Grants and Contracts Details
Description
ABSTRACT
Cerebral small vessel disease (cSVD) is an important risk factor that may arise years before the onset of vascular
contributions to cognitive impairment and dementia (VCID). cSVD is characterized by in-vivo neuroimaging
biomarkers including enlarged perivascular spaces (ePVS). PVS are the site of interchange between interstitial
fluid and cerebrospinal fluid, driven by arterial pulsatility, which is believed to play a role in the removal of brain
waste. Reduced clearance may lead to enlargement of the PVS and subsequent accumulation of toxic solutes
characteristic of neurodegeneration. Given their presence in brain regions that support cognition, we hypothesize
that quantitative, cross-sectional ePVS counts in cognitively normal older adults could serve as an early
biomarker of VCID. Specifically, we anticipate ePVS will predict cognitive dysfunction and increased white matter
lesion burden after three years. We will test this hypothesis in a cohort of 121 cognitively normal older adults
ranging in age from 60-86 at baseline. Participants are scanned on a 3T Siemens Prisma magnetic resonance
imaging scanner with a 64-channel head coil. ePVS are manually counted by an experienced rater blinded to
participant demographics following consensus guidelines using T1 MPRAGE, T2 FLAIR, and Quantitative
Susceptibility Mapping images. All ePVS are counted in a single, axial slice of four brain regions with high ePVS
burden including the centrum semiovale (CSePVS), basal ganglia (BGePVS), hippocampus, and midbrain. Aim
1 will test the hypothesis that CSePVS predict longitudinal changes in executive function, a specific cognitive
domain affected in VCID. Our preliminary data using the same cohort show a negative relationship between
CSePVS and baseline Montreal Cognitive Assessment (MoCA) score, a standardized screening tool of global
cognition. Aim 2 will test the hypothesis that baseline CSePVS burden predicts increased deep white matter
hyperintensity (WMH) volume in the centrum semiovale after three years. This expands on preliminary findings
that CSePVS are positively related to whole brain WMH volume, a marker of advanced cSVD. In Aim 3, regional
cerebrovascular reactivity (CVR), a measure of arterial compliance, will be analyzed using a novel BOLD-fMRI
testing paradigm, as a potential mechanistic contributor of ePVS. The cross-sectional relationship between
BGePVS and basal ganglia CVR will be analyzed to capitalize on our preliminary data which show a negative
relationship between BGePVS and global CVR. We will further test an alternative hypothesis that cerebrospinal
fluid amyloid-beta 42, a biomarker of AD pathology and waste accumulation, is more closely associated with
ePVS than CVR. These experiments will be carried out at the University of Kentucky Magnetic Resonance and
Imaging Center and the Sanders-Brown Center on Aging, under the direction of an expert team of scientist and
clinician mentors. This F30 predoctoral fellowship will provide the requisite experience, training, and knowledge
to aid the trainee’s transition into the next step of his career as a scientist-neuroradiologist in the field of
neuroscience of aging measuring similar endpoints using basic and translational neuroimaging techniques.
Status | Finished |
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Effective start/end date | 5/10/23 → 5/9/24 |
Funding
- National Institute on Aging: $42,262.00
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