Ginkgo Biloba Extract Is Comparable With Donepezil in Improving Functional Recovery in Alzheimer’s Disease: Results From a Multilevel Characterized Study Based on Clinical Features and Resting-State Functional Magnetic Resonance Imaging

Background: Ginkgo biloba extract (GBE) and donepezil have been reported to be effective in patients with Alzheimer’s disease (AD). Nonetheless, how these drugs impact spontaneous brain activities and how they consequently improve functional recovery are currently unclear. Objectives: This study was to explore the efficacy of GBE vs. donepezil and their add-on efficacy on functional recovery and the adaption of spontaneous brain activities following pharmacologic treatment in patients with AD. Methods: Patients with AD were enrolled and assigned to the GBE group (n = 50), the donepezil group (n = 50), or the combined group (n = 50). Neuropsychological assessments, including minimum mental state examination (MMSE), Alzheimer’s disease assessment scale-cognition (ADAS-Cog), instrumental activity of daily living (IADL), geriatric depression scale (GDS), neuropsychiatric inventory (NPI), and quality of life in Alzheimer’s disease (QOL-AD), were conducted at baseline, 1 month, 3 months, and 6 months. Resting-state functional magnetic resonance imaging (rs-fMRI) was collected to compare the amplitude of low-frequency fluctuation (ALFF), percent amplitude of fluctuation (PerAF), regional homogeneity (ReHo), and degree centrality (DC) at baseline and 6 months. Results: No major significant differences were detected in all comparisons between groups across all follow-up time points. For intragroup comparison, MMSE and ADAS-Cog scores differed significantly across all follow-ups in three groups. The combined group showed significant improvement of GDS scores between baseline and 6 months (p = 0.007). The GBE group (p = 0.044) and donepezil group (p = 0.012) demonstrated significant improvement of NPI scores between baseline and 6 months. Significant correlations were observed between IADL and ALFF in the right gyrus rectus (p = 0.03) and in the left superior cerebellum gyrus (p = 0.01), between GDS and ALFF in the right middle temporal gyrus (p = 0.01), between NPI and PerAF in the left fusiform gyrus (p = 0.03), and between MMSE and ReHo in right superior frontal gyrus (p = 0.04). Conclusion: GBE was comparable with donepezil in the improvement of functional recovery in patients with AD while the combined application of GBE and donepezil seems unnecessary. GBE-mediated improvement of functional recovery was characterized by decreased ALFF values in the right gyrus rectus and decreased PerAF values in the left fusiform gyrus. These featured variations of imaging metrics in specific brain regions may serve as biomarkers in the monitoring of the therapeutic efficacy of GBE.