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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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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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Human development, inequality, and their associations with brain structure across 29 countries
(Royal College of Psychiatrists, 2025)
Vicente Medel
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Luz M. Alliende
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Richard Bethlehem
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Jakob Seidlitz
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Grace Ringlein
2
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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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Functional Capacity in Activities of Daily Living in the Alzheimer’s Disease Continuum
(Wiley, 2024-12)
Fernando Henriquez
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Carmen Dominguez
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Fabrissio Grandi
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Cecilia Gonzalez Campo
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Patricio Riquelme Contreras
The most common and prevalent dementia worldwide is Alzheimer’s disease (AD). AD is a continuum composed of Subjective Cognitive Impairment (SCD), Mild Cognitive Impairment (MCI), and Alzheimer’s Disease dementia (ADD) stage. One of the main clinical variables in patients with dementia is performance in functional capacity since its alterations are associated with poor prognosis and disease progression. Functional capacity is measured through activities of daily living (ADL), which are divided into three domains: i) Basic (BADL), ii) Instrumental (IADL), and iii) Advanced (AADL). The study aimed to characterize the performance of the different stages of the AD continuum in the ADL domains and their association with cognitive abilities.</jats:p></jats:sec><jats:sec><jats:title>Method</jats:title><jats:p>A cross‐sectional study of subjects at different stages of the AD continuum was conducted: Healthy Controls (CTR) (n = 17), SCD (n = 77), MCI (n = 30), and ADD (n = 23), who were matched for age, sex, and education. ADLs were estimated using The Technology‐Activities of Daily Living Questionnaire (T‐ADLQ), which assesses the three domains and a total score. T‐ADLQ performance was compared across groups and correlated with cognitive ability instruments (ACE‐III and IFS).</jats:p></jats:sec><jats:sec><jats:title>Result</jats:title><jats:p>The results showed that patients with ADD performed worse on the BADL, IADL, and total ADLs compared to the other three groups. There were no significant differences between the CTR, SCD, and MCI on the BADL, IADL, and total ADLs. However, the AADL, in addition to differentiating the ADD patients from the other three groups, also showed differences between CTR and MCI subjects and between SCD and MCI subjects (Table 1 and Figure 1). The correlation study showed that AADL correlated significantly with global cognitive and executive function assessment (Figure 2).</jats:p></jats:sec><jats:sec><jats:title>Conclusion</jats:title><jats:p>AADL shows progressive functional impairment at different stages of the AD continuum, which is further associated with global cognitive and executive function performances. As one progresses to a more advanced stage of the disease continuum, the performance of ADLs, especially AADLs, worsens, which could indicate a marker of disease progression, allowing for better patient follow‐up.
1
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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
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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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Multivariate word properties in fluency tasks reveal markers of Alzheimer's dementia
(2023)
Franco J. Ferrante
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Joaquín Migeot
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Agustina Birba
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Lucía Amoruso
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Gonzalo Pérez
<jats:title>Abstract</jats:title><jats:sec><jats:title>INTRODUCTION</jats:title><jats:p>Verbal fluency tasks are common in Alzheimer's disease (AD) assessments. Yet, standard valid response counts fail to reveal disease‐specific semantic memory patterns. Here, we leveraged automated word‐property analysis to capture neurocognitive markers of AD vis‐à‐vis behavioral variant frontotemporal dementia (bvFTD).</jats:p></jats:sec><jats:sec><jats:title>METHODS</jats:title><jats:p>Patients and healthy controls completed two fluency tasks. We counted valid responses and computed each word's frequency, granularity, neighborhood, length, familiarity, and imageability. These features were used for group‐level discrimination, patient‐level identification, and correlations with executive and neural (magnetic resonanance imaging [MRI], functional MRI [fMRI], electroencephalography [EEG]) patterns.</jats:p></jats:sec><jats:sec><jats:title>RESULTS</jats:title><jats:p>Valid responses revealed deficits in both disorders. Conversely, frequency, granularity, and neighborhood yielded robust group‐ and subject‐level discrimination only in AD, also predicting executive outcomes. Disease‐specific cortical thickness patterns were predicted by frequency in both disorders. Default‐mode and salience network hypoconnectivity, and EEG beta hypoconnectivity, were predicted by frequency and granularity only in AD.</jats:p></jats:sec><jats:sec><jats:title>DISCUSSION</jats:title><jats:p>Word‐property analysis of fluency can boost AD characterization and diagnosis.</jats:p></jats:sec><jats:sec><jats:title>Highlights</jats:title><jats:p><jats:list list-type="bullet"> <jats:list-item><jats:p>We report novel word‐property analyses of verbal fluency in AD and bvFTD.</jats:p></jats:list-item> <jats:list-item><jats:p>Standard valid response counts captured deficits and brain patterns in both groups.</jats:p></jats:list-item> <jats:list-item><jats:p>Specific word properties (e.g., frequency, granularity) were altered only in AD.</jats:p></jats:list-item> <jats:list-item><jats:p>Such properties predicted cognitive and neural (MRI, fMRI, EEG) patterns in AD.</jats:p></jats:list-item> <jats:list-item><jats:p>Word‐property analysis of fluency can boost AD characterization and diagnosis.</jats:p></jats:list-item> </jats:list></jats:p></jats:sec>
3Scopus© Citations 10
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Interoception Primes Emotional Processing: Multimodal Evidence from Neurodegeneration
(2021)
Paula C. Salamone
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Agustina Legaz
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Lucas Sedeño
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Sebastián Moguilner
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Matías Fraile-Vazquez
7Scopus© Citations 80
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Dementia in Latin America: Paving the way toward a regional action plan
(2020)
Mario Alfredo Parra
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Sandra Baez
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Lucas Sedeño
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Cecilia Gonzalez Campo
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Hernando Santamaría‐García
2Scopus© Citations 115
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Multimodal neurocognitive markers of naturalistic discourse typify diverse neurodegenerative diseases
(2021)
Agustina Birba
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Sol Fittipaldi
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Judith C Cediel Escobar
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Cecilia Gonzalez Campo
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Agustina Legaz
<jats:title>Abstract</jats:title> <jats:p>Neurodegeneration has multiscalar impacts, including behavioral, neuroanatomical, and neurofunctional disruptions. Can disease-differential alterations be captured across such dimensions using naturalistic stimuli? To address this question, we assessed comprehension of four naturalistic stories, highlighting action, nonaction, social, and nonsocial events, in Parkinson’s disease (PD) and behavioral variant frontotemporal dementia (bvFTD) relative to Alzheimer’s disease patients and healthy controls. Text-specific correlates were evaluated via voxel-based morphometry, spatial (fMRI), and temporal (hd-EEG) functional connectivity. PD patients presented action–text deficits related to the volume of action–observation regions, connectivity across motor-related and multimodal-semantic hubs, and frontal hd-EEG hypoconnectivity. BvFTD patients exhibited social–text deficits, associated with atrophy and spatial connectivity patterns along social-network hubs, alongside right frontotemporal hd-EEG hypoconnectivity. Alzheimer’s disease patients showed impairments in all stories, widespread atrophy and spatial connectivity patterns, and heightened occipitotemporal hd-EEG connectivity. Our framework revealed disease-specific signatures across behavioral, neuroanatomical, and neurofunctional dimensions, highlighting the sensitivity and specificity of a single naturalistic task. This investigation opens a translational agenda combining ecological approaches and multimodal cognitive neuroscience for the study of neurodegeneration.</jats:p>
2Scopus© Citations 39

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