Cerebral microbleeds: Prevalence and relationship to amyloid burden

Abstract

Objective: To describe the prevalence of cerebral microbleeds (CMBs) and determine the association between CMBs and β-amyloid burden on PET.

Methods: From the population-based Mayo Clinic Study of Aging, 1,215 participants (53% male) underwent 3-tesla MRI scans with T2* gradient recalled echo sequences from October 2011 to February 2017. A total of 1,123 participants (92%) underwent ¹¹C-Pittsburgh compound B (PiB)-PET scans. The prevalence of CMBs was derived by adjusting for nonparticipation and standardizing to the Olmsted County, MN, population. The relationship between β-amyloid burden and CMB presence and location was tested using logistic regression models. Ordinal logistic models tested the relationship between CMB frequency and β-amyloid burden.

Results: Two hundred seventy-four participants (22.6%) had at least one CMB. CMB frequency increased with age by decade (11% aged 60-69 years, 22% 70-79 years, and 39% 80 years and older). After adjusting for age, sex, and hypertension, PiB standardized uptake value ratio (SUVR) was associated with increased odds of a CMB. The association between PiB SUVR and CMBs was location-specific; PiB SUVR was associated with lobar CMBs but not deep CMBs. Age, hypertension, and PiB SUVR were associated with increasing CMB count. CMB density was greatest in parietal and occipital regions; β-amyloid burden correlated with concentration of CMBs in all lobar regions. Among participants with multiple CMBs, greater PiB uptake occurred in the pre- and postcentral gyri superiorly, the superior parietal lobe and precuneus, the angular gyrus, inferior temporal gyrus, and temporal poles.

Conclusions: The prevalence of CMBs increases with age. In this population-based sample, β-amyloid load was associated with lobar but not with deep CMBs.

Figure 1. Distribution of individual cerebral microbleeds at baseline

Figure 2. Three-dimensional brain renderings showing results of PiB-PET analysis in participants with multiple CMBs compared to those with no CMBs

Participants with multiple CMBs (≥2) had greater PiB-PET uptake in the left pre- and postcentral gyri superiorly, the superior parietal and precuneus bilaterally, the left angular gyrus, left inferior temporal gyrus, and bilateral temporal poles. Results shown after family-wise error correction at the cluster level, with higher t values shown in darker blue. Renders created using Brain Net Viewer (Xia et al.) (nitrc.org/projects/bnv/). CMB = cerebral microbleed; PiB = Pittsburgh compound B.