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Introduction: To describe the protocol and findings of the instrumental validation of three imaging-based biomarker kits selected by the MarkVCID consortium: free water (FW) and peak width of skeletonized mean diffusivity (PSMD), both derived from diffusion tensor imaging (DTI), and white matter hyperintensity (WMH) volume derived from fluid attenuation inversion recovery and T1-weighted imaging., Methods: The instrumental validation of imaging-based biomarker kits included inter-rater reliability among participating sites, test-retest repeatability, and inter-scanner reproducibility across three types of magnetic resonance imaging (MRI) scanners using intra-class correlation coefficients (ICC)., Results: The three biomarkers demonstrated excellent inter-rater reliability (ICC >0.94, P -values < .001), very high agreement between test and retest sessions (ICC >0.98, P -values < .001), and were extremely consistent across the three scanners (ICC >0.98, P -values < .001)., Discussion: The three biomarker kits demonstrated very high inter-rater reliability, test-retest repeatability, and inter-scanner reproducibility, offering robust biomarkers suitable for future multi-site observational studies and clinical trials in the context of vascular cognitive impairment and dementia (VCID)., Competing Interests: Dr. Pauline Maillard is a consultant for Boston University, outside of the scope of the current work. Dr. Hanzhang Lu has no conflict of interest to report. Dr. Konstantinos Arfanakis is on the advisory board for External Advisory Committee, NIH‐funded clinical research study titled “Determinants of Incident Stroke Cognitive Outcomes and Vascular Effects on RecoverY Network (DISCOVERY).” Dr. Brian T. Gold has no conflict of interest to report. Dr. Christopher E. Bauer has no conflict of interest to report. Dr. Valentinos Zachariou has no conflict of interest to report. Dr. Lara Stables has no conflict of interest to report. Dr. Danny J.J. Wang has no conflict of interest to report. Dr. Kay Jann has no conflict of interest to report. Dr. Sudha Seshadri is a consultant for Biogen. Dr. Marco Duering reports honoraria for lectures from Pfizer (payment to Dr. Duering), Bayer (payment to Dr. Duering,) and Sanofi Genzyme (payment to institution). is a consultant for Roche Pharma (payment to institution) and Hovid Berhad, and participates on the Executive committee of the VAS‐COG Society. Laura J. Hillmer has no conflict of interest to report. Dr. Gary A. Rosenberg has no conflict of interest to report. Dr. Haykel Snoussi has no conflict of interest to report. Dr. Farshid Sepehrband has a patent pending for Mapping Perivascular Space using magnetic resonance imaging. Dr. Mohamad Habes is a consultant for Biogen on ARIA. Baljeet Singh has no conflict of interest to report. Dr. Joel H. Kramer has received royalties from Pearson, Inc. Dr. Roderick A. Corriveau has no conflict of interest to report. Herpreet Singh has no conflict of interest to report. Kristin Schwab has no conflict of interest to report. Dr. Karl G. Helmer has no conflict of interest to report. Dr. Steven M. Greenberg is a consultant for Roche (payment to Dr. Greenberg) and Washington University/IQVIA (payment to Dr. Greenberg), Bayer (payment to Dr. Greenberg), Biogen (payment to Dr. Greenberg), and receives royalties or licenses from Up‐To‐Date (payment to Dr. Greenberg). Dr. Charles DeCarli is a consultant to Novartis on a safety trial for heart failure. Dr. Arvind Caprihan has no conflict of interest to report. Dr. Claudia L. Satizabal has received support for attending meetings and/or travel from the NIH (payment to Dr. Satizabal)., (© 2021 The Authors. Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring published by Wiley Periodicals, LLC on behalf of Alzheimer's Association.)

The research into vascular contributions to cognitive impairment and dementia (VCID) aims to understand the importance of cerebrovascular biology in cognitive decline. Prevention and treatment of VCID is poised to have major impact on dementia-related disease burden and is thus a critical emerging objective in dementia research. This article presents VCID consortia focused on multidisciplinary approaches to identify key pathologic targets and develop diagnostic tools with the goal of bridging the divide between basic research and clinical trials. Members of these multi-institute, multidisciplinary consortia provide a prospective on the history and emerging science of VCID and how VCID consortia can address some of the more complex questions in VCID and drive the field forward. These consortia, and others like them, are uniquely suited to tackle some of the most difficult obstacles in translating research to the clinic.

White matter hyperintensities (WMHs) are frequently seen on brain magnetic resonance imaging scans of older people. Usually interpreted clinically as a surrogate for cerebral small vessel disease, WMHs are associated with increased likelihood of cognitive impairment and dementia (including Alzheimer's disease [AD]). WMHs are also seen in cognitively healthy people. In this collaboration of academic, clinical, and pharmaceutical industry perspectives, we identify outstanding questions about WMHs and their relation to cognition, dementia, and AD. What molecular and cellular changes underlie WMHs? What are the neuropathological correlates of WMHs? To what extent are demyelination and inflammation present? Is it helpful to subdivide into periventricular and subcortical WMHs? What do WMHs signify in people diagnosed with AD? What are the risk factors for developing WMHs? What preventive and therapeutic strategies target WMHs? Answering these questions will improve prevention and treatment of WMHs and dementia.