Linking chronic cerebral hypoperfusion to cognitive impairment and dementia
KH group's research investigates the mechanisms underlying cognitive decline relevant to Cerebral Vascular disease and Alzheimer's disease (AD) with the aim to identify novel targets for therapeutic strategies to slow the rate of cognitive decline and prevent dementia. Chronic cerebrovascular pathology is a leading cause of dementia, and arguably represents the most important modifiable risk factor for Alzheimer's disease. Despite this importance, the mechanisms and pathways contributing to cognitive impairment have largely remained elusive. Central to the pathophysiology of cerebral microvascular disease is likely to be disruption of the finely tuned interplay between the cells in the neurovascular unit (NVU) that form an essential bridge between blood and neuron. The molecular basis of NVU dysfunctions that lead to cerebral microvascular disease and dementia, and the molecular signals underlying cross-talk between different cell types of the NVU, are still poorly understood and are a focus of our research in experimental models and human post-mortem tissues. The work demonstrates several important and common pathogenetic features including susceptibility to myelin damage, microvascular inflammation and breakdown of the blood brain barrier. Potential targets for drug intervention at different points in the neurovascular unit have been identified and are currently being explored in pre-clinical models.