PROJECT SUMMARY/ABSTRACT: Increasing evidence suggests that brain perivascular
spaces play important roles in intracerebral fluid transport and brain homeostasis. Enlarged
perivascular spaces (PVS) have reported associations with aging, mild cognitive impairment
(MCI), and Alzheimer’s disease (AD). However, the utility of this biomarker as an imaging
predictor of AD is not fully known. To advance progress in AD, early disease biomarkers must be
developed. PVS are linked with biological changes that occur early during the course of AD,
including dysfunctional intracerebral fluid regulation, neuroinflammation, and small vessel
disease. Yet, substantial gaps in knowledge persist with regard to optimal methods of PVS
detection and quantitation in live humans. To advance knowledge on PVS effects in humans, a
harmonized, non-biased, and time-efficient technique of PVS quantification must be employed in
diseased cohorts. In this project, an open-source automated Frangi filter technique of PVS
detection will be used to detect PVS and assess their associations with AD in a large, well
characterized, underserved Appalachian community cohort. PVS will be analyzed globally and in
specific brain regions in aging, MCI, and AD and PVS longitudinal changes will be examined. This
work will leverage a rich resource of existing clinical and imaging material available from the
Rockefeller Neuroscience Institute Memory Health Clinic and will produce novel data pertaining
to PVS metrics. The hypothesis is that PVS serve as a predictor for AD. In Aim 1, we will examine
the associations of static PVS metrics with a diagnosis of AD and cognitive decline. In Aim 2, we
will examine the associations of longitudinal PVS metrics with a diagnosis of AD and cognitive
decline. In both aims, we will investigate how relationships of PVS metrics differ by age, sex,
education history, and comorbid diseases. Overall, these studies have the potential to uncover
new knowledge regarding optimal methods of PVS measurement, interpretation, and detection in
persons at risk of developing AD. This project may reveal new diagnostic and prognostic factors
for AD while elucidating appropriate methods for studying PVS in the setting of other age-related
neurological conditions.