Effects of Carotid Artery Stiffness on Cerebral Small-Vessel Disease and Cognition

Abstract

BACKGROUND: Carotid artery stiffness is associated with cognitive impairment and dementia, but the underlying mechanisms remain unknown. We examined the associations of carotid artery stiffness with cerebral small-vessel disease markers, cognition, and dementia subtypes in a memory clinic cohort. METHODS AND RESULTS: A total of 272 participants underwent carotid ultrasonography, 3 Tesla brain magnetic resonance imaging, and neuropsychological assessment. Carotid ultrasonography was used to assess β-index, pressure-strain elastic modulus, and pulse-wave velocity-β. Brain magnetic resonance images were graded for cerebral small-vessel disease markers, including white matter hyperintensities, lacunes, and cerebral microbleeds. Participants were classified as having no cognitive impairment, cognitive impairment and no dementia, or dementia subtyped as Alzheimer disease and vascular dementia. Cognition was assessed using National Institute of Neurological Disorders and Stroke– Canadian Stroke Network harmonization battery. After adjusting for age, sex, cardiovascular risk factors, and diseases, multivariable models showed that β-index (β=0.69; P=0.002), elastic modulus (β=0.78; P<0.001), and pulse-wave velocity-β (β=0.80; P<0.001) were associated with white matter hyperintensities, and elastic modulus (odds ratio [OR], 1.39 [95% CI, 1.04–1.85]) and pulse-wave velocity-β (OR, 1.47 [95% CI, 1.10–1.98]) were independently associated with lacunes. Similarly, β-index (OR, 2.04 [95% CI, 1.14– 4.13]), elastic modulus (OR, 2.22 [95% CI, 1.25– 4.42]), and pulse-wave velocity-β (OR, 2.50 [95% CI, 1.36– 5.18]) were independently associated with vascular dementia. Carotid stiffness measures were independently associated with worse performance in global cognition, visuomotor speed, visuospatial function, and executive function. These associations became largely nonsignificant after further adjusting for cerebral small-vessel disease markers. CONCLUSIONS: In memory clinic patients, carotid artery stiffness was associated with white matter hyperintensities and lacunes, impairment in global and domain-specific cognition, and causative subtypes of dementia, particularly vascular. The effects of carotid stiffness on cognition were not independent of, and were partially mediated by, cerebral small-vessel disease.