Study design GBE dose/preparation Duration Subjects Purpose Main results References Patients with memory complaints, SMI, and MCI R, DB, PC 240 mg of GBE once daily or placebo (61) Test the effect of GBE on cognitive functions associated with prefrontal dopamine GBE caused a mild increase in prefrontal dopamine; there were indications for enhanced cognitive flexibility and for ameliorated response inhibition results Beck et al., 2016 [61 ] R, DB, PC 240 mg of GBE once daily or placebo 12 weeks (300) Evaluate the effects of GBE on cognition and quality of life in patients with very mild cognitive impairment GBE improved the cognitive ability and quality of life of patients Grass-Kapanke, 2011 [63 ] R, PC, DB, MC 240 mg of GBE once daily or placebo 24 weeks (160) Test the effect of GBE on NPS and cognition in patients with MCI GBE improved NPS and cognition; the extract was safe and well tolerated Gavrilova et al., 2014 [62 ] Patients with dementia R, DB, PC 240 mg of GBE once daily 22 weeks (400) Test the efficacy of GBE on NPS of dementia GBE statistically superior to placebo in ameliorating NPS (e.g., irritability, apathy, and anxiety) Scripnikov et al., 2007 [64 ] Systematic review 240 mg of GBE once daily 22 weeks (1628) Demonstrate efficacy of GBE in dementia with BPSD Improvements of quality of life, cognition, and BPSD activities of daily living clinical global impression Von Gunten et al., 2016 [66 ]12 , 166 –168 ]) Meta-analysis and systematic review Different dosages of GBE Not available Demented patients Test the efficacy of GBE in ameliorating symptoms of demented patients GBE improved cognitive function and activities of everyday life in patients with dementia Brondino et al., 2013 [72 ]12 , 67 –69 , 79 , 166 , 169 , 170 ]) Meta-analysis of randomized placebo controlled trials 120 mg or 240 mg of GBE per day or placebo 22-26 weeks (2684) Evaluate evidence for efficacy of GBE in dementia Confirmation of efficacy of GBE and good tolerability Gauthier and Schlaefke, 2014 [70 ]12 , 69 , 166 , 167 , 169 , 171 ]) Systematic review and meta-analysis of randomized controlled trials 240 mg of GBE once daily 22-26 weeks (2561) Evaluate the clinical efficacy and adverse effects of GBE in dementia and cognitive decline GBE was found more effective than placebo in decelerating cognition deficits and in improving daily life activities and NPS in dementia Tan et al., 2015 [65 ]12 , 62 , 69 , 167 , 169 –174 ]) Meta-analysis of randomized controlled clinical trials 240 mg/day 22 or 24 weeks Old patients aged over 60 years Effects of GBE on anxiety, dementia, and depression in aging patients Improvements in dementia, anxiety, and depression Kasper, 2015 [73 ] ([12 , 166 –168 ]) Meta-analysis of randomized controlled trials 240 mg of GBE once daily 22 or 24 weeks (1628) Test the effects of GBE on BPSD of demented patients Significant superiority of GBE to placebo in improving BPSD and therefore caregiver experience Savaskan et al., 2017 [74 ]12 , 166 –168 ]) Bivariate meta-analysis Different dosages of GBE Approximately 6 months Demented patients Evaluate baseline risk on the treatment effect and assess the efficacy of GBE on cognitive symptoms of dementia GBE was effective at improving cognitive functions in dementia after 6 months of treatment Wang et al., 2010 [71 ]12 , 67 , 69 , 166 , 169 , 170 ]) R, DB, PC, PG, MC 160 mg or 240 mg of GBE daily 24 weeks (214) To assess the efficacy of GBE in aged demented patients or patients with age-related memory loss No beneficial effect of GBE for demented or age-related memory-impaired patients Van Dongen, 2000 [75 ] R, DB, PC, PG 120 mg of GBE daily 6 months 176 mildly to moderately demented patients Assess the efficacy and safety of GBE for treating dementia in early stages GBE not beneficial in mild to moderate dementia after a 6-month treatment McCarney et al., 2008 [76 ] Cochrane analysis of R, DB, PC trials Different GBE doses ranging from low to high Different treatment periods Aging with dementia or cognitive impairment Assess the efficacy and safety of GBE in dementia and cognitive impairment GBE displays unreliable and inconsistent evidence in being beneficial for demented people Birks and Evans, 2009 [77 ] Patients with AD and vascular dementia R, DB, PC 120 mg of GBE, 60 mg of GBE, or placebo 6 months (90) Evaluate the efficacy and safety of GBE in vascular demented patients GBE slowed down the cognitive deterioration in vascular demented patients, effect shown in only one of the four neuropsychological tests Demarin et al., 2017 [78 ] Review of R, PC 120 mg of GBE twice daily or 240 mg of GBE once daily 22 or 24 weeks (1294) Test the efficacy of GBE in older patients with AD/vascular dementia with NPS Confirmation of efficacy of GBE and good tolerability Ihl, 2013 [79 ]12 , 166 , 167 , 175 ]) Systematic review and meta-analysis GBE extract 12-52 weeks (2372) Evaluate the effects of GBE in AD and vascular and mixed dementias Superiority of GBE to placebo in improving everyday life activities in mainly the AD type of dementia Weinmann et al., 2010 [80 ]67 –69 , 166 , 169 , 173 , 175 ]) Systematic review and meta-analysis 240 mg and 120 mg of GBE daily 24 weeks Patients with MCI or AD Assess the effectiveness and safety of GBE in treating MCI and AD There is an indication for the beneficial effect of GBE in MCI and AD but the results were inconsistent Yang et al., 2016 [81 ] (AD: [67 , 68 , 169 , 170 , 174 –176 ]; MCI: [62 ]) Systematic review of randomized controlled trials 240 mg of GBE daily Patients with mildly to moderately severe and severe AD Assess the beneficial effect of GBE in AD Evidence of beneficial effects of GBE in amelioration cognition, every day activities, and psychopathological symptoms but great heterogeneity among the results Janssen et al., 2010 [82 ]67 , 69 , 166 , 169 ]) Prevention R, DB, PC, PG 120 mg of GBE twice daily 5 years Adults 70 years or older with occasional memory problems Efficacy of long-term use of GBE for the prevention of AD in aging with memory complaints GBE did not reduce the incidence of AD compared to placebo GuidAge study, Vellas et al., 2012 [83 ] R, DB, PC 120 mg of GBE twice daily Every 6 months from 2000 to 2008 (3069) Test whether GBE delays or prevents global or domain-specific cognitive impairment in aging GBE did not prevent cognitive decline in aging Snitz et al., 2009 [84 ] R, DB, PC 120 mg of GBE twice daily 5 years (3000) Assess the ability of GBE in the prevention of dementia in normal aging or those with MCI GBE does not prevent dementia GEM study, DeKosky et al., 2006 [87 ] Systematic review and meta-analysis 240 mg of GBE daily Not available Nondemented patients aged 70 years or older Evaluate the efficacy of GBE for the prevention of dementia in nondemented adults GBE is not able to prevent the development of dementia Charemboon and Jaisin, 2015 [86 ] ([83 , 85 ])
