Volume, density, and thickness brain abnormalities in mild cognitive impairment: an ALE meta-analysis controlling for age and education

Brain Imaging Behav. 2022 Oct;16(5):2335-2352. doi: 10.1007/s11682-022-00659-0. Epub 2022 Apr 13.


Prior meta-analyses have provided important information regarding which brain areas are structurally compromised in individuals with mild cognitive impairment (MCI). These studies have not however separated volume, density, and thickness, controlled for important demographic influences, considered null findings, or recognized studies indicating increased brain volumes in MCI individuals. Furthermore, there is a question as to whether deficits extend into cortical regions, and also into the thalamus. This study aims to address these issues using activation likelihood estimation (ALE) analyses with a sample size more than twice that of prior meta-analyses. A total of 71 studies were identified and entered into the ALE analysis which consisted of 2262 with MCI and 1902 healthy controls. Three major clusters were identified showing decreased gray matter volume in the MCI group compared to controls, with the most salient decreases being in the hippocampus, parahippocampal gyrus, and the amygdala. Reduced thalamic volume was also observed, but to a lesser extent. Density was reduced in the left hippocampus, while thickness was reduced in the uncus. No significant cluster emerged from an ALE meta-analysis of studies finding volume increases in MCI individuals. While the MCI group was significantly older and less educated than controls, controlling for these factors still resulted in significant, albeit attenuated findings. These results support hippocampal and parahippocampal deficits in MCI, and further highlight the amygdala, thalamus, and uncus as other areas to be considered in future MCI studies.

Keywords: Amygdala; Brain structure; Mild cognitive impairment; Parahippocampal; hippocampus.

Publication types

  • Meta-Analysis
  • Review

MeSH terms

  • Brain / diagnostic imaging
  • Brain Diseases*
  • Cognitive Dysfunction* / diagnostic imaging
  • Gray Matter / diagnostic imaging
  • Hippocampus
  • Humans
  • Magnetic Resonance Imaging / methods