White matter lesions and lacunar infarcts are independently and differently associated with brain atrophy: the SMART-MR study.

Objective: To investigate the independent association of white matter lesions (WML) and lacunar infarcts (LI) with measures of global brain atrophy on MRI.

Methods: Within the SMART-MR study, a cohort study among patients with manifest arterial disease, cross-sectional analyses were performed in 840 patients (mean age 58 +/- 10 years, 80% male) without cortical, large subcortical or infratentorial infarcts. Brain segmentation was used to quantify volumes of brain tissue, cerebrospinal fluid and WML. Total brain volume, ventricular volume and cortical gray matter volume were divided by intracranial volume to obtain brain parenchymal fraction (BPF), ventricular fraction (VF) and cortical gray matter fraction (GMF). Location and number of infarcts were rated visually.

Results: Mean +/- SD BPF was 79.3 +/- 2.8%, mean +/- SD VF was 2.01 +/- 0.95%, and mean +/- SD GMF was 36.6 +/- 3.3%. Linear regression analyses, adjusted for age, sex, vascular risk factors, intima media thickness and LI showed that in patients with moderate to severe WML (upper quartile) BPF was lower (-0.51%; 95% CI -0.93 to -0.08%), VF was higher (0.48%; 95% CI 0.31-0.65%) and GMF was lower (-1.48%; 95% CI -2.07 to -0.88%) than in patients with few WML (lower quartile). Presence of LI was associated with lower BPF (-0.52%; 95% CI -0.96 to -0.07%) and higher VF (0.25%; 95% CI 0.07-0.42%), but not with GMF, independent of WML and other potential confounders.

Conclusion: WML are associated with total, subcortical and cortical brain atrophy, whereas LI are associated with total and subcortical atrophy, but not with cortical atrophy, suggesting an independent role for WML and LI in the pathogenesis of brain atrophy.