Ginkgo biloba for cognitive impairment and dementia

BACKGROUND: Dementia is a neurocognitive disorder that interferes with cognition and independent functioning. Common dementia subtypes include Alzheimer's disease, vascular dementia, and mixed type. Mild cognitive impairment (MCI) is a risk factor for dementia, and subjective cognitive complaints may be the earliest manifestation. Although cholinesterase inhibitors may help reduce some cognitive and behavioral symptoms, there is no established treatment that cures or slows dementia progression. Ginkgo biloba (ginkgo) is a popular herbal preparation that is used to improve brain and circulatory health, and neuroprotective effects are biologically plausible. OBJECTIVES: To assess the benefits and harms of Ginkgo biloba for the treatment of people with cognitive impairment or dementia. SEARCH METHODS: We searched the Cochrane Dementia and Cognitive Improvement Group's register, MEDLINE, Embase, four other databases, and two trials registries on 8 December 2022. The search was updated in MEDLINE, Embase, CENTRAL, and the trials registers on 18 November 2024. SELECTION CRITERIA: We included randomized controlled trials (RCTs) comparing ginkgo with placebo, usual treatment, or other treatments for cognitive problems in people with cognitive complaints or diagnoses of MCI or dementia. DATA COLLECTION AND ANALYSIS: Two review authors independently selected trials, extracted data, and assessed studies for risk of bias. Key outcomes were global clinical status, global cognitive function, activities of daily living (ADLs), adverse events (AEs), and serious adverse events (SAEs) at six months. When clinically appropriate, we pooled data using a random-effects model and expressed treatment effects as mean differences (MDs), standardized mean differences (SMDs), or risk ratios (RRs), each with its 95% confidence interval (CI). We used GRADE methods to assess the certainty of the evidence for each estimate. MAIN RESULTS: We included 82 studies with 10,613 participants; 72 studies with 9783 participants provided extractable data. Four studies were at low risk of bias in all domains. Below we present data for the comparison of ginkgo versus placebo in people with different clinical conditions. Subjective cognitive impairment Three studies (597 participants) compared ginkgo with placebo for people with subjective cognitive complaints. Based on one study that lasted six months, it is uncertain whether ginkgo has any effect on global clinical status measured on a five-point Likert scale (MD 0.00, 95% CI -0.33 to 0.33; P = 1.00; 1 study, 197 participants; very low-certainty evidence). There were no data on cognition or ADLs. One study reported no difference in minor side effects between treatment groups and did not mention SAEs. A larger study lasting three months found that the risk of AEs may be higher with ginkgo versus placebo. It provided very uncertain evidence on the risk of SAEs. Multiple sclerosis and cognitive impairment Two studies (164 participants) tested ginkgo versus placebo over three months in people with multiple sclerosis and cognitive problems. Ginkgo probably has little or no effect on cognition measured on the Perceived Deficits Questionnaire (MD -0.09, 95% CI -0.41 to 0.22; P = 0.55, I² = 0%; 2 studies, 152 participants; moderate-certainty evidence). There were no data on global clinical status or ADLs. The studies suggested no important difference in numbers of AEs between groups, and there was no indication of SAEs due to ginkgo. Mild cognitive impairment Twelve studies (1913 participants) tested ginkgo against placebo in people with MCI. At six months, moderate-certainty evidence suggests that ginkgo probably has little to no effect on global clinical status measured on the Clinical Dementia Rating Scale (MD -0.03, 95% CI -0.06 to 0.01; 3 studies, 631 participants; I² = 0%), cognition measured on the Alzheimer's Disease Assessment Scale - cognition (MD -0.07, 95% CI -0.67 to 0.51; I² = 0%; 2 studies, 508 participants), and ADLs measured on the Instrumental ADL scale (MD -0.05, 95% CI -0.29 to 0.19; 1 study, 350 participants). There may be little or no difference between ginkgo and placebo at up to 12 months in the risk of AEs (RR 0.98, 95% CI 0.77 to 1.24; I² = 58%; 7 studies, 991 participants, 379 events; low-certainty evidence), and there is little or no difference in the risk of SAEs (RR 0.95, 95% CI 0.82 to 1.09; I² = 0%; 3 studies, 714 participants, 327 events; high-certainty evidence). Dementia Thirteen studies (3288 participants) compared ginkgo with placebo for dementia. At six months, low-certainty evidence suggests that people taking ginkgo may have better global clinical status on a six-point Likert scale (lower is better; MD -0.06, 95% CI -1.00 to -0.20; I² = 88%; 5 studies, 1359 participants), better cognition measured by decreases on a short cognitive performance test (Syndrom-Kurztest; MD -1.86, 95% CI -3.48 to -0.24; I² = 96%; 9 studies, 2801 participants), and slightly better ADLs measured on the ADL International Scale (MD -0.19, 95% CI -0.35 to -0.03; I² = 91%; 8 studies, 2571 participants). There is probably little or no difference between ginkgo and placebo in the risk of AEs at up to 12 months (RR 0.95, 95% CI 0.90 to 1.00; I² = 0%; 9 studies, 2746 participants, 1480 events; moderate-certainty evidence). There may be little or no difference in risk of SAEs at six months (RR 0.88, 95% CI 0.58 to 1.33; I² = 0%; 6 studies, 2463 participants, 89 events; low-certainty evidence). AUTHORS' CONCLUSIONS: In people with cognitive complaints, we are unsure whether ginkgo improves global clinical status at six months, and it may be associated with an increased risk of AEs at three months. Ginkgo probably has no benefit at three months for cognition in multiple sclerosis; numeric data on AEs were unavailable, but studies did not suggest concerns. In people with MCI, ginkgo probably has little or no effect at six months on global status, cognition, or ADLS. There may be little or no difference in AEs, and there is little or no difference in SAEs, at up to 12 months. In people with dementia, there may be small to moderate benefits at six months for global status, cognition, and ADLs. There is probably little or no difference in AEs at up to 12 months, and there may be no difference in SAEs.