Abstract
OBJECTIVE: Patients with amnestic mild cognitive impairment (aMCI) are thought to be highly susceptible to developing Alzheimer's disease (AD). The study aimed to investigate the possibilities of plasma-biomarkers for individual patient identification of aMCI and prediction of episodic memory. METHODS: We recruited 87 healthy controls and 68 aMCI patients in this study; and 22/68 aMCI patients completed 3-year follow-up visits, with six aMCI patients converting to AD. An ultrasensitive quantitative method was employed to measure the levels of plasma biomarkers. RESULTS: Relative to healthy controls, the aMCI patients showed significantly higher levels of plasma neurofilament light (NfL) and lower levels of plasma Aβ40, Aβ42 and Aβ42/Aβ40 ratio (all P values <0.01). Using multivariate relevance vector regression models, we further demonstrated plasma biomarkers could accurately predict baseline Rey's Auditory Verbal Learning Test-20 min delayed recall (AVLT-DR) scores (r = 0.362, P value <0.001) and 3-year longitudinal AVLT-DR changes (r = 0.365, P value <0.001) for individual aMCI patients; plasma-indicators contributed most to the predictions including total-tau and NfL. Finally, by using support vector machine model, the combination of plasma Aβ42/Aβ40, mini-mental state examination (MMSE) score, and hippocampal/parahippocampal volume had the highest accuracy of 77.42% (sensitivity = 72.06%, specificity = 81.61%) for identifying aMCI patients. CONCLUSION: We provided support to the use of plasma total-tau and NfL as simple biomarkers to predict the severity of episodic memory deficit for individual aMCI patients and aMCI progression, and further demonstrated that the combination of plasma Aβ42/Aβ40, hippocampal/parahippocampal volume, and MMSE score could serve as an integrated screening tool to select aMCI individuals.