Neuropathologic and clinical correlates of cerebral microbleeds in community‐based older adults

Abstract

Cerebral microbleeds (CMBs) are common in older adults and have been linked to hypertension, cognitive decline, and CAA. However, it remains unclear what the neuropathologic correlates of CMBs are in community-based older adults. The aim of this study was to determine the neuropathologic and clinical correlates of CMBs in community-based older adults when controlling for demographic factors, and also to investigate the relationship between neuropathologies and the location of CMBs in the brain. A total of 289 participants from two longitudinal cohort studies of aging, the Rush Memory and Aging Project and Religious Orders Study, were included in this work. Participants received annual clinical evaluation and cognitive assessment, ex-vivo MRI, and neuropathologic examination by a board-certified neuropathologist (blinded to clinical and imaging findings) on one brain hemisphere (Fig. 1). A total of 8 pathologies were assessed (Fig. 2). Manual identification of CMBs on ex-vivo T2*-weighted gradient echo images was done by an experienced rater blinded to all clinical and pathological information. The total number of CMBs as well as the number of CMBs per lobe were recorded for each participant. Poisson regression was used to investigate the associations of the total and regional number of CMBs with neuropathologies and clinical factors, controlling for demographics and postmortem interval. A significance threshold of p<0.01 was used after applying Bonferroni correction. The total number of CMBs in the whole brain was associated with CAA (beta=0.0517, p<0.0001), diabetes (beta=0.0997, p<0.0001), and arteriosclerosis (beta=0.0535, p=0.0007). The number of CMBs in the frontal lobe was also associated with CAA (beta=0.0796, p<0.0001), diabetes (beta=0.1531, p<0.0001), and arteriosclerosis (beta=0.0792, p<0.0001). The number of CMBs in the occipital and temporal lobes were correlated with diabetes (beta=0.2208, p=0.0006). In the basal ganglia, there was a slight association between number of microbleeds and microinfarcts (beta=0.1774, p=0.0075). The present study on the neuropathologic and clinical correlates of cerebral microbleeds combined detailed neuropathologic examination and ex-vivo MRI in a large number of community-based older adults. CMBs were shown to be associated with CAA, arteriosclerosis, and diabetes in the whole brain and in the frontal lobe.