Archives for February 2012

Ginkgo Biloba for Treatment of Dementia

Cochrane Database Syst Rev. 2009 Jan 21;(1):CD003120.

Ginkgo biloba for cognitive impairment and dementia.

Birks J, Grimley Evans J.

Centre for Statistics in Medicine, University of Oxford, Wolfson College, Linton Road, Oxford, UK, OX2 6UD.



Extracts of the leaves of the maidenhair tree, Ginkgo biloba, have long been used in China as a traditional medicine for various disorders of health. A standardized extract is widely prescribed for the treatment of a range of conditions including memory and concentration problems, confusion, depression, anxiety, dizziness, tinnitus and headache.

The mechanisms of action are thought to reflect the action of several components of the extract and include increasing blood supply by dilating blood vessels, reducing blood viscosity, modification of neurotransmitter systems, and reducing the density of oxygen free radicals.


To assess the efficacy and safety of Ginkgo biloba for dementia or cognitive decline.

Search Strategy

The Specialized Register of the Cochrane Dementia and Cognitive Improvement Group (CDCIG), The Cochrane Library, MEDLINE, EMBASE, PsycINFO, CINAHL and LILACS were searched on 20 September 2007 using the terms: ginkgo*, tanakan, EGB-761, EGB761, “EGB 761” and gingko*. The CDCIG Specialized Register contains records from all major health care databases (The Cochrane Library, MEDLINE, EMBASE, PsycINFO, CINAHL, LILACS) as well as from many trials databases and grey literature sources.

Selection Criteria

Randomized, double-blind studies, in which extracts of Ginkgo biloba at any strength and over any period were compared with placebo for their effects on people with acquired cognitive impairment, including dementia, of any degree of severity.

Data Collection and Analysis

Data were extracted from the published reports of the included studies, pooled where appropriate and the treatment effects or the risks and benefits estimated.

Main Results

36 trials were included but most were small and of duration less than three months. Nine trials were of six months duration (2016 patients). These longer trials were the more recent trials and generally were of adequate size, and conducted to a reasonable standard. Most trials tested the same standardised preparation of Ginkgo biloba, EGb 761, at different doses, which are classified as high or low.

The results from the more recent trials showed inconsistent results for cognition, activities of daily living, mood, depression and carer burden. Of the four most recent trials to report results three found no difference between Ginkgo biloba and placebo, and one found very large treatment effects in favour of Ginkgo biloba.

There are no significant differences between Ginkgo biloba and placebo in the proportion of participants experiencing adverse events.A subgroup analysis including only patients diagnosed with Alzheimer’s disease (925 patients from nine trials) also showed no consistent pattern of any benefit associated with Ginkgo biloba.


Ginkgo biloba appears to be safe in use with no excess side effects compared with placebo. Many of the early trials used unsatisfactory methods, were small, and publication bias cannot be excluded. The evidence that Ginkgo biloba has predictable and clinically significant benefit for people with dementia or cognitive impairment is inconsistent and unreliable.



Impact of Smoking on Cognitive Decline in Early Old Age

Arch Gen Psychiatry. 2012 Jun;69(6):627-35. doi: 10.1001/archgenpsychiatry.2011.2016.

Impact of smoking on cognitive decline in early old age: the Whitehall II cohort study.

Sabia S1, Elbaz A, Dugravot A, Head J, Shipley M, Hagger-Johnson G, Kivimaki M, Singh-Manoux A.



Smoking is a possible risk factor for dementia, although its impact may have been underestimated in elderly populations because of the shorter life span of smokers.


To examine the association between smoking history and cognitive decline in the transition from midlife to old age.


Cohort study.


The Whitehall II study. The first cognitive assessment was in 1997 to 1999, repeated over 2002 to 2004 and 2007 to 2009.


Data are from 5099 men and 2137 women in the Whitehall II study, mean age 56 years (range, 44-69 years) at the first cognitiveassessment.

Outcome Measures

The cognitive test battery was composed of tests of memory, vocabulary, executive function (composed of 1 reasoning and 2 fluency tests), and a global cognitive score summarizing performance across all 5 tests. Smoking status was assessed over the entire study period. Linear mixed models were used to assess the association between smoking history and 10-year cognitive decline, expressed as z scores.


In men, 10-year cognitive decline in all tests except vocabulary among never smokers ranged from a quarter to a third of the baseline standard deviation. Faster cognitive decline was observed among current smokers compared with never smokers in men (mean difference in 10-yeardecline in global cognition=-0.09 [95% CI, -0.15 to -0.03] and executive function=-0.11 [95% CI, -0.17 to -0.05]).

Recent ex-smokers had greaterdecline in executive function (-0.08 [95% CI, -0.14 to -0.02]), while the decline in long-term ex-smokers was similar to that among never smokers. In analyses that additionally took dropout and death into account, these differences were 1.2 to 1.5 times larger. In women, cognitive decline did not vary as a function of smoking status.


Compared with never smokers, middle-aged male smokers experienced faster cognitive decline in global cognition and executive function. In ex-smokers with at least a 10-year cessation, there were no adverse effects on cognitive decline.



Risk of Mortality among Antipsychotics Use in Dementia Patients

Am J Psychiatry. 2012 Jan;169(1):71-9. doi: 10.1176/appi.ajp.2011.11030347. Epub 2011 Oct 31.

Risk of mortality among individual antipsychotics in patients with dementia.

Kales HC1, Kim HM, Zivin K, Valenstein M, Seyfried LS, Chiang C, Cunningham F, Schneider LS, Blow FC.



The use of antipsychotics to treat the behavioral symptoms of dementia is associated with greater mortality. The authors examined the mortality risk of individual agents to augment the limited information on individual antipsychotic risk.


The authors conducted a retrospective cohort study using national data from the U.S. Department of Veterans Affairs (fiscal years 1999-2008) for dementia patients age 65 and older who began outpatient treatment with an antipsychotic (risperidone, olanzapine, quetiapine, or haloperidol) or valproic acid and its derivatives (as a nonantipsychotic comparison). The total sample included 33,604 patients, and individual drug groups were compared for 180-day mortality rates. The authors analyzed the data using multivariate models and propensity adjustments.


In covariate-adjusted intent-to-treat analyses, haloperidol was associated with the highest mortality rates (relative risk=1.54, 95% confidence interval [CI]=1.38-1.73) followed by risperidone (reference), olanzapine (relative risk=0.99, 95% CI=0.89-1.10), valproic acid and its derivatives (relative risk=0.91, 95% CI=0.78-1.06), and quetiapine (relative risk=0.73, 95% CI=0.67-0.80). Propensity-stratified and propensity-weighted models as well as analyses controlling for site of care and medication dosage revealed similar patterns.

The mortality risk with haloperidol was highest in the first 30 days but decreased significantly and sharply thereafter. Among the other agents, mortality risk differences were most significant in the first 120 days and declined in the subsequent 60 days during follow-up.


There may be differences in mortality risks among individual antipsychotic agents used for treating patients with dementia. The use of valproic acid and its derivatives as alternative agents to address the neuropsychiatric symptoms of dementia may carry associated risks as well.