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Middle aged carotid plaque and cognitive functions in later life: a population-based study.

Shin, G.; Siddiquee, A. T.; Lee, M.-H.; Kang, J. C.; Hwang, Y.; Lee, S.; Kim, B.; Kim, Y.; Shin, C.; Kim, N.

2026-03-23 neurology
10.64898/2026.03.23.26349039 medRxiv
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Background and ObjectivesCarotid plaque reflects systemic atherosclerosis and may serve as an early marker of cognitive decline, but its longitudinal association with cognitive trajectories remains unclear. We investigated whether carotid plaque status (small-to-medium size) was associated with cognitive performance over time in a population-based cohort. MethodsThis prospective cohort study followed-up neuropsychological assessment battery quadrennially in two cycles (2015-2018 and 2019-2022) from the baseline (2011-2014). Of 2,819 participants, 2,176 participants who were free of dementia and cerebrovascular disease at baseline with cognitive function testing at least two time points over the follow-up time were analyzed. Carotid plaque assessed by B-mode ultrasound sonography five segments were scanned in both left and right sides. The plaques were graded based on vessel thickness and the diameter of the lumen (none, small-to-medium, and large). We categorized our participants into without (none) and with the plaques (small-to-medium, and large combined) at baseline. The main outcomes were multivariable adjusted mean differences of cognitive test performances by baseline plaque status over time. The neuropsychological assessment battery included story recall, visual reproductions, verbal fluency, trail making, digit symbol - coding, and Stroop tests. ResultsOf the total, 291 (13.4%) participants had carotid plaque at baseline. There were no differences at baseline and 4-year. At 8-year follow-up, participants with carotid plaque performed significantly worse than participants without carotid plaque in visual reproduction delayed recall [mean difference -0.525 (95% CI: -0.915 to -0.135), p=.008], Stroop word reading [mean difference -2.732 (95% CI: -5.164 to -0.300), p=.028] and color reading [mean difference -3.573 (95% CI: -5.199 to -1.948), p<.001]. Additionally, participants with carotid plaque performed lower than those without carotid plaque on logical memory delayed recall [mean difference -1.577 (95% CI: -2.843 to -0.311), p=.015] at 8-year follow-up period. DiscussionIn this large cohort study, carotid plaque status at baseline was independently associated with in cognitive function decline, especially in non-verbal memory and executive functioning over 8-year follow-up period in the general population. Therefore, it may be important for earlier intervention on carotid plaque to preserve neurological health in middle-aged to older population.

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