Abstract
AimsExcessive arterial pulsatility may contribute to cognitive decline and risk of dementia via damage to the fragile cerebral microcirculation. We hypothesized that the intensity of downstream-travelling pulsatile waves measured by wave intensity analysis in the common carotid artery during mid- to late-life would be associated with subsequent cognitive decline.Methods and resultsDuplex Doppler ultrasound was used to calculate peak forward-travelling compression wave intensity (FCWI) within the common carotid artery in 3191 individuals [mean ± standard deviation (SD), age = 61 ± 6 years; 75% male] assessed as part of the Whitehall II study in 2003–05. Serial measures of cognitive function were taken between 2002–04 and 2015–16. The relationship between FCWI and cognitive decline was adjusted for sociodemographic variables, genetic and health-related risk factors, and health behaviours. Mean (SD) 10-year change in standardized global cognitive score was -0.39 (0.18). Higher FCWI at baseline was associated with accelerated cognitive decline during follow-up [difference in 10-year change of global cognitive score per 1 SD higher FCWI = −0.02 (95% confidence interval −0.04 to −0.00); P = 0.03]. This association was largely driven by cognitive changes in individuals with the highest FCWI [Q4 vs. Q1–Q3 = −0.05 (−0.09 to −0.01), P = 0.01], equivalent to an age effect of 1.9 years. Compared to other participants, this group was ∼50% more likely to exhibit cognitive decline (defined as the top 15% most rapid reductions in cognitive function during follow-up) even after adjustments for multiple potential confounding factors [odds ratio 1.49 (1.17–1.88)].ConclusionElevated carotid artery wave intensity in mid- to late-life predicts faster cognitive decline in long-term follow-up independent of other cardiovascular risk factors.
Highlights
Cognitive impairment and dementia are major contributing factors to morbidity and mortality in the elderly, but the causes and risk factors responsible for their development are still poorly understood
Recent cross-sectional[2,3,4,5] and prospective[6,7,8] studies suggest a potential link between arterial phenotypes in mid-life and the development of adverse structural brain changes, accelerated cognitive decline, and increased risk of dementia.[7,9,10,11,12]. This relationship may become more pronounced from middle-age, when a combination of vascular ageing and long-term exposure to cardiovascular disease (CVD) risk factors interact to augment the intensity of arterial pulsatility via a disproportionate stiffening of the aorta and the subsequent transmission of excess wave energy into the major arteries supplying the brain.[13,14]. While this association is supported by studies using surrogate markers such as aortic pulse-wave velocity and carotid pulse pressure (PP),[2,6,7,11] a direct relationship between the likely mechanism responsible for downstream small vessel damage—an increase in the intensity of pulsatile waves travelling through the carotid arteries towards the brain—and future cognitive decline has never been examined
We investigated this relationship in a large cohort of adults recruited to the Whitehall II study; an ongoing longitudinal study of >3000 participants with novel carotid wave intensity measures performed in mid- to-late-life and in whom serial measures of cognitive function were available over 11–14 years of follow-up
Summary
Cognitive impairment and dementia are major contributing factors to morbidity and mortality in the elderly, but the causes and risk factors responsible for their development are still poorly understood. Recent cross-sectional[2,3,4,5] and prospective[6,7,8] studies suggest a potential link between arterial phenotypes in mid-life and the development of adverse structural brain changes, accelerated cognitive decline, and increased risk of dementia.[7,9,10,11,12] This relationship may become more pronounced from middle-age, when a combination of vascular ageing and long-term exposure to cardiovascular disease (CVD) risk factors interact to augment the intensity of arterial pulsatility via a disproportionate stiffening of the aorta and the subsequent transmission of excess wave energy into the major arteries supplying the brain.[13,14] While this association is supported by studies using surrogate markers such as aortic pulse-wave velocity and carotid pulse pressure (PP),[2,6,7,11] a direct relationship between the likely mechanism responsible for downstream small vessel damage—an increase in the intensity of pulsatile waves travelling through the carotid arteries towards the brain—and future cognitive decline has never been examined. We hypothesized that the peak intensity of the carotid artery forwardtravelling compression wave in mid- to late-life would be associated with subsequent cognitive decline, and in particular that those with the highest forward compression wave intensity (FCWI) would exhibit the most pronounced decline in cognitive function, independent of other well-established cardiovascular risk factors
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