's disease blood-based biomarkers: the AGUEDA randomized controlled trial

We examined whether a 24-week resistance training program influenced brain amyloid-{beta} (A{beta}) and Alzheimers Disease (AD)-related blood-based biomarkers. Ninety cognitively normal, physically inactive older adults aged 65-80 years were randomly allocated to a 24-week resistance training program (three [~]60-min supervised sessions/week) or a wait-list control group. Primary analyses assessed exercise-induced changes in brain A{beta} (Centiloid values) and plasma ptau217/A{beta}1-42 IPMS ratio. Secondary analyses examined ptau217/A{beta}42 SIMOA ratio, ptau217, ptau181 and A{beta}42/40, as well as potential interactions with sex, age, education, apolipoprotein {varepsilon}4 (APOE4) status, amyloid PET-positivity, and comorbidities. The intervention produced no significant differences on brain A{beta} or AD-related blood-based biomarkers (p>0.05) compared to the control group. However, the ptau217/A{beta}1-42 IPMS ratio showed a small, non-significant increase in the control group (SMD = 0.162; 95% CI: -0.159 to 0.483) while remaining stable in the exercise group (SMD = 0.01; 95% CI: -0.291 to 0.310) with a similar trend for ptau217/A{beta}42 SIMOA. Moderator analyses indicated differential responses by amyloid PET-positivity and APOE4 status on brain A{beta} (p for interaction<0.05), with increases observed in APOE4 carriers and amyloid PET-positive individuals in the control group, whereas those allocated to the exercise intervention reduced their levels. The specificity observed within our subgroups suggests that resistance exercise may serve as a targeted intervention to modulate AD pathophysiology, raising new questions regarding its broader role in the delay of the disease in vulnerable populations.