65 White matter hyperintensity shape and cognitive decline over 5 years 4 4.2 INTRODUCTION Cerebral small vessel disease (SVD) is associated with cognitive decline and is an important contributor to occurrence of dementia in older adults.1,2 A key MRI marker of SVD is white matter hyperintensities (WMH), which become evident as hyperintense lesions on T2-weighted MRI scans. Total WMH volume is a commonly used MRI marker and is related to cognitive decline.3,4 However, WMH volume is a relatively crude marker that only shows a moderate association with cognitive decline and is also not specific for underlying pathophysiological changes. In recent studies, WMH shape has been introduced as a more descriptive measure related to severity and progression of WMH compared to WMH volume alone.5–7 For example, a more irregular shape of periventricular/confluent WMH has been associated with an increased long-term risk for ischemic stroke and mortality.5 Furthermore, our previous study showed that a more irregular shape of periventricular/confluent WMHs was associated with an increased long-term dementia risk in community-dwelling older adults over 10 years.6 However, the association between WMH shape and decline in different cognitive domains remains unknown. We hypothesized that a more irregular WMH shape is associated with increased cognitive decline over 5.2 years, especially in the memory domain. The current study therefore aimed to investigate the association of WMH shape and decline in three cognitive domains over 5 years’ time in community-dwelling older adults. 4.3 METHODS 4.3.1 Participants & study design The study is based on the AGES-Reykjavik study cohort.8 This 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 prior to any experiments. Baseline brain MRI scans were acquired from 2002 to 2006. Five years later the follow-up visit took place from 2007 to 2011. The participants underwent cognitive testing at baseline and follow-up. A total of 2560 participants were included in the current study. A flow-chart describing the exclusion of participants for the current study is shown in supplementary figure S.4.9.1. 4.3.2 Baseline characteristics and cardiovascular risk factors Education level and smoking status were collected via questionnaires. The highest completed education level (primary school, secondary school, college or university) was entered. Non-smokers were defined as persons who never smoked, former regular smokers of at least 100 cigarettes or 20 cigars in a lifetime were categorized
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