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January 15, 2019; 92 (3) Article

Cerebral microbleeds

Prevalence and relationship to amyloid burden

Jonathan Graff-Radford, Hugo Botha, Alejandro A. Rabinstein, Jeffrey L. Gunter, Scott A. Przybelski, Timothy Lesnick, John Huston, Kelly D. Flemming, Gregory M. Preboske, Matthew L. Senjem, Robert D. Brown, Michelle M. Mielke, Rosebud O. Roberts, Val J. Lowe, David S. Knopman, Ronald C. Petersen, Walter Kremers, Prashanthi Vemuri, Clifford R. Jack, Kejal Kantarci
First published December 19, 2018, DOI: https://doi.org/10.1212/WNL.0000000000006780
Jonathan Graff-Radford
From the Departments of Neurology (J.G.-R., H.B., A.A.R., K.D.F., R.D.B., M.M.M., R.O.R., D.S.K., R.C.P.), Radiology (J.L.G., J.H., G.M.P., M.L.S., V.J.L., P.V., C.R.J., K.K.), and Health Sciences Research (S.A.P., T.L., M.M.M., R.O.R., W.K.), Mayo Clinic, Rochester, MN.
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Hugo Botha
From the Departments of Neurology (J.G.-R., H.B., A.A.R., K.D.F., R.D.B., M.M.M., R.O.R., D.S.K., R.C.P.), Radiology (J.L.G., J.H., G.M.P., M.L.S., V.J.L., P.V., C.R.J., K.K.), and Health Sciences Research (S.A.P., T.L., M.M.M., R.O.R., W.K.), Mayo Clinic, Rochester, MN.
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Alejandro A. Rabinstein
From the Departments of Neurology (J.G.-R., H.B., A.A.R., K.D.F., R.D.B., M.M.M., R.O.R., D.S.K., R.C.P.), Radiology (J.L.G., J.H., G.M.P., M.L.S., V.J.L., P.V., C.R.J., K.K.), and Health Sciences Research (S.A.P., T.L., M.M.M., R.O.R., W.K.), Mayo Clinic, Rochester, MN.
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Jeffrey L. Gunter
From the Departments of Neurology (J.G.-R., H.B., A.A.R., K.D.F., R.D.B., M.M.M., R.O.R., D.S.K., R.C.P.), Radiology (J.L.G., J.H., G.M.P., M.L.S., V.J.L., P.V., C.R.J., K.K.), and Health Sciences Research (S.A.P., T.L., M.M.M., R.O.R., W.K.), Mayo Clinic, Rochester, MN.
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Scott A. Przybelski
From the Departments of Neurology (J.G.-R., H.B., A.A.R., K.D.F., R.D.B., M.M.M., R.O.R., D.S.K., R.C.P.), Radiology (J.L.G., J.H., G.M.P., M.L.S., V.J.L., P.V., C.R.J., K.K.), and Health Sciences Research (S.A.P., T.L., M.M.M., R.O.R., W.K.), Mayo Clinic, Rochester, MN.
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Timothy Lesnick
From the Departments of Neurology (J.G.-R., H.B., A.A.R., K.D.F., R.D.B., M.M.M., R.O.R., D.S.K., R.C.P.), Radiology (J.L.G., J.H., G.M.P., M.L.S., V.J.L., P.V., C.R.J., K.K.), and Health Sciences Research (S.A.P., T.L., M.M.M., R.O.R., W.K.), Mayo Clinic, Rochester, MN.
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John Huston III
From the Departments of Neurology (J.G.-R., H.B., A.A.R., K.D.F., R.D.B., M.M.M., R.O.R., D.S.K., R.C.P.), Radiology (J.L.G., J.H., G.M.P., M.L.S., V.J.L., P.V., C.R.J., K.K.), and Health Sciences Research (S.A.P., T.L., M.M.M., R.O.R., W.K.), Mayo Clinic, Rochester, MN.
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Kelly D. Flemming
From the Departments of Neurology (J.G.-R., H.B., A.A.R., K.D.F., R.D.B., M.M.M., R.O.R., D.S.K., R.C.P.), Radiology (J.L.G., J.H., G.M.P., M.L.S., V.J.L., P.V., C.R.J., K.K.), and Health Sciences Research (S.A.P., T.L., M.M.M., R.O.R., W.K.), Mayo Clinic, Rochester, MN.
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Gregory M. Preboske
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Matthew L. Senjem
From the Departments of Neurology (J.G.-R., H.B., A.A.R., K.D.F., R.D.B., M.M.M., R.O.R., D.S.K., R.C.P.), Radiology (J.L.G., J.H., G.M.P., M.L.S., V.J.L., P.V., C.R.J., K.K.), and Health Sciences Research (S.A.P., T.L., M.M.M., R.O.R., W.K.), Mayo Clinic, Rochester, MN.
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Robert D. Brown Jr
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Michelle M. Mielke
From the Departments of Neurology (J.G.-R., H.B., A.A.R., K.D.F., R.D.B., M.M.M., R.O.R., D.S.K., R.C.P.), Radiology (J.L.G., J.H., G.M.P., M.L.S., V.J.L., P.V., C.R.J., K.K.), and Health Sciences Research (S.A.P., T.L., M.M.M., R.O.R., W.K.), Mayo Clinic, Rochester, MN.
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Rosebud O. Roberts
From the Departments of Neurology (J.G.-R., H.B., A.A.R., K.D.F., R.D.B., M.M.M., R.O.R., D.S.K., R.C.P.), Radiology (J.L.G., J.H., G.M.P., M.L.S., V.J.L., P.V., C.R.J., K.K.), and Health Sciences Research (S.A.P., T.L., M.M.M., R.O.R., W.K.), Mayo Clinic, Rochester, MN.
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Val J. Lowe
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David S. Knopman
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Ronald C. Petersen
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Walter Kremers
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Prashanthi Vemuri
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Clifford R. Jack Jr
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Kejal Kantarci
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Citation
Cerebral microbleeds
Prevalence and relationship to amyloid burden
Jonathan Graff-Radford, Hugo Botha, Alejandro A. Rabinstein, Jeffrey L. Gunter, Scott A. Przybelski, Timothy Lesnick, John Huston, Kelly D. Flemming, Gregory M. Preboske, Matthew L. Senjem, Robert D. Brown, Michelle M. Mielke, Rosebud O. Roberts, Val J. Lowe, David S. Knopman, Ronald C. Petersen, Walter Kremers, Prashanthi Vemuri, Clifford R. Jack, Kejal Kantarci
Neurology Jan 2019, 92 (3) e253-e262; DOI: 10.1212/WNL.0000000000006780

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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.

Glossary

AD=
Alzheimer disease;
ANTs=
Advanced Normalization Tools;
ARIA-H=
amyloid-related imaging abnormalities–hemosiderin;
CAA=
cerebral amyloid angiopathy;
CMB=
cerebral microbleed;
GRE=
gradient recalled echo;
MCALT=
Mayo Clinic Adult Lifespan Template;
MCSA=
Mayo Clinic Study of Aging;
PiB=
Pittsburgh compound B;
SUVR=
standardized uptake value ratio

Footnotes

  • Go to Neurology.org/N for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.

  • Editorial, page 121

  • CME Course: NPub.org/cmelist

  • Received March 16, 2018.
  • Accepted in final form September 10, 2018.
  • © 2018 American Academy of Neurology
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