Abstract
AIMS: Excessive 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 RESULTS: Duplex 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)]. CONCLUSION: Elevated carotid artery wave intensity in mid- to late-life predicts faster cognitive decline in long-term follow-up independent of other cardiovascular risk factors.