¹Institute of Pharmaceutical Biology, Goethe-University Frankfurt, Frankfurt am Main, Germany
²Institute of Medical Statistics and Computational Biology, University of Cologne, Cologne, Germany
³ClinCompetence Cologne GmbH, Cologne, Germany
⁴Leibniz Institute for Psychology (ZPID), Trier, Germany

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Background: Anticholinergic drugs as well as polypharmacy are frequently associated with a decline in cognitive function [1] and other adverse effects. The potential to evoke undesired anticholinergic drug effects can be assessed using the German ACB (Anti-Cholinergic Burden) score and a value of >2 should be avoided [2]. In cases where the utilization of anticholinergic drugs cannot be circumvented and deprescribing is difficult, alternative medication strategies are necessary to prevent adverse effects like cognitive impairment.

The utilization of monographed Ginkgo biloba L. leaf extracts (GBE) is conceivable because of their recognized effectiveness and good tolerability [3]. Moreover, preclinical animal studies have already shown that GBE antagonizes cognitive deficits induced by anticholinergic drugs [4].

Our study aimed to investigate the role of GBE in the context of polypharmacy by examining the prevalence of concomitant medication and the potential ACB arising from them. In addition, we assessed the perceived effectiveness and tolerability of GBE in relation to the number of co-medications and the presence of critical ACB scores (>2).

Materials and Methods: We retrospectively analyzed real-world outcomes reported by patients using GBE to treat cognitive impairment. The sample was taken from the pharmacoepidemiologic database PhytoVIS, in which personal therapy experiences with herbal medicinal products were collected alongside with information on drug utilization patterns, comorbidities and comedication [5]. For all cases with concomitant medication, we determined the number of co-medications (categorized as +1, +2, or ≥3) and the cumulative anticholinergic burden using the German ACB score [2]. Descriptive statistics and non-parametric bivariate statistical tests (Spearman correlation) were applied to assess associations between variables.

Results: Out of 191 patients, two third took GBE alongside with concomitant medication (64.9%; n=124), whereby about half (48.4 %, n=60) took one additional drug, nearly a third (31.5 %, n=39) took two, and a fifth (20.2 %, n=25) three or more; the number of concomitant drugs increased with advancing age (Spearman ρ=0.44, p<0.001***).

Perceived effectiveness of GBE was high: 90,6 % (n=173) reported a therapeutic benefit, regardless of any concomitant medication. Tolerability was similarly favorable: 89 % (n=170) experienced no adverse events. There was no correlation between the perceived effectiveness and tolerability and the number of co-medications (Spearman ρ_Eff=0.05, p=0.478; ρ_Tol=0.06, p=0.452).

Regarding the ACB, almost three quarters (71.8 %, n=89) took exclusively non-anticholinergic drugs; among those taking at least one anticholinergic agent (28.2 %, n=35), cumulative ACB scores were generally low (ACB=1 in 23.4 % (n=29), ACB=2 in 1.6 % (n=2), and a critical ACB >2 in 3.2 % (n=4)). The four patients with a ACB >2 were all older than 50 years with multiple comorbidities and co-medications. In all four cases GBE was rated as therapeutically effective and without any adverse events.

Conclusion: Our results demonstrate that GBE is an effective and well tolerated option for the treatment of cognitive impairment, even in combination with multiple co-medications. Despite limited number of cases with critical ACB >2 (n=4), our study exhibited excellent outcomes. Retrospective longitudinal studies with larger samples including population based health and outcome studies would help to further clarify the potential of GBE in managing cognitive impairment related to polypharmacy and anticholinergic therapies.

References

[1] Fox C, Smith T, Maidment I, Chan WY, Bua N, Myint PK, Boustani M, Kwok CS, Glover M, Koopmans I, Campbell N. Effect of medications with anti-cholinergic properties on cognitive function, delirium, physical function and mortality: a systematic review. Age Ageing. 2014 Sep;43(5):604-15. DOI: 10.1093/ageing/afu096
[2] Kiesel EK, Hopf YM, Drey M. An anticholinergic burden score for German prescribers: score development. BMC Geriatr. 2018 Oct 11;18(1):239. DOI: 10.1186/s12877-018-0929-6
[3] European Medicines Agency (Committee on Herbal Medicinal Products - HMPC). Final assessment report on Ginkgo biloba L., folium. Reference Number: EMA/HMPC/321095/2012. EMA; 2015. Available from: https://www.ema.europa.eu/en/medicines/herbal/ginkgo-folium
[4] Zhang GJ, Zheng D, Yu H, Luo XP, Wu W. Ginkgo Biloba Extract Ameliorates Scopolamine-induced Memory Deficits via Rescuing Synaptic Damage. Curr Med Sci. 2022 Jun;42(3):474-82. DOI: 10.1007/s11596-022-2582-8
[5] Wegener T, Nieber K, Kraft K, Siegmund S, Kelber O, Jobst D, Steinhoff B. Versorgungsforschung mit pflanzlichen Arzneimitteln – Die pharmakoepidemiologische Datenbank PhytoVIS. Zeitschrift für Phytotherapie. 2021;42(03):127-35. DOI: 10.1055/a-1406-4253