Ginkgo Biloba for Alzheimer's Disease: From Mixed Dementia Trials to Biomarker-Confirmed Mild Cognitive Impairment-What Have We Learned over Two Decades, and Is There Finally a Bit of Hope?

Abstract

Ginkgo biloba products have been used for decades for cognitive symptoms, yet the clinical evidence in Alzheimer's disease (AD) remains modest and heterogeneous. This review revisits key symptomatic and prevention trials and summarizes how systematic reviews and meta-analyses have informed ongoing clinical skepticism, often citing small effect sizes, limited patient-centered meaningfulness, short follow-up, and repeated trial designs. We suggest that long-standing ambiguity reflects multiple, overlapping sources of heterogeneity, including mixed-pathology recruitment, variable dosing and exposure duration, inconsistent outcome frameworks, and limited integration of biological readouts; differences across preparations and characterization practices may further contribute to variability. In the biomarker era, AD is increasingly defined biologically, and amyloid PET-confirmed cohorts offer a clearer test by reducing diagnostic noise and enabling mechanism-adjacent interpretation. Recent studies in amyloid PET-positive MCI/AD report clinical preservation alongside directional changes in plasma oligomerization tendency (MDS-OAβ), with decreases in treated groups compared with increases in controls. While such findings cannot, by design, establish disease-modifying effects, they provide a biologically anchored context for interpreting modest clinical signals. We conclude with practical recommendations to align cohort biology, stage, exposure certainty, duration, endpoints, and biomarker panels in next-generation trials of Ginkgo preparations in early AD-spectrum disease.