50 Chapter 3 The difference of the results depending on WMH type might support the notion that deep and periventricular/confluent WMH are resulting from different underlying pathologies.26,27 Different baseline WMH shape patterns were associated with progression of different cerebrovascular disease markers at the 5-year follow-up, which shows that WMH shape might be indicative of the type of cerebrovascular disease progression at an early stage. The strengths of the current study are the automatic assessment of WMH shape and volume, and the longitudinal study design with a relatively long follow-up. Significant external validity is added to the study by the large sample size from the general population. A limitation of the current study is the use of a 1.5T MRI system, which was a common field strength for clinical MRI scanners at the time of data collection. MRI images with a lower signal-to-noise ratio or spatial resolution could have resulted in a less accurate WMH shape estimation. However, we have reported on significant associations with cerebrovascular disease markers despite this limitation. Another limitation of our study is that lacunes were not scored separately, but were scored in the category of subcortical infarcts. However, we expect the possible effect of this to be small as the prevalence of large subcortical infarct is very low. Another limitation of our study could be that the strength of the associations found in the current study may have been influenced and weakened by selective loss to follow-up. It is likely that participants who had died, refused or were not eligible for a follow-up MRI were less healthy than the participants who did undergo the follow-up. This could have resulted in an underestimation of the associations shown in our study. In conclusion, our findings show that WMH shape may be indicative of the type of cerebrovascular disease marker progression. This underlines the significance of WMH shape to aid in the assessment of cerebrovascular disease progression. 3.6 ACKNOWLEDGEMENTS The AGES study was funded by National Institutes of Health-contract N01-AG-1-2100, the National Institute on Aging Intramural Research Program, Hjartavernd, and the Icelandic Parliament. This work was supported by an Alzheimer Nederland grant (WE.03-2019-08) to Jeroen de Bresser. 3.7 DISCLOSURE M.J.P. van Osch reports to be an unpaid member of a clinical trial steering committee of Alnylam.
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