Comparison of cortical thickness in patients with early-stage versus late-stage amnestic mild cognitive impairment

Background and purpose: Disappointing outcomes from clinical trials involving amyloid-modifying therapies for Alzheimer's disease (AD) have prompted more focus on the concept of early-stage (E) amnestic mild cognitive impairment (E-aMCI). However, limited evidence suggests that E-aMCI may represent aMCI at a very early stage of AD. Furthermore, the nature of the progression of E-aMCI to late-stage aMCI (L-aMCI) remains unclear. Therefore, the aim of the present study was to characterize patterns of cortical thinning in both E-aMCI and L-aMCI patients. Methods: Cortical thicknesses were measured in 190 patients with aMCI and 147 subjects with normal cognition. In accordance with memory test scores involving delayed recall items, aMCI patients were divided into two subgroups, containing 73 E-aMCI subjects with milder memory impairment [scores between -1.5 standard deviation (SD) and -1.0 SD compared with age- and education-matched norms] and 117 L-aMCI subjects with more severe memory impairment (scores lower than -1.5 SD). Results: Compared with controls, the E-aMCI group exhibited cortical thinning in the left medial temporal and insular regions, whereas the L-aMCI group showed cortical thinning in widespread regions, including the bilateral dorsolateral prefrontal, anterior and medial temporal, and temporo-parietal association cortices, and the precuneus. When the two aMCI groups were directly compared, the L-aMCI group showed greater cortical thinning in the right superior prefrontal, medial temporal, posterior cingulate and lateral parietal cortices. Conclusion: Our findings suggest that E-aMCI might represent an early symptomatic stage of AD. Furthermore, L-aMCI might resemble AD more closely than E-aMCI, in terms of the topography of cortical thinning.