Ginkgo biloba for preventing cognitive decline in older adults: a randomized trial

Beth E Snitz, Ellen S O'Meara, Michelle C Carlson, Alice M Arnold, Diane G Ives, Stephen R Rapp, Judith Saxton, Oscar L Lopez, Leslie O Dunn, Kaycee M Sink, Steven T DeKosky, Ginkgo Evaluation of Memory (GEM) Study Investigators, Richard L Nahin, Barbara C Sorkin, Michelle Carlson, Linda Fried, Pat Crowley, Claudia Kawas, Paulo Chaves, Sevil Yasar, Patricia Smith, Joyce Chabot, John Robbins, Katherine Gundling, Sharene Theroux, Lisa Pastore, Lewis Kuller, Roberta Moyer, Cheryl Albig, Gregory Burke, Steve Rapp, Dee Posey, Margie Lamb, Robert Hörr, Joachim Herrmann, Richard A Kronmal, Annette L Fitzpatrick, Fumei Lin, Cam Solomon, Alice Arnold, Steven DeKosky, Judith Saxton, Oscar Lopez, Beth Snitz, M Ilyas Kamboh, Diane Ives, Leslie Dunn, Curt Furberg, Jeff Williamson, Nancy Woolard, Kathryn Bender, Susan Margitic, Russell Tracy, Elaine Cornell, William Rothfus, Charles Lee, Rose Jarosz, Richard Grimm, Jonathan Berman, Hannah Bradford, Carlo Calabrese, Rick Chappell, Kathryn Connor, Gail Geller, Boris Iglewicz, Richard S Panush, Richard Shader, Beth E Snitz, Ellen S O'Meara, Michelle C Carlson, Alice M Arnold, Diane G Ives, Stephen R Rapp, Judith Saxton, Oscar L Lopez, Leslie O Dunn, Kaycee M Sink, Steven T DeKosky, Ginkgo Evaluation of Memory (GEM) Study Investigators, Richard L Nahin, Barbara C Sorkin, Michelle Carlson, Linda Fried, Pat Crowley, Claudia Kawas, Paulo Chaves, Sevil Yasar, Patricia Smith, Joyce Chabot, John Robbins, Katherine Gundling, Sharene Theroux, Lisa Pastore, Lewis Kuller, Roberta Moyer, Cheryl Albig, Gregory Burke, Steve Rapp, Dee Posey, Margie Lamb, Robert Hörr, Joachim Herrmann, Richard A Kronmal, Annette L Fitzpatrick, Fumei Lin, Cam Solomon, Alice Arnold, Steven DeKosky, Judith Saxton, Oscar Lopez, Beth Snitz, M Ilyas Kamboh, Diane Ives, Leslie Dunn, Curt Furberg, Jeff Williamson, Nancy Woolard, Kathryn Bender, Susan Margitic, Russell Tracy, Elaine Cornell, William Rothfus, Charles Lee, Rose Jarosz, Richard Grimm, Jonathan Berman, Hannah Bradford, Carlo Calabrese, Rick Chappell, Kathryn Connor, Gail Geller, Boris Iglewicz, Richard S Panush, Richard Shader

Abstract

Context: The herbal product Ginkgo biloba is taken frequently with the intention of improving cognitive health in aging. However, evidence from adequately powered clinical trials is lacking regarding its effect on long-term cognitive functioning.

Objective: To determine whether G. biloba slows the rates of global or domain-specific cognitive decline in older adults.

Design, setting, and participants: The Ginkgo Evaluation of Memory (GEM) study, a randomized, double-blind, placebo-controlled clinical trial of 3069 community-dwelling participants aged 72 to 96 years, conducted in 6 academic medical centers in the United States between 2000 and 2008, with a median follow-up of 6.1 years.

Intervention: Twice-daily dose of 120-mg extract of G. biloba (n = 1545) or identical-appearing placebo (n = 1524).

Main outcome measures: Rates of change over time in the Modified Mini-Mental State Examination (3MSE), in the cognitive subscale of the Alzheimer Disease Assessment Scale (ADAS-Cog), and in neuropsychological domains of memory, attention, visual-spatial construction, language, and executive functions, based on sums of z scores of individual tests.

Results: Annual rates of decline in z scores did not differ between G. biloba and placebo groups in any domains, including memory (0.043; 95% confidence interval [CI], 0.034-0.051 vs 0.041; 95% CI, 0.032-0.050), attention (0.043; 95% CI, 0.037-0.050 vs 0.048; 95% CI, 0.041-0.054), visuospatial abilities (0.107; 95% CI, 0.097-0.117 vs 0.118; 95% CI, 0.108-0.128), language (0.045; 95% CI, 0.037-0.054 vs 0.041; 95% CI, 0.033-0.048), and executive functions (0.092; 95% CI, 0.086-0.099 vs 0.089; 95% CI, 0.082-0.096). For the 3MSE and ADAS-Cog, rates of change varied by baseline cognitive status (mild cognitive impairment), but there were no differences in rates of change between treatment groups (for 3MSE, P = .71; for ADAS-Cog, P = .97). There was no significant effect modification of treatment on rate of decline by age, sex, race, education, APOE*E4 allele, or baseline mild cognitive impairment (P > .05).

Conclusion: Compared with placebo, the use of G. biloba, 120 mg twice daily, did not result in less cognitive decline in older adults with normal cognition or with mild cognitive impairment.

Trial registration: clinicaltrials.gov Identifier: NCT00010803.

Figures

Figure
Figure
Flow of Participants Through the Ginkgo Evaluation of Memory Study and Longitudinal Cognitive Decline Analysis

References

    1. DeKosky ST, Williamson JD, Fitzpatrick AL, et al. Ginkgo Evaluation of Memory (GEM) Study Investigators Ginkgo biloba for prevention of dementia: a randomized controlled trial. JAMA. 2008;300(19):2253–2262.
    1. Barnes PM, Bloom B, Nahin RL. Complementary and Alternative Medicine Use Among Adults and Children: United States, 2007. US Dept of Health and Human Services; Washington, DC: 2008. National Health Statistics Reports.
    1. Huang S-Y, Jeng C, Kao S-C, Yu JJ-H, Liu D-Z. Improved haemorrheological properties by Ginkgo biloba extract (Egb 761) in type 2 diabetes mellitus complicated with retinopathy. Clin Nutr. 2004;23(4):615–621.
    1. Chen X, Salwinski S, Lee TJ. Extracts of Ginkgo biloba and ginsenosides exert cerebral vasorelaxation via a nitric oxide pathway. Clin Exp Pharmacol Physiol. 1997;24(12):958–959.
    1. Pietri S, Maurelli E, Drieu K, Culcasi M. Cardioprotective and anti-oxidant effects of the terpenoid constituents of Ginkgo biloba extract (EGb 761) J Mol Cell Cardiol. 1997;29(2):733–742.
    1. Hadjiivanova CI, Petkov VV. Effect of Ginkgo biloba extract on beta-adrenergic receptors in different rat brain regions. Phytother Res. 2002;16(5):488–490.
    1. Huguet F, Tarrade T. Alpha 2-adrenoceptor changes during cerebral ageing: the effect of Ginkgo biloba extract. J Pharm Pharmacol. 1992;44(1):24–27.
    1. Luo Y, Smith JV, Paramasivam V, et al. Inhibition of amyloid-beta aggregation and caspase-3 activation by the Ginkgo biloba extract EGb761. Proc Natl Acad Sci U S A. 2002;99(19):12197–12202.
    1. Kaschel R. Ginkgo biloba: specificity of neuropsychological improvement–a selective review in search of differential effects. Hum Psychopharmacol. 2009;24(5):345–370.
    1. Allain H, Raoul P, Lieury A, LeCoz F, Gandon JM, d'Arbigny P. Effect of two doses of Ginkgo biloba extract (EGb 761) on the dual-coding test in elderly subjects. Clin Ther. 1993;15(3):549–558.
    1. Kennedy DO, Scholey AB, Wesnes KA. The dose-dependent cognitive effects of acute administration of Ginkgo biloba to healthy young volunteers. Psychopharmacology (Berl) 2000;151(4):416–423.
    1. Hindmarch I. Activity of Ginkgo biloba extract on short-term memory [in French] Presse Med. 1986;15(31):1592–1594.
    1. van Dongen M, van Rossum E, Kessels A, Sielhorst H, Knipschild P. Ginkgo for elderly people with dementia and age-associated memory impairment: a randomized clinical trial. J Clin Epidemiol. 2003;56(4):367–376.
    1. Wesnes KA, Ward T, McGinty A, Petrini O. The memory enhancing effects of a Ginkgo biloba/Panax ginseng combination in healthy middle-aged volunteers. Psychopharmacology (Berl) 2000;152(4):353–361.
    1. DeKosky ST, Fitzpatrick A, Ives DG, et al. GEMS Investigators The Ginkgo Evaluation of Memory (GEM) study: design and baseline data of a randomized trial of Ginkgo biloba extract in prevention of dementia. Contemp Clin Trials. 2006;27(3):238–253.
    1. Fitzpatrick AL, Fried LP, Williamson J, et al. GEM Study Investigators Recruitment of the elderly into a pharmacologic prevention trial: the Ginkgo Evaluation of Memory Study experience. Contemp Clin Trials. 2006;27(6):541–553.
    1. Diagnostic and Statistical Manual of Mental Disorders. 4th ed. American Psychiatric Association; Washington, DC: 2000.
    1. Hughes CP, Berg L, Danziger WL, Coben LA, Martin RL. A new clinical scale for the staging of dementia. Br J Psychiatry. 1982;140:566–572.
    1. Winblad B, Palmer K, Kivipelto M, et al. Mild cognitive impairment—beyond controversies, towards a consensus: report of the International Working Group on Mild Cognitive Impairment. J Intern Med. 2004;256(3):240–246.
    1. Snitz BE, Saxton J, Lopez OL, et al. GEM Study Investigators Identifying mild cognitive impairment at baseline in the Ginkgo Evaluation of Memory (GEM) study. Aging Ment Health. 2009;13(2):171–182.
    1. Teng EL, Chui HC. The Modified Mini-Mental State (3MS) Examination. J Clin Psychiatry. 1987;48(8):314–318.
    1. Mohs RC. The Alzheimer's Disease Assessment Scale. Int Psychogeriatr. 1996;8(2):195–203.
    1. Brandt J, Spencer M, Folstein M. The telephone interview for cognitive status. Neuropsychiatry Neuropsychol Behav Neurol. 1988;1:111–117.
    1. Delis DC. California Verbal Learning Test. Psychological Corp; New York, NY: 1987.
    1. Becker JT, Boller F, Saxton J, McGonigle-Gibson KL. Normal rates of forgetting of verbal and non-verbal material in Alzheimer's disease. Cortex. 1987;23(1):59–72.
    1. Lopez OL, Becker JT, Jagust WJ, et al. Neuropsychological characteristics of mild cognitive impairment subgroups. J Neurol Neurosurg Psychiatry. 2006;77(2):159–165.
    1. Saxton J, Ratcliff G, Munro CA, et al. Normative data on the Boston Naming Test and two equivalent 30-item short forms. Clin Neuropsychol. 2000;14(4):526–534.
    1. Spreen O, Strauss E. A Compendium of Neuropsychological Tests. Oxford University Press; New York, NY: 1998.
    1. Reitan RM. Validity of the Trail-Making Tests as an indication of organic brain damage. Percept Mot Skills. 1958;8:271–276.
    1. Trenerry MR, Crosson B, DeBoe J, Lever WR. Stroop Neuropsychological Screening Test. Psychological Assessment Resources; Odessa, FL: 1989.
    1. Schwartz BS, Glass TA, Bolla KI, et al. Disparities in cognitive functioning by race/ethnicity in the Baltimore Memory Study. Environ Health Perspect. 2004;112(3):314–320.
    1. Solomon PR, Adams F, Silver A, Zimmer J, DeVeaux R. Ginkgo for memory enhancement: a randomized controlled trial. JAMA. 2002;288(7):835–840.
    1. Dodge HH, Zitzelberger T, Oken BS, Howieson D, Kaye J. A randomized placebo-controlled trial of Ginkgo biloba for the prevention of cognitive decline. Neurology. 2008;70(19 pt 2):1809–1817.
    1. Bernick C, Katz R, Smith NL, et al. Cardiovascular Health Study Collaborative Research Group Statins and cognitive function in the elderly: the Cardiovascular Health Study. Neurology. 2005;65(9):1388–1394.
    1. Rapp SR, Espeland MA, Shumaker SA, et al. WHIMS Investigators Effect of estrogen plus progestin on global cognitive function in postmenopausal women: the Women's Health Initiative Memory Study: a randomized controlled trial. JAMA. 2003;289(20):2663–2672.
    1. Birks J, Grimley Evans J. Ginkgo biloba for cognitive impairment and dementia. Cochrane Database Syst Rev. 2009;(1):CD003120.

Source: PubMed

Sponsors en medewerkers

Medische omstandigheden

Geneesmiddelinterventies

3
Abonneren