Altschuler Florencia, Canziani Verónica, Fraile-Vázquez Matías, Gonzalez-Gomez Raul, Hernández Hernán, Baez Sandra, Migeot Joaquín, Fittipaldi Sol, Maito Marcelo Adrian, Legaz Agustina, Godoy Maria Eugenia, Moguilner Sebastián, Cruzat Josephine, Coronel-Oliveros Carlos, Tagliazucchi Enzo, Garcia Hernando Santamaria, Reyes Pablo, Matallana Diana L, Avila-Funes José Alberto, Slachevsky Andrea, Behrens María I, Custodio Nilton, Cardona Juan Felipe, Brusco Luis Ignacio, Bruno Martin A, Ortiz Ana L Sosa, Pina-Escudero Stefanie D, Takada Leonel T, Resende Elisa de Paula Franca, Possin Katherine L, de Oliveira Maira Okada, Hu Kun, Lawlor Brian, Yokoyama Jennifer S, Miller Bruce, Lopera Francisco, Garcia Adolfo Martin, Medel Vicente, Ibañez Agustin, Campo Cecilia Gonzalez
Cognitive Neuroscience Center (CNC), Universidad de San Andrés, Ciudad Autónoma de Buenos Aires, Buenos Aires, 1644, Argentina.
Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Ciudad Autónoma de Buenos Aires, C1033AAJ, Argentina.
Alzheimers Res Ther. 2025 Aug 12;17(1):188. doi: 10.1186/s13195-025-01832-5.
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).
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.
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.
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.
脑白质高信号（WMHs）是正常衰老和病理性衰老的核心表现，可能与社会和身体暴露组的地理差异有关。以往的研究尚未考察脑白质高信号负担对不同地理区域的健康对照者（HCs）、阿尔茨海默病（AD）患者和行为变异型额颞叶痴呆（bvFTD）患者神经退行性变和认知的影响。本研究通过评估脑白质高信号负担对来自拉丁美洲（LA）和美国（US）的有或无痴呆症参与者的影响，填补了这一空白。
该研究包括994名参与者，其中包括来自拉丁美洲和美国的健康对照者（n = 402）、AD患者（n = 359）和bvFTD患者（n = 233）。使用基于体素的脑成像方法（p < 0.05，经多重比较的家族性错误校正，最小聚类大小 = 50体素），评估并比较拉丁美洲和美国各组（健康对照者、AD患者和bvFTD患者）之间的脑白质高信号及其与灰质（GM）萎缩的关联（通过GM体积和皮质厚度评估）。采用多元回归分析来检验脑白质高信号负担、脑白质高信号 - GM关联的地理差异，以及脑白质高信号对认知表现的影响（通过简易精神状态检查评估）。
仅在拉丁美洲队列中，所有组（健康对照者、AD患者、bvFTD患者）的脑白质高信号负荷越高，GM萎缩越严重，存在一种特定的神经退行性模式，涉及眶额、扣带回和颞叶区域。拉丁美洲的健康对照者比美国的健康对照者脑白质高信号负荷更高，且这种影响取决于GM萎缩。最后，脑白质高信号负担对痴呆症患者的认知表现有负面影响，在美国的bvFTD患者中观察到的影响更大。
脑白质高信号对拉丁美洲队列中的神经退行性变影响更为显著，对健康对照者影响更严重，且拉丁美洲的健康对照者脑白质高信号负担也高于美国的健康对照者。这可能会增加患痴呆症的风险。此外，脑白质高信号负担对认知的影响存在差异，在美国的bvFTD患者中观察到的负面影响更大。这些发现突出了脑白质高信号相关疾病的地理差异，为未来针对性研究提供了有价值的见解。
