Jasmin Annica Kuhn-Keller

39 White matter hyperintensity shape and long-term progression of cerebrovascular disease 3 3.2 INTRODUCTION Most healthy older adults have changes on brain MRI scans related to cerebrovascular disease. The most common cerebrovascular changes are white matter hyperintensities (WMHs). These WMHs are associated with long term dementia occurrence and cognitive decline.1,2 However, the structural correlates of these associations remain unknown. Different quantitative MRI markers exist to study WMH, such as the commonly used WMH volume. However, this marker can be considered rather crude and is disease-unspecific. This hinders more in-depth investigations related to disease mechanisms. In recent studies, WMH shape was introduced as a novel marker that may provide a more detailed and more disease specific characterization of WMH compared to WMH volume. Previous studies have shown that a more irregular shape of periventricular/confluent WMH is associated with the occurrence of future stroke and increased mortality in patients with an increased vascular burden.3 Moreover, a more irregular shape of periventricular/confluent WMHs was associated with an increased long-term risk for dementia.4 These studies indicate that different WMH shape patterns are probably related to different underlying pathologies (e.g. gliosis, fiber loss, and demyelination).5 This could provide crucial information about potential disease progression. We hypothesized that different WMH shape patterns are related to different types of underlying pathologies and that some shape patterns may be related to progression of specific cerebrovascular markers. We therefore aimed to investigate the association between baseline WMH shape and progression of cerebrovascular disease markers over 5.2 years in community-dwelling older adults. 3.3 METHODS 3.3.1 Participants & study design Data from the AGES Reykjavik study was used in the current study.6 The study was approved by the Icelandic National Bioethics Committee, VSN:00-063, and the institutional review board responsible for the National Institute on Aging (NIA) research; all participants signed informed consent. Brain MRI scans were acquired at baseline from 2002 to 2006 and approximately five years later at follow-up from 2007 to 2011. A flow-chart describing the inclusion and exclusion of participants in the current study is shown in figure 3.1. Of the 4614 included participants, a total of 654 participants were excluded after MRI quality control (WMH oversegmentation: n = 124;

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