Dementia with Lewy bodies (DLB) is a neurodegenerative condition often co-occurring with Alzheimer’s disease (AD) pathology. Characterizing white matter tissue microstructure using Neurite Orientation Dispersion and Density Imaging (NODDI) may help elucidate the biological underpinnings of white matter injury in individuals with DLB. In this study, diffusion tensor imaging (DTI) and NODDI metrics were compared in 45 patients within the dementia with Lewy bodies spectrum (mild cognitive impairment with Lewy bodies (n = 13) and probable dementia with Lewy bodies (n = 32)) against 45 matched controls using conditional logistic models. We evaluated the associations of tau and amyloid-β with DTI and NODDI parameters and examined the correlations of AD-related white matter injury with Clinical Dementia Rating (CDR). Structural equation models (SEM) explored relationships among age, APOE ε4, amyloid-β, tau, and white matter injury. The DLB spectrum group exhibited widespread white matter abnormalities, including reduced fractional anisotropy, increased mean diffusivity, and decreased neurite density index. Tau was significantly associated with limbic and temporal white matter injury, which was, in turn, associated with worse CDR. SEM revealed that amyloid-β exerted indirect effects on white matter injury through tau. We observed widespread disruptions in white matter tracts in DLB that were not attributed to AD pathologies, likely due to α-synuclein-related injury. However, a fraction of the white matter injury could be attributed to AD pathology. Our findings underscore the impact of AD pathology on white matter integrity in DLB and highlight the utility of NODDI in elucidating the biological basis of white matter injury in DLB.

路易体痴呆 (DLB) 是一种神经退行性疾病，通常与阿尔茨海默病 (AD) 病理同时发生。使用神经突定向弥散和密度成像 (NODDI) 表征白质组织微观结构可能有助于阐明 DLB 患者白质损伤的生物学基础。在这项研究中，比较了 45 名路易体痴呆患者（路易体轻度认知障碍 ( n = 13) 和可能的路易体痴呆 ( n = 32)）患者的弥散张量成像 (DTI) 和 NODDI 指标使用条件逻辑模型进行 45 个匹配对照。我们评估了 tau 蛋白和淀粉样蛋白-β 与 DTI 和 NODDI 参数的关联，并检查了 AD 相关白质损伤与临床痴呆评分 (CDR) 的相关性。结构方程模型 (SEM) 探索了年龄、APOE ε4、β 淀粉样蛋白、tau 蛋白和白质损伤之间的关系。 DLB谱组表现出广泛的白质异常，包括各向异性分数降低、平均扩散率增加和神经突密度指数降低。 Tau 与边缘和颞叶白质损伤显着相关，而边缘和颞叶白质损伤又与较差的 CDR 相关。 SEM显示β淀粉样蛋白通过tau蛋白对白质损伤产生间接影响。我们观察到 DLB 中白质束存在广泛的破坏，这些破坏并非归因于 AD 病理，可能是由于 α-突触核蛋白相关损伤所致。然而，白质损伤的一小部分可能归因于 AD 病理。我们的研究结果强调了 AD 病理学对 DLB 中白质完整性的影响，并强调了 NODDI 在阐明 DLB 中白质损伤的生物学基础方面的效用。