Jasmin Annica Kuhn-Keller

14 Chapter 1 1.5 AIM AND OUTLINE OF THIS THESIS The overarching aim of this thesis is to exploit the shape of WMHs to better characterize WMH and thereby to improve the clinical interpretation of WMHs and to investigate whether it could predict clinical outcome. This thesis is mostly based on non-demented and community-dwelling older individuals. Moreover, a study set up focusing on a memory-clinic population will be discussed to get more pathologyfocused insights into the formation of WMH. In Chapter 2, the association of different cardiovascular risk factors with WMH shape was investigated in older adults as included in the Biomarker Development for Postoperative Cognitive Impairment in the Elderly (BIOCOG) study. The study included non-demented older adults scheduled for major elective surgery. Next, in Chapter 3, it was examined whether WMH shape is related to long-term progression of cerebrovascular disease in the AGES Reykjavik dataset. Besides WMH, different types of infarcts, microbleeds and enlarged perivascular spaces and their relationship with WMH shape were evaluated in this chapter. In Chapter 4, the focus was on investigating the association between baseline WMH shape and cognitive decline measured in three different domains (memory, executive function, and processing speed) over 5.2 years in the AGES Reykjavik dataset. In Chapter 5, the association of baseline WMH shape and long-term dementia risk after up to 13.4 years was assessed in the AGES Reykjavik study. In Chapter 6, brain MRI phenotypes were obtained using a hierarchical clustering method in the AGES Reykjavik dataset. In a second step, it was investigated whether these phenotypes are related to long-term risk (10 years) for dementia. In Chapter 7, a novel prospective cross-sectional study is presented applying WMH shape markers and other cutting-edge MRI techniques to further understand processes involved in SVD. This WHIte MAtter hyperintensity Shape and glymphatics (WHIMAS) study is focused on brain MRI determinants of cognitive impairment in geriatric clinic outpatients. Lastly, in Chapter 8, the main findings of this thesis and future directions of research are discussed.

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