PROJECT: JTC2011: BIODVAS

Vascular cognitive impairment (VCI) is a type of dementia that is thought to have vascular origins. It affects 7% of the population over 65 years of age and nearly 50% of those aged 80 years, which makes it the second leading cause of dementia after Alzheimer?s disease. The prevalence of VCI is expected to double in the next 30 years, which will make VCI a priority for health services. Clinicians will be under pressure to achieve faster diagnosis and find effective treatments. This will be a considerable challenge because VCI is poorly understood. Urgent developments in neuroimaging are necessary in order to improve diagnosis, and a better understanding of disease mechanisms is absolutely necessary if a potential therapy is to be developed. The current proposal aims to make significant advances in both respects. We will develop and characterize experimental animal models of VCI. This will be accomplished by reducing the blood flow to the brain, and will result in degeneration of the subcortical white matter that is comparable to the human condition. In parallel, we will establish a sophisticated neuroimaging strategy using magnetic resonance imaging (MRI) that can be used for early detection of brain pathology in these animals. Since the same technology is also available in humans, we hope to make recommendation regarding identification and stratification of patients with VCI. Finally, we will use a combination of pharmacology and transgenic animal models to obtain mechanistic insight into the disease. The pharmacological approach will investigate two potential therapeutic agents: one that improves blood flow, and another that increases the amount of a neurotransmitter in the brain. The second approach will investigate the role of the inflammatory response in disease progression using transgenic animals in which the inherent brain microglia can be selectively depleted in combination with anti-inflammatory drugs.