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Neural embedding of frailty in cognitively unimpaired aging and dementia across Latin America
(Wiley, 2026-04)
Joaquin Migeot
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Olivia Wen
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Raul Gonzalez‐Gomez
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Hernan Hernandez
;
David Aguillon
<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>
2
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The exposome of brain aging across 34 countries
(Springer Science and Business Media LLC, 2026-04-03)
Agustina Legaz
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Sebastian Moguilner
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Pablo Barttfeld
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Jhosmary Cuadros Castro
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Dante Sebastián Galván Rial
Scopus© Citations 7 1
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Blood-based AT(N) biomarkers for Alzheimer’s disease and frontotemporal lobar degeneration in Latin America
(Springer Science and Business Media LLC, 2026-02-13)
Ariel Caviedes
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Felipe Cabral-Miranda
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Paulina Orellana
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Hernán Hernández
;
Raul Gonzalez-Gomez
2
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Cardiovascular risk factors and the allostatic interoceptive network in dementia
(Oxford University Press (OUP), 2025-10)
Jessica L Hazelton
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Joaquín Migeot
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Raul Gonzalez-Gomez
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Florencia Altschuler
;
Claudia Duran-Aniotz
2
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Social exposome and brain health outcomes of dementia across Latin America
(Springer Science and Business Media LLC, 2025-09-11)
Joaquin Migeot
;
Stefanie D. Pina-Escudero
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Hernan Hernandez
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Raul Gonzalez-Gomez
;
Agustina Legaz
A multidimensional social exposome (MSE)—the combined lifespan measures of education, food insecurity, financial status, access to healthcare, childhood experiences, and more—may shape dementia risk and brain health over the lifespan, particularly in underserved regions like Latin America. However, the MSE effects on brain health and dementia are unknown. We evaluated 2211 individuals (controls, Alzheimer’s disease, and frontotemporal lobar degeneration) from a non-representative sample across six Latin American countries. Adverse exposomes associate with poorer cognition in healthy aging. In dementia, more complex exposomes correlate with lower cognitive and functional performance, higher neuropsychiatric symptoms, and brain structural and connectivity alterations in frontal-temporal-limbic and cerebellar regions. Food insecurity, financial resources, subjective socioeconomic status, and access to healthcare emerge as critical predictors. Cumulative exposome measures surpass isolated factors in predicting clinical-cognitive profiles. Multiple sensitivity analyses confirm our results. Findings highlight the need for personalized approaches integrating MSE across the lifespan, emphasizing prevention and interventions targeting social disparities.
1
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White matter hyperintensities and their impact in brain structure and function in alzheimer’s disease and behavioral variant frontotemporal dementia across Latin America and the United States: a cross-sectional study
(Springer Science and Business Media LLC, 2025-08-12)
Florencia Altschuler
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Verónica Canziani
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Matías Fraile-Vázquez
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Raul Gonzalez-Gomez
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Hernán Hernández
<jats:title>Abstract</jats:title> <jats:sec> <jats:title>Background</jats:title> <jats:p>White matter hyperintensities (WMHs) are a core manifestation of normal and pathological aging and are potentially linked to geographical differences in social and physical exposomes. Previous studies have not examined the impact of WMHs burden on neurodegeneration and cognition in healthy controls (HCs) and patients with Alzheimer’s disease (AD) and behavioral variant frontotemporal dementia (bvFTD) across geographic regions. This study addressed this gap by assessing the impact of WMHs burden on participants with and without dementia from Latin America (LA) and the United States (US).</jats:p> </jats:sec> <jats:sec> <jats:title>Methods</jats:title> <jats:p>The study comprised 994 participants, including HCs (<jats:italic>n</jats:italic> = 402), AD (<jats:italic>n</jats:italic> = 359), and bvFTD subjects (<jats:italic>n</jats:italic> = 233) from LA and the US. WMHs and their association with grey matter (GM) atrophy, assessed through GM volume and cortical thickness, were evaluated and compared among groups (HCs, AD, and bvFTD) in LA and the US using a voxel-wise brain imaging approach (<jats:italic>p</jats:italic> < 0.05 family-wise error-corrected for multiple comparisons, minimum cluster size = 50 voxels). Multiple regressions analysis were employed to examine geographic differences in WMHs burden, WMHs-GM associations, and the effect of WMHs on cognitive performance, as assessed by the Mini-Mental State examination.</jats:p> </jats:sec> <jats:sec> <jats:title>Results</jats:title> <jats:p>In the LA cohort only, higher WMHs load was associated with greater GM atrophy across all groups (HCs, AD, bvFTD), with a specific neurodegenerative pattern involving orbitofrontal, cingulate, and temporal areas. HCs from LA showed a greater WMHs load than their US counterparts, and this effect was dependent on GM atrophy. Finally, WMHs burden negatively impacted cognitive performance in dementia subjects, with a greater effect observed in bvFTD subjects from the US.</jats:p> </jats:sec> <jats:sec> <jats:title>Conclusion</jats:title> <jats:p>WMHs have a more pronounced impact on neurodegeneration across the LA cohort, with a worse impact on HCs, which also show higher WMHs burden than their US counterparts. This could increase the risk of developing dementia. Moreover, WMHs burden differentially impacts cognition, with a greater negative effect observed in bvFTD subjects from the US. These findings highlight geographic variations in WMHs-related conditions, offering valuable insights for tailored future research.</jats:p> </jats:sec>
2Scopus© Citations 5
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Qualitative and quantitative educational disparities and brain signatures in healthy aging and dementia across global settings
(Elsevier BV, 2025-04)
Raul Gonzalez-Gomez
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Josephine Cruzat
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Hernán Hernández
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Joaquín Migeot
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Agustina Legaz
Scopus© Citations 4 3
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Structural inequality linked to brain volume and network dynamics in aging and dementia across the Americas
(Springer Science and Business Media LLC, 2024-12-27)
Agustina Legaz
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Florencia Altschuler
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Raul Gonzalez-Gomez
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Hernán Hernández
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Sandra Baez
Scopus© Citations 10 3
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Educational disparities in brain health and dementia across Latin America and the United States
(2024)
Raul Gonzalez‐Gomez
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Agustina Legaz
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Sebastián Moguilner
;
Josephine Cruzat
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Hernán Hernández
<jats:title>Abstract</jats:title><jats:sec><jats:title>BACKGROUND</jats:title><jats:p>Education influences brain health and dementia. However, its impact across regions, specifically Latin America (LA) and the United States (US), is unknown.</jats:p></jats:sec><jats:sec><jats:title>METHODS</jats:title><jats:p>A total of 1412 participants comprising controls, patients with Alzheimer's disease (AD), and frontotemporal lobar degeneration (FTLD) from LA and the US were included. We studied the association of education with brain volume and functional connectivity while controlling for imaging quality and variability, age, sex, total intracranial volume (TIV), and recording type.</jats:p></jats:sec><jats:sec><jats:title>RESULTS</jats:title><jats:p>Education influenced brain measures, explaining 24%–98% of the geographical differences. The educational disparities between LA and the US were associated with gray matter volume and connectivity variations, especially in LA and AD patients. Education emerged as a critical factor in classifying aging and dementia across regions.</jats:p></jats:sec><jats:sec><jats:title>DISCUSSION</jats:title><jats:p>The results underscore the impact of education on brain structure and function in LA, highlighting the importance of incorporating educational factors into diagnosing, care, and prevention, and emphasizing the need for global diversity in research.</jats:p></jats:sec><jats:sec><jats:title>Highlights</jats:title><jats:p><jats:list list-type="bullet"> <jats:list-item><jats:p>Lower education was linked to reduced brain volume and connectivity in healthy controls (HCs), Alzheimer's disease (AD), and frontotemporal lobar degeneration (FTLD).</jats:p></jats:list-item> <jats:list-item><jats:p>Latin American cohorts have lower educational levels compared to the those in the United States.</jats:p></jats:list-item> <jats:list-item><jats:p>Educational disparities majorly drive brain health differences between regions.</jats:p></jats:list-item> <jats:list-item><jats:p>Educational differences were significant in both conditions, but more in AD than FTLD.</jats:p></jats:list-item> <jats:list-item><jats:p>Education stands as a critical factor in classifying aging and dementia across regions.</jats:p></jats:list-item> </jats:list></jats:p></jats:sec>
Scopus© Citations 15 2
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Author Correction: Brain clocks capture diversity and disparities in aging and dementia across geographically diverse populations
(2024)
Sebastian Moguilner
;
Sandra Baez
;
Hernan Hernandez
;
Joaquín Migeot
;
Agustina Legaz
9Scopus© Citations 1

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