ArticleAlzheimer's research & therapy2025
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.
Article in Alzheimer's research & therapy, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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Who cites it
7 citing papers in PubMed.
- Alzheimer neuropathological change, α-synuclein and transactive response DNA-binding protein of 43 kDa expression in children and young adult brains from forensic autopsies: Value for early measurement of abnormal protein expression prevalence in neurodegenerative diseases.Journal of neuropathology and experimental neurology · 2026Article
- Temporal order of clinical, imaging, and biomarker changes in frontotemporal lobar degeneration-associated syndromes.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- White matter hyperintensities are associated with locus coeruleus atrophy and astrocytic βAlzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Mapping the neurovascular landscape in aging and dementia: cerebral small vessel disease markers in a multicenter Latin American cohort.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Contextualizing Blood-Based Biomarkers for Dementia Globally.Journal of neurochemistry · 2026Review
- Cross-sectional and longitudinal cognitive trajectories associated with dementia comorbidity clusters: Results from a 10-year follow-up real-world outpatient memory clinic in Brazil.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Retinal microvascular alterations reflect cerebral small vessel disease burden in frontotemporal dementia: a multimodal OCTA-MRI Study.Alzheimer's research & therapy · 2025Article
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40 authors.
Funding
Abstract
backgroundWhite 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).
methodsThe 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.
resultsIn 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.
conclusionWMHs 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.
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