10-Year Study Demonstrates Increased Rate of Cognitive Decline In Patients with Elevated Carotid Artery Pulse Intensity

A study led by Dr. Scott Chiesa published in the European Heart Journal showed that an elevated carotid artery intensity in mid-to-late life was associated with a faster rate of cognitive decline over long-term follow-up. This association was independent of other known cardiovascular risk factors.

Although cognitive impairment and dementia are one of the major contributors to morbidity and mortality, there is still known about its causes and risk factors. There is a need to understand the underlying mechanism leading to the progression of cognitive impairment and dementia in order to create strategies to target this pathway. There have been recent studies that showed an association between specific arterial phenotypes and an increased risk of dementia and accelerated cognitive decline.  This association may be even more pronounced in patients with multiple cardiovascular risk factors, where the arterial stiffening associated can intensify this effect. The authors sought to investigate whether there the intensity of the carotid artery pulse traveling towards the brain has an association with cognitive decline.

The Whilehall II study is an ongoing longitudinal study that followed patients between the ages of 33 and 55. Novel carotid wave intensity was measured in mid-to-late life in these patients. These patients were followed for up to 11 to 14 years. Carotid artery wave intensity was measured in 4,105 participants. Wave intensity (WI) provides a non-invasive measure of the net energy carried by waves within the arterial system. The authors focused on peak intensity (forward traveling compression wave intensity, FCWI). Cognitive function was also assessed at baseline and ten years later. The cognitive function test provides a comprehensive assessment of cognitive function and included memory, executive function, and fluency. Additionally, significant cognitive decline was also assessed and was defined as being in the top 15% of most rapid reductions in cognitive function. Patients were divided into quartiles according to their FCWI. The relationship between FCWI and cognitive decline was adjusted for various demographic, genetic and health-related risk factors.

The mean change and standard deviation in the cognitive score for the entire population were -0.39 (0.18). The investigators found that a higher FCWI at baseline was associated with a greater degree of cognitive decline after ten years. With every increase in the standard deviation of FCWI, there was a 0.02 decrease in the global cognitive score (95% CI -0.04-0.00, p = 0.03). This association was mainly driven by changes in patients with the highest FCWI score (4^th quartile vs 1^st-3^rd quartile = 0.05 decrease in the cognitive score (95% CI -0.09 to -0.01, p = 0.01). This was equivalent to an age effect of 1.9 years. Compared to participants in the lower three quartiles, the 4^th quartile exhibited around 50% of significant cognitive decline (Odds ratio 1.49, 95% CI 1.17-1.88).

In this longitudinal study, the investigators showed that an increased carotid FCWI was associated with a greater decrease in cognitive function for over ten years. This effect was more profound in patients in the highest quartile. There is evidence to suggest that the process underlying various forms of dementia including Alzheimer’s occurs decades before the first sign of dementia is present. The authors hypothesized that the increased pulsations that occur as a result of structural changes in the arteries could potentially damage the fragile microcirculation of the brain and subsequently lead to the development of cerebral small vessels. When discussing the clinical significance of these findings, the authors wrote “Our findings provide support for a link between cardiovascular health in mid- to late-life and risk of dementia in later life, and therefore, have important clinical implications. Given the well-publicized failure of multiple Phase III dementia outcome trials carried out in the later stages of the disease our findings highlight the importance of early strategies to slow or prevent vascular disease and cognitive decline.” Ultimately, Interventions to lower carotid artery FCWI could potentially delay the progression of cognitive decline.