Better Vascular Function Correlates with a Slower Decline of the Brain
Age-related declines in cardiovascular health correlate well with neurodegeneration, particularly vascular dementia. The brain is an energy-intensive organ, and reductions in delivery of nutrients have a definite impact. Beyond that there is also the matter of small-scale damage to tiny blood vessels that occurs as a result of dysfunction in the vascular system: rising blood pressure combined with failing mechanisms in blood vessel walls leads to ruptures that produce tiny areas of damage. A range of other mechanisms are also candidates for linking vascular health with brain health in later life. For here and now, one of the lessons to take away is that better maintenance of fitness and vascular health will likely also postpone cognitive decline in old age. It is further worth considering that any of the near future rejuvenation therapies capable of reversing loss of cardiovascular function will also likely help the brain.
Age-related decreases in vascular health are a common finding in the literature and represent one of many potential mechanisms that contribute to declines in the integrity of the aged brain. Identifying clinical markers of vascular health that serve as surrogate signs of brain health is paramount for early intervention and prevention efforts. Ideal markers of vascular health would be non-invasive, able to detect early changes in vascular function, easily administered in clinical settings, and related to neuroimaging techniques that are sensitive to age-related vascular decline.
Neuroimaging indicators of white matter (WM) health, including fractional anisotropy (FA) and WM hyperintensities (WMHs), are sensitive biomarkers of age-related vascular decline. WMHs are associated with increased pulse-wave velocity, a measure of conduit artery stiffness, and FA is significantly decreased in vascular disease. In addition, changes in FA appear to precede the manifestation of irreversible WM lesions, and are predictive of future cerebrovascular incidents. Despite this evidence, less is known about the relationship between these neuroimaging predictors and early detectors of cardiovascular disease, such as endothelial function.
The vascular endothelium is a single cell layer lining all blood vessels. It plays a critical role in regulating vascular tone by mediating the relationship between luminal blood flow and arterial smooth muscle. When compromised, the endothelium contributes to the pathogenesis of vascular disease. Advancing age is associated with endothelial dysfunction, and endothelial dysfunction is associated with Alzheimer's disease and vascular dementia. Moreover, blood markers of chronic endothelial dysfunction are associated with rarefaction of WM. Collectively, these findings suggest that endothelial function may play a critical role in combating age-related declines in brain health.
Endothelial function can be measured non-invasively through the use of digital pulse amplitude technology, which allows for the assessment of vascular function at the fingertip. This measure of peripheral arterial tone (PAT) is correlated with changes in vascular tone using flow-mediated dilation techniques. Little is known about the relationship between endothelial function and WM health. Endothelial cells mediate vessel caliber, and age-related endothelial dysfunction may induce vasoconstriction and chronic hypoperfusion of WM. Ischemia can then lead to myelin degeneration and selective oligodendrocyte death. Recent findings support this mechanism by demonstrating a relationship between microvessel caliber and normal appearing WM.
The Trail Making Test (TMT) is a reliable and valid assessment of executive function that is related to WM health and overall brain health. In the present study, we used a non-invasive measure of PAT to test the hypothesis that endothelial function is associated with WM health and executive function. We then expanded on these findings by exploring the potential relationships between a measure of executive function, the TMT, and both WM health and reactive hyperemia. Our results demonstrate that a peripheral measure of endothelial function, reactive hyperemia index (RHI), is positively correlated with WM microstructure in the corpus callosum in older adults, but is not related to WMH volume. The results from tractography analyses suggest that portions of the corpus callosum most strongly correlated with WM microstructure were those involved in higher-level cognitive processes. These findings motivate future longitudinal studies aimed to determine if increasing endothelial function, through lifestyle modification, attenuates age-related declines in WM microstructure and executive function.