# White matter and small vessel disease in older adults

> **NIH NIH R01** · VANDERBILT UNIVERSITY MEDICAL CENTER · 2020 · $642,445

## Abstract

As the population continues to age, cognitive decline and dementia are becoming increasingly important public
health issues. While Alzheimer's disease is the most common cause of dementia, it is becoming increasingly
evident that cerebrovascular mechanisms underlie cognitive impairment with mixed pathology accounting for at
least half of all dementia cases. A majority of clinical research linking cerebrovascular mechanisms to cognitive
impairment has focused on neuroimaging evidence of small vessel disease, such as white matter
hyperintensities (WMHs) and silent lacunar infarcts. Less attention has been given to serum or cerebrospinal
fluid (CSF) biomarkers that may be precursors to overt cerebrovascular disease evidence on neuroimaging.
We propose to leverage an existing local cohort, the Vanderbilt Memory & Aging Project, to examine
noninvasive serum and CSF biomarkers in relation to cognitive functioning and neuroimaging markers of small
vessel disease, white matter integrity, and microcirculation in older adults. Since the Vanderbilt Memory &
Aging Project cohort's inception in 2012, we have completed serial visits (baseline, 18-months, 36-months)
with key covariate ascertainment, neuropsychological assessment, multimodal 3T brain MRI, and fasting blood
and CSF acquisition, including maintaining a biosample repository on older adults free of clinical stroke and
dementia at enrollment. Thus, we are very well positioned to examine proteomic serum and CSF biomarkers in
relation to cross-sectional and longitudinal neuroimaging and cognitive outcomes. Results from this
collaborative effort will provide a dynamic understanding of axonal injury, amyloid deposition, tau aggregation,
and neurodegeneration associations with small vessel disease, white matter integrity, and microcirculatory
health. Results will yield important applications for investigations examining the natural history, analytic
epidemiology, prevention, clinical diagnosis, prognosis, and disease management of age-related and
pathological changes in small vessel, white matter, and microcirculatory health.

## Key facts

- **NIH application ID:** 9934963
- **Project number:** 5R01AG056534-04
- **Recipient organization:** VANDERBILT UNIVERSITY MEDICAL CENTER
- **Principal Investigator:** ANGELA L. JEFFERSON
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $642,445
- **Award type:** 5
- **Project period:** 2017-09-15 → 2022-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9934963

## Citation

> US National Institutes of Health, RePORTER application 9934963, White matter and small vessel disease in older adults (5R01AG056534-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9934963. Licensed CC0.

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