Advanced brain age and longitudinal cognitive decline in healthy older adults

Abstract Advanced brain age relative to chronological age may predict cognitive decline in healthy aging, but prospective evidence remains limited. We tested whether the brain age gap (BAG) predicts cognition and 5-year cognitive decline in the AGES-Reykjavik Study. Participants with structural MRI and neuropsychological data were included cross-sectionally ( n = 4,606); mean age 76.4y; 58% female) and longitudinally ( n = 2,561; mean follow-up 5.2y). BAG was estimated from T1-weighted MRI. Mixed-effects models examined BAG effects on Memory (M), processing speed (PS), and executive function (EF), adjusting for age, sex, and education. Higher BAG was associated with worse cognition across all domains (β = -0.037 to -0.047, all p < 0.001). BAG significantly predicted greater decline in M (β = -0.007, p = 0.046); subgroup analyses revealed steeper decline in M and EF with advanced brain age. BAG predicts longitudinal cognitive decline beyond chronological age, supporting its utility as a biomarker in preventative care of healthy aging.