Group differences (aMCI vs controls and AD vs controls) in categorical variables were examined by using the Fisher’s exact test. Group differences in continuous variables were examined by using the independent sample t-test or Mann–Whitney U-test. The temporal ordering (controls, aMCI, AD) of the cognitive tests, Aβ and tau biomarkers, and cytokines were examined by using the P trend analysis. The association between plasma biomarkers (including Aβ, tau, and cytokines biomarkers) and annual change in MMSE score in the aMCI and AD groups was assessed using partial correlation with adjustment for age, education level, body mass index, and apolipoprotein E (APOE) genotype (i.e., the proportion of individuals who carry the APOE ε4 allele). Receiver operating characteristic (ROC) curve analysis was performed for the statistically significant plasma biomarkers in the partial correlation analysis. Using cognitive decline (a change in the annual MMSE score ≥ 2) as the outcome, the utility of individual plasma biomarkers to identify the outcome was evaluated using the area under the ROC curve (AUC). The highest AUC value of the cytokine was combined with each Aβ and tau biomarker for a combined AUC analysis. The 95% confidence interval (CI) for the AUC was calculated using the DeLong’s test. All tests were 2-tailed and P < 0.05 was considered statistically significant. No adjustment of multiple testing (multiplicity) was performed in this study. Data analyses were conducted using SPSS 25 (IBM SPSS Inc, Chicago, IL, United States).

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