171 Summary 9 Whether WMH shape is related to long-term progression of cerebrovascular disease in community-dwelling older adults was examined in Chapter 3 in a large population-based longitudinal study (the Age, Gene/Environment Susceptibility (AGES) Reykjavik study). The relationship of baseline WMH shape and WMH volume increase, different types of infarcts, microbleeds and enlarged perivascular spaces at follow-up were studied in this chapter. A more irregular shape of periventricular/ confluent WMH at baseline was associated with a larger increase in WMH volume over time, and with occurrence of new subcortical infarcts, new microbleeds, new enlargement of perivascular spaces, and new cerebellar infarcts at the 5.2-year follow-up. Furthermore, less elongated and more irregularly shaped deep WMHs were associated with a larger increase in WMH volume, and new cortical infarcts at followup. A less elongated shape of deep WMH was associated with new microbleeds at follow-up. Our findings show that WMH shape may be indicative of the type of cerebrovascular disease progression. This underlines the significance of WMH shape to aid in the prediction of cerebrovascular disease progression. 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 community-dwelling older adults in the AGES Reykjavik dataset. A more complex shape of periventricular/confluent WMH was related to cognitive decline in the memory domain, the executive function domain and the processing speed domain over 5.2 years. No associations were found between deep WMH shape and cognitive decline in any of the cognitive domains. These findings show that in community-dwelling older adults, WMH shape patterns may be indicative of cognitive decline in a relatively short time-frame. This supports the evidence of WMH shape being a valuable marker that may be used to predict cognitive outcome related to cerebrovascular disease progression. In Chapter 5, the association of baseline WMH shape and long-term dementia risk after 9.9 ± 2.6 years was assessed in community-dwelling older adults in the AGES Reykjavik study. A more irregular shape of periventricular/confluent WMH, higher periventricular/confluent WMH volume and higher deep WMH volume were associated with an increased long-term dementia risk. WMH shape markers may in the future be useful in determining patient prognosis and may aid in patient selection for future preventive treatments in community-dwelling older adults. In Chapter 6 brain MRI phenotypes were obtained using a hierarchical clustering method in community-dwelling older adults in the AGES Reykjavik dataset. In a second step, it was investigated whether these phenotypes were related to long-
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