title: Voxel-based meta-analysis of grey matter changes in Alzheimer's disease.
abstract: BACKGROUND
  Voxel-based morphometry (VBM) using structural brain MRI has been widely used for the assessment of impairment in Alzheimer's disease (AD), but previous studies in VBM studies on AD remain inconsistent.
  
  
  OBJECTIVE
  We conducted meta-analyses to integrate the reported studies to determine the consistent grey matter alterations in AD based on VBM method.
  
  
  METHODS
  The PubMed, ISI Web of Science, EMBASE and Medline database were searched for articles between 1995 and June 2014. Manual searches were also conducted, and authors of studies were contacted for additional data. Coordinates were extracted from clusters with significant grey matter difference between AD patients and healthy controls (HC). Meta-analysis was performed using a new improved voxel-based meta-analytic method, Effect Size Signed Differential Mapping (ES-SDM).
  
  
  RESULTS
  Thirty data-sets comprising 960 subjects with AD and 1195 HC met inclusion criteria. Grey matter volume (GMV) reduction at 334 coordinates in AD and no GMV increase were found in the current meta-analysis. Significant reductions in GMV were robustly localized in the limbic regions (left parahippocampl gyrus and left posterior cingulate gyrus). In addition, there were GM decreases in right fusiform gyrus and right superior frontal gyrus. The findings remain largely unchanged in the jackknife sensitivity analyses.
  
  
  CONCLUSIONS
  Our meta-analysis clearly identified GMV atrophy in AD. These findings confirm that the most prominent and replicable structural abnormalities in AD are in the limbic regions and contributes to the understanding of pathophysiology underlying AD.
authors.affiliation: Department of Neurology, Qingdao Municipal Hospital, School of Medicine, Qingdao University, No.5 Donghai Middle Road, Qingdao, Shandong Province 266071 China.
authors.forename: Wen-Ying
authors.initials: WY
authors.lastname: Wang
authors.affiliation: Department of Neurology, Qingdao Municipal Hospital, School of Medicine, Qingdao University, No.5 Donghai Middle Road, Qingdao, Shandong Province 266071 China ; College of Medicine and Pharmaceutics, Ocean University of China, Qingdao, 266011 China ; Department of Neurology, Qingdao Municipal Hospital, Nanjing Medical University, Nanjing, 266071 China.
authors.forename: Jin-Tai
authors.initials: JT
authors.lastname: Yu
authors.affiliation: Brainnetome Center, Institute of Automation, Chinese Academy of Sciences, Beijing, 100190 China ; National Laboratory of Pattern Recognition, Institute of Automation, Chinese Academy of Sciences, Beijing, 100190 China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Neurology, Qingdao Municipal Hospital, School of Medicine, Qingdao University, No.5 Donghai Middle Road, Qingdao, Shandong Province 266071 China.
authors.forename: Rui-Hua
authors.initials: RH
authors.lastname: Yin
authors.affiliation: Department of Neurology, Qingdao Municipal Hospital, Nanjing Medical University, Nanjing, 266071 China.
authors.forename: Hui-Fu
authors.initials: HF
authors.lastname: Wang
authors.affiliation: Department of Neurology, Qingdao Municipal Hospital, School of Medicine, Qingdao University, No.5 Donghai Middle Road, Qingdao, Shandong Province 266071 China.
authors.forename: Jun
authors.initials: J
authors.lastname: Wang
authors.affiliation: College of Medicine and Pharmaceutics, Ocean University of China, Qingdao, 266011 China.
authors.forename: Lin
authors.initials: L
authors.lastname: Tan
authors.affiliation: Department of Psychosis Studies, Institute of Psychiatry, King's College London, London, UK ; Research Unit, FIDMAG Germanes Hospitala'ries-CIBERSAM, Sant Boi de Llobregat, Barcelona, Spain.
authors.forename: Joaquim
authors.initials: J
authors.lastname: Radua
authors.affiliation: Department of Neurology, Qingdao Municipal Hospital, School of Medicine, Qingdao University, No.5 Donghai Middle Road, Qingdao, Shandong Province 266071 China ; College of Medicine and Pharmaceutics, Ocean University of China, Qingdao, 266011 China ; Department of Neurology, Qingdao Municipal Hospital, Nanjing Medical University, Nanjing, 266071 China.
authors.forename: Lan
authors.initials: L
authors.lastname: Tan
keywords: Alzheimer’s disease (AD); Effect size signed differential mapping (ES-SDM); Grey matter (GM); Magnetic resonance imaging (MRI); Meta-analysis; Voxel-based morphometry (VBM)
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