TY - JOUR
T1 - Cerebral microbleeds
T2 - Prevalence and relationship to amyloid burden
AU - Graff-Radford, Jonathan
AU - Botha, Hugo
AU - Rabinstein, Alejandro A.
AU - Gunter, Jeffrey L.
AU - Przybelski, Scott A.
AU - Lesnick, Timothy
AU - Huston, John
AU - Flemming, Kelly D.
AU - Preboske, Gregory M.
AU - Senjem, Matthew L.
AU - Brown, Robert D.
AU - Mielke, Michelle M.
AU - Roberts, Rosebud O.
AU - Lowe, Val J.
AU - Knopman, David S.
AU - Petersen, Ronald C.
AU - Kremers, Walter
AU - Vemuri, Prashanthi
AU - Jack, Clifford R.
AU - Kantarci, Kejal
N1 - Funding Information:
J. Graff-Radford: funded by the National Institute on Aging of the NIH under award K76AG057015. H. Botha, A. Rabinstein, J. Gunter, S. Przybelski, T. Lesnick, J. Huston III, K. Flemming, G. Preboske, M. Senjem, and R. Brown, Jr. report no disclosures relevant to the manuscript. M. Mielke reports consulting for Lysosomal Therapeutics Inc. and Eli Lilly and Company and receiving research funding from the NIH, Biogen, and Roche. R. Roberts reports receiving research funding from the NIH, Roche, and Biogen. V. Lowe reports consulting for Bayer Schering Pharma, Merck Research, and Piramal Imaging Inc. and receives research support from GE Healthcare, Siemens Molecular Imaging, Avid Radiopharmaceuticals, the NIH (National Institute on Aging, National Cancer Institute), the Elsie and Marvin Dekelboum Family Foundation, the Liston Family Foundation, and the MN Partnership for Biotechnology and Medical Genomics. D. Knopman receives research support from the NIH and the Robert H. and Clarice Smith and Abigail Van Buren Alzheimer’s Disease Research Program of the Mayo Foundation. He serves on a data safety monitoring board for Lundbeck Pharmaceuticals and for the Dominantly Inherited Alzheimer Network study and is an investigator in clinical trials sponsored by Biogen, TauRx Pharmaceuticals, Lilly Pharmaceuticals, and the Alzheimer’s Disease Treatment and Research Institute, University of Southern California. R. Petersen works as a consultant for Merck Inc., Roche Inc., Biogen Inc., Eli Lilly and Company, and Genentech Inc.; receives publishing royalties for Mild Cognitive Impairment (Oxford University Press, 2003); and receives research support from the NIH and the Robert H. and Clarice Smith and Abigail Van Buren Alzheimer’s Disease Research Program of the Mayo Foundation. W. Kremers reports receiving research funding from AstraZe-neca, Biogen, and Roche. P. Vemuri receives research funding from the NIH. C. Jack, Jr. receives research funding from the NIH and the Alexander Family Alzheimer’s Disease Research Professorship at Mayo Clinic, and consults for Eli Lilly and serves on the data safety monitoring board for Roche but accepts no honoraria for these services. K. Kantarci serves on the data safety monitoring board for Takeda Global Research & Development Center, Inc., and receives research support from the NIH. Go to Neurology.org/N for full disclosures.
Funding Information:
Research reported in this publication was supported by the National Institute on Aging of the NIH under award K76AG057015 and the NIH (AG006786, AG011378, NS097495, AG16574), and the GHR Foundation. The study was also made possible using the resources of the Rochester Epidemiology Project (NIA/NIH grant AG034676).
Publisher Copyright:
© American Academy of Neurology 2018.
PY - 2019/1/15
Y1 - 2019/1/15
N2 - ObjectiveTo describe the prevalence of cerebral microbleeds (CMBs) and determine the association between CMBs and β-amyloid burden on PET.MethodsFrom 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.ResultsTwo 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.ConclusionsThe prevalence of CMBs increases with age. In this population-based sample, β-amyloid load was associated with lobar but not with deep CMBs.
AB - ObjectiveTo describe the prevalence of cerebral microbleeds (CMBs) and determine the association between CMBs and β-amyloid burden on PET.MethodsFrom 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.ResultsTwo 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.ConclusionsThe prevalence of CMBs increases with age. In this population-based sample, β-amyloid load was associated with lobar but not with deep CMBs.
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U2 - 10.1212/WNL.0000000000006780
DO - 10.1212/WNL.0000000000006780
M3 - Article
C2 - 30568001
AN - SCOPUS:85060016546
VL - 92
SP - E253-E262
JO - Neurology
JF - Neurology
SN - 0028-3878
IS - 3
ER -