Fellowship for Libecap: Investigating Enlarged Perivascular Spaces as a Neuroimaging Biomarker of Cerebral Small Vessel Disease

Grants and Contracts Details

Description

Cerebral small vessel disease (cSVD) is an important risk factor leading to development of vascular contributions to cognitive impairment and dementia (VCID). cSVD is characterized by in-vivo neuroimaging biomarkers including enlarged perivascular spaces (ePVS). PVS are fluid-filled spaces believed to play a role in the glymphatic system’s removal of waste from the brain. Reduced clearance may lead to enlargement of the PVS and subsequent accumulation of toxic solutes characteristic of neurodegeneration. Due to 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. We will investigate ePVS in a cohort of 121 cognitively normal older adults ranging in age from 60-86. Participants are scanned on a 3T Siemens Prisma scanner with a 64-channel head coil. All ePVS will be counted on T1 MPRAGE and T2 FLAIR images by an experienced rater blinded to participant demographics. ePVS are manually counted in a single, representative slice in the axial plane of the white matter centrum semiovale (CSePVS), basal ganglia, hippocampus, and midbrain. Our preliminary data show a negative relationship between CSePVS and baseline Montreal Cognitive Assessment (MoCA) score, a screening tool of cognitive dysfunction, and a positive relationship between CSePVS and whole brain white matter hyperintensity volume, a marker of advanced cSVD. Longitudinal relationships will be explored between baseline ePVS burden and changes to MoCA and WMH burden. We will also analyze ePVS in relation to baseline and longitudinal working memory performance, a cognitive domain affected by VCID. Lastly, 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. Preliminary data show a negative relationship between basal ganglia ePVS and global CVR. We will further test an alternative hypothesis that cerebrospinal fluid amyloid-beta 42, a biomarker of AD pathology, is more closely associated with ePVS than CVR. Our preliminary results support the investigation of ePVS as an early neuroimaging biomarker of cSVD-related dysfunction that could aid in identifying new therapeutic targets to attenuate cerebrovascular damage leading to VCID.
StatusFinished
Effective start/end date1/1/225/9/23

Funding

  • American Heart Association: $43,270.00

Fingerprint

Explore the research topics touched on by this project. These labels are generated based on the underlying awards/grants. Together they form a unique fingerprint.