Luckey Alison M, Ghosh Saptaparni, Wang Chen-Pin, Beiser Alexa, Bernal Rebecca, Li Zhiguang, Mbangdadji Djass, Fadaee Elyas, Snoussi Haykel, Dediós Angel Gabriel Velarde, Trevino Hector A, Goss Monica, Hillmer Laura J, Bauer Christopher E, Staffaroni Adam M, Stables Lara, Albert Marilyn, Himali Jayandra J, Mosley Thomas H, Forsberg Lars, Guðnason Vilmundur, Singh Baljeet, Singh Herpreet, Schwab Kristin, Kramer Joel H, Rosenberg Gary A, Helmer Karl G, Greenberg Steven M, Habes Mohamad, Wang Danny J J, Gold Brian T, Lu Hanzhang, Caprihan Arvind, Fornage Myriam, Launer Lenore J, Arfanakis Konstantinos, Seshadri Sudha, DeCarli Charles, Maillard Pauline, Satizabal Claudia L
Glenn Biggs Institute for Alzheimer's & Neurodegenerative Diseases, University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA.
Department of Neurology, Boston Chobanian & Avedisian University School of Medicine, Boston, Massachusetts, USA.
Alzheimers Dement. 2024 Dec;20(12):8814-8824. doi: 10.1002/alz.14345. Epub 2024 Nov 21.
Peak-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.
We 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.
Higher 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.
Our 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.
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.
脑小血管病（SVD）的神经影像学标志物——骨架化平均扩散率峰宽（PSMD）已显示出优异的工具特性。在此，我们扩展工作以对PSMD进行生物学验证。
我们纳入了血管性认知障碍和痴呆的生物标志物（MarkVCID - 1）联盟的396名参与者以及三个重复样本（基因组流行病学心脏与衰老研究队列=6172名、拉什大学医学中心=287名、加利福尼亚大学戴维斯分校阿尔茨海默病研究中心=567名）。PSMD通过使用自动算法从扩散张量成像中得出。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指标相关联。
在MarkVCID - 1中，较高的PSMD与较低的一般认知相关，独立于年龄、性别、教育程度和颅内体积（β[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重复。此外，PSMD解释了除白质高信号之外的认知状态。
我们的生物学验证工作支持开展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病的易感性/风险生物标志物。
骨架化平均扩散率峰宽（PSMD）是一种新型的小血管病神经影像学生物标志物。先前的工具验证研究表明PSMD是一种可靠的生物标志物。这项生物学验证研究表明高PSMD与较差的认知相关。PSMD解释了除白质高信号之外的认知功能。未来的临床验证将在临床试验中评估PSMD作为血管性认知障碍和痴呆生物标志物的作用。
