Cerebral Small Vessel Disease as a General Microvascular Issue Rather than a Specifically Atherosclerotic Issue

The aging of large blood vessels in the brain, and their resulting dysfunctions, are quite different from those of the small vessels, the microvasculature. Large vessels are predominantly affected by atherosclerosis, the buildup of fatty plaques that weaken and narrow blood vessels, leading to the catastrophic structural failure of a stroke. Small vessels, on the other hand, appear to be affected by a collection of mechanisms that cause functional deterioration, such as pathological amyloid deposition, with atherosclerosis as only one of that list of harmful processes. This is the point made in the open access paper here, in any case, in which the authors emphasize that cerebral small vessel disease is not as well understood as researchers would like it to be.

Cerebral small vessel disease (SVD) is a leading cause of cognitive decline and functional loss in the elderly. Cerebral SVD is recognised by the resultant parenchymal lesions rather than the underlying small vessel alterations themselves, and typically manifests as lacunar lesions, diffuse white matter lesions (leucoaraiosis) and/or microbleeds. Accordingly, cerebral white matter hyperintensities (WMH) on MRI scan are recognised surrogates of cerebral SVD. Although the aetiopathogenic mechanisms of cerebral SVD are unclear, there is a clear distinction from cerebral large vessel disease. Indeed, with the exception of hypertension, conventional cardiovascular risk factors such as diabetes and hyperlipidaemia have inconsistent correlation with cerebral SVD. Further, after accounting for age and the traditional vascular risk factors, much of the variance in WMH volume remains unexplained.

Cerebral WMH predict incident stroke, dementia, heart failure, disability, and mortality. Despite the lack of correlation with conventional cardiovascular risk factors and with no supporting evidence base, current treatment strategies for managing cerebral WMH are extrapolated from the general management guidelines for the treatment of atherosclerotic disease. As a result, treatment strategies focusing on the use of antiplatelet, statins, aggressive blood pressure (BP) lowering and (in people with diabetes) aggressive glycaemic control may not be effective in the treatment of cerebral SVD. The absence of specific treatments for cerebral SVD precipitates the need for clear targets or strategies for the treatment of cerebral SVD.

We propose the search for such targets should focus on the underlying pathology of cerebral SVD, focusing specifically on the regulation of cerebral microcirculation. However, in order to identify potential treatment strategies, knowledge of the systemic correlates of cerebral SVD is required. As WMH are present in patients with and without history of previous CVD, we aimed to explore this in a general population sample of older adults enriched with patients with proven cerebral SVD.

Link: https://doi.org/10.18632/aging.203557

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