10 Chapter 1 1.1 AGEING AND DEMENTIA With an ageing population age-related diseases such as dementia will continue to increase in the coming years.1 This will create an increasing burden for society and health care systems.1 There are several types of dementia, the most common ones being Alzheimer’s disease, vascular dementia, frontotemporal dementia and Lewy body dementia.2 Multiple co-existing diseases contribute to the dementia phenotype and cardiovascular risk factors are an important contributor. Cerebrovascular disease is an umbrella term for a range of conditions that result in pathological changes in or surrounding the cerebral blood vessels.3 Large vessel disease, a type of cerebrovascular disease, is caused by atherosclerosis in the upstream arteries leading to the brain and is a major cause of ischemic stroke.4,5 Cerebral small vessel disease (SVD) refers to a group of pathological changes affecting the cerebral small arteries, arterioles, capillaries and venules of the brain.3 SVD is a major contributor to ischemic stroke, cognitive decline, and dementia.6 SVD cannot be referred to as a single disease, but should be considered a combination of radiological features that can be caused by different genetic and non-genetic diseases.3 Examples of genetic SVD forms are Dutch-type cerebral amyloid angiopathy (D-CAA) and cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). Genetic forms of SVD typically have a more early time of onset compared to the sporadic forms. The main types of cerebral SVD that occur in older adults are ischemic SVD (including e.g. arteriolosclerosis)4 and sporadic cerebral amyloid angiopathy (CAA), where amyloid is deposited in the walls of the cerebral blood vessels increasing the risk for hemorrhage.3 SVD often starts with asymptomatic changes in the vasculature and parenchyma, which can be captured best in population-based studies or in targeted studies in genetic cases. To date, treatment options are limited for vascular dementia. There are some preventive life-style changes and several new pharmaceutical options that make it important to select patients at an early stage. For example, a new pharmaceutical trial on CAA will start in 2024, also including patients with Dutch-type cerebral amyloid angiopathy7 For patient selection and especially when aiming for the earlier disease stages, specific markers are currently lacking. This thesis aims to identify and characterize novel specific SVD markers. 1.2 NEUROIMAGING IN CEREBRAL SVD Magnetic resonance imaging (MRI) has developed a lot since its introduction in the early 1980s. Today, MRI is a versatile technique that allows the investigation of brain changes in humans in a non-invasive manner both in clinical as well as in research settings. Changes in blood vessel properties caused by SVD, such as arteriolosclerosis, lipohyalinosis, and fibrinoid necrosis are difficult to image directly
RkJQdWJsaXNoZXIy MTk4NDMw