TY - JOUR
T1 - Neuroimaging correlates of Cerebral microbleeds the ARIC study (Atherosclerosis Risk in Communities)
AU - Graff-Radford, Jonathan
AU - Simino, Jeannette
AU - Kantarci, Kejal
AU - Mosley, Thomas H.
AU - Griswold, Michael E.
AU - Windham, B. Gwen
AU - Sharrett, A. Richey
AU - Albert, Marilyn S.
AU - Gottesman, Rebecca F.
AU - Jack, Clifford R.
AU - Vemuri, Prashanthi
AU - Knopman, David S.
N1 - Funding Information:
The Atherosclerosis Risk in Communities Study is performed as a collaborative study supported by National Heart, Lung, and Blood Institute (NHLBI) contracts (HHSN268201100005C, HHSN 268201100006C, HHSN268201100007C, HHSN268201100008C, HHSN268201100009C, HHSN268201100010C, HHSN2682011000 11C, and HHSN268201100012C). Neurocognitive data are collected by U01 2U01HL096812, 2U01HL096814, 2U01HL096899, 2U01HL096902, 2U01HL096917 from the National Institutes of Health (NIH; NHLBI, National Institute of Neurological Disorders and Stroke, National Institute on Aging, National Institute on Deafness and Other Communication Disorders) and with previous brain MRI examinations funded by R01-HL70825 from the NHLBI. Dr Graff-Radford is funded by the National Institute of Aging (K76 AG057015-01).
Funding Information:
Dr Graff-Radford receives funds from the Myron and Jane Hanley Career Development Award. Dr Kantarci serves on the Data Safety Monitoring Board for Takeda Global Research & Development Center, Inc; the data monitoring boards of Pfizer and Janssen Alzheimer Immunotherapy; and is funded by the National Institutes of Health (NIH). Dr Knopman served on a Data Safety Monitoring Board for Lilly Pharmaceuticals and for Lundbeck Pharmaceuticals and for the DIAN study (Dominantly Inherited Alzheimer Network); served as a consultant to TauRx Pharmaceuticals was an investigator in clinical trials sponsored by Baxter and Elan Pharmaceuticals in the past 2 years; is currently an investigator in a clinical trial sponsored by TauRx; and receives support from the NIH. Dr Jack serves as a consultant for Janssen, Bristol-Meyer-Squibb, General Electric, and Johnson & Johnson; is involved in clinical trials sponsored by Allon and Baxter, Inc; and receives research support from Pfizer, Inc, and the NIA. Dr Richey Sharrett is funded by the NIH. Dr Albert is funded by the NIH. Dr Moseley is funded by the NIH. Dr Vemuri is funded by the NIH. Dr Gottesman is Associate Editor for Neurology. Dr Gwen Windham is an investigator in a clinical trial sponsored by ACADIA Pharmaceuticals, received travel support related to this study, but does not receive financial compensation. The other authors report no conflicts.
Publisher Copyright:
© 2017 American Heart Association, Inc.
Copyright:
Copyright 2018 Elsevier B.V., All rights reserved.
PY - 2017/11
Y1 - 2017/11
N2 - Background and Purpose: Cerebral microbleed (CMB) location (deep versus strictly lobar) may elucidate underlying pathology with deep CMBs being more associated with hypertensive vascular disease and lobar CMBs being more associated with cerebral amyloid angiopathy. The objective of this study was to determine whether neuroimaging signs of vascular disease and Alzheimer pathology are associated with different types of CMBs. Methods: PAmong 1677 nondemented ARIC (Atherosclerosis Risk in Communities) participants (mean age=76±5 years; 40% men; 26% black) with 3-Tesla MRI scans at the fifth examination (2011-2013), we fit multinomial logistic regression models to quantify relationships of brain volumes (Alzheimer disease signature regions, total gray matter, frontal gray matter, and white matter hyperintensity volumes), infarct frequencies (lacunar, nonlacunar, and total), and apolipoprotein E (number of ϵ4 alleles) with CMB location (none, deep/mixed, or strictly lobar CMBs). Models were weighted for the sample selection scheme and adjusted for age, sex, education, hypertension, ever smoking status, diabetes mellitus, race site membership, and estimated intracranial volume (brain volume models only). Results: Deep/mixed and strictly lobar CMBs had prevalences of 8% and 16%, respectively. Larger white matter hyperintensity burden, greater total infarct frequency, smaller frontal volumes (in women only), and smaller total gray matter volume were associated with greater risk of both deep and lobar CMBs relative to no CMBs. Greater white matter hyperintensity volume was also associated with greater risk of deep relative to lobar CMBs. Higher lacunar and nonlacunar infarct frequencies were associated with higher risk of deep CMBs, whereas smaller Alzheimer disease signature region volume and apolipoprotein E ϵ4 homozygosity were associated with greater risk of lobar CMBs. Conclusions: CMBs are a common vascular pathology in the elderly. Markers of hypertensive small-vessel disease may contribute to deep CMBs while cerebral amyloid angiopathy may drive development of lobar CMBs.
AB - Background and Purpose: Cerebral microbleed (CMB) location (deep versus strictly lobar) may elucidate underlying pathology with deep CMBs being more associated with hypertensive vascular disease and lobar CMBs being more associated with cerebral amyloid angiopathy. The objective of this study was to determine whether neuroimaging signs of vascular disease and Alzheimer pathology are associated with different types of CMBs. Methods: PAmong 1677 nondemented ARIC (Atherosclerosis Risk in Communities) participants (mean age=76±5 years; 40% men; 26% black) with 3-Tesla MRI scans at the fifth examination (2011-2013), we fit multinomial logistic regression models to quantify relationships of brain volumes (Alzheimer disease signature regions, total gray matter, frontal gray matter, and white matter hyperintensity volumes), infarct frequencies (lacunar, nonlacunar, and total), and apolipoprotein E (number of ϵ4 alleles) with CMB location (none, deep/mixed, or strictly lobar CMBs). Models were weighted for the sample selection scheme and adjusted for age, sex, education, hypertension, ever smoking status, diabetes mellitus, race site membership, and estimated intracranial volume (brain volume models only). Results: Deep/mixed and strictly lobar CMBs had prevalences of 8% and 16%, respectively. Larger white matter hyperintensity burden, greater total infarct frequency, smaller frontal volumes (in women only), and smaller total gray matter volume were associated with greater risk of both deep and lobar CMBs relative to no CMBs. Greater white matter hyperintensity volume was also associated with greater risk of deep relative to lobar CMBs. Higher lacunar and nonlacunar infarct frequencies were associated with higher risk of deep CMBs, whereas smaller Alzheimer disease signature region volume and apolipoprotein E ϵ4 homozygosity were associated with greater risk of lobar CMBs. Conclusions: CMBs are a common vascular pathology in the elderly. Markers of hypertensive small-vessel disease may contribute to deep CMBs while cerebral amyloid angiopathy may drive development of lobar CMBs.
KW - Apolipoprotein e4
KW - Cerebral microbleed
KW - Intracerebral hemorrhage
KW - Magnetic resonance imaging
KW - Neuroimaging
UR - http://www.scopus.com/inward/record.url?scp=85032154938&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85032154938&partnerID=8YFLogxK
U2 - 10.1161/STROKEAHA.117.018336
DO - 10.1161/STROKEAHA.117.018336
M3 - Article
C2 - 29018129
AN - SCOPUS:85032154938
VL - 48
SP - 2964
EP - 2972
JO - Stroke
JF - Stroke
SN - 0039-2499
IS - 11
ER -