Ultrasound and dynamic functional imaging in vascular cognitive impairment and alzheimer's disease

Background: The vascular contributions to neurodegeneration and neuroinflammation may be assessed by magnetic resonance imaging (MRI) and ultrasonography (US). This consensus statement summarizes the methodology for these widely available, safe and relatively low cost tools and reviews recent work highlighting their potential utility as biomarkers for differentiating subtypes of cognitive impairment and dementia, tracking disease progression, and evaluating response to treatment in various neurocognitive disorders. Methods: At the 9th International Congress on Vascular Dementia Ljubljana, Slovenia, October 2015) a writing group of experts was formed to develop a consensus statement on the utility of US and arterial spin labeling (ASL) as neurophysiological markers of normal ageing, vascular cognitive impairment (VCI) and Alzheimer's disease (AD). Original articles, systematic literature reviews, guidelines and expert opinions published until January 2016 were critically analysed to summarize existing evidence, indicate gaps in current knowledge, and, when appropriate, suggest standards of use for the most widely used US and ASL applications. Results: Cerebral hypoperfusion has been linked to cognitive decline either as a risk or an aggravating factor. Hypoperfusion as a consequence of microangiopathy, macroangiopathy or cardiac dysfunction, can promote or accelerate neurodegeneration, blood-brain barrier disruption and neuroinflammation. US can evaluate the cerebrovascular tree for pathological structure and functional changes contributing to cerebral hypoperfusion. Microvascular pathology and hypoperfusion at the level of capillaries and small arterioles can also be assessed by ASL, an MRI- signal. Despite increasing evidence supporting the utility of these methods in detection of microvascular pathology, cerebral hypoperfusion, neurovascular unit dysfunction and, most importantly, disease progression, incomplete standardization and missing validated cut off values limit their use in daily routine. Conclusions: US and ASL are promising tools with excellent temporal resolution, which will have a significant impact on our understanding of the vascular contributions to VCI and AD and may also be relevant for assessing future prevention and therapeutic strategies for these conditions. Our final conclusion refers to recommendations regarding the use of non-invasive imaging techniques to investigate the functional consequences of vascular burden in dementia.