RESUMO
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 nâ=â1,131 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 (pâ=â0.034). When controlling for HOMA-IR, eCRF was no longer associated with cognitive speed/flexibility (pâ=â0.383). HOMA-IR had a significant indirect effect on the eCRF-cognition relationship (Bâ=â0.025, CIâ=â[0.003,0.051]). eCRF was not associated with working memory (pâ=â0.236), immediate memory (pâ=â0.345), or verbal learning/memory (pâ=â0.650). CONCLUSION: Among older adults at risk for AD, peripheral insulin resistance mediates the relationship between CRF and cognitive speed.