Incidental cerebral microbleeds and cerebral blood flow in elderly individuals

Abstract

IMPORTANCE: Cerebral microbleeds (CMBs) are collections of blood breakdown products that are a common incidental finding in magnetic resonance imaging of elderly individuals. Cerebral microbleeds are associated with cognitive deficits, but the mechanism is unclear. Studies show that individuals with CMBs related to symptomatic cerebral amyloid angiopathy have abnormal vascular reactivity and cerebral blood flow (CBF), but, to our knowledge, abnormalities in cerebral blood flow have not been reported for healthy individuals with incidental CMBs. OBJECTIVE: To evaluate the association of incidental CMBs with resting-state CBF, cerebral metabolism, cerebrovascular disease, β-amyloid (Aβ), and cognition. DESIGN, SETTING, AND PARTICIPANTS: A cross-sectional study of 55 cognitively normal individuals with a mean (SD) age of 86.8 (2.7) years was conducted from May 1, 2010, to May 1, 2013, in an academic medical center in Pittsburgh; data analysis was performed between June 10, 2013, and April 9, 2015. INTERVENTIONS: 3-Tesla magnetic resonance imaging was performed with susceptibility-weighted imaging or gradient-recalled echo to assess CMBs, arterial spin labeling for CBF, and T1- and T2-weighted imaging for atrophy, white matter hyperintensities, and infarcts. Positron emission tomography was conducted with fluorodeoxyglucose to measure cerebral metabolism and Pittsburgh compound B for fibrillar Aβ. Neuropsychological evaluation, including the Clinical Dementia Rating scale, was performed. MAIN OUTCOMES AND MEASURES: Magnetic resonance images were rated for the presence and location of CMBs. Lobar CMBs were subclassified as cortical or subcortical. Measurements of CBF, metabolism, and Aβ were compared with the presence and number of CMBs with voxelwise and region-of-interest analyses. RESULTS: The presence of cortical CMBs was associated with significantly reduced CBF in multiple regions on voxelwise and region-of-interest analyses (percentage difference in global CBF, -25.3%; P = .0003), with the largest reductions in the parietal cortex (-37.6%; P < .0001) and precuneus (-31.8%; P = .0006). Participants with any CMBs showed a nonsignificant trend toward reduced CBF. Participants with cortical CMBs had a significant association with greater prevalence of infarcts (24% vs 6%; P = .047) and demonstrated a trend to greater prevalence of deficits demonstrated on the Clinical Dementia Rating scale (45% vs 19%; P = .12). There was no difference in cortical amyloid (measured by Pittsburgh compound B positron emission tomography) between participants with and without CMBs (P =.60). CONCLUSIONS AND RELEVANCE: In cognitively normal elderly individuals, incidental CMBs in cortical locations are associated with widespread reductions in resting-state CBF. Chronic hypoperfusion may put these people at risk for neuronal injury and neurodegeneration. Our results suggest that resting-state CBF is a marker of CMB-related small-vessel disease.