Higher Cardiorespiratory Fitness Is Associated With Younger Brain Age In Late Adulthood

PURPOSE: Higher cardiorespiratory fitness (CRF) is associated with the preservation of the hippocampus and prefrontal cortical brain areas in healthy older adults, yet the relationship between CRF and the construct of “brain age” remains unclear. Brain age, defined as the difference between brain-predicted age based on structural magnetic resonance imaging (MRI) data and chronological age (brain-predicted age difference; brain-PAD), has served as a biomarker for accelerated structural brain aging or preservation of brain health. In this study, we investigated whether higher CRF in cognitively normal older adults would be associated with younger brain age and whether the association was moderated by chronological age, sex, education, or APOE e4 genotype. METHODS: Baseline data from 648 healthy older adults (mean age = 69.88 ± 3.75 years) participating in the Investigating Gains in Neurocognition in an Intervention Trial of Exercise (IGNITE) was included in the analysis. Peak oxygen uptake (VO2peak) to determine cardiorespiratory fitness was assessed through a peak graded treadmill test to volitional fatigue. Brain-predicted age was determined from T1-weighted images using the brainageR algorithm; then brain-PAD was calculated by subtracting chronological age from brain-predicted age. Multiple regression models were used to examine the association between CRF and brain-PAD. RESULTS: As predicted, higher VO2peak was associated with younger brain age (β = -0.121, p = 0.022) after controlling for chronological age, sex, testing site, education, Body Mass Index, APOE e4 carrier status, and T1 image quality. Moreover, sex had a moderating effect on the association between VO2peak and brain-PAD (β = -0.186, p = 0.030) such that higher CRF preferentially benefited males compared to females in decelerating brain age. Neither chronological age, education, nor APOE e4 genotype (all p > 0.05) moderated the association between VO2peak and brain-PAD. CONCLUSIONS: These findings suggest that higher CRF may help decelerate brain aging in late adulthood, especially for males. Results from the IGNITE intervention will help reveal whether a year-long aerobic exercise intervention can be effective at slowing biomarkers of brain aging and whether such changes mediate improvements in cognitive performance.