Voxelwise meta-analysis of gray matter anomalies in Alzheimer's disease and mild cognitive impairment using anatomic likelihood estimation

J Neurol Sci. 2012 May 15;316(1-2):21-9. doi: 10.1016/j.jns.2012.02.010. Epub 2012 Mar 3.


Background: Many voxel-based morphometry studies in Alzheimer's disease (AD) and mild cognitive impairment (MCI) yielded not entirely consistent results. We conducted meta-analyses of gray matter anomalies to identify robust neuroanatomical changes between them.

Methods: A systematic review of voxel-based morphometry studies of patients with AD and MCI relative to healthy comparison subjects in PubMed, Embase databases from January 1995 to 29 April, 2011 was conducted. The anatomical distribution of the coordinates of gray matter differences was meta-analyzed using anatomical likelihood estimation (ALE). Separate maps of gray matter changes were constructed, and subtraction meta-analysis between AD and MCI was also performed.

Results: Thirty-five AD studies and twenty-four MCI studies were included in the meta-analysis. Extensive gray matter deficits were present in the medial temporal lobe (including entorhinal cortex, hippocampus, parahippocampus, amygdala and uncus), thalamus, temporal, parietal, frontal and cingulate and insular cortices in AD. In MCI, gray matter reductions were identified in the medial temporal lobe (including entorhinal cortex, hippocampus, parahippocampus, amygdala and uncus), temporal, thalamus, and cingulate cortex. Subtraction meta-analysis found more severe gray matter deficit mainly in the left medial lobe (including parahippocampus, amygdala and hippocampus).

Conclusions: Our meta-analysis identified similar distributions of neuroanatomical changes in AD and MCI, which are consistent with the hierarchical model of neuropathological alterations of neurofibrillary tangles in AD and MCI. Subtraction analysis provided evidence that the left MTL may be a neuroanatomical marker to evaluate disease progression from MCI to AD.

Publication types

  • Case Reports
  • Comparative Study
  • Meta-Analysis
  • Research Support, Non-U.S. Gov't
  • Review
  • Systematic Review

MeSH terms

  • Alzheimer Disease / diagnosis
  • Alzheimer Disease / etiology
  • Alzheimer Disease / pathology*
  • Brain Mapping / methods*
  • Brain Mapping / statistics & numerical data
  • Cerebral Cortex / pathology*
  • Cognitive Dysfunction / complications
  • Cognitive Dysfunction / pathology*
  • Disease Progression*
  • Humans
  • Likelihood Functions
  • Stereotaxic Techniques