Specific Aims

Aim 1

To identify the extent and characteristics of white matter injury that influence cognitive and health outcomes.

  • Degree of white matter injury described by weighted measures of Free Water, FA and WMH
  • Impact of location and amount of white matter injury burden on cognitive and health outcomes
  • Relation of risk modifiers such as vascular risk factors, risk factor control, pre-existing neurodegenerative conditions (AD biomarkers), genetic susceptibility (WMH polygenic risk score, AD polygenic risk score), race/ethnicity and sex on cognitive and health outcomes
  • Influence of recognized and novel blood biomarkers of inflammation and endothelial dysfunction on white matter injury burden

Aim 2

Evaluate mechanisms of progression of white matter injury on cognition and health outcomes.
  • Evaluate the association between amount and specific location of white matter injury progression on cognitive decline and health outcomes
  • Evaluate the impact of progression of concurrent AD pathology blood biomarkers in relation to white matter injury progression on cognitive decline and health outcomes
  • Evaluate the impact of change in recognized and novel markers of inflammation and endothelial dysfunction on progression of white matter injury
  • Evaluate the impact of vascular risk factors, vascular disease, inflammation and endothelial dysfunction on cognition and health outcomes, independent of baseline level and progression of white matter injury.

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 personalized medical management and planning needed by patients with white matter lesions, both for need for care as was inclusion criteria for future therapeutic studies.
  • Validate the risk prediction model for precision medicine outcomes using multiple epidemiological cohorts to confirm the generalizability of our findings and potential use for population screening

About the Study

This is a 5-year observational study that involves clinical examination, clinical diagnosis, neuropsychological testing, MRI and blood sampling at 3 visits over three years among 2,250 diverse participants with cognitive complaints.

Cerebrovascular Measures
  • White matter hyperintensities
  • Free Water
  • Fractional Anisotropy
  • White Matter Hyperintensities
  • Cerebral Microbleeds
  • Incident MR infarcts
Hypothesized Causal Factors
  • Age
  • Vascular Risk Factors
  • Concurrent vascular disease
  • AD pathology
  • WMH Genetics
  • Change in cognition
  • Change in diagnosis
  • Stroke/MI/Death


Partipating Centers and Scientific Sites

Research amplifies existing Alzheimer's Disease Research Centers (ADRC)

  • Each ADRC selected has a track record of successful recruitment of diverse participants
  • Emphasizes existing participants
  • Efficient - no duplicated effort for clinical cores
  • Supplements existing data collection
  • Supplements existing recruitment efforts
  • Pays for blood samples, DNA sampling and advanced Magnetic Resonance Imaging
  • Returns plasma ATN, AD/VCID genetic risk scores, quantitative MRI results


By using an existing and mature research infrastructure we can most efficiently implement large scale research of Vascular Contributions to Cognitive Impairment and Dementia.