Rahma Boulahya, Montreal Heart Institute

Supervisor: Marie Lordkipanidzé, Montreal Heart Institute

The limited success of current treatments of cognitive impairment has led to a search for early markers of cognitive impairment that could predict future progression. One focus has been on peripheral artery disease (PAD), as patients suffering from PAD have been shown to perform more poorly on tests of cognitive function than their normotensive or hypertensive counterparts without established vascular disease, but less severely than patients having had a stroke, suggesting a continuum of progression with increasing vascular burden. Platelet dysfunction is a key pathophysiological element in PAD leading towards increased thrombotic risk and stroke. Whether platelet dysfunction could also be a contributor towards cognitive impairment in PAD remains unknown.

The Brain-Derived Neurotrophic Factor (BDNF) is a neurotrophin implicated in the homeostatic maintenance of the central and peripheral nervous system in ageing. In cognitively healthy adults followed up for 10 years, reduced levels of BDNF preceded cognitive impairment and dementia onset, even after adjustment for tradition risk factors. BDNF is present in large quantities in blood, where it is almost exclusively stored in platelets and released upon platelet activation at the site of vascular injury. Local application of BDNF improved the recovery of neuronal function after ischemic injury in several animal models. Thus, strategies to increase BDNF delivery at sites of cerebral vascular damage could be of particular interest in preventing the progression of vascular cognitive impairment (VCI) in patients with vascular burden. It remains to be determined whether platelet dysfunction, such as seen in PAD, results in abnormal BDNF levels in blood which could contribute to VCI, and whether current antiplatelet strategies used in PAD could have an incidence on platelet BDNF storage and release.

The project is aligned with the Network’s Priority Research Area Theme 2: Identifying novel methods of early detection of vascular conditions. With the use of the Montreal Heart Institute (MHI) Biobank, the project will leverage a large cohort of cases and controls, to identify factors associated with vascular dysfunction.  The results may further lead to the development of novel biomarker assays in vascular diseases and prevention of VCI, including circulating levels of BDNF and markers of platelet activity.