THE INDEPENDENT EFFECT OF CEREBRAL MICROBLEEDS ON COGNITION

Abstract

The presence of small vessel disease (SVD) is associated with cognitive impairment. However, among the many components of SVD, the contribution of CMBs to cognitive impairment remain elusive. Our aim was to determine if cerebral microbleeds (CMBs) contribute to global and specific cognitive domains in addition to that contributed by other measures of small vessel disease burden in an Asian cohort. Subjects participating in a multimodal imaging study having a diagnosis of mild cognitive impairment (MCI), mild Alzheimer's disease (AD) or healthy control (HC) were recruited. CMB were quantified on SWI images, while white matter hyperintensity (WMH) and lacunes were quantified on FLAIR images. All quantifications were performed by a single neurologist blinded to the clinical and cognitive measures. Cognitive measures included global cognition (Montreal Cognitive Assessment), frontal cognition (Frontal Assessment Battery, Color Trails and Digit Span) and non-frontal cognition (Delayed recall and Block Design) were evaluated. The interactions among variables were determined using linear regression analysis, adjusted for age, educational level, and the presence of SVD. Subsequently, the isolated effects of CMBs (location and number) on specific cognitive domains were analyzed. 143 subjects (37 MCI, 56 mild AD and 50 HC) with a mean age of 64 years and mean years of education of 11 years were analyzed. Subjects with mild AD had the highest WMH burden compared to MCI and controls (5.9±3.8 vs. 4.4±3.6 vs. 3.7±3.0; p=0.005). CMB load was highest among AD, followed by HC and MCI. The presence of CMBs acted as an independent predictor for worsening non-frontal cognition among patients with SVD (β=-0.8; p=0.038). At the multivariable level, the total number of lobar CMBs was correlated to worsening global cognitive scores (β=-0.2; p=0.021), after adjusting for demographics, educational level and other parameters of SVD. Educational level was negatively associated with cognitive decline (p<0.001). The presence of chronic lacunes was negatively correlated with frontal cognition (β=-1.1; p=0.038). CMBs contribute to cognitive impairment in MCI and AD, specifically to non-frontal cognition independent of WMH and lacunes.