Association of Ischemic Imaging Phenotype With Progression of Brain Atrophy and Cerebrovascular Lesions on MRI: The SMART-MR Study

Background and Objective

To investigate the association of silent vascular lesions, imaging negative ischemia, and symptomatic cerebrovascular disease with long-term progression of brain atrophy and cerebrovascular lesions in patients with arterial disease.


Within the Second Manifestations of Arterial Disease–Magnetic Resonance (SMART-MR) study, stroke status of participants at baseline was classified as no cerebrovascular disease (reference group, n = 829), symptomatic cerebrovascular disease (n = 206), silent vascular lesion (n = 157), and imaging-negative ischemia (n = 90) according to clinical and MRI findings. With the use of linear mixed models, changes in brain and white matter hyperintensity (WMH) volumes at baseline and during 12 years of follow-up were studied in stroke classifications. Relative risks were estimated for new infarcts during follow-up associated with stroke classifications. Analyses were adjusted for age, sex, cardiovascular risk factors, and medications.


Symptomatic cerebrovascular disease associated with 0.35 SD (95% confidence interval [CI] 0.24–0.47) smaller brain volume and 0.61 SD (95% CI 0.48–0.74) larger WMH volume at baseline and increased risk for new infarcts during follow-up (risk ratio [RR] 2.89, 95% CI 2.00–4.16). Silent vascular lesions were associated with 0.15 SD (95% CI 0.01–0.88) smaller brain volume, 0.02 SD (95% CI 0.01–0.03) steeper brain atrophy slope, and 0.48 SD (95% CI 0.32–0.64) larger WMH volume at baseline, in addition to increased risk for lacunes (RR 2.08, 95% CI 1.48–2.94). Individuals with imaging-negative ischemia had increased risk for cortical infarcts (RR 2.88, 95% CI 2.17–3.82).


Patients with symptomatic cerebrovascular disease, silent vascular lesions, or imaging-negative ischemia have a different course of brain volume loss and cerebrovascular lesion development. These findings may have implications for future stroke risk and dementia and need further investigation.

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