Yusuke Yakushiji1, Duncan Wilson1, Gareth Ambler1, Andreas Charidimou1, Alexa Beiser1, Mark A van Buchem1, Charles DeCarli1, Ding Ding1, Villi Gudnason1, Hideo Hara1, Toshio Imaizumi1, Katsuhiko Kohara1, Hyung-Min Kwon1, Lenore J Launer1, Vincent Mok1, Thanh Phan1, Sarah R Preis1, José Rafael Romero1, Sudha Seshadri1, Velandai Srikanth1, Yuki Takashima1, Yoshito Tsushima1, Zhaolu Wang1, Philip A Wolf1, Yunyun Xiong1, Shuhei Yamaguchi1, David J Werring2. 1. From the Stroke Research Center, Department of Brain Repair & Rehabilitation, Institute of Neurology (Y.Y., D.W., A.C., D.J.W.), and Department of Statistical Science (G.A.), UCL, London, UK; Division of Neurology (Y.Y., H.H.), Department of Internal Medicine, Saga University Faculty of Medicine, Japan; Department of Neurology (A.B., S.R.P., J.R.R., S.S., P.A.W.), Boston University and the NHLBI's Framingham Heart Study; Department of Biostatistics (A.B., S.R.P.), Boston University, MA; Department of Radiology (M.A.v.B.), Leiden University Medical Center, the Netherlands; Department of Neurology (C.D.), University of California Davis; Department of Neurology (D.D.), Huashan Hospital, Fudan University, Shanghai, China; Icelandic Heart Association (V.G.), Kopavogur; University of Iceland (V.G.), Reykjavik; Department of Neurosurgery (T.I.), Kushiro City General Hospital; Faculty of Collaborative Regional Innovation (K.K.), Ehime University, Matsuyama, Japan; Department of Neurology (H.-M.K.), SMG-SNU Boramae Medical Center, Seoul, Republic of Korea; Intramural Research Program (L.J.L.), National Institute on Aging, Bethesda, MD; Therese Pei Fong Chow Research Center for Prevention of Dementia (V.M., Z.W., Y.X.), Department of Medicine and Therapeutics, The Chinese University of Hong Kong, China; Stroke and Aging Research Group, Department of Medicine, School of Clinical Science at Monash Health (T.P., V.S.), and Department of Medicine, Peninsula Health and Clinical School, Central Clinical School (V.S.), Monash University, Melbourne, Australia; Center for Emotional and Behavioral Disorders (Y. Takashima), Hizen Psychiatric Center, Saga, Japan; Department of Diagnostic Radiology and Nuclear Medicine (Y. Tsushima), Gunma University Graduate School of Medicine; Research Program for Diagnostic and Molecular Imaging (Y. Tsushima), Division of Integrated Oncology Research, Gunma University Initiative for Advanced Research, Maebashi; and Department of Neurology (S.Y.), Faculty of Medicine, Shimane University, Izumo, Japan. 2. From the Stroke Research Center, Department of Brain Repair & Rehabilitation, Institute of Neurology (Y.Y., D.W., A.C., D.J.W.), and Department of Statistical Science (G.A.), UCL, London, UK; Division of Neurology (Y.Y., H.H.), Department of Internal Medicine, Saga University Faculty of Medicine, Japan; Department of Neurology (A.B., S.R.P., J.R.R., S.S., P.A.W.), Boston University and the NHLBI's Framingham Heart Study; Department of Biostatistics (A.B., S.R.P.), Boston University, MA; Department of Radiology (M.A.v.B.), Leiden University Medical Center, the Netherlands; Department of Neurology (C.D.), University of California Davis; Department of Neurology (D.D.), Huashan Hospital, Fudan University, Shanghai, China; Icelandic Heart Association (V.G.), Kopavogur; University of Iceland (V.G.), Reykjavik; Department of Neurosurgery (T.I.), Kushiro City General Hospital; Faculty of Collaborative Regional Innovation (K.K.), Ehime University, Matsuyama, Japan; Department of Neurology (H.-M.K.), SMG-SNU Boramae Medical Center, Seoul, Republic of Korea; Intramural Research Program (L.J.L.), National Institute on Aging, Bethesda, MD; Therese Pei Fong Chow Research Center for Prevention of Dementia (V.M., Z.W., Y.X.), Department of Medicine and Therapeutics, The Chinese University of Hong Kong, China; Stroke and Aging Research Group, Department of Medicine, School of Clinical Science at Monash Health (T.P., V.S.), and Department of Medicine, Peninsula Health and Clinical School, Central Clinical School (V.S.), Monash University, Melbourne, Australia; Center for Emotional and Behavioral Disorders (Y. Takashima), Hizen Psychiatric Center, Saga, Japan; Department of Diagnostic Radiology and Nuclear Medicine (Y. Tsushima), Gunma University Graduate School of Medicine; Research Program for Diagnostic and Molecular Imaging (Y. Tsushima), Division of Integrated Oncology Research, Gunma University Initiative for Advanced Research, Maebashi; and Department of Neurology (S.Y.), Faculty of Medicine, Shimane University, Izumo, Japan. d.werring@ucl.ac.uk.
Abstract
OBJECTIVE: We investigated differences in the anatomical distribution of cerebral microbleeds (CMBs) on MRI, hypothesized to indicate the type of underlying cerebral small vessel disease (SVD), between Eastern and Western general populations. METHODS: We analyzed data from 11 studies identified by a PubMed search between 1996 and April 2014 according to the Preferred Reporting Items for a Systematic Review and Meta-analysis of Individual Participant Data. Study quality measures indicated low or medium risk of bias. We included stroke-free participants from populations aged between 55 and 75 years, categorized by geographic location (Eastern or Western). We categorized CMB distribution (strictly lobar, deep and/or infratentorial [D/I], or mixed [i.e., CMBs located in both lobar and D/I regions]). We tested the hypothesis that Eastern and Western populations have different anatomical distributions of CMBs using multivariable mixed effects logistic regression analyses adjusted for age, sex, and hypertension and clustering by institution. RESULTS: Among 8,595 stroke-free individuals (mean age [SD] 66.7 [5.6] years; 48% male; 42% from a Western population), 624 (7.3%) had CMBs (strictly lobar in 3.1%; D/I or mixed in 4.2%). In multivariable mixed effects models, Eastern populations had higher odds of D/I or mixed CMBs (adjusted odds ratio 2.78, 95% confidence interval [CI] 1.77-4.35) compared to Western populations. Eastern populations had a higher number of D/I or mixed CMBs (adjusted prevalence ratio 2.83, 95% CI 1.27-6.31). CONCLUSIONS: Eastern and Western general populations have different anatomical distributions of CMBs, suggesting differences in the spectrum of predominant underlying SVDs, with potential implications for SVD diagnosis and treatment.
OBJECTIVE: We investigated differences in the anatomical distribution of cerebral microbleeds (CMBs) on MRI, hypothesized to indicate the type of underlying cerebral small vessel disease (SVD), between Eastern and Western general populations. METHODS: We analyzed data from 11 studies identified by a PubMed search between 1996 and April 2014 according to the Preferred Reporting Items for a Systematic Review and Meta-analysis of Individual Participant Data. Study quality measures indicated low or medium risk of bias. We included stroke-freeparticipants from populations aged between 55 and 75 years, categorized by geographic location (Eastern or Western). We categorized CMB distribution (strictly lobar, deep and/or infratentorial [D/I], or mixed [i.e., CMBs located in both lobar and D/I regions]). We tested the hypothesis that Eastern and Western populations have different anatomical distributions of CMBs using multivariable mixed effects logistic regression analyses adjusted for age, sex, and hypertension and clustering by institution. RESULTS: Among 8,595 stroke-free individuals (mean age [SD] 66.7 [5.6] years; 48% male; 42% from a Western population), 624 (7.3%) had CMBs (strictly lobar in 3.1%; D/I or mixed in 4.2%). In multivariable mixed effects models, Eastern populations had higher odds of D/I or mixed CMBs (adjusted odds ratio 2.78, 95% confidence interval [CI] 1.77-4.35) compared to Western populations. Eastern populations had a higher number of D/I or mixed CMBs (adjusted prevalence ratio 2.83, 95% CI 1.27-6.31). CONCLUSIONS: Eastern and Western general populations have different anatomical distributions of CMBs, suggesting differences in the spectrum of predominant underlying SVDs, with potential implications for SVD diagnosis and treatment.
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