Ultrasound and dynamic functional imaging in vascular cognitive impairment and Alzheimer’s disease

Abstract

BackgroundThe vascular contributions to neurodegeneration and neuroinflammation may be assessed by magnetic resonance imaging (MRI) and ultrasonography (US). This review summarises the methodology for these widely available, safe and relatively low cost tools and analyses 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.MethodsAt the 9th International Congress on Vascular Dementia (Ljubljana, Slovenia, October 2015) a writing group of experts was formed to review the evidence on the utility of US and arterial spin labelling (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 September 2016 were critically analysed to summarise existing evidence, indicate gaps in current knowledge and, when appropriate, suggest standards of use for the most widely used US and ASL applications.ResultsCerebral 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 standardisation and missing validated cut-off values limit their use in daily routine.ConclusionsUS 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 work provides recommendations regarding the use of non-invasive imaging techniques to investigate the functional consequences of vascular burden in dementia.

Update on the Neurobiology of Vascular Cognitive Impairment: From Lab to Clinic

“…A widespread decrease in CBF has been found in VaD, especially in bilateral frontal and parietal areas, but also in confluent WMLs [67] and post-stroke patients [68]. Moreover, ASL patterns seem to follow the progression of cognitive decline, suggesting a promising role as a biomarker of disease progression [64]. However, due to the low perfusion levels and long arterial arrival times in the white matter, to date the ASL is considered not as sensitive to perfusion changes in the deep white matter as in the cortex [69].…”

“…Regions of neuroinflammatory disruption of BBB, quantified and visualized by dynamic contrast-enhanced MRI [63], resulted in a significantly increased BBB permeability in VCI patients compared to controls [54]. Moreover, cerebral hypoperfusion as a consequence of microangiopathy, macroangiopathy or cardiac failure, can promote or accelerate BBB disruption, neuroinflammation, and neurodegeneration [64,65]. In this context, the arterial spin labelling (ASL) is a modern MRI technique that allows brain perfusion to be measured non-invasively at the tissue level and to assess intracranial vascular compliance [66].…”

“…Finally, previous studies have applied transcranial Doppler ultrasound (TCD) to explore the relationship between cerebral hemodynamics and brain lesions attributed to small vessel disease in cognitive disorders [64,[130][131][132]. As known, TCD is a non-invasive and feasible neurosonological technique able to evaluate CBF velocity, arterial perfusion integrity, and intracranial small vessel compliance [133,134].…”

“…As known, TCD is a non-invasive and feasible neurosonological technique able to evaluate CBF velocity, arterial perfusion integrity, and intracranial small vessel compliance [133,134]. The microangiopathy, demonstrated both in VaD and AD, might lead to arteriolosclerosis, vasoconstriction, and vascular stiffness, thus resulting in decreased arterial diameter and CBF [64,135,136]. In a recent TCD study [137], mild VCI patients showed a hemodynamic pattern of cerebral hypoperfusion and enhanced vascular resistance, likely arising from small vessels and then extending to larger arteries.…”

Nanotherapy for Early Dementia: Targeting Senile Dementia

“…This therapeutic approach receives added impetus from continual findings of cerebrovascular pathology (Beishon et al 2017;Goldwaser et al 2016;Hishikawa et al 2016;Kapasi and Schneider 2016;Kelleher and Soiza 2013;Malojcic et al 2017;McAleese et al 2016;Muche et al 2017;Nelson et al 2016;Nielsen et al 2017;Noh et al 2016;Perrotta et al 2016;Raz et al 2016;Weekman et al 2016) and brain arterial aging (Calabrese et al 2016;Cooper and Mitchell 2016;Gutierrez et al 2016;Kelleher and Soiza 2013;Malojcic et al 2017;Nagata et al 2016;Raz et al 2016;Toth et al 2017) accompanying Alzheimer's disease. Similarly, there is an apparent endothelium-dysfunction involvement Bhat 2015;Carradori et al 2016;Chao et al 2016;Devraj et al 2016;Di Marco et al 2015;Festoff et al 2016;Gangoda et al 2016;Hishikawa et al 2016;Hostenbach et al 2016;Kahlil et al 2016;Kelleher and Soiza 2013;Koizumi at al.…”