Jasmin Annica Kuhn-Keller

142 Chapter 7 7.1 ABSTRACT Sporadic cerebral small vessel disease (SVD) has heterogeneous underlying pathology and current SVD MRI markers do not accurately capture this heterogeneity. Novel ultra-high field (7T) brain MRI markers provide a window of opportunity to study early changes and potential determinants of SVD. White matter hyperintensity (WMH) shape is a relatively novel MRI marker of SVD and has shown prognostic potential. However, the exact microstructural changes within or surrounding WMHs or potential causes related to WMH shape variations are unknown. Furthermore, impaired brain clearance via the recently discovered brain glymphatic system may be another early change or potential cause of SVD. In the WHIMAS (white matter hyperintensity shape and glymphatics study) we aim to study the link between WMH and especially their shape with brain clearance and other MRI markers on ultra-high field (7T) brain MRI and show if these markers are associated with cognitive functioning in older adults with memory complaints. The WHIMAS is a cross-sectional study that will be conducted at the Leiden University Medical Center (LUMC). Fifty outpatients from the memory/geriatric clinic, aged 65 years or older will be recruited for a 3T and a 7T MRI scan, as well as a standardised neuropsychological test battery (domains: memory, executive function, visuoconstruction, and processing speed). We will assess WMH shape markers (solidity, convexity, concavity index, fractal dimension, and eccentricity) and brain clearance markers (CSF-BOLD-coupling, CSF-mobility) and study their relation to other MRI markers and cognitive functioning. We aim to understand variations in WMH shape and find their relation to cerebral SVD and markers of brain clearance and cognitive functioning. These markers early in the disease process of SVD are extremely important as they may represent a basis for future patient selection for lifestyle interventions or for treatment trials aimed at prevention of dementia.

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