Gray matter asymmetries in aging and neurodegeneration: A review and meta-analysis

Abstract

Inter-hemispheric asymmetries are a common phenomenon of the human brain. Some evidence suggests that neurodegeneration related to aging and disease may preferentially affect the left-usually language- and motor-dominant-hemisphere. Here, we used activation likelihood estimation meta-analysis to assess gray matter (GM) loss and its lateralization in healthy aging and in neurodegeneration, namely, mild cognitive impairment (MCI), Alzheimer's dementia (AD), Parkinson's disease (PD), and Huntington's disease (HD). This meta-analysis, comprising 159 voxel-based morphometry publications (enrolling 4,469 patients and 4,307 controls), revealed that GM decline appeared to be asymmetric at trend levels but provided no evidence for increased left-hemisphere vulnerability. Regions with asymmetric GM decline were located in areas primarily affected by neurodegeneration. In HD, the left putamen showed converging evidence for more pronounced atrophy, while no consistent pattern was found in PD. In MCI, the right hippocampus was more atrophic than its left counterpart, a pattern that reversed in AD. The stability of these findings was confirmed using permutation tests. However, due to the lenient threshold used in the asymmetry analysis, further work is needed to confirm our results and to provide a better understanding of the functional role of GM asymmetries, for instance in the context of cognitive reserve and compensation. Hum Brain Mapp 38:5890-5904, 2017. © 2017 Wiley Periodicals, Inc.

Keywords: ALE; Huntington's disease; Parkinson's disease; VBM; aging; dementia.

Figure 1

PRISMA flow diagram of study selection.

Figure 2

ALE results: Patterns of gray matter decline (in red) and asymmetries in gray matter decline (in blue), separately in healthy aging (A), MCI (B), AD (C), and HD. Coordinates [x/y/z] are provided in MNI space. L indicates left and R indicates right. [Color figure can be viewed at http://wileyonlinelibrary.com]

Figure 3

ROI‐based ALE: Probabilistic “true” foci locations across lobes and hemispheres. L indicates left and R indicates right. MCI = mild cognitive impairment; AD = Alzheimer's dementia, HD = Huntington's disease. [Color figure can be viewed at http://wileyonlinelibrary.com]

Figure 4

MACM results for regions showing GM asymmetries. Yellow: seed regions used for each analysis. Red: co‐activation patterns with the original seed. Blue: co‐activation patterns with the flipped, contralateral seed. Green: Contrast/difference between original and flipped MACM results. Purple: Conjunction (minimum statistic) analysis between original and flipped MACM results. Coordinates [x/y/z] are provided in MNI space. L indicates left and R indicates right. [Color figure can be viewed at http://wileyonlinelibrary.com]