Song Hyun, Bharadwaj Pradyumna K, Grilli Matthew D, Raichlen David A, Habeck Christian G, Huentelman Matthew J, Hishaw Georg A, Trouard Theodore P, Alexander Gene E
Department of Psychology, University of Arizona, Tucson, AZ, USA.
Evelyn F. McKnight Brain Institute, University of Arizona, Tucson, AZ, USA.
NPJ Aging. 2025 May 28;11(1):44. doi: 10.1038/s41514-025-00234-z.
White matter hyperintensity (WMH) lesions associated with small vessel cerebrovascular disease (CVD) are common structural neuroimaging findings in older adults. Greater global brain WMH burden related to aging has been implicated in dementia but has also been linked to brain atrophy and cognitive dysfunction in old age. We sought to investigate the regionally distributed association of global WMH lesion load with subcortical gray matter (SGM) volumes using a multivariate network analysis method in 178 community-dwelling, healthy older adults (mean age = 69.77 ± 10.22 years). We additionally applied mediation models with WMH-related subcortical volumetric differences as a mediator to evaluate a potential global WMH-related vascular risk pathway leading to cognitive aging. Global WMH burden was associated with a regionally distributed pattern of SGM atrophy involving bilateral putamen and left nucleus accumbens, with relative volume increases in bilateral caudate nucleus. Mediation analyses revealed that increasing age predicted greater WMH-SGM pattern expression, which then predicted slowed processing speed that was, in turn, associated with decrements in other age-sensitive cognitive domains of memory, executive functioning, and fine motor function. These results suggest that the multivariate WMH-SGM pattern and its association with processing speed may provide an important early indicator of age-related decrements in higher-order cognitive processes, reflecting a potential link between CVD and broader cognitive dysfunction across multiple domains in healthy aging.
与小血管性脑血管疾病（CVD）相关的白质高信号（WMH）病变是老年人常见的结构神经影像学表现。与衰老相关的全脑WMH负担加重已被认为与痴呆有关，但也与脑萎缩和老年认知功能障碍有关。我们试图使用多变量网络分析方法，在178名居住在社区的健康老年人（平均年龄=69.77±10.22岁）中，研究全脑WMH病变负荷与皮质下灰质（SGM）体积的区域分布关联。我们还应用以WMH相关的皮质下体积差异为中介的中介模型，来评估一条潜在的与全脑WMH相关的血管风险途径，该途径导致认知衰老。全脑WMH负担与SGM萎缩的区域分布模式有关，包括双侧壳核和左侧伏隔核萎缩，双侧尾状核相对体积增加。中介分析显示，年龄增长预示着WMH-SGM模式表达增加，进而预示着处理速度减慢，而处理速度减慢又与记忆、执行功能和精细运动功能等其他年龄敏感认知领域的减退有关。这些结果表明，多变量WMH-SGM模式及其与处理速度的关联，可能为高阶认知过程中与年龄相关的减退提供一个重要的早期指标，反映了CVD与健康衰老过程中多个领域更广泛的认知功能障碍之间的潜在联系。
