74 Chapter 4 In the present study, the effect sizes of the associations between WMH shape and cognitive decline showed differences between cognitive domains. The effect sizes for the associations of WMH shape with memory and processing speed were roughly similar, while the effect sizes for executive function were relatively smaller. An explanation could be that different WMH shape patterns are related to different underlying pathology resulting in different effects on the brain, and possibly on different cognitive domains. SVD is a whole-brain disease and with MRI we are only able to capture the tip of the iceberg of the disease process. WMH shape could therefore convey additional information on why some cognitive domains are affected earlier or to a greater extent than others. In our study the effect sizes of the association between WMH markers and cognitive decline per domain are quite similar for WMH shape compared to WMH volume, especially for the WMH shape marker concavity index. As these associations were largely independent of WMH volume, this shows that WMH shape is an important and relevant additional marker besides WMH volume alone. Furthermore, in otherwise healthy older adults WMHs are commonly seen and at the moment the exact prognostic meaning for an individual is unclear. Since not all individuals with WMH will eventually develop cognitive decline or dementia, it is challenging to successfully identify individuals who are at a higher risk. Specific WMH patterns—defined by type and shape—may improve this early identification within risk-MR-phenotypes. A important strength of our study is the large cohort from the general population, which gives the study a large external validity and aids generalizability. Moreover, automated image processing techniques, in combination with extensive visual quality checks are other strengths of our study. Furthermore, the study contains a full neuropsychological assessment at two time points (baseline and follow-up). The use of a 1.5T MRI system could be considered a limitation of our study. While these systems were standard at the time of data collection, most 1.5T research MRI scanners have now been replaced with 3T MRI systems. Another limitation of our study could be selective loss to follow-up as participants who develop the most cognitive decline over time are most likely to be lost-to-follow-up. Nevertheless, despite these limitations significant associations between WMH shape markers and cognitive decline in different domains were found in our study. In conclusion, our findings show that WMH shape patterns may be indicative of relatively short-term cognitive decline in community-dwelling older adults. This supports the evidence of WMH shape being a valuable marker that may be used to assess and predict cognitive outcome related to cerebrovascular disease progression.
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