INTRODUCTION

This study investigated the associations of brain age gap (BAG)-a biological marker of brain resilience-with life exposures, neuroimaging measures, biological processes, and cognitive function.

METHODS

We derived BAG by subtracting predicted brain age from chronological age in 739 septuagenarians without dementia or neurological disorders. Robust linear regression models assessed BAG associations with life exposures, plasma inflammatory and metabolic biomarkers, magnetic resonance imaging, and cerebrospinal fluid biomarkers of neurodegeneration and vascular brain injury, and cognitive performance.

RESULTS

Greater BAG (older-looking brains) was associated with physical inactivity, diabetes, and stroke, while prediabetes was related to lower BAG, that is, younger-looking brains. Physical activity mitigated the link between obesity and BAG. Greater BAG was associated with greater small vessel disease burden, white-matter alterations, inflammation, high glucose, poorer vascular-related cognitive domains. Sex-specific associations were identified.

DISCUSSION

Vascular-related lifestyles and health shape brain appearance. Inflammation and insulin-related processes may be keys to understanding vascular cognitive disorders.

HIGHLIGHTS

BAG, reflecting deviations from CA, can indicate resilience. Diabetes, stroke, and low physical activity link to "older" brains (greater BAG). Physical activity yielded to "younger" brains in septuagenarians with obesity. High cerebrovascular burden, inflammation, and glucose associate with "older" brains. Sex differences were detected in all BAG-associated factors.