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Abstract

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. Ann Neurol 2011;