Grant: Project Grant

Brain small blood vessel disease (SVD) is seen on Magnetic Resonance Imaging (MRI) as white spots and patches in 95% of people over 65. Most commonly SVD appears white spots or patches called white matter hyperintensities (WMH), which can significantly contribute to cognitive decline, dementia and falls in the 20% who have extensive WMH. Our data suggests that extensive WMH arise from wall thickening in small veins draining toward the large cavities, called ventricles, deep in the brain through which cerebrospinal fluid circulates. This venous scarring, driven by hypertension or other vascular risks, increases back pressure resulting in leakage and fluid build-up around the ventricles, which interferes with clearance of amyloid from the brain. Amyloid is a toxic protein, previously only visible at autopsy under a microscope. Advances in radiotracers now make amyloid and tau, hallmark pathologies in AD, visible on Positron Emission Tomography (PET) scanning. However, the relationships of WMH, tau and amyloid are not well understood. To fill this knowledge gap, patients with severe WMH undergo 3T MRI, amyloid and glucose PET imaging at baseline. They have repeat scans 2 years later to determine if WMH, amyloid build-up and cognitive decline occur and are linked. Tau imaging performed at one year will clarify associations of this other toxic AD protein to cognitive decline. 130 participants with extensive WMH are currently being recruited from stroke and memory clinics, but funding is needed to reach the total and do all the follow ups. Participants in the Alzheimer Disease Neuroimaging Initiative who have a milder burden of WMH will provide comparison. Older adults with WMH represent a potentially treatable at-risk group for AD. Treatments for both conditions are in development, and natural history data is urgently needed, particularly when both conditions as each may be at an earlier more treatable stage of pathological development.