Many aspects of aging correlate with one another, only some of which are directly causally connected, rather than emerging from the same underlying cell and tissue damage that drives aging as a whole. We might expect dysfunction in the vascular system to contribute directly to neurodegeneration and loss of function in the brain. Stiffening of blood vessel walls causes hypertension, which in turn leads to a greater pace of rupture of capillaries throughout the body. Each of these events is individually insignificant, a very tiny stroke in effect, but this adds up over time. The more structural damage to the brain, the worse the outcome.
In recent years, through the growing investigations and the more in-depth understanding of aortic stiffness, it was found that aortic stiffness is not only related to increased risk of cardiovascular diseases and related mortality but also involved in the aging changes of brain and cognitive function. With advancing age, the aortic vessel wall's elastic fibers are gradually reduced and replaced by collagen fibers or deposition of calcification, which impairs aorta's elasticity and causes aortic stiffness. The stiffening and loss of recoil in the aorta would transmit excessive and damaging pulsatile load to the peripheral arteries of body organs. Theoretically, the brain is more susceptible to pulsatile damage due to its low-resistance and high-flow characteristics. Aortic stiffness was reported to be closely associated with cerebral structural changes, primarily the cerebral small vessel disease and brain atrophy. There have been studies that focus on the relationship between aortic stiffness and cognitive function. However, their results were inconsistent.
Among various pulse wave velocity (PWV) measurements for aortic stiffness, carotid-femoral PWV (cfPWV) that measure the PWV along the aortic and aortoiliac pathways is the recommended gold-standard non-invasive technique to assess aortic stiffness because of its reliability and feasibility, which is highly related with magnetic resonance imaging (MRI) directly measuring PWV. While brachial-ankle PWV (baPWV) or femorotibial PWV (ftPWV), the commonly used PWV index measured outside the main aortic track, reflects mainly the stiffness of the small arteries rather than pure aortic stiffness, its predicted value in cardiovascular disease is still controversial. Thus, considering the validation in clinic practice, we performed a systematic review and meta-analysis about the association between aortic stiffness measured using the validated aortic PWV and cognitive function, risk of cognitive impairment, or dementia to help clarify the association between aortic stiffness and cognitive function in the aging process.
Thirty-nine studies were included in the qualitative analysis, and 29 studies were included in the quantitative analysis. The aortic PWV was inversely associated with memory and processing speed in the cross-sectional analysis. In the longitudinal analysis, the high category of aortic PWV associated with a 44% increased risk of cognitive impairment compared with low PWV, and the risk of cognitive impairment increased 3.9% per 1 m/s increase in aortic PWV. Further, meta-regression analysis showed that age significantly increased the association between high aortic PWV and cognitive impairment risk.