Vascular risk factors and dementia: how to move forward?

Abstract

In recent years, accumulating evidence has suggested that vascular risk factors contribute to Alzheimer disease (AD). Vascular dementia had been traditionally considered secondary to stroke and vascular disease. It has been traditionally distinguished from AD, considered to be a purely neurodegenerative form of dementia. However, in light of this more recent literature, it appears that there is a spectrum: ranging from patients with pure vascular dementia to patients with pure AD and including a large majority of patients with contributions from both Alzheimer and vascular pathologies. In this article, we discuss the impact of vascular risk factors on AD and its consequences at the individual level and at the population level by highlighting the concept of attributable risk. We then discuss the key questions and next steps involved in designing a therapeutic trial to control vascular risk factors for the prevention of dementia.

Figure Reconsidering the classification of dementia Schematic diagram of common dementias depicts proposed alternative classification of dementia. Alzheimer disease (AD) and vascular dementia (VaD) fall on a continuous spectrum of disease, composed of a gradient of features of both AD and VaD (center panel; see text for detailed discussion). Neurodegenerative mechanisms play a greater role on the left side of the spectrum (upper panel). The impact of subcortical lesions of cerebral small-vessel disease increases to the right of the spectrum (lower panel). Note white matter hyperintensities on FLAIR sequences (left), lacunar lesions on T1-weighted sequences (arrowheads, center), and cerebral microhemorrhages on gradient-echo sequences (arrowheads, right). These silent brain lesions may, in part, mediate the risk of dementia associated with vascular risk factors.