Study

Sample size and cognition status of ginkgo group at baseline

Inclusion criteria

Study type

Age range/ Mean age (years)

Total daily dose/ formulation/ duration

Parameters/ Measurements

Results

[33] Becks et al., 2016

61 (G = 31; P = 30) elderly volunteers with subjective memory impairment (SMI)

- PRMQ 20.1 ± 3.8 (perspective scale)

- PRMQ 20.3 ± 3.0 (retrosp. scale)

- WASI 105 ± 6.3

- CERAD-PLUS 1.6 ± 31.2

SMI indicated by at least one item answered with “rather often” or “very often” or at least five questions answered “sometimes” in PRMQ

WASI IQ scale range ≥ 85 to ≤115

CERAD-PLUS with z-scores range −1 to +1 (to age, gender and educational level) or z-scores range −2 to +1 (maximum of 3 subtests age, gender and educational level)

Monocenter, randomized double-bind placebo controlled

50 to 65 years

Mean age in ginkgo group 57.5 ± 4.6 years

EGb 761 at 240 mg/day for 56 ± 4 days

Primary goal: evaluate EGb 761 efficacy by behavioral performance in the cognitive tasks, fMRI during cognitive task performance and TSST:

1) Task-set-switching (cognitive flexibility)

2) Go-NoGo task

3) Delayed-response task

4) Prospective memory

5) Daily prospective memory (postcard)

6) Task-related fMRI- BOLD-signals (cognitive tasks combined with fMRI

7) The Trier Social Stress-Test (TSST)

8) Safety

1) Task-switch-cost decreased in GBE compared to placebo (Group × Time × Switch-Costs p = 0.018, multiple tests uncorrected), indicating improved cognitive flexibility

2) Go-NoGo-task reaction-times corrected for error-rates indicated a trend for improved response inhibition (p = 0.052)

3) No significant treatment effect detected

4) No significant treatment effect detected

5) Only numerically improved performance in EGb group

6) No significant treatment effect by fMRI-data (in all 4-task p > 0.05)

7) No significant effect on salivary cortisol

8) Extract was safe and well tolerated. Most frequent side effect was headache with higher prevalence in GBE group (59.4% versus 40% in placebo)

[32] Scherrer et al., 2015**

2854 community-based elderly subjects with spontaneous memory complaints without dementia at inclusion

- MMSE 27.6 ± 1.9

- Geriatric depression scale 6.7 ± 4.1

Spontaneously reporting a memory complaint

MMSE > 25 in GP’s office (in hospital site MMSE is done as complementary scale)

Short anxiety battery test (Covi anxiety scale) < 6, (only if subjects screened at GP site)

Geriatric depression scale < 15

Participants with MCI were not excluded

Post-hoc analysis (GuidAge study-Vellas et al. 2012)

aged ≥70 years

EGb 761 at 2x 120 mg/day for 5 years

Primary goal: to evaluate EGb 761 efficacy on conversion rate of memory complaint to dementia of Alzheimer type

1) Time to event analysis using Fleming-Harrington test

1) The hazard function for conversion to dementia in the placebo group was significantly different from that in the GBE treatment group (p = 0.0054), suggesting a late effect of EGb 761

[25] Vellas et al., 2012

2854 (G = 1406; P = 1414) community-based elderly subjects with spontaneous memory complaints to primary care practitioner

without dementia at inclusion

- MMSE 27.6 ± 1.9

- Geriatric depression scale 6.7 ± 4.1

Spontaneously reporting a memory complaint

MMSE> 25 in GP’s office (in hospital site MMS is done as complementary scale)

Short anxiety battery test (Covi anxiety scale) < 6, (only if subjects screened at GP site)

Geriatric depression scale < 15

Participants with MCI were not excluded

Multicenter, double bind randomized parallel group placebo controlled (GuidAge study)

aged ≥ 70 years

Mean age in ginkgo group 76.4 ± 4.4 years

EGb 761 at 120 mg bid for 5 years

Primary outcome: incidence of AD after 5 years. Furthermore:

1) Annual cognitive, functional and dementia assessments by: MMSE, The Clinical Dementia Rating (CDR), The Free and Cued Selective Reminding Test (FCSRT), trail making test, verbal fluency, visual analogue scales, instrumental activities of daily living and geriatric depression scale

2) Combined incidence of Alzheimer’s disease or mixed dementia (i.e., Alzheimer’s disease with a vascular component)

3) Safety

1) Primary outcome: After 5 years 61 participants (out of 1406) in the ginkgo group were diagnosed with probable Alzheimer’s disease (1.2 cases per 100 person-years) compared with 73 participants (out of 1414) in the placebo group (1.4 cases per 100 person-years; hazard ratio [HR] 0.84, 95% CI 0.60 - 1.18; p = 0.306, but the risk was not proportional over time.

2) In subgroup analysis significant differences in Alzheimer’s disease incidence were reported in men, people who consumed alcohol at baseline, and individuals who received ginkgo biloba extract for at least 4 years but this should be interpreted with caution.

3) Incidence of adverse events was similar in both groups

4) There was a problem with the predefined statistical test which was chosen assuming proportional hazards. Hazards were found to increase during study period

5) The study was inconclusive due to lower than expected incidence of Alzheimer’s disease; the GuidAge trial was unable to reach primary endpoint criterion (decreased conversion to Alzheimer’s disease in 5 years of follow-up)