Carotid atherosclerosis and progression of brain atrophy: the SMART-MR study

OBJECTIVE: Atherosclerosis has been implicated in the development of brain atrophy. However, support for this association comes from cross-sectional studies.

METHODS: Within the Second Manifestations of ARTerial disease-Magnetic Resonance (SMART-MR) study, a prospective cohort study among patients with symptomatic atherosclerotic disease (mean age ± standard deviation, 58 ± 10 years; 80% men), magnetic resonance imaging of the brain was performed in 1,232 patients at baseline (2001-2005) and in 663 patients at follow-up (2006-2009). Brain segmentation was used to quantify total brain volume, cortical gray matter volume, and ventricular volume as indicators of global, cortical, and subcortical atrophy. At baseline, measurements of carotid intima-media thickness (CIMT) and carotid stenosis were performed. Carotid stenosis was classified into groups 0 of 50%, 50 of 70% (moderate), and >70% (severe) and into unilateral or bilateral stenosis.

RESULTS: Cross-sectional regression analyses showed that both increased CIMT and carotid stenosis were associated with decreased relative total brain and cortical gray matter volume. Our prospective findings showed that after a mean follow-up of 3.9 years (range, 3.0-5.8 years), CIMT and moderate stenosis were not related to progression of brain atrophy. Only severe or bilateral carotid stenosis was related to progression of global atrophy (β [95% confidence interval (CI)], -0.52% [-0.84 to -0.20%], -0.94% [-1.45 to -0.43%]), cortical atrophy (β [95% CI], -0.75% [-1.37 to -0.13%], -1.34% [-2.32 to -0.35%]), and subcortical atrophy (β [95% CI], 0.06% [-0.02 to 0.16%], 0.13% [0.01 to 0.28%]).

INTERPRETATION: In a study of patients with atherosclerotic disease with 4 years of follow-up, only severe or bilateral carotid stenosis, and not moderate carotid stenosis and increased CIMT, were associated with progression of brain atrophy.