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Abstract
Objective To determine the incidence of cerebral microbleeds (CMBs) and the association of amyloid PET burden with incident CMBs.
Methods A total of 651 participants, age ≥50 years (55% male), underwent 3T MRI scans with ≥2 separate T2*-weighted gradient recalled echo sequences from October 2011 to August 2017. Eighty-seven percent underwent 11C Pittsburgh compound B (PiB) PET scans. Age-specific CMB incidence rates were calculated by using the piecewise exponential model. Using structural equation models (SEMs), we assessed the effect of amyloid load and baseline CMBs on future CMBs after considering the direct and indirect age, sex, vascular risk factors, and APOE effects.
Results Participants' mean age (SD) was 69.8 (10.0) years at baseline MRI, and 111 participants (17%) had ≥1 baseline CMB. The mean (SD) of the time interval between scans was 2.7 (1.0) years. The overall population incidence rate for CMBs was 3.6/100 person-years and increased with age: from 1.5/100 new CMBs at age 50 to 11.6/100 person-years at age 90. Using the piecewise exponential model regression, the incidence rates increased with age and the presence of baseline CMBs. The SEMs showed that (1) increasing age at MRI or carrying an APOE4 allele was associated with more amyloid at baseline, and higher amyloid, particularly occipital amyloid load, in turn increased the risk of a new lobar CMB; and (2) the presence of CMBs at baseline increased the risk of a lobar CMB and had a larger effect size than amyloid load.
Conclusions Age and APOE4 carrier status act through amyloid load to increase the risk of subsequent lobar CMBs, but the presence of baseline CMBs is the most important risk factor for future CMBs.
Glossary
- AGES-Reykjavik Study=
- Age, Gene/Environment Susceptibility–Reykjavik Study;
- CAA=
- cerebral amyloid angiopathy;
- CMB=
- cerebral microbleed;
- GRE=
- gradient-recalled echo;
- MCSA=
- Mayo Clinic Study of Aging;
- PEM=
- piecewise exponential model;
- PiB=
- Pittsburgh compound B;
- ROI=
- region of interest;
- SEM=
- structural equations model;
- 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.
- Received January 7, 2019.
- Accepted in final form July 5, 2019.
- © 2019 American Academy of Neurology
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