Cardiorespiratory fitness attenuates the influence of amyloid on cognition

Stephanie A. Schultz, Elizabeth A. Boots, Rodrigo P. Almeida, Jennifer M. Oh, Jean Einerson, Claudia E. Korcarz, Dorothy F. Edwards, Rebecca L. Koscik, Maritza N. Dowling, Catherine L. Gallagher, Barbara B. Bendlin, Bradley T. Christian, Henrik Zetterberg, Kaj Blennow, Cynthia M. Carlsson, Sanjay Asthana, Bruce P. Hermann, Mark A. Sager, Sterling C. Johnson, James H. Stein, Ozioma C. Okonkwo Schultz, S. A., Boots, E. A., Almeida, R. P., Oh, J. M., Einerson, J., Korcarz, C. E., … Okonkwo, O. C. (2015). Card

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.


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