A physically and mentally active lifestyle relates to younger brain and cognitive age

Resistance to age-related pathological changes (brain maintenance), including Alzheimer's disease, cerebrovascular disease, and neurodegeneration may promote cognitive resilience in aging. However, how lifestyle and health profiles relate to successful cognitive and brain aging remains poorly understood. In a novel, deeply phenotyped cohort of 211 cognitively unimpaired older adults (age = 71.0 ± 7.4 years, 46% female), we characterized principal components of lifestyle and health using questionnaire, fitness, and blood data. We estimated cognitive age gap (CAG) based on comprehensive neuropsychological data and brain age gap (BAG) based on brain-pathology markers, including plasma biomarkers of Alzheimer's pathology (pTau₂₁₇ and Aβ_1-42/Aβ_1-40), MRI-based measures of white matter hyperintensities, perivascular spaces, and brain atrophy. Regression analyses tested how the observed lifestyle-health profiles were related to CAG and BAG. Seven principal components explained 49% of the variance in health and lifestyle. The second component, characterized by a mentally and physically active life and low cardiovascular risk, was associated with lower CAG (β = - 0.66, p < 0.001) and BAG (β = - 0.52, p = 0.003), reflecting a younger-than-expected brain and cognitive age, respectively. The association of an active lifestyle and lower CAG was partially mediated by BAG. Higher CAG was also associated with other lifestyle components characterized by low mental stimulation. APOE-ε4 carriers exhibited higher BAG. In conclusion, a lifestyle combining low cardiovascular risk, high mental engagement throughout life and high physical activity/fitness is jointly associated with less-than-expected brain pathology and better-than-expected cognitive performance, supporting its involvement in brain maintenance and cognitive resilience to aging.