Neural embedding of frailty in cognitively unimpaired aging and dementia across Latin America

Authors: Migeot J, Wen O, Gonzalez-Gomez R, Hernandez H, Aguillon D, Avila-Funes JA, Behrens MI, Bruno MA, Custodio N, Delgado C, Duran-Aniotz C, Duron-Reyes D, García AM, Godoy ME, Hu K, Lawlor B, Li P, Maito MA, Matallana DL, Miller B, de Oliveira MO, Pina-Escudero SD, Possin KL, Resende EPF, Reyes P, Santamaria-Garcia H, Slachevsky A, Takada LT, Vergara P, Yaffe K, Yokoyama JS, Romero-Ortuño R, Ibanez A. 

Abstract: Introduction: Frailty influences dementia risk and severity. However, its role in differentiating dementia subtypes and associations with brain structural and functional alterations remain understudied, especially in Latin America.

Methods: Multi-Partner Consortium to Expand Dementia Research in Latin America data included 3461 participants (cognitively unimpaired [CU], Alzheimer’s disease [AD], and frontotemporal lobar degeneration [FTLD]) from Latin America using a frailty index constructed from 32 health-related variables. XGBoost-logistic regression models tested group discrimination, and voxel-based morphometry plus functional connectivity analyses explored neural correlates.

Results: Frailty distinguished CU from AD (area under the curve [AUC] = 0.85) and CU from FTLD (AUC = 0.88) but not AD from FTLD (AUC = 0.59). Higher frailty was linked to widespread gray matter loss, with temporal involvement in CU and stronger frontotemporal effects in dementia, particularly FTLD. Connectivity analyses showed fronto-temporo-posterior reductions and increased connectivity across the frailty network.

Discussion: Findings position frailty as a promising marker for identifying AD and FTLD relative to CU individuals, linked with brain health alterations in Latin American populations.