The vascular contribution to cognitive decline in ageing and dementia

There is increasing evidence to suggest that vascular dysfunction can contribute to cognitive decline in ageing and dementia. This dysfunction can take the form of a reduction of cerebral blood flow (CBF), a loss of blood–brain barrier (BBB) function or a combination of the two. Indeed, CBF and BBB changes may be causally linked, although this possible causality and its directionality are understudied. Appreciation of the role of vascular dysfunction in initiating cognitive decline in ageing and dementia, as well as the mechanisms involved, is important because it opens up new avenues for the development of much-needed therapies for these conditions, which are becoming major causes of death. Here we assess the evidence for the importance of vascular contributions to dementia, draw parallels with changes that occur in normal ageing and discuss the initiating cells and signalling mechanisms involved. We suggest that attempting to maintain or restore CBF should be a central aim of therapeutic strategies. Growing evidence suggests that reduced cerebral blood flow contributes to cognitive decline in ageing and dementia. Attwell and colleagues discuss the underlying mechanisms and functional consequences of vascular dysfunction in ageing, Alzheimer disease and vascular dementia, and consider the implications for therapeutic interventions.