Abstract
BackgroundVoxel-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.ObjectiveWe conducted meta-analyses to integrate the reported studies to determine the consistent grey matter alterations in AD based on VBM method.MethodsThe 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).ResultsThirty 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.ConclusionsOur 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.
Highlights
Morphometric Magnetic resonance imaging (MRI) studies have investigated focal structural abnormalities in brain tissue types, such as grey matter (GM) and white matter (WM), between groups of individuals using voxel-based morphometry (VBM)
Our meta-analysis clearly identified grey matter volume (GMV) atrophy in Alzheimer’s disease (AD)
The studies were excluded if they suffered from at least one of the following deficiencies: (1) sufficient data could not be obtained even when more information was asked from the corresponding authors by phone or email; (2) there were fewer than nine subjects in either AD group or healthy controls (HC) group; (3) the data overlapped with those of another publication; (4) there were uncorrected results and the spatial extent threshold was not reported; and (5) there was no HC group; (6) studies limit their analyses to specific region of interest (ROI); (7)
Summary
Search strategy Systematic and comprehensive searches were conducted in PubMed (http://www.ncbi.nlm.nih.gov/pubmed/), ISI Web of Science (www.isiknowledge.com), Embase (www. embase.com/), and Medline databases (http://www. medline.com/) from 1995 to 25 June 2014 using the keywords “Alzheimer’s disease” OR “AD”, AND “voxel*”, “morphometry”,OR “vbm”. Major limitations of the ROI approaches are that it requires a priori decision concerning which structures need to be evaluated and that regions showing abnormal GM volume might be part of a large ROI, or spread over different ROIs, thereby potentially reducing statistical power of the underlying morphological analysis [4]. This analysis was performed in a standard process using the SDM software A systematic wholebrain voxel-based jackknife sensitivity analysis was performed to test the replicability of the results All these processes were referred to the SDM Tutorial (http:// sdmproject.com/software/Tutorial.pdf ) and publications. The SDM software editor was contacted by email when necessary
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