Differential and subtype-specific neuroimaging abnormalities in amnestic and nonamnestic mild cognitive impairment: A systematic review and meta-analysis.

While mild cognitive impairment (MCI) has been classified into amnestic MCI (aMCI) and nonamnestic MCI (naMCI), the neuropathological bases of these two subtypes remain elusive. Here, we performed a systematic review and meta-analysis to determine the subtype specificity of neuroimaging abnormalities in MCI and to identify neural features that may differ between aMCI and naMCI. We synthesized 50 studies that used common neuroimaging modalities, including magnetic resonance imaging and positron emission tomography, to compare brain atrophy, white matter abnormalities, cortical thinning, cerebral hypometabolism, amyloid/tau deposition, or other features among aMCI, naMCI, and normal cognition. Compared with normal cognition, aMCI shows diverse neuroimaging abnormalities of large effect sizes. In contrast, naMCI exhibits restricted abnormalities of small effect sizes. Some features, including medial temporal lobe atrophy and white matter abnormalities, are shared by the two MCI subtypes. Overall, brain abnormalities are worse, if not similar, in aMCI than in naMCI. The only neuroimaging abnormality specific to aMCI is increased amyloid burden; no feature specific to naMCI was found. Taken together, our findings have elucidated the neuropathological changes that occur in aMCI and naMCI. Clarifying the neuroimaging profiles of aMCI and naMCI can improve the early identification, differentiation, and intervention of prodromal dementia.