Genetics of Vascular Cognitive Impairment.

Vascular dementia (VAD) is the second most common cause of dementia after Alzheimer’s and accounts at least 20% of dementia cases. Lesser degrees of cognitive decline due to cerebrovascular disease are even more common, and the umbrella term Vascular Cognitive Impairment (VCI) has been introduced to cover all degrees of cognitive impairment due to cerebrovascular disease, from mild impairment through to dementia.(1) In the same way that stroke is a heterogeneous disease caused by multiple different pathological processes, VCI also results from many different vascular pathologies. In principle any disease process causing cerebral ischaemia or haemorrhage can cause VCI. Neuroimaging and pathological studies have allowed division of VCI mechanisms into a number of broad groups including multiple infarcts, single strategic infarcts, intracerebral haemorrhage, hypoperfusion, and cerebral small vessel disease.(1) It is now recognised that by far the most common pathology underlying VCI is cerebral small vessel disease (SVD)(1), which is most readily seen on MRI as white matter hyperintensities and lacunar infarcts although other features which may contribute to cognitive decline include atrophy and cerebral microbleeds (CMB). In addition many of the pathologies causing SVD also predispose to intracerebral haemorrhage which itself can contribute to cognitive decline. The most popular hypothesis is that these diverse subcortical pathologies lead to damage to white matter pathways, which disrupts complex distributed cortical–subcortical circuits underlying cognitive processes such as executive function and processing speed. (2) Cerebral amyloid angiopathy (CAA) also affects the cerebral small vessels, and causes intracerebral haemorrhage and has been associated with VCI and dementia. (1)Supported by British Heart Foundation programme Grant to HSM (RG/16/4/32218 )