Influence of the Severity of Cognitive Impairment on the Effect of the <i>Ginkgo biloba</i> Extract EGb 761^® in Alzheimer’s Disease

Abstract

Objective: To explore the treatment effect of EGb 761^® (EGb) in Alzheimer’s disease depending on baseline severity. Methods: We applied stratification to the intent-to-treat data set collected during a 52-week, randomized, double-blind, placebo-controlled, parallel-group, multicenter study with 120 mg of EGb, using cutoff points of 23 and 14 for the Mini-Mental State Examination (MMSE) score. Outcome measures used were the cognitive subscale of the Alzheimer’s Disease Assessment Scale (ADAS-Cog) and the Geriatric Evaluation by Relative’s Rating Instrument (GERRI). Results: In the severity stratum 1 (MMSE >23), the placebo group did not show significant changes, while the EGb group improved significantly by 1.7 points on the ADAS-Cog and by 0.09 points on the GERRI. In the severity stratum 2 (MMSE <24), the placebo group worsened by 4.1 points on the ADAS-Cog and 0.18 points on the GERRI, whereas the EGb group showed 60% less decline on the ADAS-Cog (treatment difference of 2.5 points) and no change on the GERRI (treatment difference of 0.25 points). The most severely impaired subgroup (MMSE <15) showed slightly more pronounced worsening for both treatment groups. However, in comparison to placebo, EGb induced virtually the same magnitude of effect as was observed in the entire stratum 2. Conclusions: The results of this retrospective analysis indicated that a treatment effect favorable to EGb could be observed with respect to cognitive performance (p = 0.02) and social functioning (p = 0.001) regardless of the stage of dementia, whether mild or moderately severe. However, the relative changes from baseline measured at endpoint depended heavily on the severity at baseline. Improvement was observed in the group of patients with very mild to mild cognitive impairment, while in more severe dementia, the mean EGb effect should be considered more in terms of stabilization or slowing down of worsening, as compared to the greater deterioration observed with placebo.

Cognitive tests used in chronic adult human randomised controlled trial micronutrient and phytochemical intervention studies

“…Only seventeen studies (44 %) reported benefits of treatment on cognitive function in the expected direction (19 -23,65,68,75,77,79,80,84,86,89 -92) , of which two were graded as category A (77,80) , seven were category B (21 -23,65,79,86,90) and the rest were category C. Twelve of the seventeen RCT were flavonoid (19 -23,84,86,88 -92) including seven isoflavone studies (19 -22,84,86,89) and four G. biloba interventions (23,88,91,92) . In evaluating these effects of treatment, there was found to be considerable variability in the statistical rigour employed in individual studies.…”

“…The Rey-Osterrieth Complex Figure Test, used in four studies, showed significant positive treatment effects in two (20,91) . (23,24,68,77,88) Outcome measure (24,28,65,66,68,70 -74,76,82,86,89) Positive: flavonoid (89) Baseline measure (19,21,22,65,72) Outcome measure (25) -Y IQ: crystallised intelligence Vocabulary (WAIS) (79,91) Positive: flavonoid (19,21,22,26) Positive: flavonoid (21,22) (20,27,71,75,77,79,88) Positive: flavonoid (88) Negative: flavonoid (20) Y Y Y Exec Fn: planning Stockings of Cambridge (CANTAB) (19,21,22,26) Positive: flavonoid (19,21,22) Y Y (20,24,25,28,29,71,72,79,…”

Interações entre fármacos e medicamentos fitoterápicos à base de ginkgo ou ginseng

“…De acordo com os resultados dos ensaios clínicos randomizados, duplos-cegos e controlados, esses medicamentos são efi cazes no tratamento da claudicação intermitente (Pittler & Ernst, 2000;Jacoby& Mohler, 2004) e da insufi ciência cerebral (doença caracterizada por sintomas típicos, tais como difi culdades de concentração e memória, confusão, indisposição, cansaço, redução da performance física, ansiedade, tontura, zumbido e cefaléia) (Gerhardt et al, 1990;Kleijnen & Knipschild, 1992;Hopfenmüller, 1994), podendo constituir uma alternativa terapêutica para o tratamento de demências do tipo Alzheimer e multi-infarto (Oken et al, 1998;Rogers et al, 1998;Wettstein, 2000;Le Bars et al, 2002;Schulz, 2003) e do zumbido (Ernst & Stevinson, 1999;Drew & Davies, 2001;Morgenstern & Biermann, 2002;Rejali et al, 2004;Smith et al, 2005). Os constituintes químicos considerados ativos do ginkgo são os fl avonóides (glicosídeos de quercetina, canferol e isoramnetina) e as lactonas terpênicas (ginkgolídeos e bilobalídeo) (DeFeudis, 1998).…”

Electrical treatment of reduced consciousness: Experience with coma and Alzheimer's disease

“…On the other hand, the group of AD patients in this latter study was quite heterogeneous with respect to the stage of the disease, ranging from relatively early to advanced, and the onset of the disease, much earlier in the latter study compared to the previous studies. Severity and early onset of the disease are two conditions that might reduce treatment efficacy (CedazoMinguez & Cowburn, 2001;Ho et al, 2002;Le Bars et al, 2002).…”