Neuropathological changes in mouse models of cardiovascular diseases

Mild cognitive impairment and dementia are common disorders in the elderly. As the life span of the population in the Western world is increasing, the prevalence of cognitive disorders and the social and economic burden that coincide with that will increase. Recent data indicate that cardiovascular diseases are largely associated with an increased risk of dementia. The presence of atherosclerosis, heart failure, hypertension and small vessel disease are all associated with neuropathological changes and increased cognitive decline. Exploring the link between cardiovascular diseases and cognitive decline is important, since it could identify treatment targets for patients with cognitive impairment and dementia. The main hypothesis of this thesis is that different cardiovascular diseases in mice contribute to the development of neuropathological changes related to cognitive impairment and dementia. To test this hypothesis animal models with comparable etiology and neuropathology are needed in order to perform mechanistic studies and study cause-consequence relationships. In chapter 2 we reviewed the literature on mouse models of cardiovascular disease with reported cerebral changes in order to get an insight in which animal models are suited for vascular cognitive impairment or dementia research. These included models for atherosclerosis, heart failure, hypoperfusion, hypertension and small vessel disease. In chapter 3 we explored the distribution of atherosclerotic plaques in the common carotid artery, intracranial carotid artery and circle of Willis in different atherosclerotic mouse models. In chapter 4-6 we used mouse models of atherosclerosis, heart failure and hypoperfusion to study the effect of these cardiovascular diseases on brain pathology.