Ginkgo biloba alleviated mild neurocognitive deficits

The conclusion of a review published in the journal Neuropsychiatric Disease and Treatment in 2023 was that a proprietary Ginkgo biloba special extract led to improvements in various cognitive and neuropsychiatric symptoms in people with mild cognitive impairment and proved to be well tolerated.

The Ginkgo biloba special extract EGb® 761, which is licensed in Switzerland under the trade name Tebokan® , has been extensively investigated in numerous preclinical and clinical studies [1,2,8,9]. This demonstrated vasoregulatory and vasoprotective properties as well as an improvement in blood flow [1,2]. In addition, antioxidant properties and protection of mitochondrial function have been identified – processes that play an important role in the pathophysiology of dementia [1]. Based on these results, the Committee on Herbal Medicinal Products (HMPC ) of the European Medicines Agency (E MA) issued a recommendation for the use of EGb® 761 for “the improvement of (age-related) cognitive impairment and quality of life in mild dementia” [3]. In addition, there are various consensus-based expert recommendations and practice guidelines in which EGb® 761 is recommended for the treatment of mild cognitive impairment ( MCI) [4,5]. People with these deficits, also referred to in the DSM-5 as “mild neurocognitive disorder ” (mild NCD), are hardly restricted in their activities of daily living ( ADL), but there are measurable deficits in individual neurocognitive domains. In contrast to earlier secondary analyses, in which the positive effects of EGb® 761 in mild to moderate dementia were summarized [6,7], Hort et al. in their secondary analysis on studies in people with mild NCDs [8].

Placebo-controlled studies with a high level of evidence

The inclusion criterion of the systematic review was defined in such a way that the mild NCD should meet the DSM-5 criteria. This was classified retrospectively based on the neuropsychiatric test batteries used in the respective studies (box) or the corresponding test results [9–11]. This presupposed that the operationalization of the endpoints in the studies was chosen in such a way that the therapeutic efficacy in patients with mild NCD could be assessed, i.e. standardized neuropsychological tests, established scales for assessing neuropsychiatric symptoms and geriatric rating scales were used. A total of 9 randomized controlled double-blind clinical trials with 946 participants were selected in which patients with NCD were treated with the Ginkgo biloba extract EGb® 761 over a period of at least 8 weeks (Table 1) [8]. A further inclusion criterion was that EGb® 761 had been the only active substance taken to treat the cognitive deficits for a period of at least 8 weeks. The included studies were published between 1987 and 2019. The daily dose of EGb® 761 ranged from 120 mg to 240 mg and the treatment periods were 8 to 52 weeks. In all studies, significant improvements in cognitive function, neuropsychiatric symptoms and geriatric assessments were documented in the Ginkgo biloba study arms.

Validated neurocognitive test procedures

Treatment effects were reported for composite neuropsychological tests (ADAS-cog, MMSE, SKT), tests of working memory and short- and long-term memory (short-term storage capacity, memory test, WMS-III, face recognition, Israël’s Memory Battery). In addition, various neuropsychological tests of attention (TMT-A, WTS attention sub-tests) and executive functions (TMT-B) were used. In an assessment scale regarding the severity of dementia (CDR-SB) in patients with mild NCD, there was a trend in favor of EGb® 761, while an ADL scale for patients with MCI (ADCS-ADL-MCI-24) showed a significant treatment effect of EGb® 761. In a study with a 52-week treatment phase, progression to dementia was observed in 1 out of 104 (=0.96%) participants in the EGb® 761 arm, while this was the case in 7 out of 70 (=10%) participants in the placebo arm (p=0.0076). The Ginkgo biloba study arms proved to be superior with regard to the geriatric rating scale (SCAG) and the overall clinical impression (CGIC) and an assessment of treatment satisfaction. And in the three studies in which patients with mild NCD and depression or other relevant neuropsychiatric symptoms were included at baseline, EGb® 761 was found to be superior to placebo based on changes in the neuropychiatric inventory and the HAMD scale. EGb® 761 was also convincing in terms of its safety profile, as the rate of undesirable side effects was similar to placebo. This is an important factor in terms of patient adherence. Other drugs have also been shown to be effective for mild cognitive impairment. Whether the use of synthetic drugs such as cholinesterase inhibitors or donepezil, which are actually intended for the treatment of manifest dementia, also makes sense for people with only mild NCD, is questioned by Hort et al. in view of the broader spectrum of possible side effects [8].

Literature:

Lang F, et al: In: Wagner H, Ulrich-Merzenich G, editors. Evidence and Rational Based Research on Chinese Drugs. Springer Vienna; 2013: 431-470.
Kellermann AJ, Kloft C: Pharmacotherapy 2011; 31(5): 490-502.
EMA: HMPC. European Union Herbal Monograph on Ginkgo Biloba L., Folium. European Medicines Agency; 2015.
Kasper S, et al: World J Biol Psychiatry 2020; 21(8): 579-594.
Kandiah N, et al: CNS Neurosci Ther 2021; 27: 149-162.
Hashiguchi M, et al: J Pharm Health Care Sci 2015; 1: 14.
Gauthier S, Schlaefke S: Clin Interv Aging 2014; 9: 2065-2077.
Hort J, Duning T, Hoerr R: Neuropsychiatr Dis Treat 2023; 19: 647-660.
Swissmedic: Medicinal product information, www.swissmedicinfo.ch,(last accessed 06.03.2024)
Hoerr R, Zaudig M: Eur Arch Psychiatry Clin Neurosci 2016; 266(3): 249-259.
American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders: DSM-5. American Psychiatric Association; 2013.
Tian J, et al: Alzheimers Dement 2019; 5(1): 441-449.
Gavrilova SI, et al: Int J Geriatr Psychiatry 2014; 29(10): 1087-1095.
Grass-Kapanke B, et al: Neurosci Med 2011; 02(01): 48-56.
Schubert H, Halama P: Geriatrics Research 1993; 3(1): 45-53.
Stocksmeier U, Eberlein M: TW Neurology Psychiatry 1992; 6:74-76.
Gräßel E: Fortschr Med 1992; 110(5): 73-78.
Halama P, Bartsch G, Meng G: Fortschr Med 1988; 106(19): 408-412.
Israel L, et al: Psychol Med 1987;19(8): 1431-1439.
Wesnes K, et al: Hum Psychopharmacol 1987; 2: 159-169.