Affiliations: [a]
Wisconsin Alzheimer’s Disease Research Center and Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA
| [b]
Department of Neuroscience, Wake Forest University School of Medicine, Winston-Salem, NC, USA
| [c]
Wisconsin Alzheimer’s Institute, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA
Correspondence:
[*]
Correspondence to: Ozioma C. Okonkwo, PhD, Wisconsin Alzheimer’s Disease Research Center and Department of Medicine, University of Wisconsin School of Medicine and Public Health, J5/156M, Clinical Science Center, 600 Highland Avenue, Madison, WI 53792, USA. Tel.: +1 608 265 4479; E-mail: ozioma@medicine.wisc.edu.
Abstract: Background:Cardiorespiratory fitness (CRF) supports cognition, though it is unclear what mechanisms underly this relationship. Insulin resistance adversely affects cognition but can be reduced with habitual exercise. Objective:We investigated whether insulin resistance statistically mediates the relationship between CRF and cognition. Methods:In our observational study, we included n = 1,131 cognitively unimpaired, nondiabetic older adults from a cohort characterized by elevated Alzheimer’s disease (AD) risk. We estimated CRF (eCRF) using a validated equation that takes age, sex, body mass index, resting heart rate, and habitual physical activity as inputs. The Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) quantified insulin resistance. Standardized cognitive factor scores for cognitive speed/flexibility, working memory, verbal learning/memory, and immediate memory were calculated from a battery of neuropsychological tests. Linear regression models and bootstrapped estimates of indirect effects were used to determine whether HOMA-IR mediated significant relationships between eCRF and cognition. Results:eCRF was positively associated with cognitive speed/flexibility (p = 0.034). When controlling for HOMA-IR, eCRF was no longer associated with cognitive speed/flexibility (p = 0.383). HOMA-IR had a significant indirect effect on the eCRF-cognition relationship (B = 0.025, CI = [0.003,0.051]). eCRF was not associated with working memory (p = 0.236), immediate memory (p = 0.345), or verbal learning/memory (p = 0.650). Conclusion:Among older adults at risk for AD, peripheral insulin resistance mediates the relationship between CRF and cognitive speed.
