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.