Cistanche tubulosa-Ginkgo biloba Combination Enhances Memory via Cortico-Cerebellar Reorganization: A Randomized Controlled Trial

Abstract

Background: Age-related memory decline has emerged as a critical global public health challenge, yet few ethnopharmacological interventions have demonstrated robust clinical efficacy in improving memory and cognitive function. Objectives: This randomized, double-blind, placebo-controlled trial aimed to elucidate the neurocognitive-enhancing mechanisms of a botanical product containing Cistanche tubulosa [Schenk] Wight and Ginkgo biloba L. (CG) extracts. Methods:117 healthy participants (aged 30-65 years) were randomized to receive either CG tablets or placebo for 30 days. Clinical memory assessments and MRI scans were conducted at baseline and post-intervention. Gray matter volume (GMV), functional MRI (fMRI), and functional connectivity (FC) were analyzed using SPM12. Results: CG tablets significantly improved scores in across multiple dimensions, including directional memory, associative learning, graphic free recall, portrait memory, total memory, and Memory Quotient (all p<0.01). Subgroup analyses by age (<50 vs. ≥50) and gender confirmed the consistency of these effects. After intervention, slight reductions in GMV were observed in precentral gyrus and supplementary motor area. Notably, greater improvement in clinical memory scores was associated with lower post-intervention GMV in these regions. Concurrently, fMRI revealed increased activity in the cerebellar culmen, which positively correlated with improvements in directional memory (p=0.031) and total memory score (p=0.007). The associations between memory improvement, localized GMV reduction, and increased cerebellar activity suggests that CG may optimize neural efficiency or drive functional network reorganization. Conclusion: These findings indicated that CG supplementation enhances memory function in healthy adults. These cognitive gains are linked to specific structural and functional neural changes, particularly in motor-related areas and the cerebellum, reflecting improved neural processing. While these findings highlight CG's short-term benefits, further research is warranted to explore its long-term efficacy and broader clinical utility. This stduy was registered at the Chinese Clinical Trials Registry (https://www.chictr.org.cn/): ChiCTR2400084102.