EGb761 Trials for Mild-to-Moderate Dementia-What Have We Learned in the Past 18 years?

BACKGROUND: Dementia leads to cognitive decline affecting memory, thinking, and behavior. Current pharmaceutical treatments are symptomatic, with limited efficacy and significant drawbacks. Ginkgo biloba extract (EGb761) is being explored as an adjuvant therapy for dementia because of its potential neuroprotective effects.Areas of Uncertainty:Despite decades of study, EGb761 has not been incorporated into treatment guidelines for these conditions. This review evaluates research futility in EGb761 trials for dementia, analyzing efficacy and methodological challenges to inform future research directions. DATA SOURCES: In this review, we investigate the efficacy and adverse reactions of Ginkgo biloba extract (EGb761) as a treatment for Alzheimer disease or vascular dementia. We searched the randomized controlled trials published between 2006 and 2023 on PubMed and ScienceDirect. RESULTS: The 7 selected studies have shown that the degree of improvement in standard cognitive assessment scores [Mini-Mental State Examination (MMSE), short cognitive performance test (SKT), neuropsychiatric inventory (NPI)] was not significant enough for a substantial proportion of patients. Improvements of the SKT score with at least 3 points in the Alzheimer disease/vascular dementia groups were found only in 2 out of 7 studies, changes of less than 2 points in MMSE score were found in 2 of the studies, while an improvement of at least 4 points in NPI scores was reported in 4 out of 7 studies. We aim to understand why this extract has not reached the level of evidence to be included in guideline recommendation despite extensive research and what have we learned from systematic reviews performed since 2010? Studies included in this review have shown some improvement in outcome scores with EGb761 treatment compared with placebo, but these improvements did not reach the threshold for clinically significant enhancement in MMSE/SKT/NPI scores. Limitations such as small sample sizes, minimal score changes, predominantly placebo comparisons, and short follow-up durations make it challenging to determine the usefulness of EGb761 in dementia treatment. The changes observed and methodological constraints underscore the uncertainty surrounding the efficacy of EGb761. CONCLUSION: The findings do not consistently demonstrate the clinical utility of EGb761, and improved scores on cognitive and neuropsychiatric assessments may not necessarily translate into meaningful clinical outcomes for patients with dementia. Starting from the question "What have we learned in the past 18 years?", the answer would be: not much. Consequently, the question raised is: how long should we go on with the same conclusion, continuing to spend time and financial resources to replicate these results? Research strategies should be refined to optimize decision making and advance evidence-based care for neurocognitive disorders.