Mak Elijah, Reid Robert I, Przybelski Scott A, Lesnick Timothy G, Schwarz Christopher G, Senjem Matthew L, Raghavan Sheelakumari, Vemuri Prashanthi, Jack Clifford R, Min Hoon Ki, Jain Manoj K, Miyagawa Toji, Forsberg Leah K, Fields Julie A, Savica Rodolfo, Graff-Radford Jonathan, Jones David T, Botha Hugo, St Louis Erik K, Knopman David S, Ramanan Vijay K, Dickson Dennis W, Graff-Radford Neill R, Ferman Tanis J, Petersen Ronald C, Lowe Val J, Boeve Bradley F, O'Brien John T, Kantarci Kejal
Department of Radiology, Mayo Clinic, Rochester, MN, USA.
Department of Psychiatry, University of Cambridge, Cambridge, UK.
NPJ Parkinsons Dis. 2024 Apr 3;10(1):76. doi: 10.1038/s41531-024-00684-4.
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）是一种常与阿尔茨海默病（AD）病理共同出现的神经退行性疾病。使用神经突方向离散度和密度成像（NODDI）来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。在本研究中，利用条件逻辑模型，对45例路易体痴呆谱系患者（13例路易体轻度认知障碍和32例可能的路易体痴呆）与45例匹配的对照者进行了扩散张量成像（DTI）和NODDI指标比较。我们评估了tau蛋白和淀粉样β蛋白与DTI和NODDI参数的关联，并研究了AD相关白质损伤与临床痴呆评定量表（CDR）的相关性。结构方程模型（SEM）探索了年龄、APOE ε4、淀粉样β蛋白、tau蛋白和白质损伤之间的关系。DLB谱系组表现出广泛的白质异常，包括分数各向异性降低、平均扩散率增加和神经突密度指数降低。tau蛋白与边缘和颞叶白质损伤显著相关，而这又与更差的CDR相关。SEM显示，淀粉样β蛋白通过tau蛋白对白质损伤产生间接影响。我们观察到DLB患者白质束广泛受损，这并非由AD病理所致，可能是由于α-突触核蛋白相关损伤。然而，部分白质损伤可归因于AD病理。我们的研究结果强调了AD病理对DLB患者白质完整性的影响，并突出了NODDI在阐明DLB患者白质损伤生物学基础方面的作用。
