BACKGROUNDPeak‐width of skeletonized mean diffusivity (PSMD), a neuroimaging marker of cerebral small vessel disease (SVD), has shown excellent instrumental properties. Here, we extend our work to perform a biological validation of PSMD.METHODSWe included 396 participants from the Biomarkers for Vascular Contributions to Cognitive Impairment and Dementia (MarkVCID‐1) Consortium and three replication samples (Cohorts for Heart and Aging Research in Genomic Epidemiology = 6172, Rush University Medical Center = 287, University of California Davis Alzheimer's Disease Research Center = 567). PSMD was derived from diffusion tensor imaging using an automated algorithm. We related PSMD to a composite measure of general cognitive function using linear regression models adjusting for confounders.RESULTSHigher PSMD was associated with lower general cognition in MarkVCID‐1 independent of age, sex, education, and intracranial volume (Beta [95% confidence interval], −0.8 [−1.2, −0.4], P < 0.001). These findings were replicated in independent samples. Furthermore, PSMD explained cognitive status above and beyond white matter hyperintensities.DISCUSSIONOur biological validation work supports the pursuit of larger clinical validation studies evaluating PSMD as a susceptibility/risk biomarker of small vessel disease contributing to cognitive impairment and dementia.Highlights Peak‐width of skeletonized mean diffusivity (PSMD) is a novel small vessel disease neuroimaging biomarker. A prior instrumental validation study demonstrated that PSMD is a robust biomarker. This biological validation study shows that high PSMD relates to worse cognition. PSMD explains cognitive function above and beyond white matter hyperintensities. Future clinical validation will assess PSMD as a vascular contribution to cognitive impairment and dementia biomarker in clinical trials.

中文翻译：

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骨架化平均扩散率峰宽作为 VCID 生物标志物的生物学验证：MarkVCID 联盟


背景骨架平均弥散率 （PSMD） 的横截面是脑小血管病 （SVD） 的神经影像学标志物，已显示出优异的仪器特性。在这里，我们扩展了我们的工作以执行 PSMD 的生物学验证。方法我们包括来自血管对认知障碍和痴呆贡献的生物标志物 （MarkVCID-1） 联盟的 396 名参与者和三个复制样本 （基因组流行病学心脏和衰老研究队列 = 6172，拉什大学医学中心 = 287，加州大学戴维斯阿尔茨海默病研究中心 = 567）。PSMD 是使用自动算法从弥散张量成像得出的。我们使用调整混杂因素的线性回归模型将 PSMD 与一般认知功能的综合测量相关联。结果较高的 PSMD 与 MarkVCID-1 的一般认知水平较低相关，与年龄、性别、教育程度和颅内体积无关 （Beta [95% 置信区间]，-0.8 [-1.2，-0.4]，P < 0.001）。这些发现在独立样本中得到了复制。此外，PSMD 解释了白质高信号以外的认知状态。讨论我们的生物验证工作支持进行更大规模的临床验证研究，以评估 PSMD 作为导致认知障碍和痴呆的小血管疾病的易感性/风险生物标志物。亮点 骨架平均扩散率 （PSMD） 的峰宽是一种新型小血管疾病神经影像学生物标志物。先前的仪器验证研究表明 PSMD 是一种强大的生物标志物。这项生物学验证研究表明，高 PSMD 与较差的认知能力有关。PSMD 解释了超越白质高信号的认知功能。 未来的临床验证将在临床试验中评估 PSMD 作为对认知障碍和痴呆生物标志物的血管贡献。