Neurovascular coupling unit dysfunction and dementia: Retinal measurements as tools to move towards population-based evidence

Dysfunction of the neurovascular coupling unit may be an important contributor to dementia. The neurovascular coupling unit comprises neuronal structures (e.g. astrocytes) and vascular structures (e.g. endothelial cells) that functionally interact both at the level of the arterioles as well as at the capillary level (blood-brain barrier) to regulate optimal metabolic conditions in the brain. However, it remains unclear how and to what extent dysfunction of the neurovascular coupling unit contributes to the early-stage pathobiology of dementia. Currently, limited data are available on the association between neurovascular coupling unit dysfunction, as quantified by cerebral imaging techniques, and cognitive performance. In particular, there is a lack of population-based human data (defined as studies with a sample size ~n>500). This is an important limitation because population-based studies, in comparison with smaller clinical studies, provide data which is better representative of the general population; are less susceptible to selection bias; and have a larger statistical power to detect small associations. To acquire population-based data, however, alternative imaging techniques than cerebral imaging techniques may be required. Disadvantages of cerebral imaging techniques, which limit use in population-based studies, are that these techniques are relatively expensive, time-consuming, and/or invasive. In this review, we propose that retinal imaging techniques can be used for population-based studies: on the one hand the retina and brain have many anatomical and physiological similarities; and on the other hand retinal imaging techniques are non-invasive, highly accurate, relatively inexpensive, and require relatively short measurement time. To provide support for this concept, we provide an overview on the human (population-based) evidence on the associations of retinal indices of neurodegeneration, microvascular dysfunction, and dysfunction of the neurovascular coupling unit with magnetic resonance imaging (MRI) features of structural brain abnormalities and cognitive performance.