Ginkgo biloba for the improvement of cognitive performance in multiple sclerosis

Abstract

Objectives To determine if Ginkgo biloba (GB) improves the cognitive performance of subjects with multiple sclerosis (MS).

Methods Randomized, double-blind, placebo-controlled trial of GB, 120 mg twice a day or placebo for 12 weeks. The primary outcomes were: the long delay free recall from the California Verbal Learning Test-II; the Paced Auditory Serial Addition Test; the Controlled Oral Word Association Test; the Symbol Digit Modalities Test; Useful Field of View Test; and the color-word interference condition from the Stroop Color and Word Test.

Results On completion, the GB group (n=20) was 4.5 seconds (95% confidence interval (CI) (7.6, 0.9), P=0.015) faster than the placebo group (n=18) on the color-word interference condition of the Stroop test. Subjects who were more impaired at baseline experienced more improvement with GB (treatment*baseline interaction, F=8.10, P=0.008). We found no differences on the other neuropsychological tests. Subjects on GB reported fewer cognitive difficulties in the Retrospective Memory Scale of the Perceived Deficits Questionnaire than subjects on placebo (1.5 points, 95% CI (2.6, 0.3), P=0.016). No serious drug related side-effects occurred and GB did not alter platelet function assays.

Conclusion Overall, GB did not show a statistically significant improvement in cognitive function. A treatment effect trend, limited to the Stroop test, suggests that GB may have an effect on cognitive domains assessed by this test, such as susceptibility to interference and mental flexibility. Multiple Sclerosis 2007; 13: 376-385. http://msj.sagepub.com

Keywords

cognition double-blind method Ginkgo biloba multiple sclerosis neuropsychological tests placebos quality of life randomized controlled trials

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References

Rao SM , Leo GJ , Bernardin L. , Unverzagt F. Cognitive dysflunction in multiple sclerosis. I. Frequency, patterns, and prediction . Neurology 1991; 41: 685-91 .

Amato MP , Ponziani G. , Siracusa G. , Sorbi S. Cognitive dysflunction in early-onset multiple sclerosis: a reappraisal aflter 10 years . Arch Neurol 2001; 58: 1602606 .

DeFeudis FV Ginkgo biloba extract (EGb 761): pharmacological activities and clinical applications . Elsevier , 1991: 401.

Nathan P. Can the cognitive enhancing eflflects ofl Ginkgo biloba be explained by its pharmacology ? Med Hypotheses 2000; 55: 491-93 .

Huang SH , Duke RK , Chebib M. , Sasaki K. , Wada K. , Johnston GA Ginkgolides, diterpene trilactones ofl Ginkgo biloba, as antagonists at recombinant alpha1beta2gamma2L GABAA receptors . Eur J Pharmacol 2004; 494: 131-38 .

Koltai M. , Hosford D. , Guinot P. , Esanu A. , Braquet P. Platelet activating flactor (PAF). A review ofl its eflflects, antagonists and possible fluture clinical implications (Part I) . Drugs 1991; 42: 9-29 .

Ahlemeyer B. , Krieglstein J. Neuroprotective eflflects ofl Ginkgo biloba extract . Cell Mol Life Sci 2003; 60: 1779 ? 92 .

Oken BS , Storzbach DM , Kaye JA The eflficacy ofl Ginkgo biloba on cognitive flunction in Alzheimer disease . Arch Neurol 1998; 55: 1409-15 .

Yadav V. , Shynto L. , Morris C. , Senders A. , Baldauf-Wagner S. , Bourdette D. Use and selfl reported benefit ofl complementary and alternative medicine (CAM) among multiple sclerosis patients . Int J MS Care 2000; 8: 5-10 .

10.

Brochet B. , Guinot P. , Orgogozo JM , Confavreux C. , Rumbach L. , Lavergne V. Double blind placebo controlled multicentre study ofl ginkgolide B in treatment ofl acute exacerbations ofl multiple sclerosis. The Ginkgolide Study Group in Multiple Sclerosis . J Neurol Neurosurg Psychiatry 1995; 58: 360-62 .

11.

McDonald WI , Compston A. , Edan G. , Goodkin D. , Hartung HP , Lublin FD et al. Recommended diagnostic criteria flor multiple sclerosis: guidelines flrom the International Panel on the diagnosis ofl multiple sclerosis . Ann Neurol 2001; 50: 121-17 .

12.

Fischer JS , Jak AJ , Kniker JE , Rudick RA , Cutter G. Multiple sclerosis functional composite administration and scoring manual [online]. Retrieved flrom http://www.nationalmssociety.org/%5Cpdfl%5Cresearch%5CMSFC_manual_and_florms.pdfl

13.

Lezak MD , Howieson DB , Loring DW , Hannay J. , Fischer JS Neuropsychological assessment, flourth edition. Oxflord University Press , 2004: 519-20.

14.

Boringa JB , Lazeron RH , Reuling IE , Ader HJ , Pfennings L. , Lindeboom J. et al. The briefl repeatable battery ofl neuropsychological tests: normative values allow application in multiple sclerosis clinical practice . Mult Scler 2001; 7: 263-67 .

15.

Ball KK , Roenker DL UFOV: useful field of view. The Psychological Corporation , Harcourt Brace & Company , 1998.

16.

Oken B. , Flegal K. , Zajdel D. , Kishiyama S. , Lovera J. , Bagert B. et al. Cognition and flatigue in multiple sclerosis: potential impact ofl medications with CNS side eflflects . J Rehabil Res 2006; 43: 83-90 .

17.

Spreen O. , Strauss E. A compendium of neuropsychological tests: administration, norms, and commentary , second edition. Oxflord University Press , 1998: 736.

18.

Fischer JS , LaRocca NG , Miller DM , Ritvo PG , Andrews H. , Paty D. Recent developments in the assessment ofl quality ofl lifle in multiple sclerosis (MS) . Mult Scler 1999; 5: 251-59 .

19.

Sullivan MJ , Edgley K. , Dehoux E. A survey ofl multiple sclerosis. Part 1: perceived cognitive problems and compensatory strategy use . Can JRehabil 1990; 4: 99 ? 105 .

20.

Beck AT , Ward CH , Mendelson M. , Mock J. , Erbaugh J. An inventory flor measuring depression . Arch Gen Psychiatry 1961; 4: 561-71 .

21.

Delis D. , Jramer J. , Kaplan E. , Ober BA California Verbal Learning Test, second edition; adult version manual. The Psychological Corporation , 2000: 287.

22.

Elsabagh S. , Hartley DE , File SE Limited cognitive benefits in Stage +2 postmenopausal women aflter 6 weeks ofl treatment with Ginkgo biloba . J Psychopharmacol 2005; 19: 173-81 .

23.

Cohen RA , Fisher M. Amantadine treatment ofl flatigue associated with multiple sclerosis . Arch Neurol 1989; 46: 676-80 .

24.

Krupp LB , Christodoulou C. , Melville P. , Scherl WF , MacAllister WS , Elkins LE Donepezil improved memory in multiple sclerosis in a randomized clinical trial . Neurology 2004; 63: 1579-85 .

25.

Mix JA , Crews WD , Jr. A double-blind, placebo-controlled, randomized trial ofl Ginkgo biloba extract EGb 761 in a sample ofl cognitively intact older adults: neuropsychological findings . Hum Psychopharmacol 2002; 17: 267-77 .

26.

Fong KC , Kinnear PE Retrobulbar haemorrhage associated with chronic Gingko biloba ingestion . Postgrad Med J 2003; 79: 531-32 .

27.

Rosenblatt M. , Mindel J. Spontaneous hyphema associated with ingestion ofl Ginkgo biloba extract . N Engl J Med 1997 ; 336: 1108 .

28.

Miller LG , Freeman B. Possible subdural hematoma associated with Ginkgo biloba . J Herb Pharmacother 2002; 2: 57-63 .

29.

Rowin J. , Lewis SL Spontaneous bilateral subdural hematomas associated with chronic Ginkgo biloba ingestion . Neurology 1996; 46: 1775-76 .

30.

Vale S. Subarachnoid haemorrhage associated with Ginkgo biloba . Lancet 1998; 352: 36 .

31.

Bal Dit Sollier C, Caplain H, Drouet L. No alteration in platelet flunction or coagulation induced by EGb761 in a controlled study . Clin Lab Haematol 2003; 25: 251-53 .

32.

Kohler S. , Funk P. , Kieser M. Influence ofl a 7-day treatment with Ginkgo biloba special extract EGb 761 on bleeding time and coagulation: a randomized, placebo-controlled, double-blind study in healthy volunteers . Blood Coagul Fibrinolysis 2004; 15: 303- 309 .