Key result
Higher cardiorespiratory fitness is linked to faster cognitive speed, mediated by insulin resistance.
Why the study?
Cardiorespiratory fitness supports cognition, but the underlying mechanisms remain unclear, prompting investigation into whether insulin resistance statistically mediates this relationship.
Does cardiorespiratory fitness improve cognitive speed in cognitively unimpaired older adults at risk for Alzheimer's disease, and is this mediated by insulin resistance?
Observational (n=1,131)
Does cardiorespiratory fitness improve cognitive speed in cognitively unimpaired older adults at risk for Alzheimer's disease, and is this mediated by insulin resistance?
Effect estimate: B 0.025 (95% CI 0.003-0.051)
p-value: p=0.034
In older adults at risk for Alzheimer's disease, the positive association between cardiorespiratory fitness and cognitive speed is mediated by peripheral insulin resistance.
Supports mediation by insulin resistance in fitness-cognition links among at-risk older adults; leaves open causality and practice change pending trials.
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.
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McIntyre et al. (2023) conducted an observational in Elevated Alzheimer's disease risk (n=1,131). Estimated cardiorespiratory fitness (eCRF) was evaluated on Cognitive speed/flexibility (B 0.025, 95% CI 0.003-0.051, p=0.034). Estimated cardiorespiratory fitness was positively associated with cognitive speed, a relationship significantly mediated by insulin resistance (indirect effect B 0.025; CI 0.003-0.051).
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