Temitope Farombi, Tiago Azzi, Agustina Legaz, David Aguillón, José Alberto Avila-Funes, Maria Isabel Behrens, Martín Bruno, Juan F. Cardona, Nilton Custodio, Carolina Delgado, Stefanie Pina‐Escudero, María del Pilar Garavito Galofre, Marcelo Maito, Nahuel Magrath‐Guimet, Justin Miller, Diana Matallana, Maira Okada de Oliveira, Guido Rocatti, Elaine Resende, Andrea Slachevsky, Leonel Takada, Olivia Wen, Lina M. Zapata-Restrepo, Brian Lawlor, Kristine Yaffe, Hu K, Bruce Miller, Katherine Possin, Jennifer S. Yokoyama, Sol Fittipaldi, Adolfo M. García, Hernan Hernandez Larzabal, Hernando Santamaria‐Garcia, Enzo Tagliazzuchi, Claudia Duran‐Aniotz, Agustin Ibanez, Joaquin Migeot
INTRODUCTION: Adverse social conditions across the life course influence brain aging and dementia, yet their compounded impact on clinical phenotypes remains underexplored, particularly in Latin America, where social inequality and dementia burden are high. METHODS: We studied 3941 individuals from six Latin American countries, including cognitively unimpaired controls (CU), Alzheimer's disease (AD), and frontotemporal lobar degeneration (FTLD). A life-course questionnaire captured eight domains of social vulnerability, used to derive a social vulnerability index and latent vulnerability profiles. Brain health was characterized across 37 cognitive, functional, mental health, and dementia severity indicators. RESULTS: Higher vulnerability was mostly associated with executive and memory deficits in CU, cognitive and functional impairment in AD, and social cognition and neuropsychiatric symptoms in FTLD. Multidimensional brain health was affected across groups. DISCUSSION: Compounded social vulnerability is a key determinant of clinical expression in aging and dementia, underscoring the need for life-course-informed and equity-oriented dementia models.