98 Chapter 5 explain why we found a lower deep WMH volume in the occipital lobe in participants who developed dementia at follow-up. Based on the current and previous findings,13, 22, 18 there is evidence that WMH shape has additional diagnostic value compared to WMH volume alone. WMH shape could be used as a non-invasive independent marker next to other markers of SVD for identification of patients at risk for dementia. Identified patients at risk could undergo lifestyle changes in order to limit progression of SVD and cognitive decline.3, 5 Specific WMH patterns could also aid as surrogate markers for future drug trails aimed at treatment or prevention of SVD.4 A strength of the current study is the large sample size based on the general population, which gives the study significant external validity. Moreover, the long follow-up period and the use of automated image processing techniques, in combination with visual quality checks, are other strengths. A limitation of the study could be the use of a 1.5 Tesla MRI scanner, which was a common field strength for clinical scanners at the time of the baseline scans. Even though lower-field-strength scans with a lower resolution could have resulted in a less accurate WMH shape estimation, we reported significant associations with long-term dementia. In conclusion, we demonstrated that WMH shape is a promising marker in addition to WMH volume in relation to dementia risk. A more irregular shape of periventricular/ confluent WMHs and higher WMH volumes were associated with long-term increased dementia risk in community-dwelling older adults. These findings suggest that WMH shape markers may in the future be useful in determining patient prognosis and may aid in patient selection for future preventive treatments. 5.6 ACKNOWLEDGMENTS The authors want to thank Myriam Jaarsma-Coes for her help with the software. The Age, Gene/Environment Susceptibility- Reykjavik Study was supported by NIH contracts N01-AG-1-2100 and HHSN27120120022C, the NIA Intramural Research Program, Hjartavernd (Icelandic Heart Association), and Althingi (Icelandic Parliament). This work was supported by an Alzheimer’s Nederland grant (WE.032019-08) to Jeroen de Bresser.
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