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
Abstract Background 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...
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2025-08-01
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| author | Florencia Altschuler Verónica Canziani Matías Fraile-Vázquez Raul Gonzalez-Gomez Hernán Hernández Sandra Baez Joaquín Migeot Sol Fittipaldi Marcelo Adrian Maito Agustina Legaz Maria Eugenia Godoy Sebastián Moguilner Josephine Cruzat Carlos Coronel-Oliveros Enzo Tagliazucchi Hernando Santamaria Garcia Pablo Reyes Diana L. Matallana José Alberto Avila-Funes Andrea Slachevsky María I. Behrens Nilton Custodio Juan Felipe Cardona Luis Ignacio Brusco Martin A. Bruno Ana L. Sosa Ortiz Stefanie D. Pina-Escudero Leonel T. Takada Elisa de Paula Franca Resende Katherine L. Possin Maira Okada de Oliveira Kun Hu Brian Lawlor Jennifer S. Yokoyama Bruce Miller Francisco Lopera Adolfo Martin Garcia Vicente Medel Agustin Ibañez Cecilia Gonzalez Campo |
| author_facet | Florencia Altschuler Verónica Canziani Matías Fraile-Vázquez Raul Gonzalez-Gomez Hernán Hernández Sandra Baez Joaquín Migeot Sol Fittipaldi Marcelo Adrian Maito Agustina Legaz Maria Eugenia Godoy Sebastián Moguilner Josephine Cruzat Carlos Coronel-Oliveros Enzo Tagliazucchi Hernando Santamaria Garcia Pablo Reyes Diana L. Matallana José Alberto Avila-Funes Andrea Slachevsky María I. Behrens Nilton Custodio Juan Felipe Cardona Luis Ignacio Brusco Martin A. Bruno Ana L. Sosa Ortiz Stefanie D. Pina-Escudero Leonel T. Takada Elisa de Paula Franca Resende Katherine L. Possin Maira Okada de Oliveira Kun Hu Brian Lawlor Jennifer S. Yokoyama Bruce Miller Francisco Lopera Adolfo Martin Garcia Vicente Medel Agustin Ibañez Cecilia Gonzalez Campo |
| author_sort | Florencia Altschuler |
| collection | DOAJ |
| description | Abstract Background 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. |
| format | Article |
| id | doaj-art-9f142bdb2c9c43aa8985f3bf23c2f8db |
| institution | DOAJ |
| issn | 1758-9193 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | BMC |
| record_format | Article |
| series | Alzheimer’s Research & Therapy |
| spelling | doaj-art-9f142bdb2c9c43aa8985f3bf23c2f8db2025-08-20T03:04:22ZengBMCAlzheimer’s Research & Therapy1758-91932025-08-0117111510.1186/s13195-025-01832-5White 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 studyFlorencia Altschuler0Verónica Canziani1Matías Fraile-Vázquez2Raul Gonzalez-Gomez3Hernán Hernández4Sandra Baez5Joaquín Migeot6Sol Fittipaldi7Marcelo Adrian Maito8Agustina Legaz9Maria Eugenia Godoy10Sebastián Moguilner11Josephine Cruzat12Carlos Coronel-Oliveros13Enzo Tagliazucchi14Hernando Santamaria Garcia15Pablo Reyes16Diana L. Matallana17José Alberto Avila-Funes18Andrea Slachevsky19María I. Behrens20Nilton Custodio21Juan Felipe Cardona22Luis Ignacio Brusco23Martin A. Bruno24Ana L. Sosa Ortiz25Stefanie D. Pina-Escudero26Leonel T. Takada27Elisa de Paula Franca Resende28Katherine L. Possin29Maira Okada de Oliveira30Kun Hu31Brian Lawlor32Jennifer S. Yokoyama33Bruce Miller34Francisco Lopera35Adolfo Martin Garcia36Vicente Medel37Agustin Ibañez38Cecilia Gonzalez Campo39Cognitive Neuroscience Center (CNC), Universidad de San AndrésCognitive Neuroscience Center (CNC), Universidad de San AndrésCognitive Neuroscience Center (CNC), Universidad de San AndrésLatin American Brain Health Institute (BrainLat), Universidad Adolfo Ibañez, Metropolitan Region of SantiagoLatin American Brain Health Institute (BrainLat), Universidad Adolfo Ibañez, Metropolitan Region of SantiagoGlobal Brain Health Institute (GBHI), Trinity College DublinLatin American Brain Health Institute (BrainLat), Universidad Adolfo Ibañez, Metropolitan Region of SantiagoLatin American Brain Health Institute (BrainLat), Universidad Adolfo Ibañez, Metropolitan Region of SantiagoCognitive Neuroscience Center (CNC), Universidad de San AndrésCognitive Neuroscience Center (CNC), Universidad de San AndrésLatin American Brain Health Institute (BrainLat), Universidad Adolfo Ibañez, Metropolitan Region of SantiagoLatin American Brain Health Institute (BrainLat), Universidad Adolfo Ibañez, Metropolitan Region of SantiagoLatin American Brain Health Institute (BrainLat), Universidad Adolfo Ibañez, Metropolitan Region of SantiagoLatin American Brain Health Institute (BrainLat), Universidad Adolfo Ibañez, Metropolitan Region of SantiagoLatin American Brain Health Institute (BrainLat), Universidad Adolfo Ibañez, Metropolitan Region of SantiagoCentro de Memoria y Cognición, Hospital Universitario San IgnacioCentro de Memoria y Cognición, Hospital Universitario San IgnacioCentro de Memoria y Cognición, Hospital Universitario San IgnacioGeriatrics Department, Instituto Nacional de Ciencias Médicas y Nutrición Salvador ZubiránGeroscience Center for Brain Health and MetabolismCentro de Investigación Clínica Avanzada (CICA) and Departamento de Neurología y Neurocirugía, Departamento de Neurociencia, Facultad de Medicina, Hospital Clínico, Universidad de ChileUnit Cognitive Impairment and Dementia Prevention, Peruvian Institute of NeurosciencesFacultad de Psicología, Universidad del ValleDepartamento de Psiquiatría y Salud Mental, Facultad de Medicina, Universidad de Buenos AiresConsejo Nacional de Investigaciones Científicas y Técnicas (CONICET)Instituto Nacional de Neurología y NeurocirugíaMemory and Aging Center, Department of Neurology, University of CaliforniaGrupo de Neurologia Cognitiva e do Comportamento (GNCC), Hospital das Clinicas, Faculdade de Medicina da Universidade de São PauloGlobal Brain Health Institute (GBHI), University of CaliforniaMemory and Aging Center, Department of Neurology, University of CaliforniaGlobal Brain Health Institute (GBHI), University of CaliforniaBrigham And Women’s HospitalGlobal Brain Health Institute (GBHI), University of CaliforniaMemory and Aging Center, Department of Neurology, University of CaliforniaMemory and Aging Center, Department of Neurology, University of CaliforniaNeuroscience Research Group, Universidad de AntioquiaCognitive Neuroscience Center (CNC), Universidad de San AndrésConsejo Nacional de Investigaciones Científicas y Técnicas (CONICET)Cognitive Neuroscience Center (CNC), Universidad de San AndrésCognitive Neuroscience Center (CNC), Universidad de San AndrésAbstract Background 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.https://doi.org/10.1186/s13195-025-01832-5MRIFrontotemporal dementiaAlzheimer’s diseaseWhite Matter HyperintensitiesLatin America |
| spellingShingle | Florencia Altschuler Verónica Canziani Matías Fraile-Vázquez Raul Gonzalez-Gomez Hernán Hernández Sandra Baez Joaquín Migeot Sol Fittipaldi Marcelo Adrian Maito Agustina Legaz Maria Eugenia Godoy Sebastián Moguilner Josephine Cruzat Carlos Coronel-Oliveros Enzo Tagliazucchi Hernando Santamaria Garcia Pablo Reyes Diana L. Matallana José Alberto Avila-Funes Andrea Slachevsky María I. Behrens Nilton Custodio Juan Felipe Cardona Luis Ignacio Brusco Martin A. Bruno Ana L. Sosa Ortiz Stefanie D. Pina-Escudero Leonel T. Takada Elisa de Paula Franca Resende Katherine L. Possin Maira Okada de Oliveira Kun Hu Brian Lawlor Jennifer S. Yokoyama Bruce Miller Francisco Lopera Adolfo Martin Garcia Vicente Medel Agustin Ibañez Cecilia Gonzalez Campo 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 MRI Frontotemporal dementia Alzheimer’s disease White Matter Hyperintensities Latin America |
| title | 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 |
| title_full | 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 |
| title_fullStr | 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 |
| title_full_unstemmed | 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 |
| title_short | 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 |
| title_sort | 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 |
| topic | MRI Frontotemporal dementia Alzheimer’s disease White Matter Hyperintensities Latin America |
| url | https://doi.org/10.1186/s13195-025-01832-5 |
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