Impact of Amyloid Pathology in Mild Cognitive Impairment Subjects: The Longitudinal Cognition and Surface Morphometry Data

Abstract

The amyloid framework forms the central medical theory related to Alzheimer disease (AD), and the in vivo demonstration of amyloid positivity is essential for diagnosing AD. On the basis of a longitudinal cohort design, the study investigated clinical progressive patterns by obtaining cognitive and structural measurements from a group of patients with amnestic mild cognitive impairment (MCI); the measurements were classified by the positivity (Aβ+) or absence (Aβ−) of the amyloid biomarker. We enrolled 185 patients (64 controls, 121 patients with MCI). The patients with MCI were classified into two groups on the basis of their [18F]flubetaben or [18F]florbetapir amyloid positron-emission tomography scan (Aβ+ vs. Aβ−, 67 vs. 54 patients) results. Data from annual cognitive measurements and three-dimensional T1 magnetic resonance imaging scans were used for between-group comparisons. To obtain longitudinal cognitive test scores, generalized estimating equations were applied. A linear mixed effects model was used to compare the time effect of cortical thickness degeneration. The cognitive decline trajectory of the Aβ+ group was obvious, whereas the Aβ− and control groups did not exhibit a noticeable decline over time. The group effects of cortical thickness indicated decreased entorhinal cortex in the Aβ+ group and supramarginal gyrus in the Aβ− group. The topology of neurodegeneration in the Aβ− group was emphasized in posterior cortical regions. A comparison of the changes in the Aβ+ and Aβ− groups over time revealed a higher rate of cortical thickness decline in the Aβ+ group than in the Aβ− group in the default mode network. The Aβ+ and Aβ− groups experienced different APOE ε4 effects. For cortical–cognitive correlations, the regions associated with cognitive decline in the Aβ+ group were mainly localized in the perisylvian and anterior cingulate regions. By contrast, the degenerative topography of Aβ− MCI was scattered. The memory learning curves, cognitive decline patterns, and cortical degeneration topographies of the two MCI groups were revealed to be different, suggesting a difference in pathophysiology. Longitudinal analysis may help to differentiate between these two MCI groups if biomarker access is unavailable in clinical settings.