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Background and Purpose:  It is well known that there is a wide range of different pathological stages related to Alzheimer's disease (AD) among patients with amnestic mild cognitive impairment (aMCI). Further refinement of the stages based on neuropsychological and neuroimaging methods is important for earlier disease detection, as well as for the development and evaluation of disease-modifying interventions.   Materials and Methods:  In this cross-sectional study, 125 aMCI patients were classified into declined progressively three stages of mild, moderate and severe, utilizing the extreme groups approach (EGA) based on their memory function. Fifty-two patients, in addition to 24 cognitively normal subjects, were included in further structural MRI analyses. Characteristics of cognitive functions and brain structures across these newly defined stages were explored through general linear models.   Results:  Almost all the non-memory cognitive functions showed progressive decline as memory function deteriorated. In addition, medial structures including the right hippocampus, right lingual and left fusiform gyrus, presented with greater gray matter (GM) atrophy during the later stages of aMCI (corrected  p  < 0.05). Correlations were found between GM volume of the lingual gyrus and processing speed ( r  = 0.419,  p  = 0.003) and between the fusiform gyrus and general cognitive function ( r  = 0.281,  p  = 0.046). Moreover, both cognitive function and GM volume presented non-linear trajectories over stages of aMCI.   Conclusion:  Our study characterized the cognitive profiles along with the degree of episodic memory impairment, and these three stages of aMCI showed non-linear progressive decline in cognitive functions and GM volumes.

Multistage Grading of Amnestic Mild Cognitive Impairment: The Associated Brain Gray Matter Volume and Cognitive Behavior Characterization