PREDICTION OF CLINICAL RESPONSE TO DONEPEZIL AND MEMANTINE IN PATIENTS WITH ALZHEIMER'S DISEASES BY USING EEG CONNECTIVITY

Abstract Background High doses of acetylcholinesterase (AChE) inhibitor Donepezil and non-competitive antagonist of N-methyl-D-aspartate (NMDA) receptor Memantine are approved for the clinical treatment of mild to severe Alzheimer's disease (AD). However, it is unclear which drug is more appropriate when AD progresses from mild to moderate-severe and thus calls for a neurobiological basis for clinical decisions. Aims & Objectives by viewing AD as a disconnection syndrome, we explored brain connectivity as a biomarker for medication choice and to predict the outcomes of both Donepezil and Memantine. Method Resting-state EEG was recorded from a total of 54 AD patients (mean age=73.4±6.2, male=18, female=36) at starting medication and after treatment. The mean treatment period is 103.1±58.9 weeks. We divided the patients into two groups according to MMSE score change; a group responds to donepezil alone well(n=26), second group responds to Memantine with high doses of donepezil well(n=28). We analyzed brain connectivity among the 246 cortical regions defined by the Brainnetome atlas using the fieldtrip toolbox by evaluating spectral coherence for five frequency bands (delta, theta, alpha, beta, and gamma). We then analyzed each connectivity between groups using ANCOVA with age, sex, and the initial MMSE scores as covariates. Our study found that Memantine with high doses of donepezil group has reduced and disrupted regional connectivity in the theta and gamma frequency bands, especially between the left fronto-occipitoparietal regions (p<0.001). In the alpha frequency band, reduced regional connectivity between the left frontal and medial temporal areas was also observed(p<0.001). Discussion & Conclusion This study suggests the potential of the EEG connectivity as a biomarker to predict treatment response to AchE inhibitor and NMDA antagonist in AD. References 1)Fan, L., Li, H., Zhuo, J., Zhang, Y., Wang, J., Chen, L., Yang, Z., Chu, C., Xie, S., Laird, A.R., Fox, P.T., Eickhoff, S.B., Yu, C. Jiang, T. The Human Brainnetome Atlas: A New Brain Atlas Based on Connectional Architecture. Cerebral Cortex, 26 (8): 3508-3526,(2016) 2)Eo, J., Kang, J., Youn, T., Park, H.J. Neuropharmacological computational analysis of longitudinal electroencephalograms in clozapine-treated patients with schizophrenia using hierarchical dynamic causal modeling. Neuroimage, 120161.(2023)