Vascular contributions to cognitive impairment, clinical Alzheimer's disease, and dementia in older persons

Abstract

There is growing evidence suggesting that vascular pathologies and dysfunction play a critical role in cognitive impairment, clinical Alzheimer's disease, and dementia. Vascular pathologies such as macroinfarcts, microinfarcts, microbleeds, small and large vessel cerebrovascular disease, and white matter disease are common especially in the brains of older persons where they contribute to cognitive impairment and lower the dementia threshold. Vascular dysfunction resulting in decreased cerebral blood flow, and abnormalities in the blood brain barrier may also contribute to the Alzheimer's disease (AD) pathophysiologic process and AD dementia. This review provides a clinical-pathological perspective on the role of vessel disease, vascular brain injury, alterations of the neurovascular unit, and mixed pathologies in the Alzheimer's disease pathophysiologic process and Alzheimer's dementia. This article is part of a Special Issue entitled: Vascular Contributions to Cognitive Impairment and Dementia edited by M. Paul Murphy, Roderick A. Corriveau and Donna M. Wilcock.

Keywords: Alzheimer's disease; Dementia; Mixed pathologies; Neuropathology; Vascular.

Fig. 1.

A schematic representation showing the additive effect of vascular pathologies in the brain acts as “hits” and lowers the threshold for developing dementia. As aging in the brain occurs there is a threshold for developing dementia. Additional vascular “hits” lowers this threshold, thus accelerating the onset of dementia.