Gingko biloba May Protect Cognition in Stroke Patients

Pauline Anderson

December 20, 2017

Stroke patients treated with Gingko biloba extract (GBE) in addition to aspirin had less decline in cognitive function and better neurologic function scores than those who received placebo and aspirin, results of a small randomized trial have shown.

The new data "suggest that GBE is effective and could be recommended in the treatment of acute ischemic stroke," the authors, led by Shanshan Li, Department of Neurology, Affiliated Drum Tower Hospital of Nanjing University Medical School, and the State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, China, conclude.

The analysis also suggested that GBE did not increase the incidence of adverse events.

The study was published online December 18 in Stroke & Vascular Neurology.

Memory Herb

The prevalence of post-stroke dementia is estimated to be about 30%, the authors note. Cognitive decline after a stroke can result in vascular cognitive impairment (VCI) and Alzheimer's disease.

Gingko biloba is an ancient Chinese tree, the extract from which has long been used as a traditional herb for memory, confusion, depression, and tinnitus. Trials in Alzheimer's disease dementia, however, have been disappointing.

The current study included patients with acute ischemic stroke with a National Institutes of Health Stroke Scale (NIHSS) score of 4 to 20. Participants were from five hospitals in China.

The researchers randomly assigned these patients within 7 days of their stroke to receive 450 mg of GBE daily (in three 150-mg tablets) combined with 100 mg of aspirin daily for 6 months (180 days) or to a control group that received a placebo and the aspirin. The analysis included 342 patients, with a mean age of about 64 years. Participants were blinded to the treatment assignment.

"The ingredients of GBE are complicated, and vary by age, cultivation source and gender of the Ginkgo biloba tree," the authors note.

EGb761, a GBE product (Dr Willmar Schwabe Pharmaceuticals) used in previous clinical trials, contained about 24% flavone glycosides, 6% terpene lactones, 0.8% Ginkolide B, and less than 5 parts per million (ppm) of harmful ginkgoic acid, they note. The gingko ketone ester dispersible tablets (Jiangsu Shenlong Pharmaceutical Co) used in this trial contain 44% flavone glycosides, 10% terpene lactones, 2.5% Ginkgolide B, and less than 2 ppm of the harmful ginkgoic acid.

"Hence the GBE in this study has more protective chemicals and less harmful constituents and is expected to exert a better therapeutic effect than EGb761," they write.

The primary efficacy outcome was a decline in the Montreal Cognitive Assessment (MoCA) score at 180 days. A neuropsychological test evaluating cognitive executive function, the MoCA has a relatively high sensitivity to screening for mild cognitive disorders. Lower scores indicate more serious cognitive impairment.

Secondary outcomes included the NIHSS score, measured on a scale from 0 to 42 (lower scores suggesting better neurologic function), and the modified Rankin Scale score, measured from 0 to 6 (higher score indicating favorable neurologic function).

Additional secondary outcomes were the Barthel Index, which measures global function and activities of daily living (higher score out of 100 indicating more severe impairment) and the Mini-Mental State Examination (MMSE), which has scores from 0 to 30 (higher scores indicating better cognitive function).

Executive Function

Neuropsychological tests of executive function included the Executive Dysfunction Index (EDI), and the Webster's digit symbol test (WDT). Higher scores on the EDI and lower scores for the WDT indicate more severe impairment.

Testing took place at baseline and at 12, 30, 90, and 180 days.

The study showed a statistically significant difference in decline in MoCA scores in the GBE group compared with controls at 30, 90, and 180 days (30 days: −2.77 ± 0.21 vs −1.99 ± 0.23, P = .0116; 90 days: −3.34 ± 0.24 vs −2.48 ± 0.26, P = .0165; at 180 days: −4.00 ± 0.26 vs −2.71 ± 0.26; P = .0004).

Neurologic function was significantly improved in the GBE group compared with the control group at 12 days (P < .05) and 30 days (P < .01), in terms of mean NIHSS scores.

MRS scores were significantly improved in the GBE group compared with the control group from 30 to 180 days of follow-up (P < .01 for all time points).

And the decrease in MMSE scores was statistically higher in the GBE group than in the control group at 30, 90, and 180 days (all P < .05).

Quality of Life

The study also found an improvement in mean BI scores, which reflect activities of daily living, at 30, 90, and 180 days in the GBE group. However, these improvements were not significantly different from those in the control group.

The EDI was improved in both groups, but "more obviously" in the GBE group, the authors write (mean EDI, 7.92 ± 0.54 vs 9.80 ± 0.69 at 90 days [P = .0294] and 6.89 ± 0.52 vs 8.74 ± 0.63 at 180 days [P = .0241]; mean decline in EDI, 4.99 ± 0.44 vs 3.52 ± 0.37 at 90 days [P = .0111] and 6.04 ± 0.95 vs 4.41 ± 1.07 at 180 days [P = .0135]). 

WDT scores were improved slightly in both groups, again with the GBE group showing the most improved trend. However, the decrease in WDT was not significant except at the 30-day evaluation.

These results suggest that GBE can be recommended in stroke patients for its ability to improve quality of life as well as cognition, said the authors.

Researchers also looked at the incidence of vascular events. About 9.1% in the GBE group and 12.3% in the control group had a vascular event, but there was no significant difference in the incidence of these events (P = .343).

Notably, the GBE group did not have a higher incidence of cerebrovascular events compared with the control group (7.4% vs 9.8%; P = .424). They also did not have a higher rate of cardiovascular events.

The new data "support the notion that GBE improves the cognitive function of VCI" and may be a "promising medication" for patients with this condition, the authors write.

They believe that Gingko biloba extract might prevent cognitive decline following stroke through antiapoptosis or by boosting cerebral blood flow.

During follow-up, there were 10 adverse events. Only one of these — a vomiting episode — was considered to be possibly related to the study medication. There was no overall significant difference between the groups in terms of adverse events.

Previous research showed that GBE may increase the risk for bleeding because of its inhibition of platelet aggregation and platelet activating factor function. Clinicians should therefore be cautious when recommending GBE to patients with risk factors such as liver cirrhosis and hypertension and to those using warfarin or high-dose aspirin, said the authors.

Also, because one study showed that elderly patients taking GBE had a higher incidence of ischemic stroke and transient ischemic attack than those taking placebo, patients older than 85 years should not take more than 240 mg of GBE daily, they said.

A possible limitation of the study was its short duration. The authors stressed that the effects of long-term exposure to GBE should be verified in future investigations.

Test of Time

Reached for a comment, Joseph Hanna, MD, chair of neurology, The MetroHealth System Inc, Cleveland, Ohio, and a spokesperson for the American Stroke Association, told Medscape Medical News that remedies that endure for more than a millennium "likely have some merit."

"Ginkgo, an ancient herbal remedy for cognitive impairments, has stood the test of time amongst practitioners of traditional healers."

The new study, which used common measures of stroke recovery and cognitive decline, provides additional evidence that gingko may hasten recovery and slow cognitive loss in stroke survivors, said Dr Hanna.

However, he pointed out that the study was relatively small and was limited to those of Chinese ethnicity.

The therapy might have shown more benefit had the duration of observation been longer, said Dr Hanna. "More study is needed, but ginkgo seems headed towards more scrutiny and a fuller acceptance in western medicine."

The work was supported by the National Natural Science Foundation of China, the Science and Technology Department of Jiangsu Province, and Jiangsu Province Key Medical Discipline. The study authors and Dr Hanna have disclosed no relevant financial relationships.

Stroke Vasc Neurol. Published online December 18, 2017. Abstract

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