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.

Public Health Relevance

The incidence of Alzheimer?s disease and dementia is dramatically increasing, and there is growing recognition that cerebrovascular disease exacerbates the manifestation of cognitive symptoms and progression over time. The proposed project will evaluate serum and cerebrospinal fluid biomarkers in relation to white matter integrity, small vessel disease, microcirculatory health, and cognitive impairment among older adults.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Research Project (R01)
Project #
5R01AG056534-04
Application #
9934963
Study Section
Behavioral Medicine, Interventions and Outcomes Study Section (BMIO)
Program Officer
Mackiewicz, Miroslaw
Project Start
2017-09-15
Project End
2022-05-31
Budget Start
2020-06-01
Budget End
2021-05-31
Support Year
4
Fiscal Year
2020
Total Cost
Indirect Cost
Name
Vanderbilt University Medical Center
Department
Type
DUNS #
079917897
City
Nashville
State
TN
Country
United States
Zip Code
37232
Gifford, Katherine A; Liu, Dandan; Neal, Jacquelyn E et al. (2018) Validity and Normative Data for the Biber Figure Learning Test: A Visual Supraspan Memory Measure. Assessment :1073191118773870
Deming, Yuetiva; Dumitrescu, Logan; Barnes, Lisa L et al. (2018) Sex-specific genetic predictors of Alzheimer's disease biomarkers. Acta Neuropathol 136:857-872
Moore, Elizabeth E; Hohman, Timothy J; Badami, Faizan S et al. (2018) Neurofilament relates to white matter microstructure in older adults. Neurobiol Aging 70:233-241
Osborn, Katie E; Liu, Dandan; Samuels, Lauren R et al. (2018) Cerebrospinal fluid ?-amyloid42 and neurofilament light relate to white matter hyperintensities. Neurobiol Aging 68:18-25