Combination of EGb 761 & Acetylcholinesterase Inhibitors Reduces Cognitive Impairment and Neuropsychiatric Symptoms in Subjects with Mild Cognitive Impairment

by | May 21, 2024 | Botanicals, Brain Health, Cognitive Health, Ginkgo Biloba, Recent Articles

Written by Taylor Woosley, Science Writer. 12-month supplementation of EGb 761 either alone or in combination with AChEI was associated with improved cognitive abilities and reduced neuropsychiatric symptoms. 

agingAs we age, cognitive decline occurs gradually from normal aging to mild cognitive impairment (MCI) and dementia1. MCI is a clinical condition characterized by a reduction in memory and/or various cognitive abilities that are more pronounced than cognitive decline associated with aging but insufficiently severe enough to be diagnosed as dementia2. Approximately 10-15% of individuals with MCI develop dementia every year, compared to 1-2% in unaffected individuals3.

Currently, the only drugs used and approved by the FDA for the treatment of mild and moderate dementia are Acetylcholinesterase (AChE) inhibitors, although they have numerous side effects such as nausea and fatigue4. However, the Gingko biloba special extract, EGb 761, has also been widely used to treatment cognitive disorders5. Preclinical evidence suggests that EGb 761 exhibits beneficial effects on mitochondrial function through potent antioxidant activity, reducing oxidative cell damage, and protecting neurons from amyloid-beta (Aβ)-induced toxicity6.

Garcia-Alberca et al. conducted a retrospective analysis to analyze the efficacy of EGb 761 alone and the added effects of a combination therapy of EGb 761 plus AChEIs using service provision data of subjects with MCI from the Instituto Andaluz de Neurosciencia (IANEC) over a 12-month period. Information obtained through participant’s medical records included MCI diagnosis by a neurologist or psychiatrist, treatment option (EGb 761 alone, ACEI alone, or a combination), physical examination, neurological and psychiatric examination, neuropsychological assessment, and magnetic resonance imaging (MRI) results. Subject exclusion consisted of subjects with dementia, inflammatory brain diseases, substance abuse, and absence of a complete medical history.

Subjects were divided into three groups: EGb 761 only, AChEI only, or EGb plus AChEI. EGb 761 was supplemented at 240 mg daily and the AChEI group consumed either donepzel at 5 or 10 mg daily, galantamine at 16 or 24 mg daily, or a rivastigmine patch at 9.5 or 13.3 mg daily. Cognition, behavior, and functional performance were assessed at baseline, 6 months, and 12 months into the study by completion of the Mini-Mental State Examination (MMSE), the Rey Auditory Verbal Learning Test (RAVLT), the Symbol Digit Modalities Test (SDMT), the Boston Naming Test (BNT), the Trail Making Test (TMT). Verbal fluency was measured using the Letter fluency test (LFT) and the Category fluency test (CFT). The Neuropsychiatric Inventory (NPI) was utilized to analyze behavioral and psychological symptoms of dementia.

An analysis of variance (ANOVA) or non-parametric tests were used to assess baseline differences between the two treatment groups. Evaluation of changes in cognitive, functional, and neuropsychiatric scores were analyzed by a Mixed Model for Repeated Measures (MMRM). 133 subjects were included in the final analysis (98 female, 35 male), with a mean age of 75.66 ± 5.71 years. No significant differences were noted between groups at baseline except for sex and MCI duration (p = 0.001). Significant findings of the study include:

  • MMRM analysis of MMSE results over time shows a statistically significant time by treatment effect (F(2,130) = 20.628, p < 0.0001). EGb 761 plus AChEI performed better than the AChEI group alone at 12 months (+1.41 points, 95% CI: 0.55 to 2.27, p < 0.0001), with improvement as early as 6 months.
  • MMRM analysis showed a statistically significant time by treatment effect for RAVLT (p < 0.0001), CFT (p < 0.0001), TMT-A and TMT-B (p < 0.0001).
  • The EGb 761 plus AChEI group performed better than the AChEI group at 12-months for RAVLT (p = 0.022), CFT (p = 0.005), TMT-A (p = 0.003), and TMT-B (p < 0.0001).
  • MMRM analysis shows that the EGb 761 plus AChEI group performed better than the AChEI group at 12 months (p = 0.005), with improvements as early as 6 months.

Results of the study show that 12-month treatment of EGb 761 alone or in combination with AChEI was associated with significant reduction in cognitive impairment and neuropsychiatric symptoms. Further research should continue to explore the potential neuroprotective benefits of EGb 761. Study limitations include the retrospective nature of the study, the small sample size, and the lack of casualty due to the observational design of the study.

Source: García‐Alberca, José María, Esther Gris, and Silvia Mendoza. “Combined treatment with Ginkgo biloba extract EGb 761 plus acetylcholinesterase inhibitors improved cognitive function and neuropsychiatric symptoms in patients with mild cognitive impairment.” Alzheimer’s & Dementia: Translational Research & Clinical Interventions 8, no. 1 (2022): e12338.

© 2022 The Authors. Alzheimer’s & Dementia: Translational Research & Clinical Interventions published by Wiley Periodicals LLC on behalf of Alzheimer’s Association.

Click here to read the full text study.

Posted May 21, 2024.

Taylor Woosley studied biology at Purdue University before becoming a 2016 graduate of Columbia College Chicago with a major in Writing. She currently resides in Glen Ellyn, IL.

References:

  1. Khine WWT, Voong ML, Ng TKS, et al. Mental awareness improved mild cognitive impairment and modulated gut microbiome. Aging (Albany NY). Dec 9 2020;12(23):24371-24393. doi:10.18632/aging.202277
  2. Peng Z, Jiang H, Wang X, et al. The Efficacy of Cognitive Training for Elderly Chinese Individuals with Mild Cognitive Impairment. Biomed Res Int. 2019;2019:4347281. doi:10.1155/2019/4347281
  3. Giau VV, Bagyinszky E, An SSA. Potential Fluid Biomarkers for the Diagnosis of Mild Cognitive Impairment. Int J Mol Sci. Aug 25 2019;20(17)doi:10.3390/ijms20174149
  4. Tomino C, Ilari S, Solfrizzi V, et al. Mild Cognitive Impairment and Mild Dementia: The Role of Ginkgo biloba (EGb 761(®)). Pharmaceuticals (Basel, Switzerland). Apr 1 2021;14(4)doi:10.3390/ph14040305
  5. Kandiah N, Ong PA, Yuda T, et al. Treatment of dementia and mild cognitive impairment with or without cerebrovascular disease: Expert consensus on the use of Ginkgo biloba extract, EGb 761(®). CNS Neurosci Ther. Feb 2019;25(2):288-298. doi:10.1111/cns.13095
  6. Kandiah N, Chan YF, Chen C, et al. Strategies for the use of Ginkgo biloba extract, EGb 761(®) , in the treatment and management of mild cognitive impairment in Asia: Expert consensus. CNS Neurosci Ther. Feb 2021;27(2):149-162. doi:10.1111/cns.13536