Efficacy of Ginkgo biloba extract EGb 761® in dementia with behavioural and psychological symptoms: A systematic review

Objectives. To review current evidence of efficacy of Ginkgo biloba extract EGb 761^® in dementia with behavioural and psychological symptoms (BPSD). Methods. Randomized, placebo-controlled trials assessing the effects of EGb 761^® in dementia patients with BPSD were included if the diagnosis was made in accordance with internationally accepted criteria, the treatment period was at least 22 weeks, outcome measures covered BPSD and at least two of the following domains of assessment, i.e. cognition, activities of daily living and clinical global assessment, and methodological quality was adequate. An analysis of covariance (ANCOVA) model was used to calculate the pooled effect estimates and to compare effects of EGb 761^® and placebo; furthermore, combined risk differences of response rates were calculated. Results. Four published trials were identified, involving altogether 1,628 outpatients with mild to moderate dementia. Least-square mean differences for change from baseline in cognition, BPSD (including caregiver distress rating), activities of daily living, clinical global impression, and quality of life favoured EGb 761^® (P < 0.001 for all comparisons). Conclusions. The pooled analyses provide evidence of efficacy of EGb 761^® at a daily dose of 240 mg in the treatment of out-patients suffering from Alzheimer's, vascular or mixed dementia with BPSD.     

Gingko biloba extract EGb 761®: clinical data in dementia

Research into Gingko biloba extract EGb 761? has been ongoing for many years. Early studies showed that the extract was superior to placebo in improving symptoms of dementia, and this has been confirmed by more recent research. The GINDEM-NP, GOTADAY and GOT-IT! studies showed that 240 mg/day EGb 761? improved cognitive function, neuropsychiatric symptoms, activities of daily living, and quality of life in patients with mild to moderate dementia compared with placebo, with results reproducible in independent trials. The strength of the effect in terms of improvements in neurosensory symptoms associated with old age and dementia was strong enough to be detected by caregivers and independent clinicians. A combination of 240 mg/day EGb 761? and 10 mg/day (initially 5 mg/day) donepezil was also more effective than either drug alone. Regarding the improvement of neuropsychiatric symptoms, a cross-comparison of studies with different antidementia agents suggests that EGb 761? is at least as effective as memantine, galantamine, and donepezil. Safety data revealed no important safety concerns with EGb 761?.     

Ginkgo biloba extract EGb 761 in dementia: intent-to-treat analyses of a 24-week, multi-center, double-blind, placebo-controlled, randomized trial

In 1996, Kanowski et al. reported about the beneficial effects of ginkgo biloba special extract EGb 761 (240 mg/day) in outpatients with pre-senile and senile primary degenerative dementia of the Alzheimer type (DAT) and multi-infarct dementia (MID) of mild to moderate severity. The comparison of the results of this double-blind, placebo-controlled, randomized, multi-center study with other dementia studies is hampered by the fact that only the responder analysis of the per-protocol (PP) population, which was pre-specified in the protocol as confirmatory analysis, has been published in detail so far. Moreover, cognitive functioning was measured using the Syndrom-Kurztest (SKT), whereas results of other studies are based on the Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-cog). Therefore, the conventional intention-to-treat (ITT) analysis of this study is provided with an estimation of ADAS-cog scores based on measured SKT scores. After 24 weeks of treatment, the ITT analysis of the SKT and estimated ADAS-cog scores revealed a mean decrease in the total score by -2.1 (95 % CI: -2.7; -1.5) points and -2.7 (95 % CI: -3.5; -1.9) points, respectively, for the EGb 761 group, which indicates an improvement in cognitive function. On the contrary, the placebo group exhibited only a minimal change of -1.0 (95 % CI: -1.6; -0.3) and -1.3 (95 % CI: -2.0; -0.4) points, respectively. The changes from baseline differed significantly between treatment groups by 1.1 (SKT) and 1.4 (estimated ADAS-cog) points, respectively (P = 0.01). The Clinical Global Impression of Change (CGI, Item 2) favored the EGb 761 group with a mean difference of 0.4 points (P = 0.007). Changes in the rating related to activities of daily living (Nürnberger-Alters-Beobachtungs-Skala, NAB) showed a favorable trend for EGb 761R. A subgroup analysis regarding patients with DAT yielded comparable results. Using a decrease of at least 4 points on the estimated ADAS-cog scores as cutoff criterion for treatment response, 35 % of EGb 761-treated patients were considered responders versus only 19 % for the placebo group (P = 0.01). The results of this ITT analysis substantiate the outcomes previously obtained with a responder analysis of the per-protocol population and confirm that EGb 761 improves cognitive function in a clinically relevant manner in patients suffering from dementia. The therapeutic effect is in line with the outcome of another EGb 761 study conducted in the U.S.     

Behavioural and psychological symptoms of Alzheimer type dementia are not correlated with plasma homocysteine concentration

BACKGROUND/AIMS: Vitamin B12 and folate deficiencies have been associated with cognitive impairment and various psychiatric symptoms but not specifically with behavioural and psychological symptoms of dementia (BPSD). A limitation of previous studies in dementia was lack of concurrent homocysteine measurement especially as it may provide a better indicator of tissue activities of these vitamins. This study was designed to clarify whether a relationship exists between plasma homocysteine concentration and BPSD. METHODS: Plasma homocysteine, serum vitamin B12 and folate were measured in 23 Alzheimer's disease (AD) patients with BPSD and 27 AD patients without BPSD as determined through the use of the Neuropsychiatric Inventory (NPI). Blood levels of measured substances were also correlated with individual NPI scores and with cumulative NPI scores for different cluster of symptoms. RESULTS: There was no significant difference (p = 0.956) in the mean plasma homocysteine levels between AD patients with BPSD (17.48 micromol/l) and AD patients without BPSD (17.34 micromol/l). Similarly, there was no significant difference between the two groups in the mean serum B12 (382.61 and 391.60 pg/ml, respectively) and folate (7.95 and 10.02 ng/ml, respectively). Mean levels for both vitamins were well within the laboratory reference range. Neither individual nor cluster NPI scores correlated significantly with plasma homocysteine. CONCLUSION: This study shows for the first time that BPSD are not associated with hyperhomocysteinaemia in Alzheimer dementia. Although previous studies have identified homocysteine as an independent risk factor in AD, the results reported here do not lend weight to an aetiological role for homocysteine specifically in BPSD.     

Correlations between cognitive, behavioural and psychological findings and levels of vitamin B12 and folate in patients with dementia

BACKGROUND: Associations between low levels of folate and vitamin B12 and cognitive impairment in patients with dementia have been reported. Some studies revealed correlations between low levels of vitamin B12 and behavioural and psychological signs and symptoms of dementia (BPSD) in Alzheimer's disease (AD) patients. Given the lack of studies in frontotemporal dementia (FTD) and on folate and given the methodological shortcomings of former publications, we set up a prospective study. METHODS: At inclusion, AD (n=152) and FTD (n=28) patients underwent a neuropsychological examination. Behaviour was assessed using a battery of behavioural assessment scales. Determination of serum vitamin B12 and red cell folate levels were performed within a time frame of two weeks of inclusion. RESULTS: In both patient groups, significantly negative correlations between levels of serum vitamin B12 and red cell folate and the degree of cognitive deterioration were found. No correlations with BPSD were found in the AD patient group. In FTD patients, levels of vitamin B12 were negatively correlated with both hallucinations (p=0.022) and diurnal rhythm disturbances (p=0.036). CONCLUSIONS: The observed negative correlations between levels of vitamin B12 and folate and cognitive impairment in both AD and FTD patients, raise the possibility of a non-specific etiological role. Although levels of vitamin B12 and folate did not correlate with BPSD in AD patients, negative correlations between serum vitamin B12 levels and BPSD in FTD patients were revealed. Decreased serum vitamin B12 levels may predispose FTD patients to develop hallucinations and diurnal rhythm disturbances.     

Neurobiological basis of behavioral and psychological symptoms in dementia of the Alzheimer type

Recent dementia studies indicate that behavioral and psychological symptoms of dementia (BPSD) are not merely an epiphenomenon of cognitive impairment, but could be attributed to specific biological brain dysfunction. We describe findings from different research modalities related with BPSD (psychopathological, neuropsychological, neurochemical, and psychophysiological strategies), and attempt to reconcile them into the more integrated form. Characteristics of delusions in dementia patients should be studied in more detail from a psychopathological aspect, aiming for the integration of psychopathology and neurobiology. Imperfect integration of memory function and cognitive function, assigned to the limbic systems and association areas, respectively, may result in BPSD. More intimate collaboration of psychopathological and neurobiological study would be fruitful to promote the research in psychological basis of BPSD. Neurochemical studies indicated that density of extracellular tangles and/or PHF-tau protein have relationships with delusion or misidentification. These changes in neurochemical parameters should be the key to understanding the pathogenesis of BPSD. More importantly, neurochemical and psychological study could be linked by the research in psychophysiology. Computer-assisted electroencephalogram analysis suggests that the right posterior hemisphere shows significant age-associated change earlier than the left in the elderly. Cerebral metabolic rate by positron emission tomography study indicates that paralimbic, left medial temporal, and left medial occipital area are involved in pathogenesis of BPSD in some dementia patients.     

La importancia de los síntomas psicológicos y conductuales (SPCD) en la enfermedad de Alzheimer

Introduction

Behavioral and psychological symptoms of dementia (BPSD), present in the vast majority of patients with Alzheimer's disease (AD), cause extensive impairment in all areas, including functionality. Early diagnosis and management are critical, especially since these symptoms are not included in the Diagnostic and Statistical Manual of Mental Disorders (DSM-V) as a diagnostic criterion of AD, but only as specific features of some patients. The main purpose of this review is to highlight the importance of these behavioural and psychological symptoms of dementia, particularly in AD. In addition, we discuss why these symptoms have not been included in the latest DSM-V.

Magnitude of effect and special approach to Ginkgo biloba extract EGb 761 in cognitive disorders

In the early 70's, improvements in methodical procedures of extraction and standardization of ginkgo preparation allowed the production of a highly concentrated and stable extract (EGb 761) (definition see editorial) by the company Dr. Willmar Schwabe, which could be systematically tested in scientific programs. Consequently, numerous studies have been undertaken and provided replicable outcomes to demonstrate its efficacy in human population. EGb 761 is currently registered as an ethical drug in more than 50 countries around the world, and is prescribed for a range of neurological and vascular disorders including dementia, arterial occlusive disease, retinal deficit, and tinnitus. The following chapter will focus on the relevant data that support EGb 761 efficacy in the treatment of cognitive disorders in general, and dementia in particular. Besides the published data, the author will provide original results unveiling different factors that could interfere with EGb 761 efficacy and may be the source of the variations observed among studies in the EGb 761 literature. In the author's opinion, such factors should be taken into consideration when implementing the design of future research and optimizing individual EGb 761 response in the clinical practice. Within the framework of this new approach, the author will not only answer the question as to whether EGb 761 works over placebo in cognitive disorders, but also attempt to estimate how well it works in particular conditions.     

Ginkgo biloba special extract EGb 761 in generalized anxiety disorder and adjustment disorder with anxious mood: a randomized, double-blind, placebo-controlled trial

Ginkgo biloba special extract EGb 761, an anti-dementia drug, enhances cognitive functioning and stabilizes mood in cognitively impaired elderly subjects. Moreover, EGb 761 had been found to alleviate symptoms of anxiety in people with mental decline, therefore it was now tested for clinical efficacy in younger patients suffering from anxiety. One hundred and seven patients with generalized anxiety disorder (GAD, n=82) or adjustment disorder with anxious mood (ADWAM, n=25) according to the diagnostic and statistical manual of mental disorders, third edition - revised (DSM-III-R) were randomized to daily doses of 480 mg EGb 761, 240 mg EGb 761 or placebo for 4 weeks. Intention-to-treat (ITT) analyses were performed on the primary outcome measure, the Hamilton rating scale for anxiety (HAMA), and the secondary variables, the clinical global impression of change (CGI-C), the Erlangen anxiety tension and aggression scale (EAAS), the list of complaints (B-L'), and the patient's global rating of change. The HAMA total scores decreased by -14.3 (+/-8.1), -12.1 (+/-9.0) and -7.8 (+/-9.2) in the high-dose EGb 761, the low-dose EGb 761 and the placebo group, respectively. Changes were significantly different from placebo for both treatment groups with p=0.0003 (high-dose group) and p=0.01 (low-dose). Regression analyses revealed a dose-response trend (p=0.003). EGb 761 was significantly superior to placebo on all secondary outcome measures. It was safe and well tolerated and may thus be of particular value in elderly patients with anxiety related to cognitive decline.     

Therapeutic efficacy of the Ginkgo special extract EGb761® within the framework of the mitochondrial cascade hypothesis of Alzheimer’s disease

Objectives: The mitochondrial cascade hypothesis of dementia assumes mitochondrial dysfunction as an important common pathomechanism for the whole spectrum of age-associated memory disorders from cognitive symptoms in the elderly over mild cognitive impairment to Alzheimer’s dementia. Thus, a drug such as the Ginkgo special extract EGb 761^® which improves mitochondrial function should be able to ameliorate cognitive deficits over the whole aging spectrum.

Methods: We review the most relevant publications about effects of EGb 761^® on cognition and synaptic deficits in preclinical studies as well as on cognitive deficits in man from aging to dementia.

Results: EGb 761^® improves mitochondrial dysfunction and cognitive impairment over the whole spectrum of age-associated cognitive disorders in relevant animal models and in vitro experiments, and also shows clinical efficacy in improving cognition over the whole range from aging to Alzheimer’s or even vascular dementia.

Conclusions: EGb 761^® shows clinical efficacy in the treatment of cognitive deficits over the whole spectrum of age-associated memory disorders. Thus, EGb 761^® can serve as an important pharmacological argument for the mitochondrial cascade hypothesis of dementia.     

Ginkgo biloba and donepezil: a comparison in the treatment of Alzheimer's dementia in a randomized placebo-controlled double-blind study

The Ginkgo biloba special extract EGb 761 seems to produce neuroprotective effects in neurodegenerative diseases of multifactorial origin. There is still debate about the efficacy of Ginkgo biloba special extract EGb 761 compared with second‐generation cholinesterase inhibitors in the treatment of mild to moderate Alzheimer's dementia. Our aim is to assess the efficacy of the Ginkgo biloba special extract E.S. in patients with dementia of the Alzheimer type in slowing down the disease's degenerative progression and the patients' cognitive impairment compared with donepezil and placebo. The trial was designed as a 24‐week randomized, placebo‐controlled, double‐blind study. Patients aged 50–80 years, suffering from mild to moderate dementia, were allocated into one of the three treatments: Ginkgo biloba (160 mg daily dose), donepezil (5 mg daily dose), or placebo group. The degree of severity of dementia was assessed by the Syndrom Kurz test and the Mini‐Mental State Examination. Clinical Global Impression score was recorded to assess the change in the patients’ conditions and the therapeutic efficacy of tested medications. Our results confirm the clinical efficacy of Ginkgo biloba E.S. (Flavogin) in the dementia of the Alzheimer type, comparable with donepezil clinical efficacy. There are few published trials that have directly compared a cholinesterase inhibitor with Ginkgo for dementia. This study directly compares a cholinesterase inhibitor with Ginkgo biloba for dementia of the Alzheimer type and could be a valid contribution in this debate. Our study suggests that there is no evidence of relevant differences in the efficacy of EGb 761 and donepezil in the treatment of mild to moderate Alzheimer's dementia, so the use of both substances can be justified. In addition, this study contributes to establish the efficacy and tolerability of the Ginkgo biloba special extract E.S. in the dementia of the Alzheimer type with special respect to moderately severe stages.     

高龄老年认知功能障碍人群精神和行为异常症状的临床分析

目的研究高龄老年认知障碍人群精神和行为症状的发生率和严重程度。方法采用横断面研究方法,应用神经精神科问卷知情者版(neuropsychiatric inventory-questionnaire,NPI-Q)量表对作者医院住院和记忆门诊收治的80岁以上有记忆力障碍主诉的高龄老年人群进行调查,比较认知功能正常者和痴呆患者间精神和行为症状的发生率和严重程度。结果共纳入535例病例,其中认知功能正常组159例,痴呆组376例。NPI-Q检查结果显示,在过去1个月内高达86.7%的痴呆患者出现过至少一种精神和行为症状,而对照组的发生率为72.3%,显著低于痴呆组(P0.01)。在痴呆组,情感淡漠/漠不关心(59.8%)、夜间行为与睡眠障碍(47.3%)和易激惹/情绪不稳(46.8%)是最常见和最严重的3种表现,其中情感淡漠/漠不关心和易激惹/情绪不稳症状均显著高于认知功能正常组(P0.01)。痴呆患者组NPI-Q总分显著高于对照组(P0.01)。结论在高龄老年痴呆人群中精神和行为异常症状的发生率和严重程度均显著高于认知功能正常者,正确认识和治疗这些症状有利于提高高龄老年痴呆患者的生存质量。     

A ginkgo biloba extract promotes proliferation of endogenous neural stem cells in vascular dementia rats

The ginkgo biloba extract EGb761 improves memory loss and cognitive impairments in patients with senile dementia. It also promotes proliferation of neural stem cells in the subventricular zone in Parkinson’s disease model mice and in the hippocampal zone of young epileptic rats. However, it remains unclear whether EGb761 enhances proliferation of endogenous neural stem cells in the brain of rats with vascular dementia. In this study, a vascular dementia model was established by repeatedly clipping and reperfusing the bilateral common carotid arteries of rats in combination with an intraperitoneal injection of a sodium nitroprusside solution. Seven days after establishing the model, rats were intragastrically given EGb761 at 50 mg/kg per day. Learning and memory abilities were assessed using the Morris water maze and proliferation of endogenous neural stem cells in the subventricular zone and dentate gyrus were labeled by 5-bromo-2-deoxyuridine immunofluorescence in all rats at 15 days, and 1, 2, and 4 months after model establishment. The escape latencies in Morris water maze tests of rats with vascular dementia after EGb761 treatment were significantly shorter than the model group. Immunofluorescence staining showed that the number and proliferation of 5-bromo-2-deoxyuridine-positive cells in the subventricular zone and dentate gyrus of the EGb761-treated group were significantly higher than in the model group. These experimental findings suggest that EGb761 enhances proliferation of neural stem cells in the subventricular zone and dentate gyrus, and significantly improves learning and memory in rats with vascular dementia.     

The profile of behavioral and psychological symptoms in vascular cognitive impairment with and without dementia

Objective:

The objective of this study was to compare the occurrence and severity of behavioral and psychological symptoms of dementia (BPSD) between vascular dementia (VaD) and vascular cognitive impairment-no dementia (VCI-ND).

Materials and Methods:

Consecutive patients presenting with cognitive impairment at least 3 months after an ischemic stroke and with a Hachinski Ischemic Score ≥4 were included. VaD was diagnosed as per National Institute of Neurological Disorders and Stroke – Association Internationale pour la Recherche et l’Enseignement en Neurosciences criteria for probable VaD and VCI-ND on the lines of the Canadian study of health and aging. The severity of cognitive impairment and the behavioral/psychological symptoms were studied by means of the clinical dementia rating scale and the neuropsychiatric inventory (NPI) respectively.

Results:

All patients with VaD and 89% of those with VCI-ND had at least one BPSD. The mean no. of symptoms per patient and the total NPI scores were higher in VaD than in VCI-ND. Apathy and night-time behavior disturbances were significantly more common and severe in VaD.

Conclusions:

BPSD are very common both in VCI-ND and in VaD. The profile of BPSD is similar in both groups, albeit more severe in VaD. The net burden of BPSD is higher in VaD as compared to VCI-ND.Key Words: Behavioral and psychological symptoms, neuropsychiatric inventory, vascular cognitive impairment, vascular cognitive impairment-no dementia, vascular dementia     

Strategies for the use of Ginkgo biloba extract,EGb 761®, in the treatment and management of mild cognitive impairment in Asia: Expert consensus

BackgroundMild cognitive impairment (MCI) is a neurocognitive state between normal cognitive aging and dementia, with evidence of neuropsychological changes but insufficient functional decline to warrant a diagnosis of dementia. Individuals with MCI are at increased risk for progression to dementia; and an appreciable proportion display neuropsychiatric symptoms (NPS), also a known risk factor for dementia. Cerebrovascular disease (CVD) is thought to be an underdiagnosed contributor to MCI/dementia. The Ginkgo biloba extract, EGb 761^®, is increasingly being used for the symptomatic treatment of cognitive disorders with/without CVD, due to its known neuroprotective effects and cerebrovascular benefits.AimsTo present consensus opinion from the ASian Clinical Expert group on Neurocognitive Disorders (ASCEND) regarding the role of EGb 761^® in MCI.Materials & MethodsThe ASCEND Group reconvened in September 2019 to present and critically assess the current evidence on the general management of MCI, including the efficacy and safety of EGb 761^® as a treatment option.ResultsEGb 761^® has demonstrated symptomatic improvement in at least four randomized trials, in terms of cognitive performance, memory, recall and recognition, attention and concentration, anxiety, and NPS. There is also evidence that EGb 761^® may help delay progression from MCI to dementia in some individuals.DiscussionEGb 761^® is currently recommended in multiple guidelines for the symptomatic treatment of MCI. Due to its beneficial effects on cerebrovascular blood flow, it is reasonable to expect that EGb 761^® may benefit MCI patients with underlying CVD.ConclusionAs an expert group, we suggest it is clinically appropriate to incorporate EGb 761^® as part of the multidomain intervention for MCI.     

Cognitive and other behavioral effects of EGb 761 in animal models

Extensive pre-clinical and clinical studies conducted over more than three decades have established that EGb 761 (definition see editorial) represents a polyvalent therapeutic principle that is useful in the therapy of mildly to moderately severe dementia and other cognitive disorders. Besides cognition, other emotional and affective aspects of brain function also seem to benefit from EGb 761 treatment. Extensive behavioural studies in experimental animals are generally in line with clinical data since cognition improvement, stress protection, and antidepressive effects have been identified with this extract in proper animal models. While individual effects in all areas have been reported for adult animals and acute dosing, more pronounced effects are usually seen in aged animals and after subchronic treatment. Specifically, for the cognition improving properties pronounced beneficial effects are mainly present in those situations where cognition was impaired by aging or other noxious stimuli. Since all these conditions are associated with mitochondrial dysfunction, the stabilizing or even protecting effect of EGb 761 on mitochondrial function seems to be a major mechanism associated with many of EGb 761's behavioural effects. Bilobalide is most important in this respect. Moreover, bilobalide and the ginkgolides have recently been shown to affect chloride conductance by interfering with the function of membrane proteins related to receptor-gated chloride channels. These mechanisms are probably associated with behavioural effects requiring acute changes of neuronal activity, but might indirectly also improve mitochondrial function.     

Amyloid precursor protein metabolism is regulated toward alpha-secretase pathway by Ginkgo biloba extracts

Clinical trials report that Ginkgo biloba extracts (e.g., EGb761) reduce cognitive symptoms in age-associated memory impairment and dementia, including Alzheimer disease (AD). However, the mechanisms behind their neuroprotective ability remain to be fully established. In this study, the effect of EGb761 on the amyloid precursor protein (APP) metabolism has been investigated by both in vitro and in vivo models. To this aim, alpha-secretase, the enzyme regulating the non-amyloidogenic processing of APP and the release of alphaAPPs, the alpha-secretase metabolite, were studied in superfusates of hippocampal slices after EGb761 incubation, and in hippocampi and cortices of EGb761-treated rats. PKC translocation state was evaluated as well. EGb761 increases alphaAPPs release through a PKC-independent manner. This effect is not accompanied by a modification of either APP forms or alpha-secretase expression. Moreover, EGb761 influence on alphaAPPs release was strictly dependent on treatment dosage. Our findings suggest that the benefit of EGb761 reported by previous clinical studies is underscored by a specific biological mechanism of this compound on APP metabolism, directly affecting the release of the non-amyloidogenic metabolite. Additional research will be needed to clearly define the effective clinical relevance, thus considering EGb761 as a possible supplementary treatment in dementing diseases.     

Ginkgo biloba extract EGb 761® in the context of current developments in the diagnosis and treatment of age-related cognitive decline and Alzheimer's disease: a research perspective

In June 2011 a two-day expert meeting "The Ageing Brain" took place in Amsterdam, The Netherlands. The main aim was to discuss the available preclinical and clinical data on Ginkgo biloba special extract EGb 761? in the context of current developments in the diagnosis and treatment of age-related cognitive decline and Alzheimer's disease. 19 dementia experts covering the disciplines bio- and neurochemistry, gerontology, neurology, pharmacology, and psychiatry from Australia, Asia, Europe and North America reviewed available preclinical and clinical data for EGb 761? and identified core topics for future research. Based on a wide range of preclinical effects demonstrated for Ginkgo biloba, EGb 761? can be conceptualized as a multi-target compound with activity on distinct pathophysiological pathways in Alzheimer's disease (AD) and age-related cognitive decline. While symptomatic efficacy in dementia and mild cognitive impairment (MCI) has been demonstrated, interpretation of data from dementia prevention trials is complicated by important methodological issues. Bridging pre-clinical research and clinical research as well as deciding on suitable study designs for future trials with EGb 761? remain important questions. The participants of the "Ageing Brain" meeting on Ginkgo biloba special extract EGb 761? concluded that there is plenty of promising data, both pre-clinical and clinical, to consider future research with the compound targeting cognitive impairment in old age as a worthwhile activity.     

Psychiatric morbidity in dementia patients in a neurology-based memory clinic

The behavioral and psychological symptoms of dementia (BPSD) often present major problems for patients and their caregivers. In the past, neurologists paid less attention to such symptoms than to the cognitive symptoms of dementia. This prospective study investigated the prevalence of psychiatric morbidity in a neurology-based memory clinic and the stress of caregivers. Our patients with dementia were found to have a high prevalence of BPSD. The most frequent were anxiety, apathy, and delusion; the most distressing to caregivers were agitation, anxiety, delusion, and sleep disturbance. Using Clinical Dementia Rating (CDR), we compared BPSD between patients with mild dementia and those with moderate dementia. Only hallucinations and agitation were different significantly. Moderate dementia patients experienced these symptoms more frequently. The high prevalence of these symptoms might be explained by the fact that the cognitive symptoms were neglected or no enough information were received by many family members of patients with dementia until their own life quality was interfered and then they began to seek medical help. These symptoms and their effect of caregiver distress can be effectively reduced by pharmacologic and nonpharmacoloic managements, caregiver-focused training and education. They can be better approached by assessing neuropsychiatric symptoms regularly, educating the general population better, and treating these patients earlier.     

Influence of the severity of cognitive impairment on the effect of the Gnkgo biloba extract EGb 761 in Alzheimer's disease.

OBJECTIVE: To explore the treatment effect of EGb 761((R)) (EGb) in Alzheimer's disease depending on baseline severity. METHODS: We applied stratification to the intent-to-treat data set collected during a 52-week, randomized, double-blind, placebo-controlled, parallel-group, multicenter study with 120 mg of EGb, using cutoff points of 23 and 14 for the Mini-Mental State Examination (MMSE) score. Outcome measures used were the cognitive subscale of the Alzheimer's Disease Assessment Scale (ADAS-Cog) and the Geriatric Evaluation by Relative's Rating Instrument (GERRI). RESULTS: In the severity stratum 1 (MMSE >23), the placebo group did not show significant changes, while the EGb group improved significantly by 1.7 points on the ADAS-Cog and by 0.09 points on the GERRI. In the severity stratum 2 (MMSE <24), the placebo group worsened by 4.1 points on the ADAS-Cog and 0.18 points on the GERRI, whereas the EGb group showed 60% less decline on the ADAS-Cog (treatment difference of 2.5 points) and no change on the GERRI (treatment difference of 0.25 points). The most severely impaired subgroup (MMSE <15) showed slightly more pronounced worsening for both treatment groups. However, in comparison to placebo, EGb induced virtually the same magnitude of effect as was observed in the entire stratum 2. CONCLUSIONS: The results of this retrospective analysis indicated that a treatment effect favorable to EGb could be observed with respect to cognitive performance (p = 0.02) and social functioning (p = 0.001) regardless of the stage of dementia, whether mild or moderately severe. However, the relative changes from baseline measured at endpoint depended heavily on the severity at baseline. Improvement was observed in the group of patients with very mild to mild cognitive impairment, while in more severe dementia, the mean EGb effect should be considered more in terms of stabilization or slowing down of worsening, as compared to the greater deterioration observed with placebo.