Giuseppe Barisano

Cerebral small vessel disease (SVD) is a disease affecting the small blood vessels in the brain that contributes to the development of cognitive impairment and dementia. SVD is commonly found at autopsy in the elderly population, but its relationship with the other pathological factors of Alzheimer's Disease and Related Dementias (ADRD) as well as its role as a potential therapeutic target for dementia remain unclear. This is in part due to the lack of quantitative methods to reliably and robustly measure the early stages of SVD, which prevents risk-stratification of healthy and cognitively unimpaired individuals and the accurate longitudinal assessment of SVD, two issues that are critical for a successful clinical trial evaluating treatments for SVD. In fact, current diagnostic approaches for SVD use brain magnetic resonance imaging (MRI) to identify different signs of brain damage that are supposed to be caused by SVD. However, these signs may occur late in the course of the disease, may not be detectable in the cognitively unimpaired population, and may require advanced MRI sequences not available in all clinical centers. I developed a novel MRI tool that provides a quantitative estimate of small blood vessels and their perivascular space (PVS) in the brain in a fully-automated and robust way. My technology is widely applicable in clinical setting, even on MRI data already acquired, as it requires only a standard T1-weighted sequence typically available in clinical brain MRI scans, without the need for contrast agent injection. Preliminary results show that our PVS markers are significantly different both in older adults compared to younger individuals, and in cognitively unimpaired subjects compared with demented patients. In the proposed study, we aim to evaluate whether our PVS markers may predict dementia risk in non-demented elderly, how they relate with other vascular or Alzheimer’s disease biomarkers, and how they evolve longitudinally. If PVS structural alterations precede and directly contribute to dementia, then our markers may represent a valuable measure in ADRD clinical trials for therapies targeting SVD to combat dementia.