13 General Introduction 1 Different WMH types (periventricular/confluent and deep) and also different WMH shape patterns seem to be associated with different underlying pathological changes. A more irregular shape of WMH go hand-in-hand with more severe parenchymal changes.21–23 Furthermore, a previous study has shown that a more irregular WMH shape was associated with increased stroke risk and increased mortality in patients with manifest arterial disease.24 I hypothesize that different underlying SVD pathologies result in a different WMH shape that can be quantified by MRIbased WMH shape markers. These shape markers may provide a more detailed characterization of WMH than volume alone. 1.4 AGES-REYKJAVIK STUDY Large longitudinal population-based studies focused on ageing are rare since they are expensive and labor-intensive to carry out. This study type is, however, extremely valuable as it allows investigations with high statistical power. At the same time, they provide high external validity, since the participants of the study come from the general population with minimal inclusion bias. A substantial part of this thesis is focused on data from the Age-Gene/Environment Susceptibility (AGES)-Reykjavik study, a large population-based study.25 The AGES– Reykjavik study originates from the Reykjavik Study, a cohort established in 1967 to prospectively study cardiovascular disease in the general population of Iceland. Included participants were born between 1907 and 1935 and were living in Reykjavik in 1967. For the AGES-Reykjavik study, participants that were still alive were randomly selected for a follow-up between 2002 and 2006 when they underwent amongst other measures, a baseline brain MRI scan and cognitive assessment.26 Another visit took place between 2007 and 2011, where the same brain MRI protocol and the same cognitive assessments were repeated.27 Furthermore, the participants were followed for dementia outcome up to 13.4 years after the first MRI scan session through vital statistics and hospital records, and by the nursing home and homebased resident assessment instrument.28 The AGES-Reykjavik study is an extensive multidisciplinary study and includes besides neuroimaging and neurocognitive data also genetic, cardiovascular and musculoskeletal data.25 In the related chapters of this thesis, the focus will be on neuroimaging and neurocognitive data obtained as part of the AGES study.
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