Lim Sewon, Kim Hajin, Lee Youngjin
Department of Health Science, General Graduate School of Gachon University, Yeonsu-gu, Incheon, Republic of Korea.
Department of Radiological Science, Gachon University, Yeonsu-gu, Incheon, Republic of Korea.
PLoS One. 2025 Aug 5;20(8):e0329893. doi: 10.1371/journal.pone.0329893. eCollection 2025.
Longitudinal studies that analyze the changes in the axial diffusivity (AxD) and radial diffusivity (RD) values over time can elucidate the progression of white matter damage and its causal relationship with cognitive decline. This study aimed to investigate the longitudinal changes in white matter integrity based on AxD and RD and their association with cognitive decline in patients with mild cognitive impairment (MCI) that progressed to Alzheimer's disease (AD). Eighteen participants diagnosed with MCI at baseline and AD at the follow-up examination were selected from the AD Neuroimaging Initiative and included in this 2-year study Tract-based spatial statistics (TBSS) was used to assess longitudinal changes in WM. Voxel-wise and region-of-interest (ROI) analyses were conducted, and statistical models controlled for age, sex, education, and APOE ε4 status. Correlation and multiple regression analyses were performed to examine the association between AxD/RD changes and changes in clinical dementia rating (CDR) scores. Significant increases in AxD and RD were observed over 2 years in widespread WM tracts, including the corpus callosum, internal capsule, corona radiata, cingulum, superior longitudinal fasciculus, and fornix. AxD changes, particularly in the left retrolenticular internal capsule, left posterior corona radiata, left fornix, and right superior longitudinal fasciculus, showed significant correlations with cognitive decline. In contrast, RD changes were not significantly associated with CDR changes in any region. Multivariate regression analysis identified AxD in the left retrolenticular internal capsule as a significant independent predictor of CDR changes. AxD was sensitive to microstructural alterations in WM associated with cognitive decline during the transition from MCI to AD and may serve as a valuable biomarker for early detection and monitoring of AD progression. Longitudinal DTI analyses provide critical insights into the temporal dynamics of WM degeneration and its role in clinical deterioration.
分析轴向扩散率（AxD）和径向扩散率（RD）值随时间变化的纵向研究，能够阐明白质损伤的进展及其与认知衰退的因果关系。本研究旨在基于AxD和RD调查轻度认知障碍（MCI）进展为阿尔茨海默病（AD）患者白质完整性的纵向变化及其与认知衰退的关联。从AD神经影像倡议组织中选取了18名在基线时被诊断为MCI且在随访检查时被诊断为AD的参与者，并纳入这项为期2年的研究。基于体素的空间统计学（TBSS）用于评估白质的纵向变化。进行了体素水平和感兴趣区域（ROI）分析，统计模型控制了年龄、性别、教育程度和APOE ε4状态。进行了相关性和多元回归分析，以检验AxD/RD变化与临床痴呆评定量表（CDR）评分变化之间的关联。在2年时间里，观察到包括胼胝体、内囊、放射冠、扣带、上纵束和穹窿在内的广泛白质束中AxD和RD显著增加。AxD变化，特别是在左侧豆状核后内囊、左侧放射冠后部、左侧穹窿和右侧上纵束中，与认知衰退显著相关。相比之下，RD变化在任何区域都与CDR变化无显著关联。多变量回归分析确定左侧豆状核后内囊的AxD是CDR变化的显著独立预测因子。在从MCI转变为AD的过程中，AxD对与认知衰退相关的白质微观结构改变敏感，可能作为早期检测和监测AD进展的有价值生物标志物。纵向扩散张量成像（DTI）分析为白质变性的时间动态及其在临床恶化中的作用提供了关键见解。
