Neural embedding of frailty in cognitively unimpaired aging and dementia across Latin America
Journal
Alzheimer's & Dementia
ISSN
1552-5260
Date Issued
2026-04
Author(s)
Joaquin Migeot
Olivia Wen
Raul Gonzalez‐Gomez
Hernan Hernandez
David Aguillon
Jose Alberto Avila‐Funes
Martin A. Bruno
Nilton Custodio
Carolina Delgado
Claudia Duran‐Aniotz
Dafne Duron‐Reyes
Adolfo M. García
Maria E. Godoy
Kun Hu
Brian Lawlor
Peng Li
Marcelo Adrian Maito
Diana L. Matallana
Bruce Miller
Maira Okada de Oliveira
Stefanie D. Pina‐Escudero
Katherine L. Possin
Elisa de Paula França Resende
Pablo Reyes
Hernando Santamaria‐Garcia
Leonel T. Takada
Paulina Vergara
Kristine Yaffe
Jennifer S. Yokoyama
Roman Romero‐Ortuño
Agustin Ibanez
Type
journal-article
Abstract
<jats:title>Abstract</jats:title>
<jats:sec>
<jats:title>INTRODUCTION</jats:title>
<jats:p>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.</jats:p>
</jats:sec>
<jats:sec>
<jats:title>METHODS</jats:title>
<jats:p>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.</jats:p>
</jats:sec>
<jats:sec>
<jats:title>RESULTS</jats:title>
<jats:p>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.</jats:p>
</jats:sec>
<jats:sec>
<jats:title>DISCUSSION</jats:title>
<jats:p>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.</jats:p>
</jats:sec>
<jats:sec>
<jats:title>INTRODUCTION</jats:title>
<jats:p>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.</jats:p>
</jats:sec>
<jats:sec>
<jats:title>METHODS</jats:title>
<jats:p>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.</jats:p>
</jats:sec>
<jats:sec>
<jats:title>RESULTS</jats:title>
<jats:p>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.</jats:p>
</jats:sec>
<jats:sec>
<jats:title>DISCUSSION</jats:title>
<jats:p>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.</jats:p>
</jats:sec>