TY - JOUR
T1 - Cerebral microbleed incidence, relationship to amyloid burden
T2 - The Mayo Clinic Study of Aging
AU - Graff-Radford, Jonathan
AU - Lesnick, Timothy
AU - Rabinstein, Alejandro A.
AU - Gunter, Jeff
AU - Aakre, Jeremiah
AU - Przybelski, Scott A.
AU - Spychalla, Anthony J.
AU - Huston, John
AU - Brown, Robert D.
AU - Mielke, Michelle M.
AU - Lowe, Val J.
AU - Knopman, David S.
AU - Petersen, Ronald C.
AU - Jack, Clifford R.
AU - Vemuri, Prashanthi
AU - Kremers, Walter
AU - Kantarci, Kejal
N1 - Publisher Copyright:
© American Academy of Neurology.
PY - 2020/1/14
Y1 - 2020/1/14
N2 - ObjectiveTo determine the incidence of cerebral microbleeds (CMBs) and the association of amyloid PET burden with incident CMBs.MethodsA 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.ResultsParticipants' 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.ConclusionsAge 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.
AB - ObjectiveTo determine the incidence of cerebral microbleeds (CMBs) and the association of amyloid PET burden with incident CMBs.MethodsA 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.ResultsParticipants' 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.ConclusionsAge 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.
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U2 - 10.1212/WNL.0000000000008735
DO - 10.1212/WNL.0000000000008735
M3 - Article
C2 - 31801832
AN - SCOPUS:85077793318
SN - 0028-3878
VL - 94
SP - E190-E199
JO - Neurology
JF - Neurology
IS - 2
ER -