Fig. 4.

Therapeutic benefits of resistance exercise on cognition one year after training are mediated by preservation of AD-vulnerable hippocampal subfields. (A) Multiple regression analysis tested the unique variance accounted in the primary outcome (ADASCog) and Executive function by 18-month subiculum or CA1 atrophy (as percent change from baseline; age, sex and education were also in the model). Partial plots here show that subiculum atrophy was an independent predictor of ADAGCog13, whilst CA1 atrophy was an independent predictor of Executive function. The beta values for each of these (β = 0.28 and −0.25, respectively) were of similar magnitude to clinically meaningful predictors age (β = 0.22 and −0.30) and education (β = −0.24 and 0.53). (B) Since resistance exercise protects and preserves subiculum and CA1 volume (Fig 2C), is therapeutically effective on cognition in the long term (A), and the former predict the latter (B), we re-ran the cognitive LME model in (A) with 18-month change in subiculum volume (Δsubic; expressed as percentage change from baseline) as an additional covariate. This abolished the therapeutic effect of resistance exercise on ADASCog. Accordingly, resistance exercise-dependent plasticity of the subiculum mediates long-term therapeutic benefits on global cognition.