Table_3_Language dysfunction correlates with cognitive impairments in older adults without dementia mediated by amyloid pathology.docx

BackgroundPrevious studies have explored the application of non-invasive biomarkers of language dysfunction for the early detection of Alzheimer's disease (AD). However, language dysfunction over time may be quite heterogeneous within different diagnostic groups.
MethodPatient demographics and clinical data were retrieved from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database for the participants without dementia who had measures of cerebrospinal fluid (CSF) biomarkers and language dysfunction. We analyzed the effect of longitudinal neuropathological and clinical correlates in the pathological process of semantic fluency and confrontation naming. The mediation effects of AD biomarkers were also explored by the mediation analysis.
ResultThere were 272 subjects without dementia included in this analysis. Higher rates of decline in semantic fluency and confrontation naming were associated with a higher risk of progression to MCI or AD, and a greater decline in cognitive abilities. Moreover, the rate of change in semantic fluency was significantly associated with Aβ deposition, while confrontation naming was significantly associated with both amyloidosis and tau burden. Mediation analyses revealed that both confrontation naming and semantic fluency were partially mediated by the Aβ aggregation.
ConclusionIn conclusion, the changes in language dysfunction may partly stem from the Aβ deposition, while confrontation naming can also partly originate from the increase in tau burden. Therefore, this study sheds light on how language dysfunction is partly constitutive of mild cognitive impairment and dementia and therefore is an important clinical predictor.

背景 既往研究已探索采用语言功能障碍的非侵入性生物标志物，以早期检测阿尔茨海默病（Alzheimer's Disease, AD）。然而，不同诊断组别中的语言功能障碍随时间进展的异质性较强。
方法 本研究从阿尔茨海默病神经影像学倡议（Alzheimer's Disease Neuroimaging Initiative, ADNI）数据库中，提取无痴呆且具备脑脊液（cerebrospinal fluid, CSF）生物标志物及语言功能障碍检测数据的受试者的人口统计学与临床资料。我们分析了纵向神经病理及临床相关因素在语义流畅性与对视命名病理进程中的作用，并通过中介分析探究了AD生物标志物的中介效应。
结果 本分析共纳入272名无痴呆受试者。语义流畅性与对视命名的下降速率越快，受试者进展为轻度认知障碍（Mild Cognitive Impairment, MCI）或AD的风险越高，同时认知能力下降程度也更显著。此外，语义流畅性的变化速率与β淀粉样蛋白（Aβ）沉积显著相关，而对视命名则同时与淀粉样蛋白沉积及tau蛋白负荷显著相关。中介分析显示，对视命名与语义流畅性的下降均部分由β淀粉样蛋白聚集所介导。
结论 综上，语言功能障碍的变化可能部分源于β淀粉样蛋白沉积，而对视命名能力的下降还可部分归因于tau蛋白负荷的升高。本研究阐明了语言功能障碍是轻度认知障碍与痴呆的部分构成要素，因此其可作为重要的临床预测指标。