Broberg Dana N, Haddad Seyyed M H, Aveni Katharine, Havens Alexander, McLaughlin Paula M, Binns Malcolm A, Orange Joseph B, Arnott Stephen R, Berezuk Courtney, Casaubon Leanne K, Dowlatshahi Dar, Hassan Ayman, Nanayakkara Nuwan D, Peltsch Alicia J, Ramirez Joel, Saposnik Gustavo, Scott Christopher J M, Swartz Richard H, Symons Sean, Troyer Angela K, Roberts Angela C, Bartha Robert
Department of Medical Biophysics, Schulich School of Medicine & Dentistry, Western University, London, ON N6A 3K7, Canada.
Centre for Functional & Metabolic Mapping, Robarts Research Institute, Schulich School of Medicine & Dentistry, Western University, London, ON N6A 3K7, Canada.
Brain Commun. 2025 Apr 19;7(3):fcaf145. doi: 10.1093/braincomms/fcaf145. eCollection 2025.
Assessment of spoken language is a promising marker for cognitive impairment in individuals with cerebrovascular disease. However, the underlying neurological basis for spoken language beyond single words and sentences remains poorly defined in this cohort, particularly with respect to white matter. This study aimed to examine and compare white matter hyperintensity volumes and diffusion tensor metrics in normal-appearing white matter (NAWM) as potential correlates of spoken language performance. Baseline imaging and spoken language data were obtained from the cerebrovascular disease cohort of the Ontario Neurodegenerative Disease Research Initiative ( = 127; age: 55-85 years). Most participants had subclinical or very mild strokes, with very little to no aphasia symptoms. Spoken language samples were analysed to compute 10 different measures related to syntax, productivity, lexical diversity, fluency, and information content. Structural and diffusion MRI data were analysed to segment white matter hyperintensities and tracts. Normalized white matter hyperintensity volume, as well as average fractional anisotropy and mean diffusivity in the normal-appearing portion of eight white matter tracts, were correlated with the 10 spoken language measures using canonical correlation analyses. White matter and spoken language variate scores for individual participants then were correlated separately in male ( = 86) and female ( = 41) participants to probe potential sex differences. Spoken language performance was significantly associated with the fractional anisotropy ( = 0.51, 0.041) and mean diffusivity ( = 0.56, 0.011) of NAWM, particularly in the left superior longitudinal fasciculus, but not with white matter hyperintensity volumes ( = 0.41, 0.80) in the same tracts. Measures related to syntax, fluency, and information content loaded most strongly in the spoken language variate. No significant sex differences were found in NAWM microstructure, and female and male participants exhibited similarly strong associations between spoken language and NAWM microstructure (fractional anisotropy: = 1.44, = 0.15; mean diffusivity: = 1.03, = 0.30). These results suggest that diffusion MRI in NAWM may be superior to white matter hyperintensity volumetrics when evaluating the role of white matter tract integrity on cognitive outcomes in people with relatively mild cerebrovascular pathology. These results also demonstrate that multi-domain spoken language analysis is sensitive to underlying white matter microstructure in participants with cerebrovascular disease without significant aphasia, supporting its value as a tool for assessing cognitive status.
对患有脑血管疾病的个体而言，口语评估是认知障碍的一个很有前景的指标。然而，在这一队列中，除了单词和句子之外，口语背后的神经学基础仍未明确界定，尤其是在白质方面。本研究旨在检查和比较正常外观白质（NAWM）中的白质高信号体积和扩散张量指标，作为口语表现的潜在相关因素。基线成像和口语数据来自安大略神经退行性疾病研究倡议的脑血管疾病队列（n = 127；年龄：55 - 85岁）。大多数参与者有亚临床或非常轻微的中风，几乎没有失语症状。对口语样本进行分析，以计算与句法、生成能力、词汇多样性、流畅性和信息内容相关的10种不同测量指标。对结构和扩散MRI数据进行分析，以分割白质高信号和纤维束。使用典型相关分析，将标准化的白质高信号体积以及8条白质纤维束正常外观部分的平均分数各向异性和平均扩散率与10种口语测量指标进行相关性分析。然后分别在男性（n = 86）和女性（n = 41）参与者中，将个体参与者的白质和口语变量分数进行相关性分析，以探究潜在的性别差异。口语表现与NAWM的分数各向异性（r = 0.51，p < 0.041）和平均扩散率（r = 0.56，p < 0.011）显著相关，尤其是在左侧上纵束，但与同一纤维束中的白质高信号体积（r = 0.41，p = 0.80）无关。与句法、流畅性和信息内容相关的测量指标在口语变量中负荷最强。在NAWM微观结构方面未发现显著的性别差异，女性和男性参与者在口语和NAWM微观结构之间表现出同样强烈的关联（分数各向异性：r = 1.44，p = 0.15；平均扩散率：r = 1.03，p = 0.30）。这些结果表明，在评估白质纤维束完整性对患有相对轻度脑血管病变的人的认知结果的作用时，NAWM中的扩散MRI可能优于白质高信号体积测量。这些结果还表明，多领域口语分析对没有明显失语的脑血管疾病参与者的潜在白质微观结构敏感，支持其作为评估认知状态工具的价值。
