Social vulnerability shapes deep clinical phenotypes and brain health in aging and dementia across Latin America
Journal
Alzheimer's & Dementia
ISSN
1552-5260
Date Issued
2026-06
Author(s)
Farombi, Temitope
Azzi, Tiago
Legaz, Agustina
Aguillón, David
Avila‐Funes, José Alberto
Bruno, Martín
Cardona, Juan Felipe
Custodio, Nilton
Delgado, Carolina
Pina‐Escudero, Stefanie
Galofre, Maria del Pilar Garavito
Maito, Marcelo
Magrath‐Guimet, Nahuel
Miller, Justin B.
Matallana, Diana
de Oliveira, Maira Okada
Rocatti, Guido
Resende, Elisa de Paula França
Takada, Leonel
Wen, Olivia
Zapata‐Restrepo, Lina M.
Lawlor, Brian
Yaffe, Kristine
Hu, Kun
Miller, Bruce
Possin, Katherine
Yokoyama, Jennifer S.
Fittipaldi, Sol
García, Adolfo M.
Larzabal, Hernan Hernandez
Santamaria‐Garcia, Hernando
Tagliazzuchi, Enzo
Duran‐Aniotz, Claudia
Ibanez, Agustin
Migeot, Joaquin
Type
Article
Abstract
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.
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.