A systematic review of brain health in centenarians

Centenarians provide a unique model for studying brain health at extreme ages, yet the robustness of the methodologies and determinants remains poorly characterized. We systematically reviewed evidence on brain health in individuals aged ≥100, following PRISMA guidelines across five databases to December 2025. Twenty-four studies comprising 19,104 centenarians were included. Most assessments emphasized cognitive, functional, and psychosocial domains, while biological and neuroimaging approaches were rarely employed. Protective factors included enrichment of APOE-ε2, reduced polygenic risk for neurodegeneration, higher education, and strong social engagement. Conversely, social isolation, institutionalization, multimorbidity, and nutritional deficiencies are consistently related to brain decline. The prevalence of intact cognition ranged widely (11.6–83%), likely due to differences in study populations, assessment tools, and diagnostic criteria across studies. Despite substantial heterogeneity, the available evidence suggests that preserved brain health in centenarians is associated with a combination of biological, social, and lifestyle factors. Centenarians thus represent a critical framework for harmonizing definitions of brain health and guiding interventions aimed at preserving resilience across the lifespan.