White Matter Lesion Etiology of Dementia in the U.S. Including in Health Disparity Populations (U19 Clinical Trial not Allowed)

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Despite established associations between white matter lesions and cognitive impairment including dementia, the volume, anatomical location, and other key cellular and molecular characteristics of white matter lesions that are both necessary and sufficient are unknown, as are the comorbid clinical factors that may modify (including protect from) these effects. Therefore, this initiative will support one large prospective clinical research study in the U.S. studying individuals with white matter lesions at risk for cognitive decline to determine the magnitude and anatomical locations that are both necessary and sufficient to cause cognitive impairment and dementia. The study will include health disparities populations, and will examine additional clinical factors and comorbidities that may be effect modifiers of the relationship between white matter lesions and cognitive impairment, including dementia. Clinical trial-ready VCID biomarkers should be utilized, further developed, and/or subject to implementation research in this study. Secondary goals include: identifying clinical and mechanistic targets for future VCID interventional trials; determining interrelationships (cross-sectional and longitudinal) among white matter lesions, cerebro- and cardio-vascular disease and risk factors including dementia-relevant genes. Applicants are encouraged, when scientifically advantageous, to utilize existing resources for VCID and stroke research, e.g. MarkVCID, StrokeNet, Alzheimers Centers, and large NIH funded prospective cohort studies (e.g. Framingham, ARIC, CHS, NOMAS, etc.) as well as other dementia resources.

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