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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

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dc.contributor.authorAltschuler, Florencia
dc.contributor.authorCanziani, Verónica
dc.contributor.authorFraile, Matías
dc.contributor.authorGonzalez, Raul
dc.contributor.authorHernández, Hernán
dc.contributor.authorBaez, Sandra
dc.contributor.authorMigeot, Joaquín
dc.contributor.authorFittipaldi, Sol
dc.contributor.authorMaito, Marcelo
dc.contributor.authorLegaz, Agustina
dc.contributor.authorGodoy, Maria
dc.contributor.authorMoguilner, Sebastián
dc.contributor.authorCruzat, Josephine
dc.contributor.authorCoronel, Carlos
dc.contributor.authorTagliazucchi, Enzo
dc.contributor.authorSantamaria, Hernando
dc.contributor.authorReyes, Pablo
dc.contributor.authorMatallana, Diana
dc.contributor.authorAvila, José
dc.contributor.authorSlachevsky Chonchol, Andrea
dc.contributor.authorBehrens, María
dc.contributor.authorCustodio, Nilton
dc.contributor.authorCardona, Juan
dc.contributor.authorBrusco, Luis
dc.contributor.authorBruno, Martin
dc.contributor.authorSosa, Ana
dc.contributor.authorPina, Stefanie
dc.contributor.authorTakada, Leonel
dc.contributor.authorFranca, Elisa de Paula
dc.contributor.authorPossin, Katherine
dc.contributor.authorDe Oliveira, Maira
dc.contributor.authorHu, Kun
dc.contributor.authorLawlor, Brian
dc.contributor.authorYokoyama, Jennifer
dc.contributor.authorMiller, Bruce
dc.contributor.authorLopera, Francisco
dc.contributor.authorMartin, Adolfo
dc.contributor.authorMedel, Vicente
dc.contributor.authorIbañez, Agustin
dc.contributor.authorGonzalez, Cecilia
dc.date.accessioned2026-09-28T18:11:45Z
dc.date.available2026-09-28T18:11:45Z
dc.date.issued2025
dc.description.abstractBackground: 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). Methods: The study comprised 994 participants, including HCs (n = 402), AD (n = 359), and bvFTD subjects (n = 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 (p < 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. Results: 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. Conclusion: 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.
dc.description.versionVersión Publicada
dc.identifier.citationAltschuler, F., Canziani, V., Fraile-Vázquez, M., Gonzalez-Gomez, R., Hernández, H., Baez, S., Migeot, J., Fittipaldi, S., Maito, M. A., Legaz, A., Godoy, M. E., Moguilner, S., Cruzat, J., Coronel-Oliveros, C., Tagliazucchi, E., Garcia, H. S., Reyes, P., Matallana, D. L., Avila-Funes, J. A., Slachevsky, A., … Campo, C. G. (2025). 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. Alzheimer's research & therapy, 17(1), 188. https://doi.org/10.1186/s13195-025-01832-5
dc.identifier.doihttps://doi.org/10.1186/s13195-025-01832-5
dc.identifier.urihttps://hdl.handle.net/11447/11194
dc.language.isoen
dc.subjectAlzheimer’s disease
dc.subjectFrontotemporal dementia
dc.subjectLatin America
dc.subjectMRI
dc.subjectWhite Matter Hyperintensities
dc.titleWhite 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
dc.typeArticle
dcterms.accessRightsAcceso Abierto
dcterms.sourceAlzheimer's research & therapy
dspace.entity.typePublication
relation.isAuthorOfPublicatione25c3d3e-63b5-4e04-951a-12a4989aa772
relation.isAuthorOfPublication.latestForDiscoverye25c3d3e-63b5-4e04-951a-12a4989aa772

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