Guideline recommends Ginkgo biloba special extract

A multimodal concept is being propagated for the treatment of dementia, which includes non-pharmacological and pharmacological measures. There is a broad evidence base for a proprietary Ginkgo biloba extract for Alzheimer’s disease as well as for vascular and mixed forms of dementia. The guideline recommends this phytopharmacological preparation in particular for mild to moderate dementia symptoms to improve cognition and everyday functions.

The completely revised S3 guideline “Dementia” was published at the end of 2023 and replaces the previous version from 2016 [1]. Dementia increases exponentially with age. While around 0.1% of the population under the age of 65 is affected by dementia, the prevalence in the 80-84 age group is around 13-16% [1]. By far the most common is Alzheimer’s disease, which accounts for 60-80% of all cases; the second most common are vascular dementias caused by circulatory disorders of the brain tissue. Rarer causes include Parkinson’s disease, dementia with Lewy bodies and frontotemporal dementia, with the frequency of mixed pathologies increasing with age [2].

Treatment depends on the severity or stage of the disease

The MMST (Mini-Mental Status Test) score is commonly used to classify the severity of dementia, although it should be noted that it should be used as part of a comprehensive clinical assessment [3]. According to the MMST, a distinction is made between the following manifestations:

• easy: 20-26 points
• moderate: 10-19 points
• difficult: 0-9 points

In addition, a distinction is made between early-onset and late-onset forms of Alzheimer’s dementia, i.e. those with onset from the age of 65, usually in the late 70s or later, with slow progression and with memory impairment as the main feature. The care of people with dementia depends on the stage. Treatment options include drug and non-drug measures to treat the primary symptoms of dementia (cognitive impairment and functional impairment), as well as psychological and behavioral symptoms. Mild cognitive impairment ( MCI) is an important early or risk syndrome of dementia and is increasingly being diagnosed in clinical practice. In the future ICD-11 and DSM-5, MCI is defined as a mild neurocognitive disorder and in the context of specific neurodegenerative diseases, such as Alzheimer’s disease [4,5].

Which treatment modalities are recommended?

Among the non-pharmacological interventions, the implementation of cognitive training or cognitive stimulation is suggested for people with mild cognitive impairment. Physical training (strength training and/or aerobic training) is also rated with recommendation grade B for this patient subgroup. In a meta-analysis of 33 studies (n = 1389), the use of cognitive training also achieved a moderate effect (standardized mean difference: 0.42; 95% CI 0.23 to 0.62) on cognition in mild to moderate dementia, with indications of lasting effects after the end of the intervention. Cognitive training can be carried out by physicians, but also by (neuro-)psychologists, occupational therapists or social pedagogues.
Various symptomatic treatment options are listed for drug treatment. The spectrum of recommended synthetic pharmacotherapeutic agents for Alzheimer’s-type dementia primarily includes acetylcholine sterase (AchE) inhibitors (donepezil, galantamine, rivastigmine) and memantine**. A combination of AchE inhibitors with memantine is not recommended. According to the guideline, donepezil, galantamine or memantine can be used for vascular dementia.

** not recommended for mild Alzheimer’s dementia due to lack of evidence of efficacy

Evidence for Ginkgo biloba EGb 761®

Among phytotherapeutics, the use of Ginkgo biloba extract EGb 761® is favored. In Switzerland, this medicine is approved by health insurance companies under the trade name Tebokan® [6]. In the guideline, Ginkgo biloba EGb 761® (240 mg) is attributed a benefit for improving everyday functions and cognition, particularly in people with dementia and non-psychotic behavioral symptoms (e.g. anxiety, depression), based on corresponding study findings. Several randomized controlled trials are available on the efficacy of Ginkgo biloba EGb 761®. The study populations included people with Alzheimer’s dementia, mixed dementia and vascular dementia of mild to moderate severity. A meta-analysis of 9 studies with 2,561 people showed a statistically significant standardized mean difference of -2.86 (95% CI: -3.18 to -2.54) on cognition and -0.36 (95% CI -0.44; -0.28) on everyday functions compared to placebo. The effects were similarly pronounced in the subgroup of people with Alzheimer’s dementia as in the subgroups with mixed and vascular dementia. In the group of people with non-psychotic neuropsychiatric symptoms (e.g. anxiety, depression), the effects were greater than in the overall group. There were no increased rates of side effects in the placebo comparison [7].

The guideline authors point out that studies conducted on Ginkgo biloba EGb 761® usually have broader inclusion criteria than studies on acetylcholinesterase inhibitors or memantine. In addition, other instruments were sometimes used to record the endpoints, so that a direct comparison of the data between the interventions is only possible to a limited extent.

In addition to efficacy and general side effect rates, the issue of bleeding risk in particular is discussed. In a meta-analysis based on 18 randomized, controlled trials, the effect of standardized Ginkgo biloba leaf extracts on parameters of hemostasis in relation to bleeding risk was investigated. A comparison of the mean difference at the end of treatment or the change from baseline during treatment between the verum and placebo groups resulted in the conclusion that there was no evidence of an increased risk of bleeding [8].

Literature:

1. Bahar-Fuchs A, et al.: Cognitive training for people with mild to moderate dementia. Cochrane Database Syst Rev 2019; 3(3): CD013069.
2. DGN & DGPPN (Hrsg.): S3-Leitlinie Demenzen, Version 4.0, 28.11.2023, AWMF-Registernummer 038/013.
3. Gaugler J, et al.: Alzheimer’s disease facts and figures. Alzheimers & Dementia 2022; 18(4): 700–789.
4. Piersma D, et al.: The MMSE should not be the sole indicator of fitness to drive in mild Alzheimer’s dementia. Acta Neurol Belg 2018; 118(4): 637–642.
5. ICD-11. Internationale statistische Klassifikation der Krankheiten und verwandter Gesundheitsprobleme, 11. Revision 2023b.
6. Diagnostic and statistical manual of mental disorders: DSM-5™ (5th ed.): American Psychiatric Publishing, Inc. 2013. https://doi.org/10.1176/appi.books.9780890425596.
7. Swissmedic: Arzneimittelinformation, www.swissmedicinfo.ch, (letzter Abruf 24.06.2024)
8. Tan MS, et al.: Efficacy and adverse effects of ginkgo biloba for cognitive impairment and dementia: a systematic review and meta-analysis. J Alzheimers Dis 2015; 43(2): 589–603.
9. Kellermann AJ, Kloft C: Is there a risk of bleeding associated with standardized Ginkgo biloba extract therapy? A systematic review and meta-analysis. Pharmacotherapy 2011; 31(5): 490–502.

FAMILY PHYSICIAN PRACTICE 2024; 19(7): 29-30