Multimodal Image Analysis of Apparent Brain Age Identifies Physical Fitness as Predictor of Brain Maintenance

Maintaining a youthful brain structure and function throughout life may be the single most important determinant ofsuccessful cognitive aging. In this study, we addressed heterogeneity in brain aging by making image-based brain agepredictions and relating the brain age prediction gap (BAPG) to cognitive change in aging. Structural, functional, anddiffusion MRI scans from 351 participants were used to train and evaluate 5 single-modal and 4 multimodal predictionmodels, based on 7 regression methods. The models were compared on mean absolute error and whether they were relatedto physical fitness and cognitive ability, measured both currently and longitudinally, as well as study attrition and years ofeducation. Multimodal prediction models performed at a similar level as single-modal models, and the choice of regressionmethod did not significantly affect the results. Correlation with the BAPG was found for current physical fitness, currentcognitive ability, and study attrition. Correlations were also found for retrospective physical fitness, measured 10 years priorto imaging, and slope for cognitive ability during a period of 15 years. The results suggest that maintaining a high physicalfitness throughout life contributes to brain maintenance and preserved cognitive ability.