162 Chapter 8 The overarching aim of this thesis was to exploit the shape of WMHs for better characterization of WMHs to improve the clinical interpretation of WMHs and to investigate related disease outcomes. This thesis was mostly based on non-demented and community-dwelling older individuals. Moreover, a study set up focusing on a memory-clinic population was discussed to get more pathology-focused insights into the formation of WMH. In this chapter the methodology, the relation of the findings to other areas of research, future directions, as well as clinical implications are discussed. 8.1 KEY FINDINGS OF THIS THESIS • Different cardiovascular risk factors were found to be related to a distinct pattern of WMH shape markers in non-demented older adults (Chapter 2). • A more irregular shape of periventricular/confluent WMH was associated with a larger increase in WMH volume, and with occurrence of new subcortical infarcts, new microbleeds, enlargement of perivascular spaces, and new cerebellar infarcts 5.2 years later (Chapter 3). • A more complex shape of periventricular/confluent WMH was found to be related to cognitive decline over 5.2 years (Chapter 4). • A more irregular shape of periventricular/confluent WMH was associated with an increased long-term dementia risk over 10 years (Chapter 5). • Distinct brain MRI phenotypes were identified using hierarchical clustering that are related to varying long-term risks of developing dementia (Chapter 6). 8.2 WMH SHAPE: ADDED VALUE AND CHALLENGES Volume is a commonly used quantitative, yet crude marker to assess WMHs. In clinical practice the WMHs of two patients can be similar in volume, but can appear visually very different from each other. These visual differences can be described as differences in the shape of WMHs. The findings of this thesis and previous work justify the use of WMH shape as an additional marker to the more commonly used, but unspecific WMH volume (Chapters 2-6,1–3).There are, however, a few limitations to consider when applying WMH shape. With current methods of WMH volumetric quantification, separate measures can be obtained for deep, periventricular, and confluent WMH.3 However, for WMH shape analysis we have to merge periventricular and confluent WMH into one group, because splitting them would add an artificial edge in the WMHs which in turn could falsify the shape analysis. Early periventricular WMH will, however, represent
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