MarkVCID2 Consortium for Clinical Validation of Biomarkers of Cerebral Small Vessel Disease: Validation Framework and Baseline Characteristics.

IF 7.7 1区医学 Q1 CLINICAL NEUROLOGY

Annals of Neurology Pub Date : 2025-09-22 DOI:10.1002/ana.78040

Steven M Greenberg, Marylin S Albert, Hongyu An, Konstantinos Arfanakis, Arnold M Evia, Arvind Caprihan, Andria L Ford, Myriam Fornage, Gregory S Day, Jason D Hinman, Gregory A Jicha, Amir H Kashani, Joel H Kramer, Christian Lachner, Jin-Moo Lee, Peiying Liu, Hanzhang Lu, Pauline Maillard, Ronald C Petersen, Bruce M Psaty, John M Ringman, Gary A Rosenberg, Claudia L Satizabal, Sean I Savitz, Julie A Schneider, Sudha Seshadri, Prashanthi Vemuri, Danny J J Wang, Donna M Wilcock, B Gwen Windham, Rong Zhang, Carissa Tuozzo, Herpreet Singh, Sue Moy, Vilma Okey-Ewurum, Courtney B Page, Hillary Mulder, Pia Kivisäkk, Deborah Blacker, Lidiya Mazina, Karl G Helmer, Kristin Schwab, Lisa M Wruck, Roderick A Corriveau

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引用次数: 0

Abstract

Objective: To establish a framework for validating candidate biomarkers of cerebral small vessel diseases (SVD) associated with cognitive impairment and characterize individuals enrolled by the MarkVCID2 consortium under this framework.

Methods: Participants age 60 to 90 years were enrolled across 17 MarkVCID2 sites. Recruitment was targeted to enrich in cognitive symptoms (mild dementia, mild cognitive impairment, subjective cognitive decline), defined risk factors (diabetes mellitus, advanced hypertension), and Black/African American, White, and Hispanic/Latino subgroups. Enrolled participants underwent baseline visits that included cognitive testing, multimodal magnetic resonance imaging (MRI), and biofluid collection. Provisional risk for SVD-related cognitive decline was estimated primarily by baseline cognitive symptoms plus SVD risk factors. Adjudicated risk status was estimated by cognitive symptoms plus presence of moderate-to-severe white matter hyperintensities, microbleeds, or lacunes on baseline MRI.

Results: MarkVCID2 enrolled 1883 individuals age 73.4 ± 7.5 years, 65.0% female, 24.2% Hispanic, and 27.1% non-Hispanic Black. Among enrollees, 44.8% were provisionally designated high-risk. After baseline MRI, 48.5% were categorized as adjudicated high-risk status, with substantial recategorization both from low- to high-risk (primarily because of MRI lesions without SVD risk factors) and high- to low-risk (primarily suspected cognitive impairment at screening not confirmed by baseline testing).

Interpretation: MarkVCID2 baseline data indicate successful enrollment of diverse individuals enriched in factors associated with SVD-related cognitive decline. Changes over 3 years of longitudinal follow-up will be analyzed to validate the candidate biomarkers for 2 projected contexts of use: subject selection (identifying likelihood of future SVD progression) and study outcome (efficiently measuring SVD progression). ANN NEUROL 2025.

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脑血管疾病生物标志物临床验证MarkVCID2联盟：验证框架和基线特征。

目的：建立一个框架，验证与认知障碍相关的脑血管疾病（SVD）候选生物标志物，并在此框架下对MarkVCID2联盟招募的个体进行表征。方法：在17个MarkVCID2站点招募年龄在60至90岁的参与者。招募的目标是丰富认知症状（轻度痴呆、轻度认知障碍、主观认知能力下降）、确定的危险因素（糖尿病、晚期高血压）以及黑人/非裔美国人、白人和西班牙裔/拉丁裔亚组。入组的参与者进行了基线访问，包括认知测试、多模态磁共振成像（MRI）和生物体液收集。SVD相关认知能力下降的临时风险主要通过基线认知症状加SVD危险因素来估计。通过认知症状加上基线MRI上出现中度至重度白质高信号、微出血或腔隙来评估判定的风险状态。结果：MarkVCID2入组1883例，年龄73.4±7.5岁，65.0%为女性，24.2%为西班牙裔，27.1%为非西班牙裔黑人。在入组者中，44.8%被临时指定为高危人群。基线MRI后，48.5%的患者被归类为确定的高风险状态，并从低到高风险（主要是因为MRI病变没有SVD危险因素）和高到低风险（主要是筛查时怀疑的认知障碍，未被基线测试证实）重新分类。解释：MarkVCID2基线数据表明，成功入组的不同个体富含与svd相关的认知衰退相关的因素。将分析3年纵向随访的变化，以验证候选生物标志物在两种预计使用背景下的有效性：受试者选择（确定未来SVD进展的可能性）和研究结果（有效测量SVD进展）。Ann neurol 2025。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Annals of Neurology 医学-临床神经学

CiteScore

18.00

自引率

1.80%

发文量

270

审稿时长

3-8 weeks

期刊介绍： Annals of Neurology publishes original articles with potential for high impact in understanding the pathogenesis, clinical and laboratory features, diagnosis, treatment, outcomes and science underlying diseases of the human nervous system. Articles should ideally be of broad interest to the academic neurological community rather than solely to subspecialists in a particular field. Studies involving experimental model system, including those in cell and organ cultures and animals, of direct translational relevance to the understanding of neurological disease are also encouraged.