Novel MRI markers of small vessel disease in relation to Alzheimer’s disease

Abstract

AbstractBackgroundVascular brain injury, particularly small vessel disease (SVD), is a common cause of cognitive decline and is detected on brain MRI in the majority of patients with dementia, including Alzheimer’s disease (AD). Established MRI markers of SVD related brain injury are white matter hyperintensities, lacunar infarcts, microbleeds and enlarged perivascular spaces. Yet, these MRI markers clearly do not cover the full extent of SVD related injury. Also, these lesions represent an end‐stage of injury to the parenchyma, rather than the actual abnormalities that occur in the small vessels themselves. In my presentation I will address a novel marker of more subtle parenchymal injury, cortical microinfarcts (CMI), and emerging markers of cerebral small vessel function.MethodsEstimates from autopsy studies are that 100s to 1000s of CMI may be present in the brain of a single affected individual. High field strength imaging on 7Tesla MRI and further developments onto 3Tesla MRI has enabled in vivo detection of the largest CMI, and MRI rating criteria have been published. 7Tesla MRI is also used to zoom in on the small vessels themselves, and markers of cerebral small vessel function are emerging.ResultsMRI studies in patients with a clinical diagnosis of AD observe a CMI prevalence ranging between 8‐55%. These studies allow to investigate potential causes and consequences of CMI for the first time in vivo. It appears that CMI relate with worse clinical outcome and may be caused by various etiologies, including hypoperfusion, microemboli, and SVD pathology, in particular cerebral amyloid angiopathy. The novel measures of small vessel function that will be reviewed include measures of small vessel reactivity, and measures of blood flow velocity and pulsatility in individual penetrating arteries (diameter 100‐800 µm). Initial studies show abnormalities of these measures in patients when compared with healthy controls. I will review ongoing studies in patients with hereditary and sporadic SVD that aim to establish the value of these small vessel function markers in clinical research.ConclusionWith these efforts we aim to advance insight into disease processes in SVD to help better understand the mechanisms underlying cognitive impairment and dementia.