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.
The authors SC and HS-G acknowledge the support of Pontifi cia Universidad Javeriana and the D43 Research Training for Equity in Alzheimer's Disease and Brain Health in Colombia 2024 program. This research was funded by NIH D43 Fogarty (Research Training for Equity in Alzheimer’s Disease and Brain Health in Colombia, number: 1D43TW012455-01A1). H.S.-G. is supported by National Institutes of Health grant 1R01AG082056-01A1, “Social Epigenetics of Alzheimer’s Disease and Related Dementias in Latin American Countries”; National Institutes of Health Fogarty International Center grant 1D43TW012455-01A1, “Research Training for Equity in Alzheimer’s Disease and Brain Health in Colombia”; the Multi-partner Consortium to Expand Dementia Research in Latin America (ReDLat2), supported by the Fogarty International Center, National Institutes of Health; National Institute on Aging grants R01AG057234, R01AG075775, R01AG021051, and R01AG083799; CARDS-NIH; Alzheimer’s Association grant SG-20-725707; Rainwater Charitable Foundation–The Bluefield Project to Cure FTD; Global Brain Health Institute; European Union Horizon Europe, Marie Skłodowska-Curie Actions grant 101236426, CliCBrain, DOI 10.3030/101236426; Colombia, Ministerio de Ciencia, Tecnología e Innovación; Orquídeas Colombia, Ministerio de Ciencia, Tecnología e Innovación; and Global Brain Health Institute and Alzheimer’s Association grant GBHI ALZ UK-23-971135, “Brain Health in Individuals with Exposure to High Violence in Colombia”.
A.I. is supported by grants from the Multi-partner Consortium to Expand Dementia Research in Latin America [ReDLat2, supported by the Fogarty International Center (FIC), National Institutes of Health, National Institute on Aging (R01AG057234, R01AG075775, R01AG021051, R01AG083799, NIH-NIDA 75N95022C00031), Alzheimer’s Association (SG-20-725707), Rainwater Charitable Foundation–The Bluefield Project to Cure FTD, and Global Brain Health Institute; ANID/FONDECYT Regular (1250091, 1210176, and 1220995); ANID/PIA/ANILLOS ACT210096; ANID/SIA/FONDEF IDEA I+D ID26I10627; JPI JPND-Care, DISCeRN 2025–Health and Social Care Research with a Focus on the Moderate and Late Stages of Neurodegenerative Diseases; FONDEF ID20I10152; ANID/FONDAP 15150012; Wellcome Trust award for BRAIN-CLIMA: Investigating the Combined Impact of Heat and Air Pollution on Blood-Brain Barrier Integrity and Brain Aging in Latin America (335293/Z/25/Z); Wellcome Leap CARE Program (CARE-2025-0883490149) for the project “Advancing Female-Specific Predictive Models and Risk Assessment Tools for Alzheimer’s Disease in the US and Latin America”; CliCBrain (Horizon ID: 101236426; DOI 10.3030/101236426, Marie Skłodowska-Curie Actions–MSCA); and Wellcome Discovery Award GRACE-Epi (326117/Z/25/Z). Pontificia Universidad Javeriana, PhD Program in Neuroscience, Bogotá, Colombia Sandra Milena Castelblanco-Toro & Hernando Santamaría-García Hospital Universitario San Ignacio Centro de Memoria y Cognición, Intellectus, Bogotá, Colombia Centre for Age-Related Medicine (SESAM), Stavanger University Hospital, Stavanger, Norway SynaptIA – Inteligencia artificial para la investigación en salud mental, Bogotá, Colombia Amsterdam University Medical Center, Alzheimer Center Amsterdam, Department of Neurologylog, Amsterdam, The Netherlands Neurochemistry Laboratory, Department of Laboratory Medicine, Amsterdam University Medical Center, Vrije Universiteit, Amsterdam, the Netherlands Amsterdam Neuroscience, Neurodegeneration, Amsterdam, the Netherlands Global Brain Health Institute, University of California, San Francisco, CA, USA Bruce Miller, Victor Valcour & Hernando Santamaría-García Memory and Aging Center, Department of Neurology, University of California, San Francisco, CA, USA Colombian Centenarians Alliance, Bogotá, Colombia Universidad de la Costa, Barranquilla, Colombia BrainLat Institute, Universidad Adolfo Ibanez, Santiago, Chile Global Brain Health Institute, Trinity College Dublin, Dublin, Ireland Barcelonaβeta Brain Research Center (BBRC), Pasqual Maragall Foundation, 08005 Barcelona, Spain Cognitive Neuroscience Center (CNC), Universidad de San Andrés, Buenos Aires, Argentina Department of Biophysics, School of Medicine, Istanbul Medipol University, 34815 Istanbul, Türkiye Universidad Nacional de Colombia, Bogotá, Colombia Correspondence to Sandra Milena Castelblanco-Toro or Hernando Santamaría-García. The authors declare no competing interests.
Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. Open Access This article is licensed under a Creativ
Extract — continue reading at the source.
