Journal of the International Neuropsychological Society. 2015 Nov; 21(10):841-50.
Objective: To examine cross-sectionally whether higher cardiorespiratory fitness (CRF) might favorably modify amyloid-β (Aβ)-related decrements in cognition in a cohort of late-middle-aged adults at risk for Alzheimer’s disease (AD). Methods: Sixty-nine enrollees in the Wisconsin Registry for Alzheimer’s Prevention participated in this study. They completed a comprehensive neuropsychological exam, underwent 11C Pittsburgh Compound B (PiB)-PET imaging, and performed a graded treadmill exercise test to volitional exhaustion. Peak oxygen consumption (VO2peak) during the exercise test was used as the index of CRF. Forty-five participants also underwent lumbar puncture for collection of cerebrospinal fluid (CSF) samples, from which Aβ42 was immunoassayed. Covariate-adjusted regression analyses were used to test whether the association between Aβ and cognition was modified by CRF. Results: There were significant VO2peak*PiB-PET interactions for Immediate Memory (p= .041) and Verbal Learning & Memory (p= .025). There were also significant VO2peak*CSF Aβ42 interactions for Immediate Memory (p<.001) and Verbal Learning & Memory (p <.001). Specifically, in the context of high Aβ burden—i.e., increased PiB-PET binding or reduced CSF Aβ42—individuals with higher CRF exhibited significantly better cognition compared with individuals with lower CRF. Conclusion: In a late-middle-aged, at-risk cohort, higher CRF is associated with a diminution of Aβ-related effects on cognition. These findings suggest that exercise might play an important role in the prevention of AD.