144 Chapter 7 MRI scans, already showed changes in structural integrity and hemodynamics at baseline.13,14 Furthermore, WMH typically localize at vascular endzones and progress along more proximal parts of the perforating arteries.15 How the perforating arteries are affected depends on the underlying pathological changes, such as large vessel atheromas at the origin of perforating arteries, small vessel atheromas or microembolisms.16,17 These pathological changes may lead to hypoperfusion, defective cerebrovascular reactivity, and blood-brain barrier dysfunction,11 which in turn may be related to increase of WMH and thus also changes in their shape.12,17 Previous studies have also indicated that WMH shape may provide a better indication of underlying pathophysiological mechanisms than WMH volume alone and may harbor strong prognostically relevant information.12,18–20 SVD is a heterogeneous disease with many possible underlying causes. An important factor leading to brain changes in SVD might be impaired clearance of waste products, which has been linked to aging and dementia pathology.7 The process of brain clearance is postulated to be partly driven by the glymphatic system, where cerebrospinal fluid (CSF) and interstitial fluid ‘flush’ brain tissue and transport waste products out of the brain via perivascular spaces. Some first studies have shown that in cerebral amyloid angiopathy and Alzheimer’s dementia glymphatic function might be impaired.21 Currently, brain clearance related processes can only be studied invasively in humans, for example by contrast-enhanced MRI following intrathecal injection.22 This limitation made it difficult to implement research related to glymphatic dysfunction into clinical study protocols. However, recently developed novel ultra-high field (7T) brain MRI markers provide a window of opportunity to study the human glymphatic system in a non-invasive way. 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 high field (3T) and ultra-high field (7T) brain MRI. Furthermore, we aim to study the relation between WMH shape and glymphatics markers and cognitive functioning. Studying these imaging markers in SVD is important because at an early stage cerebral SVD is a target for preventive treatment that may postpone or even prevent the occurrence of dementia and stroke. Our study contributes to the first steps in this research into early detection of dementia. We specifically strive for early detection of the potentially treatable/modifiable part of the dementia pathology, namely SVD. Previous studies have already shown that early lifestyle interventions in populations at risk can slow the pathophysiological processes of cerebral SVD.23–25 However, it is currently impossible to non-invasively identify individuals who have an increased risk of dementia at an early stage of the disease and who may benefit most
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