Decreased plasma clusterin is associated with increased cardiorespiratory fitness as a response to aerobic exercise in older adults with Alzheimer's disease in the FIT‐AD Trial

Abstract

AbstractBackgroundA recent study suggests that plasma clusterin increases with exercise and enhances neurogenesis and reduces neuroinflammation in sedentary mice. The same study also reports a positive association between changes in plasma clusterin and walking distance as response to exercise in older adults with amnestic mild cognitive impairment. The objective of this study is to examine whether aerobic exercise increases plasma clusterin and the correlations between changes in plasma clusterin and cardiorespiratory fitness as response to aerobic exercise in older adults with Alzheimer's disease (AD) in the FIT‐AD trial.MethodsThe FIT‐AD Trial is a Phase II randomized controlled trial to investigate the effects of a 6‐month, individualized, moderate‐intensity cycling intervention on cognition in community‐dwelling older adults with mild‐to‐moderate AD. The FIT‐AD subjects were randomly assigned on a 2:1 ratio to cycling and stretching (control) for six months. Fasting blood plasma samples were collected at baseline (n=26), 3 and 6 months. Plasma clusterin concentration was measured by an ELISA kit (R&D Systems, Minneapolis, MN). Symptom‐limited peak cycle‐ergometer test was used to assess VO2peak, a gold‐standard measure of cardiorespiratory fitness. Student t's test was used to examine changes in plasma clusterin concentrations between cycling and stretching groups. Linear regression was used to correlate changes in plasma clusterin concentration with changes in VO2peak.Results3‐ or 6‐ month changes in plasma clusterin concentrations did not significantly differ between groups However, correlations between 3‐month changes in plasma clusterin (µg/mL) and 3‐ or 6‐month changes in VO2peak (L/min) were significant regardless group assignment (beta‐coefficients [standard error (SE)]: ‐ 4.2×10‐2 [1.8×10‐2] L/min change in VO2peak per µg/mL change in plasma clusterin and ‐ 4.0×10‐2 [1.4×10‐2], respectively), and in cycling group only (‐ 4.8×10‐2 [1.6×10‐2] and ‐ 3.9×10‐2 [0.9×10‐2], respectively), but not in the stretching (control) group.ConclusionThis preliminary study does not support the previous findings. Instead, it reports a significant negative correlation between 3‐month change in plasma clusterin concentration and 3‐ or 6‐ months change in VO2peak as response to aerobic exercise with in older adults with AD. Future studies are needed to validate the study findings.