143 Study protocol of the WHIMAS 7 7.2 STRENGTHS AND LIMITATIONS OF THIS STUDY • In depth study of the link between white matter hyperintensities and especially their shape with brain clearance and other MRI markers on ultra-high field (7T) brain MRI in a memory clinic population. • Advanced and novel imaging techniques will be used both at 3T and ultra-high field (7T) MRI combined with novel advanced image processing techniques. • In depth study of the relation between white matter hyperintensity shape and glymphatics markers and cognitive functioning. • This observational study serves to steer future investigations and could be extended into a longitudinal study. • The studied markers early in the disease process of cerebral small vessel disease 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. 7.3 INTRODUCTION Dementia is often characterized by a combination of neurovascular and neurodegenerative disease processes and mixed pathologies are common.1 The most common mixed pathology is Alzheimer’s dementia (AD) and cerebral small vessel disease (SVD).2,3 SVD contributes to the clinical phenotype of dementia in around 45% of dementia cases.2–4 There are two main types SVD in an ageing population. One is SVD due to arteriolosclerosis, often related to hypertension.5 The other one is cerebral amyloid angiopathy, characterized by progressive amyloid accumulation in the vessel walls.5 Current SVD markers, such as white matter hyperintensities of presumed vascular origin (WMH), are unspecific and they fail to accurately capture the heterogeneity of SVD pathology. Therefore, novel brain MRI markers are needed to identify early changes and potential determinants of SVD. These markers are extremely important early in the disease process of SVD as they may represent a basis for future patient selection for lifestyle interventions or as outcome markers for treatment trials (such as currently being developed for cerebral amyloid angiopathy6 aimed at prevention of dementia. WMH are the key brain MRI manifestation of cerebral SVD.7 Around 92% of all individuals over 60 years of age have WMHs8–10 and a higher WMH burden is a risk factor for occurrence of stroke and dementia.10 Especially the volume of WMH has been extensively studied, but this is a generic and non-specific marker that only has modest prognostic value.11 Although there is considerable variation in the shape of WMH, this marker has received only little attention.12 Recent studies have shown that normal appearing white matter around WMH that will progress on follow-up
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