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Neuroimaging Correlates of Cerebral Microbleeds: The ARIC Study (Atherosclerosis Risk in Communities)
Jonathan Graff-Radford1, Jeannette Simino2, Kejal Kantarci2
1From the Departments of Neurology (J.G.R., D.S.K.) and Radiology (K.K., C.R.J., P.V.), Mayo Clinic, Rochester, MN; Department of Data Science, Gertrude Ford MIND Center (J.S., M.E.G.) and Department of Medicine (T.H.M., B.G.W.), University of Mississippi Medical Center, Jackson; Department of Neurology (M.S.A., R.F.G.), Johns Hopkins University, Baltimore, MD; and Department of Epidemiology (A.R.S., R.F.G.), Johns Hopkins Bloomberg School of Public Health, Baltimore, MD. GraffRadford.Jonathan@mayo.edu.
Background And Purpose:
Cerebral microbleed (CMB) location (deep versus strictly lobar) may elucidate underlying pathology with deep CMBs being more associated with hypertensive vascular disease and lobar CMBs being more associated with cerebral amyloid angiopathy. The objective of this study was to determine whether neuroimaging signs of vascular disease and Alzheimer pathology are associated with different types of CMBs.
Methods:
Among 1677 nondemented ARIC (Atherosclerosis Risk in Communities) participants (mean age=76±5 years; 40% men; 26% black) with 3-Tesla MRI scans at the fifth examination (2011-2013), we fit multinomial logistic regression models to quantify relationships of brain volumes (Alzheimer disease signature regions, total gray matter, frontal gray matter, and white matter hyperintensity volumes), infarct frequencies (lacunar, nonlacunar, and total), and apolipoprotein E (number of ε4 alleles) with CMB location (none, deep/mixed, or strictly lobar CMBs). Models were weighted for the sample selection scheme and adjusted for age, sex, education, hypertension, ever smoking status, diabetes mellitus, race site membership, and estimated intracranial volume (brain volume models only).
Results:
Deep/mixed and strictly lobar CMBs had prevalences of 8% and 16%, respectively. Larger white matter hyperintensity burden, greater total infarct frequency, smaller frontal volumes (in women only), and smaller total gray matter volume were associated with greater risk of both deep and lobar CMBs relative to no CMBs. Greater white matter hyperintensity volume was also associated with greater risk of deep relative to lobar CMBs. Higher lacunar and nonlacunar infarct frequencies were associated with higher risk of deep CMBs, whereas smaller Alzheimer disease signature region volume and apolipoprotein E ε4 homozygosity were associated with greater risk of lobar CMBs.
Conclusions:
CMBs are a common vascular pathology in the elderly. Markers of hypertensive small-vessel disease may contribute to deep CMBs while cerebral amyloid angiopathy may drive development of lobar CMBs.
Insights
Cerebral microbleeds (CMBs) in older adults are linked to different underlying pathologies. Deep CMBs suggest hypertensive disease, while lobar CMBs indicate cerebral amyloid angiopathy, impacting Alzheimer
Area of Science:
- Neurology
- Radiology
- Gerontology
Background:
- Cerebral microbleeds (CMBs) are common in the elderly.
- CMB location may indicate underlying pathology: deep CMBs with hypertensive vascular disease, lobar CMBs with cerebral amyloid angiopathy.
Purpose of the Study:
- To investigate the association between neuroimaging signs of vascular disease and Alzheimer pathology with different CMB locations.
Main Methods:
- Analysis of 3-Tesla MRI scans from 1677 nondemented Atherosclerosis Risk in Communities (ARIC) participants.
- Multinomial logistic regression models used to assess relationships between brain volumes, infarct frequencies, apolipoprotein E status, and CMB location (none, deep/mixed, strictly lobar).
- Models were weighted and adjusted for various demographic and clinical factors.
Main Results:
- Larger white matter hyperintensity burden and greater infarct frequency were associated with increased risk of both deep and lobar CMBs.
- Deep CMBs were linked to higher lacunar and nonlacunar infarct frequencies.
- Lobar CMBs were associated with smaller Alzheimer disease signature region volume and apolipoprotein E ε4 homozygosity.
Conclusions:
- Hypertensive small-vessel disease markers may contribute to deep CMBs.
- Cerebral amyloid angiopathy may drive the development of lobar CMBs.
- CMB location provides insights into associated pathologies in the elderly.
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