Biological validation of peak-width of skeletonized mean diffusivity as a VCID biomarker: The MarkVCID Consortium

IF 11.1 1区医学 Q1 CLINICAL NEUROLOGY Alzheimer's & Dementia Pub Date : 2024-11-21 DOI:10.1002/alz.14345

Alison M. Luckey, Saptaparni Ghosh, Chen-Pin Wang, Alexa Beiser, Rebecca Bernal, Zhiguang Li, Djass Mbangdadji, Elyas Fadaee, Haykel Snoussi, Angel Gabriel Velarde Dediós, Hector A. Trevino, Monica Goss, Laura J. Hillmer, Christopher E. Bauer, Adam M. Staffaroni, Lara Stables, Marilyn Albert, Jayandra J. Himali, Thomas H. Mosley, Lars Forsberg, Vilmundur Guðnason, Baljeet Singh, Herpreet Singh, Kristin Schwab, Joel H. Kramer, Gary A. Rosenberg, Karl G. Helmer, Steven M. Greenberg, Mohamad Habes, Danny J. J. Wang, Brian T. Gold, Hanzhang Lu, Arvind Caprihan, Myriam Fornage, Lenore J. Launer, Konstantinos Arfanakis, Sudha Seshadri, Charles DeCarli, Pauline Maillard, Claudia L. Satizabal

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Abstract

BACKGROUND

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.

METHODS

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.

RESULTS

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.

DISCUSSION

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.

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.

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将骨架化平均扩散率峰值宽度作为 VCID 生物标记物的生物学验证MarkVCID 联合会

骨架化平均扩散率峰值宽度（PSMD）是脑小血管疾病（SVD）的神经影像标记物，具有出色的仪器特性。在此，我们扩展了我们的工作，对 PSMD 进行了生物学验证。

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来源期刊

Alzheimer's & Dementia 医学-临床神经学

CiteScore

14.50

自引率

5.00%

发文量

299

审稿时长

3 months

期刊介绍： Alzheimer's & Dementia is a peer-reviewed journal that aims to bridge knowledge gaps in dementia research by covering the entire spectrum, from basic science to clinical trials to social and behavioral investigations. It provides a platform for rapid communication of new findings and ideas, optimal translation of research into practical applications, increasing knowledge across diverse disciplines for early detection, diagnosis, and intervention, and identifying promising new research directions. In July 2008, Alzheimer's & Dementia was accepted for indexing by MEDLINE, recognizing its scientific merit and contribution to Alzheimer's research.