PROJECT SUMMARY – Overall Initially identified on MRI in 1986 as “…incidental lesions of uncertain clinical significance associated with cerebrovascular risk factors”, white matter hyperintensities (WMH) are a common consequence of the aging process exacerbated by vascular risk factors. WMH also influence cognition and evolution of WMH are associated with declines in both memory and executive function while extensive WMH predict incident MCI, stroke and dementia. WMH and infarction also have a negative impact on cognition independent or in addition to concurrent amyloid status. The impact of WMH is consistent with evidence that clinical dementia is a multifactorial processes. The impact of WMH on dementia is also consistent with the fact that dementia risk scales emphasize the role of vascular risk in dementia prediction. As the US population becomes increasingly older and more diverse, the number of Americans with dementia is expected to rise substantially, particularly for those with concomitant vascular disease. Importantly, the impact of vascular disease on dementia risk may be exacerbated in African Americans and Hispanics, who are at greater risk for vascular disease and for whom vascular disease may play a larger role in clinical dementia. As awareness of dementia increases, it is becoming common to see individuals presenting for clinical assessment with minor cognitive complaints. Neuroimaging studies frequently identify “incidental” WMH, usually ascribed to “microvascular disease” by radiologists, raising patient concerns about their brain health and future risk for dementia. To date, however, we are not aware of any studies that have comprehensively examined the impact of individual and combined MRI measures of white matter injury on cognitive performance among a diverse, non-demented, stroke free population with cognitive complaints over an extended period of observation. To address this important gap in scientific knowledge, we propose the following aims: Aim 1. To identify the extent and characteristics of white matter injury that influence cognitive and health outcomes Aim 2. Evaluate Mechanisms of progression of White Matter (WM) Injury on Cognition and Health Outcomes Aim. 3. Based on findings from Aims 1 and 2, build and validate a predictive risk model with the ultimate goal of increasing the understanding of precision medical management and planning needed by patients with white matter lesions, both for need for care as was inclusion criteria for future therapeutic studies. Impact: Given recent data showing that the impact of vascular risk factors on dementia can be modified by effective treatment in later life potentially lessening population burden of dementia, developing strategies that recognize and precisely treat the contribution of VCID to dementia burden is a public health imperative.

PROJECT NARRATIVE – Overall As the US population becomes increasingly older and more diverse, the number of Americans with dementia is expected to rise substantially, particularly among those with concomitant vascular disease. The Clinical significance of INciDEntal white matter lEsions on MRI in a Diverse population with cognitive complaints (INDEED) proposes to comprehensively examine the impact of individual and combined MRI measures of white matter injury on cognitive performance among a diverse, non-demented, stroke free population with cognitive complaints over an extended period of observation.