Elevated markers of atherosclerosis and lower carotid distensibility associated with dementia
Association of Carotid Intima-Media Thickness and Other Carotid Ultrasound Features With Incident Dementia in the ARIC-NCS
Introduction and methods
There is a growing body of literature that suggests that atherosclerosis is associated with increased risk of dementia [1-3]. In addition, arterial stiffening may contribute to the development of cerebral small-vessel disease which could influence brain function [4,5]. This study assessed the relationship between carotid measurements (carotid intima-media thickness [cIMT], interadventitial diameter [IAD] and presence of carotid plaque) and arterial stiffness (measured as carotid distensibility) with incident dementia.
This analysis included 12 459 participants from the ARIC (Atherosclerosis Risk in Communities) study. The ARIC study is a population-based cohort with White and Black individuals from 4 communities in the US [6]. Arterial indices were measured at baseline (between 1990 and 1992) and participants were followed for a median of 24 years. Included participants in this analysis had no prevalent CV events, prevalent dementia or missing carotid measurements or missing covariate information at baseline. The mean age of included participants was 57 years at baseline, 57% were women and 23% were Black. During follow-up, dementia was ascertained either by in-person cognitive assessments at ARIC visits, by Telephone Instrument of Cognitive Status - modified telephone interviews or informant interviews, or on the basis of ICD hospitalization discharge codes or death certificate codes.
Main results
- Participants in the highest quintile of cIMT (>0.85 mm) had an increased risk of incident dementia compared to participants in the lowest quintile (>0.60 mm), after multivariable adjustments (HR 1.25, 95%CI 1.08-1.13). Abnormal cIMT (defined as >0.9 mm) was associated with increased risk of incident dementia (HR 1.15, 95%CI 1.03-1.29), compared with normal cIMT.
- Highest quintile of IAD (8.36-13.43 mm) was also associated with an increased risk of incident dementia compared to the lowest quintile (<6.89 mm), after multivariable adjustments (HR 1.22, 95%CI 1.04-1.43).
- In a model where all vessel measures were included, cIMT continuous per 1 SD increment was an independent predictor for dementia (HR 1.08, 95%CI 1.03-1.13), while IAD continuous per 1 SD increment was not (HR 1.02, 95%CI 0.95-1.09).
- Presence of carotid plaque was not associated with incident dementia after multivariable adjustments.
- Higher distensibility was associated with lower dementia risk. Highest quintile of carotid distensibility (>21.95 10^-3/kPa) was associated with a lower risk of incident dementia compared to the lowest quintile (<11.31 10^-3/kPa), after multivariable adjustments (HR 0.76, 95%CI 0.63-0.91). In addition, carotid distensibility per 1 SD increment was an independent predictor of dementia when all vessel measures were included in the model (HR 0.89, 95%CI 0.84-0.95).
Conclusion
This analysis in a community-based cohort showed that elevated cIMT and IAD and lower carotid distensibility were associated with increased risk of incident dementia. Presence of carotid plaque was not associated with incident dementia. cIMT and carotid distensibility were independent predictors of dementia, while IAD was not. However, the authors also mention that it is possible that atherosclerosis and arterial stiffness are not truly independent risk factors for dementia. They could also be markers that reflect lifetime exposure to vascular risk factors, which are in turn linked to dementia.
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