Low-grade carotid artery stenosis is associated with progression of brain atrophy and cognitive decline. The SMART-MR study

Abstract

Asymptomatic low-grade carotid artery stenosis (LGCS) is a common finding in patients with manifest arterial disease, however its relationship with brain MRI changes and cognitive decline is unclear. We included 902 patients (58 ± 10 years; 81% male) enrolled in the Second Manifestations of Arterial Disease - Magnetic Resonance (SMART-MR) study without a history of cerebrovascular disease. LGCS was defined as 1-49% stenosis on baseline carotid ultrasound, whereas no LGCS (reference category) was defined as absence of carotid plaque. Brain and white matter hyperintensity (WMH) volumes and cognitive function were measured at baseline and after 4 (n = 480) and 12 years (n = 222) of follow-up. Using linear mixed-effects models, we investigated associations of LGCS with progression of brain atrophy, WMH, and cognitive decline. LGCS was associated with greater progression of global brain atrophy (estimate -0.03; 95%CI, -0.06 to -0.01; p = 0.002), and a greater decline in executive functioning (estimate -0.02; 95%CI, -0.031 to -0.01; p < 0.001) and memory (estimate -0.012; 95%CI, -0.02 to -0.001; p = 0.032), independent of demographics, cardiovascular risk factors, and incident brain infarcts on MRI. No association was observed between LGCS and progression of WMH. Our results indicate that LGCS may represent an early marker of greater future brain atrophy and cognitive decline.

Keywords: Brain atrophy; cognitive decline; cohort studies; low-grade carotid artery stenosis; white matter hyperintensity.

Figure 1.

Longitudinal relationship between executive functioning (z-score), low-grade carotid stenosis, and no stenosis. Age of patients at each visit was chosen as the time variable. The shaded grey area represents the 95% confidence interval. Results adjusted for sex, education level, large infarcts on MRI, lacunes on MRI, hypertension, diabetes mellitus, body mass index, smoking pack years, alcohol use and practice effect.

Figure 2.

Longitudinal relationship between memory (z-score), low-grade carotid stenosis, and no stenosis. Age of patients at each visit was chosen as the time variable. The shaded grey area represents the 95% confidence interval. Results adjusted for sex, education level, large infarcts on MRI, lacunes on MRI, hypertension, diabetes mellitus, body mass index, smoking pack years, alcohol use and practice effect.