Aggregation of hyperphosphorylated tau protein is currently one of the most reliable indicators of Alzheimer's pathology and cognitive impairment in older adults. However, it would be useful to have a non-invasive, accessible proxy measure that does not rely on Positron Emission Tomography (PET). We used data from multi-shell diffusion-weighted imaging (DWI) to assess indices from the Neurite Orientation Dispersion and Density Imaging (NODDI) model to determine possible proxies for tau and relationship with cognitive impairment. After controlling for age, sex, and the time difference between the scan acquisitions (DWI vs. PET), we used multiple factor analysis (MFA) to assess the fit between NODDI indices (orientation dispersion [ODI], neurite density [NDI], and free-water [fISO]), cortical thickness, and tau binding (via PET). We used data from 80 participants from the ADNI-3 sample who had a multi-shell DWI and an [18F]AV-1451 (tau) PET scan. Of these 80, 49 individuals were considered cognitively normal older adults (age ~74 years), 26 individuals had a diagnosis of mild cognitive impairment (age ~75 years), and five individuals had Alzheimer's dementia (age ~78 years). fISO and tau shared a large amount of spatial overlap, and both strongly correlated with the first MFA dimension. Macrostructural features (such as cortical thickness and subcortical volume) introduced in a follow-up analysis were less related to this first MFA dimension than fISO and eight percent less than tau. Subsequent mediation analyses demonstrated that fISO mediated the relationship between cortical thickness and tau, explaining all of the variance. Microstructural features derived from advanced DWI acquisitions such as fISO may be useful proxies for tau. Cortical fISO, rather than cortical thickness, may represent the impact of tau on the brain (and, by extension, cognition).

中文翻译：

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体内皮层微观结构：替代和不结合MCI /老年痴呆症的老年人的Tauopathy和认知功能障碍的代理人

目前，高磷酸化tau蛋白的聚集是老年人阿尔茨海默氏病和认知障碍的最可靠指标之一。但是，采用不依赖正电子发射断层扫描（PET）的非侵入性，可访问的代理措施将很有用。我们使用来自多壳扩散加权成像（DWI）的数据来评估神经突方向弥散和密度成像（NODDI）模型的指标，以确定tau的可能代理以及与认知障碍的关系。在控制了年龄，性别和两次扫描获取之间的时间差（DWI与PET）之后，我们使用了多因素分析（MFA）来评估NODDI指标（方向分散度[ODI]，神经突密度[NDI]，和自由水[fISO]），皮质厚度和tau结合（通过PET）。我们使用来自ADNI-3样本的80名参与者的数据，这些参与者进行了多壳体DWI和[18F] AV-1451（tau）PET扫描。在这80名患者中，有49名被认为是认知正常的老年人（约74岁），有26名被诊断为轻度认知障碍（约75岁），有5名患有阿尔茨海默氏痴呆症（约78岁）。fISO和tau共享大量的空间重叠，并且都与第一个MFA维度密切相关。后续分析中引入的宏观结构特征（例如皮质厚度和皮质下体积）与第一个MFA尺寸的关系比fISO少，比tau少8％。随后的调解分析表明，fISO介导了皮层厚度和tau之间的关系，解释了所有差异。从先进的DWI采集（例如fISO）获得的微观结构特征可能是tau的有用代理。皮质fISO而非皮质厚度可能代表tau对大脑的影响（并扩展为认知）。