Blood pressure increases with age, driven by loss of elasticity in blood vessels, among other things, leading to the medical condition of hypertension. Here, researchers examine the complex associations between higher blood pressure and greater loss of cognitive function in later life; while it is well known that hypertension damages the physical structure of the brain, to pick one example, when it comes to the end result of cognitive decline a full catalog of the contributing factors and how these processes interact in detail has yet to be established. That said, it is certainly possible to accelerate the progression of higher blood pressure by leading a sedentary lifestyle or becoming overweight, and both of those line items correlate well with greater cognitive decline. While that much is under our control, there is unfortunately all too little that can be done about stiffening of blood vessels at the present time. Real progress on that front will require implementation of some of the SENS rejuvenation therapies, such as a way to break down the cross-links that build up in the extracellular matrix of blood vessel walls.
Despite strong evidence for a positive association between midlife hypertension and late-life cognitive impairment, the relationship between late-life hypertension and cognitive function remains unclear. Observed inconsistencies between studies partly reflect variations in study design and populations. Another likely factor is unmeasured heterogeneity, within populations, as regard the timing and duration of exposure to hypertension, which in turn could influence its effects and potential modifiability. Such investigations would benefit from a proxy measure representing the duration of exposure to hypertension. A potential proxy or surrogate measure is pulse pressure (PP), partly reflecting arterial stiffness, measured as the difference between systolic blood pressure (SBP) and diastolic blood pressure (DBP). PP is potentially a better measure of the chronic effects of hypertension than blood pressure itself. PP increases with age and is associated with a number of cardiovascular risk factors and outcomes. Arterial stiffness appears related to Alzheimer's disease (AD) pathology, providing a potential vascular marker that is more closely related to AD than other cardiovascular measures. However, evidence remains conflicted as to the association of cognitive performance with arterial stiffness, whether measured as PP or through ultrasound determined pulse wave velocity.
Here, we explored the relationships between longitudinal change in PP and cognitive performance in multiple cognitive domains over 5 years and how these relationships were influenced by initial (baseline) blood pressure (BP). As an increase in PP typically reflects significant vascular remodeling and stiffening, we hypothesized that those with increasing PP over time would have a greater decline in cognition. When evaluating distinct longitudinal profiles of PP change over the same time period and accounting for attrition, we identified differences in cognitive change that (1) varied by trajectory of PP change, (2) varied by cognitive domain, (3) varied by age, between the youngest-old and oldest-old, and (4) was significantly influenced by baseline SBP. Importantly, we found that an increasing or persistently high PP was associated with less cognitive decline than in those with low, stable PP but only if baseline SBP was below the median. However, in those starting with higher baseline SBP, it was age, rather than PP group, that influenced cognitive decline the most, with increasing age being associated with greater decline. These findings underscore the importance of identifying the sources of heterogeneity within a population to understand the complex relationships between late life vascular health and cognitive decline and possibly help explain some of the discrepancies in the literature.
The four PP trajectory groups that we identified appear to capture the major categories along a spectrum of possible patterns (stable high or low and increasing or decreasing). They also suggest that different pathways to a specific PP level, rather than the PP itself, have distinct implications for cognition. We can only speculate about the potential mechanisms underlying the noted associations between PP and cognition. These results might indicate that with advancing age, which is also associated with an age-related arterial stiffening, that cognitive function, particularly executive function, becomes increasingly reliant on an additional mechanisms such as adequate cardiac output. However, with advancing age and chronic exposure to higher PP this eventually becomes detrimental, as was supported by the findings in those starting with higher SBP. This was supported by a recent study showing that those with previously elevated SBP were at greatest risk for having evidence of regional white matter changes that support executive cognitive function. In the groups with slowly and rapidly increasingly PP, there was a general pattern of less decline in cognitive function that was most pronounced in those starting at lower SBP. Our findings support speculation that an initial elevation in PP might in fact provide some protection against the effects of hypoperfusion on cognition, particularly in the oldest-old.