Cerebral microbleed incidence, relationship to amyloid burden: The Mayo Clinic Study of Aging

Jonathan Graff-Radford, Timothy Lesnick, Alejandro A. Rabinstein, Jeff Gunter, Jeremiah Aakre, Scott A. Przybelski, Anthony J. Spychalla, John Huston, Robert D. Brown, Michelle M. Mielke, Val J. Lowe, David S. Knopman, Ronald C. Petersen, Clifford R. Jack, Prashanthi Vemuri, Walter Kremers, Kejal Kantarci

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)e190-e199
JournalNeurology
Volume94
Issue number2
DOIs
StatePublished - Jan 14 2020

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Amyloid
Incidence
Structural Models
Positron-Emission Tomography
Alleles
Magnetic Resonance Imaging
Population

ASJC Scopus subject areas

  • Clinical Neurology

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Graff-Radford, J., Lesnick, T., Rabinstein, A. A., Gunter, J., Aakre, J., Przybelski, S. A., ... Kantarci, K. (2020). Cerebral microbleed incidence, relationship to amyloid burden: The Mayo Clinic Study of Aging. Neurology, 94(2), e190-e199. https://doi.org/10.1212/WNL.0000000000008735

Cerebral microbleed incidence, relationship to amyloid burden : The Mayo Clinic Study of Aging. / Graff-Radford, Jonathan; Lesnick, Timothy; Rabinstein, Alejandro A.; Gunter, Jeff; Aakre, Jeremiah; Przybelski, Scott A.; Spychalla, Anthony J.; Huston, John; Brown, Robert D.; Mielke, Michelle M.; Lowe, Val J.; Knopman, David S.; Petersen, Ronald C.; Jack, Clifford R.; Vemuri, Prashanthi; Kremers, Walter; Kantarci, Kejal.

In: Neurology, Vol. 94, No. 2, 14.01.2020, p. e190-e199.

Research output: Contribution to journalArticle

Graff-Radford J, Lesnick T, Rabinstein AA, Gunter J, Aakre J, Przybelski SA et al. Cerebral microbleed incidence, relationship to amyloid burden: The Mayo Clinic Study of Aging. Neurology. 2020 Jan 14;94(2):e190-e199. https://doi.org/10.1212/WNL.0000000000008735
Graff-Radford, Jonathan ; Lesnick, Timothy ; Rabinstein, Alejandro A. ; Gunter, Jeff ; Aakre, Jeremiah ; Przybelski, Scott A. ; Spychalla, Anthony J. ; Huston, John ; Brown, Robert D. ; Mielke, Michelle M. ; Lowe, Val J. ; Knopman, David S. ; Petersen, Ronald C. ; Jack, Clifford R. ; Vemuri, Prashanthi ; Kremers, Walter ; Kantarci, Kejal. / Cerebral microbleed incidence, relationship to amyloid burden : The Mayo Clinic Study of Aging. In: Neurology. 2020 ; Vol. 94, No. 2. pp. e190-e199.
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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.

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AU - Vemuri, Prashanthi

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N2 - 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.

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