Yingfeng Ge ¹ Jianan Yin ¹ Caie Chen ¹ Shuo Yang ¹ Yuduan Han ¹ Chonglong Ding ¹ Jiaming Zheng ² Yifan Zheng ^3* Jinxin Zhang ^1*

• ¹ School of Public Health, Sun Yat-sen University, Guangzhou, China
• ² Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China
• ³ Department of Neurology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China

Background: As a clinical precursor to Alzheimer's disease (AD), amnestic mild cognitive impairment (aMCI) bears a considerably heightened risk of transitioning to AD compared to cognitively normal elders. Early prediction of whether aMCI will progress to AD is of paramount importance, as it can provide pivotal guidance for subsequent clinical interventions in an early and effective manner. Methods: A total of 107 aMCI cases were enrolled and their electroencephalogram (EEG) data were collected at the time of the initial diagnosis. During 18-month followup period, 42 individuals progressed to AD (PMCI), while 65 remained in the aMCI stage (SMCI). Spectral, nonlinear, and functional connectivity features were extracted from the EEG data, subjected to feature selection and dimensionality reduction, and then fed into various machine learning classifiers for discrimination. The performance of each model was assessed using 10-fold cross-validation and evaluated in terms of accuracy (ACC), area under the curve (AUC), sensitivity (SEN), specificity (SPE), positive predictive value (PPV), and F1-score. Results: Compared to SMCI patients, PMCI patients exhibit a trend of "high to low" frequency shift, decreased complexity, and a disconnection phenomenon in EEG signals. An epoch-based classification procedure, utilizing the extracted EEG featuresand k-nearest neighbor (KNN) classifier, achieved the ACC of 99.96%, AUC of 99.97%, 3 SEN of 99.98%, SPE of 99.95%, PPV of 99.93%, and F1-score of 99.96%. Meanwhile, the subject-based classification procedure also demonstrated commendable performance, achieving an ACC of 78.37%, an AUC of 83.89%, SEN of 77.68%, SPE of 76.24%, PPV of 82.55%, and F1-score of 78.47%.Aiming to explore the EEG biomarkers with predictive value for AD in the early stages of aMCI, the proposed discriminant framework provided robust longitudinal evidence for the trajectory of the aMCI cases, aiding in the achievement of early diagnosis and proactive intervention.