Ginkgo biloba for mild to moderate dementia in a community setting: a pragmatic, randomised, parallel-group, double-blind, placebo-controlled trial

Save this PDF as:
 WORD  PNG  TXT  JPG

Size: px
Start display at page:

Download "Ginkgo biloba for mild to moderate dementia in a community setting: a pragmatic, randomised, parallel-group, double-blind, placebo-controlled trial"

Transcription

1 INTERNATIONAL JOURNAL OF GERIATRIC PSYCHIATRY Int J Geriatr Psychiatry 2008; 23: Published online 9 June 2008 in Wiley InterScience ( Ginkgo biloba for mild to moderate dementia in a community setting: a pragmatic, randomised, parallel-group, double-blind, placebo-controlled trial Rob McCarney 1 *, Peter Fisher 2, Steve Iliffe 3, Robbert van Haselen 4, Mark Griffin 3, Jan van der Meulen 5 and James Warner 1 1 Department of Psychological Medicine, Imperial College London, UK 2 Royal London Homœopathic Hospital, UK 3 Department of Primary Care and Population Sciences, UCL, UK 4 International Institute for Integrated Medicine, France 5 London School of Hygiene and Tropical Medicine, UK SUMMARY Objectives Doubt over the cost-effectiveness of the cholinesterase inhibitors in dementia has renewed interest in alternative treatments such as Ginkgo biloba. We aimed to determine the effectiveness and the safety profile of Ginkgo biloba for treating early stage dementia in a community setting. Methods We conducted a community-based, pragmatic, randomised, double-blind, parallel-group trial where participants were given a standardised extract of Ginkgo biloba (120 mg daily) or a placebo control for 6 months. Our primary outcomes were cognitive functioning (ADAS-Cog) and participant and carer-rated quality of life (QOL-AD). Results We recruited 176 participants, mainly through general practices. In the ANCOVA model with baseline score as a co-variate (n ¼ 176), Ginkgo did not have a significant effect on outcome at six months on either the ADAS-Cog score (p ¼ 0.392), the participant-rated QOL-AD score ( p ¼ 0.787) nor the carer-rated QOL-AD score ( p ¼ 0.222). Conclusion We found no evidence that a standard dose of high purity Ginkgo biloba confers benefit in mild-moderate dementia over 6 months. Copyright # 2008 John Wiley & Sons, Ltd. key words Ginkgo biloba; Alzheimer disease; vascular dementia; randomised controlled trials BACKGROUND Current prescribing guidelines from the National Institute for Health and Clinical Excellence (2006) severely restrict the use of cholinesterase inhibitors (AChls). Safe, inexpensive and effective alternatives are needed for treating dementia and there is much interest in the use of the herbal medicine Ginkgo (McCarney and Warner, 2007). The benefit of Ginkgo however remains unclear. A recent Cochrane review (Birks et al., 2002), concluded that while a small effect is suggested the evidence is inconsistent. The null *Correspondence to: Dr R. McCarney, St Charles Hospital, Exmoor Street, London, W10 6DZ, UK. Copyright # 2008 John Wiley & Sons, Ltd. hypothesis was that compared to placebo, Ginkgo biloba taken for 6 months by community-dwelling individuals with mild to moderate dementia has no effect on cognitive functioning and the participant s quality of life. METHODS We conducted a community-based, pragmatic, randomised, double-blind, parallel-group trial where participants were given a standardised extract of Ginkgo biloba (120 mg daily) or a placebo control for 6 months. We were interested in the effect of Ginkgo vs placebo, which is reported here, but also attempted to quantify the Hawthorne effect (effect of trial Received 21 November 2007 Accepted 10 April 2008

2 an rct of ginkgo for dementia 1223 participation on treatment response) which is reported elsewhere (McCarney et al., 2007). The trial was approved by South West Multi-Centre Research Ethics Committee (ref: MREC/02/6/35) and was registered with Current Controlled Trials (ISRCTN ). The trial was designed and executed in collaboration with consumer representatives from the Alzheimer s society (UK) and monitored by an international advisory board (IAB), independent of the trial steering committee. Participants We recruited participants in Greater London (UK) and adjoining regions through referrals from general practices, old age psychiatrists and other health care professionals; and from direct responses to advertising in Alzheimer Society newsletters, London-based newspapers, and posters in Age Concern centres. As this was a pragmatic study, we recruited people with a clinical diagnosis of dementia made by the referring clinician rather than diagnostic criteria such as the National Institute of Neurological and Communicative Diseases and Stroke/ Alzheimer s Disease and Related Disorders Association (NINCDS-ADRDA) (McKhann et al., 1984), which are unlikely to be used widely in clinical settings. Inclusion criteria were: aged 55 years or over; presence of a carer; informed consent or if lacking capacity, their assent and the agreement of their nominated carer; sufficient command of English; clinical diagnosis of dementia (subsequently sub-classified using DSM-IV criteria) (American Psychiatric Association, 2000); a Mini Mental State Examination (MMSE) (Folstein et al., 1975) score of inclusive; living in the community. Exclusion criteria were: use of Ginkgo in 2 weeks prior to the baseline assessment; commencement of cholinesterase inhibiting drugs within 2 months of baseline or during follow-up; concomitant warfarin therapy; known bleeding abnormalities [a link has been suggested between life-threatening risk of haemorrhage (Vale, 1998; Kayne, 2001) and the ingestion of Ginkgo; therefore we considered a history of abnormal clotting or the use of anti-coagulation therapy grounds for exclusion]. Interventions Participants were randomised to receive either active treatment or placebo for 6 months. Active treatment was a standardised, concentrated Ginkgo biloba extract (EGb ) containing 24% Ginkgo-flavone glycosides and 6% terpene lactones; which are thought to be the active principles in the extract. To facilitate blinding, the lactose-based placebo were identically packaged and labelled, physically indistinguishable tablets containing traces of quinine hydrochloride to mimic the bitter taste of Ginkgo. A placebo such as this had been used before (van Dongen et al., 2000). The trial medication was manufactured in accordance with European Union Standards and purchased from Schwabe Pharma (Willmar-Schwabe-Str. 4, Karlsruhe, Germany), who certified its purity. Both treatments were supplied in blister packs marked with the days of the week. Participants were requested to take one 60 mg tablet twice a day for a total daily dose of 120 mg over the 6 months of follow-up. Follow-up In order to assess the Hawthorne effect, participants were randomised to standard follow-up (with visits at baseline and 2, 4 and 6 months post randomisation) or minimal follow-up (with an abbreviated assessment at baseline and a full assessment at 6 months). We conducted the assessments in the participant s or their carer s home (see Table 1). Outcomes The primary outcome measures were: (i) cognitive functioning, as measured by the ADAS-Cog (Rosen et al., 1984), a 0 70 point scale with a higher score indicating worse cognition; and (ii) quality of life, rated by the participant and their nominated carer, as measured by the QOL-AD (Logsdon et al., 1999). Both 13-item scales, scoring between points with a higher score indicating better quality of life. Secondary outcome measures were: (i) psychopathology and the resulting distress to the carer, as measured by the Neuro-Psychiatric Inventory with caregiver Distress scale (NPI-D) (Cummings et al., 1994), a 12-item scale scoring for psychopathology and 0 60 for caregiver distress; (ii) caregiver-reported daily living and social behaviour score, as measured by the Geriatric Evaluation by Relative s Rating Instrument (GERRI) (Schwartz, 1983), a 49-item scale scored 1 5 for each item and averaged for the overall score, a higher score indicating greater impairment; (iii) caregiver-reported burden of caring as measures by the 12-item Zarit Burden Interview (ZBI) (Bedard et al., 2001), scoring 0 48 with a higher score indicating greater burden; (iv) a report of caregiver health, as measured by the visual analogue scale of the European Quality of Life Visual Analogue Scale (EQ-VAS) (The EuroQol

3 1224 r. mccarney ET AL. Table 1. Administration of outcome measures Time point in study Intensive follow-up group Minimal follow-up group Questionnaire Subject* Questionnaire Subject* Baseline 0 ADAS-Cog, QOL-AD, Participant ADAS-Cog, QOL-AD Participant NPI-D, GERRI EQ-5D, ZBI Carer EQ-5D, ZBI Carer 2 months ADAS-Cog, QOL-AD, Participant NPI-D EQ-5D, ZBI Carer 4 months ADAS-Cog, QOL-AD, Participant NPI-D EQ-5D, ZBI Carer End of study 6 months ADAS-Cog, QOL-AD, Participant ADAS-Cog, QOL-AD, Participant NPI-D, GERRI NPI-D, GERRI EQ-5D, ZBI Carer EQ-5D, ZBI Carer *Subject denotes person assessed by measure. Some assessments are completed by the carer but reporting on the participant (e.g. GERRI and NPI-D). For measures such as this the participant is the subject. Group, 1990), scoring with higher score indicating better health; (v) a caregiver-reported global measure of benefit, by asking at the final follow-up, If you could continue the medication the person you care for has been receiving in this trial, would you (do you feel that it has helped him/her)? (Answer: yes or no); (vi) blood coagulation times as measures by Activated Clotting Time (ACT) using near-patient testing with the Coaguchek Pro DM 1 (Roche Diagnostics, Germany). All outcome measures, except the global measure, are previously validated tools (and in most cases commonly) used in dementia trials. All outcomes were administered by a trained researcher during a home visit. The ADAS-Cog was scored by the researcher; all other measures were scored by the participant or their carer. The field researchers were given full training in the use of the instruments and regular reviews were held amongst the researchers to ensure consistency in scoring the ADAS-Cog. In keeping with the pragmatic nature of the study, other interventions were allowed during the trial, but commencement of an AChI was grounds for withdrawal. Therefore some contamination of the interventions (through factors such as education, support from local voluntary organisations and undeclared use of Ginkgo or AChIs) was possible. To evaluate the impact of this, at each follow-up visit information about non-trial Ginkgo use and visits to secondary care services was sought. All changes in conventional treatments were recorded at the 6-month assessment. Sample size We calculated sample size for an analysable sample of 200 participants based on 80% power and a between-group difference of four points (on a 70-point scale) on the ADAS-Cog, which is the lower limit of what we would regard as clinically significant, with a SD of 11 points (Raskind et al., 2000) using a two-tailed significance level of 5%. Randomisation procedure and blinding A22factorial design with two separate randomisations, resulting in participants being randomised to one of four arms, was employed. Both factors consisted of two levels: medication group (Ginkgo and placebo); and level of follow-up (minimal or standard). This produced four groups: the Ginkgo group with standard follow-up, the Ginkgo group with minimal follow-up, the placebo group with standard follow-up and the placebo group with minimal follow-up. The randomisation codes were generated using the computer algorithm RCODE v.4.8 (Schwabe, 2002). Study medication was randomised in blocks of two and blocks were allocated to a general practice when a participant was recruited from that practice. Participants were allocated a code on entry into the trial by the researcher. Researchers undertaking the analysis and the trial statistician remained blind until completion of the analysis defined in the analysis protocol. Participants, their carers and clinicians responsible for the participant (GPs and consultants) remained

4 an rct of ginkgo for dementia 1225 blinded to the allocation during their participation. Participants were de-blinded in the event of a serious adverse event or once all participants in that block completed or withdrew from the study. The deblindings were administered by members of the study team not directly involved in the evaluation and were concealed from assessors and statistician. Success of blinding was tested by asking the researcher undertaking assessments and the carer to indicate whether they believed the participant had been taking Ginkgo or placebo. Statistical methods The analyses reported here were all planned a priori and documented in an analysis protocol. The primary analysis was intention to treat (ITT), with individuals analysed in their randomisation group, irrespective of whether they completed the trial. In order to adjust for baseline scores, when comparing the outcomes between the treatment groups, analysis of co-variance (ANCOVA) was used. Normal distributions were assumed for the ANCOVA analyses and were checked using residuals from the regression models. If data showed substantial deviations from these assumptions, appropriate transformations were used. Adjusted differences in means (b) are presented so that a positive b value favours Ginkgo and negative value favours placebo; with 95% Confidence Intervals (CI) and p-values. Where these assumptions were not met distribution-free statistical tests were employed. Interaction between treatment group and follow-up group was assessed. To take account of missing data in the ITT analysis, missing baseline data were imputed using hot decking, where values were selected at random from donors amongst the non-missing data set that had similar values for the filter variables. The filter variable for ADAS-Cog score was the MMSE score and for all other variables were age, sex and randomisation group. For the 6-month data, multiple imputation techniques were used with five imputations using a predictive model based approach with ordinary least-squares regression; from a distribution using baseline score, follow-up group and treatment group. Standard analysis (ANCOVA) was used for each of the resulting data sets generated by the imputation process then combined using standard explicit formulae (Rubin and Schenker, 1991). All imputed data were assumed missing at random. Adverse events were initially evaluated by clinicians in the study team (PF and JW) and were described and recorded by treatment group in line with ICH Good Clinical Practice guidelines (ICH, 1997). Serious events were referred to the IAB. The causal relationship to the trial medication, MedDRA disease classification and category of AE were also recorded. Two further analyses were undertaken: an analysis using all evaluable (i.e. non-imputed) data available at 6 months only and a per-protocol analysis. The perprotocol analysis investigated the effect of adherence to the treatment on the primary outcome variables. To be included in this analysis, participants needed to have: completed the study; had relevant data collected (with no imputation for missing data); been followed-up at all time points (according to his or her allocation to minimal or standard follow-up); and taken 80% or more of allocated medication. Planned sub-group analyses were conducted on individuals who: (i) were not taking AChIs during the trial and (ii) had never taken Ginkgo before. The analysis was conducted using SPSS v.13 (SPSS Corporation, 2004) and STATA v.8.1 (STATA Corporation, 2003). The multiple imputation analysis was conducted using SOLAS v.3.2 (Statistical Solutions Ltd, 2001). RESULTS Figure 1 details participant flow through the trial. Recruitment took place between February 2003 and June Baseline demographic and clinical characteristics are presented in Table 2. A total of 119 GP practices agreed to recruit participants for the trial (representing 388 individual GPs). One hundred and thirty-two participants (75%) were recruited through their GP; 29 (16%) through psychiatrists and 15 (9%) from other sources (mainly other health professionals and advertisements). All analyses are reported so that a positive value favours Ginkgo and a negative value favours placebo, irrespective of the way the scale is scored. ITT analysis There was no significant interaction between the two factors of treatment group and level of follow-up. In the ANCOVA model with baseline score as a co-variate (n ¼ 176), compared to placebo, Ginkgo did not have a significant effect on outcome at 6 months on either the ADAS-Cog score (adjusted mean difference b ¼ 0.823; 95% CI 2.701, 1.055; p ¼ 0.392), the participant-rated QOL-AD score (b ¼ 0.187; 95% CI 1.542, 1.168; p ¼ 0.787) nor the carer-rated QOL-AD score (b ¼ 0.981; 95% CI 2.551, 0.589; p ¼ 0.222).

5 1226 r. mccarney ET AL. Figure 1. Participant flowchart. Analysis with evaluable data Treatment group did not have a significant effect on outcome at 6 months on either the ADAS-Cog score (n ¼ 140; b ¼ 0.608; 95%CI 2.609, 1.393; p ¼ 0.549), the participant-rated QOL-AD score (n ¼ 142; b ¼ 0.431; 95%CI 1.717, 0.856; p ¼ 0.509) nor the carer-rated QOL-AD score (n ¼ 131; b ¼ 0.963; 95%CI 2.597, 0.670; p ¼ 0.245). Per protocol analysis Treatment group did not have a significant effect on outcome at 6 months on either the ADAS-Cog score (n ¼ 104; b ¼ 1.583; 95% CI 3.972, 0.807; p ¼ 0.192), the carer-rated QOL-AD score (n ¼ 97; b ¼ 0.077; 95% CI 1.667, 1.820; p ¼ 0.931) nor the participant QOL-AD score (n ¼ 103; b ¼ 0.652; 95% CI 2.219, 0.916; p ¼ 0.411). Sub-group analyses Sub-group analyses were conducted using participants who were not on an AChI at baseline (n ¼ 118); and on those who had never taken Ginkgo before (n ¼ 135). No significant differences emerged (data not shown). The ITT analyses are only reported here. Analysis of ADAS-Cog score amongst those not on an AChI showed there was no significant effect of treatment group using imputed data (b ¼ 0.095; 95% CI 2.481, 2.291; p ¼ 0.938). Neither was there a significant effect of treatment group on carer-rated QOL-AD (b ¼ ; 95% CI 2.854, 1.323; p ¼ 0.474); or on participant-rated QOL-AD (b ¼ 0.363; 95% CI 1.981, 1.255; p ¼ 0.661). Amongst participants who had never taken Ginkgo before (n ¼ 135), there was no significant effect of treatment group on ADAS-Cog score (b ¼ 1.306; 95% CI 3.785, 1.736; p ¼ 0.304); carer-rated QOL-AD score (b ¼ ; 95% CI 2.547, 1.405; p ¼ 0.572); or participant-rated QOL-AD (b ¼ 0.983; 95% CI 2.483, 0.518; p ¼ 0.202). Secondary outcomes Global outcome, as judged by the carer in response to the question on whether they would continue with the treatment, was not found to be significantly related to treatment group (number who said yes in

6 an rct of ginkgo for dementia 1227 Table 2. Baseline demographic and clinical characteristics of participants, by treatment group Participants: total sample Characteristic Placebo group (n ¼ 88) Ginkgo group (n ¼ 88) Total sample (n ¼ 176) Mean age (7.53) 79.3 (7.77) 79.5 (7.63) Females, Males 2 56, 32 (63.6%) 51, 37 (58.0%) 107, 69 (60.8%) Ethnicity 2 White: 83 (94.3%) Mixed: 1 (1.1%) Asian: 1 (1.1%) Black: 3 (3.4%) White: 84 (95.5%) Asian: 2 (2.3%) Black: 2 (2.3%) White: 167 (94.9%) Mixed: 1 (0.6%) Asian: 3 (1.7%) Black: 5 (3.4%) Median years of education (9.0, 13.1) 10.0 (9.0, 14.0) 10.0 (9.0, 13.3) Median Indices of Multiple 17.1 (5.9, 44.2) 20.5 (7.3, 40.7) 19.0 (6.3, 43.2) Deprivation score 3 Number with Alzheimer s disease, 76, 12 (86.4%) 72, 16 (81.8%) 148, 28 (84.1%) vascular dementia diagnosis 2 Evidence of vascular pathology 2 44 (50.0%) 42 (47.7%) 86 (48.9%) Median MMSE score (13.0, 25.1) 23.0 (16.9, 26.0) 22.0 (15.0, 26.0) Mean ADAS-Cog score (10.3) 20.4 (8.2) 22.7 (9.6) Median duration of dementia in years (1.0, 8.8) 3.0 (1.2, 7.2) 3.0 (1.0, 8.0) AChI use 2 29 (33.0%) 29 (33.0%) 58 (33.0%) NSAID use 2 47 (53.4%) 51 (58.0%) 98 (55.7%) Previous Ginkgo use 2 8 (10.0%) Missing n ¼ 8 21 (25.0%) Missing n ¼ 4 29 (17.7%) Missing n ¼ 12 Mean participant-rated Qol-AD score (6.1) Missing n ¼ (5.5) Missing n ¼ (5.8) Missing n ¼ 5 Mean carer-rated Qol-AD score (6.4) Missing n ¼ (6.9) Missing n ¼ (6.6) Missing n ¼ 15 Median 12-item ZBI score (5.9, 25.3) 15.0 (5.0, 27.4) Missing n ¼ (5.4, 26.6) Missing n ¼ 3 Median EQ-VAS score (50.0, 95.0) 77.0 (44.0, 95.0) Missing n ¼ (50.0, 95.0) Participants: intensive follow-up group only Characteristic Placebo group (n ¼ 45) Ginkgo group (n ¼ 43) Total sample (n ¼ 88) Median NPI score (0.0, 29.2) Missing n ¼ (0.0, 28.5) Missing n ¼ (0.0, 28.8) Mean GERRI total score (0.42) 2.58 (0.49) 2.56 (0.45) Carers Characteristic Placebo group (n ¼ 88) Ginkgo group (n ¼ 88) Total sample (n ¼ 176) Mean age (12.9) Missing n ¼ (14.5) Missing n ¼ (13.7) Missing n ¼ 11 Females, Males 2 78, 10 (88.6%) 74, 14 (84.1%) 152, 24 (86.4%) Number who are the partner of the participant 2 43 (48.9%) 50 (56.8%) 93 (52.8%) Number who live-in 2 57 (64.8%) 58 (65.9%) 115 (65.3%) Number who are the informal (unpaid) carer 2 84 (95.5%) 85 (96.6%) 169 (96.0%) 1 Mean scores are reported with standard deviations. 2 Numbers reported with percentage of group (e.g. Ginkgo group); or percentage of females or AD sufferers respectively. 3 Median scores are reported with 10th and 90th percentiles. 4 In England and Wales, Indices of Multiple Depreivation scores are a way of quantifying the relative poverty of an area and are linked to postcodes (ODPM, 2005). the placebo group was 36 (51%) and 29 (43%) in the Ginkgo group; x 2 ¼ 0.911; df ¼ 1; p ¼ 0.340). Further secondary outcomes are detailed in Table 3. Blinding Of those carers followed up at 6 months who responded to the question on blinding, approximately half declined to guess whether their care-recipient received Ginkgo or placebo during the trial (n ¼ 66; 49%). For the remainder (n ¼ 69; 51%), blinding was effective (k ¼ 0.18; p ¼ 0.115). The researchers were also effectively blinded: of the 129 evaluable cases the researcher did not hazard a guess in approximately half (n ¼ 62) and the level of agreement in the remaining 67 was poor (k ¼ 0.081; p ¼ 0.462). Safety (adverse events and coagulation times) A total of 63 adverse events were recorded by 57 of the participants (the greatest number reported by any one individual was three). Of these, 29 were in the placebo

7 1228 r. mccarney ET AL. Table 3. Adjusted difference in means for primary and secondary outcomes Measure N Adjusted difference in means (95% CI) 1 P-value ADAS-Cog ( 2.701, 1.055) Participant-rated QOL-AD ( 1.542, 1.168) Carer-rated QOL-AD ( 2.551, 0.589) NPI ( 9.176, 0.152) NPI-D ( 5.325, 0.597) GERRI ( 0.241, 0.003) ZBI ( 2.463, 2.429) EQ-VAS ( 5.922, 2.579) Positive values favour Ginkgo. 2 No significant differences were found in the analyses with evaluable data or in the per-protocol analyses. 3 Outcome measure administered at baseline in standard follow-up group only. 4 Significant difference found in the analysis with evaluable data (n ¼ 75; B ¼ 0.142; 95% CI 0.027, 0.257; p ¼ 0.016) and in the per protocol analysis (n ¼ 51; B ¼ 0.156; 95% CI 0.033, 0.279; p ¼ 0.014); in both cases, it indicates a more favourable outcome in the placebo group. group and 28 were in the Ginkgo group. There was one fatal cerebral haemorrhage in the Ginkgo group, this was the subject of an emergency code break and was referred to the IAB, who considered that it did not justify terminating the trial. Table 4 details the MedDRA classifications of the adverse events by treatment group. There was no significant difference in clotting time at six months for participants who adhered to the treatment regime and had evaluable data (n ¼ 93; b ¼ 1.843; 95% CI 0.488, 4.133; p ¼ 0.113). DISCUSSION We found no evidence that a standard dose (120 mg daily) of high purity Ginkgo biloba conferred benefit in mild-moderate dementia over 6 months. The only significant findings (analysis with evaluable data and per protocol analysis of carer-rated function, as measured by the GERRI) favoured the placebo group. The mean difference found between the groups on the GERRI was 0.12 points, which is unlikely to be clinically significant (Erkinjuntti et al., 2002). This study was conducted independently of the pharmaceutical industry and funded by a National charity. Studies funded by the pharmaceutical industry generally show larger effect sizes compared with independent studies (Lexchin et al., 2003; Perlis et al., 2005). Strengths of this study include the use of a placebo laced with quinine, to reduce the risk of de-blinding; and standardised outcome measures to allow a direct comparison with other dementia trials. Our results suggest that Ginkgo is ineffective in this context. There are alternative explanations for our findings, although we consider them to be improbable. Because of the recruitment shortfall, type II error is a possibility but unlikely. There was no apparent trend in our results (the nonsignificant differences mostly favoured placebo) and we consider this study to have had sufficient power to reliable detect any clinically significant Table 4. MedDRA classification of the adverse events by treatment group MedDRA category Placebo group Ginkgo group Serious Total Serious Total 006 Infections and infestations Blood and lymphatic system Metabolism and nutrition Psychiatric Nervous system Ear and labyrinth Cardiac Vascular Respiratory, thoracic and mediastinal Gastrointestinal Hepatobiliary Skin and subcutaneous tissue Musculoskeletal and connective tissue Renal and urinary Reproductive system and breast Grand total

8 an rct of ginkgo for dementia 1229 KEY POINTS Despite numerous trials, the effectiveness of Ginkgo biloba in the treatment of dementia remains unclear We found no evidence that taking Ginkgo for six months improves cognition or quality of life, compared to placebo differences: the sample size we achieved would have detected a difference of 6 points on the ADAS-cog with over 90% power. The differences in baseline ADAS-Cog scores between the treatment groups were due to chance as the trial was randomised and fully concealed. All analyses took account of these differences in baseline score between groups. While it would have been of interest to conduct sub-group analyses looking at for example diagnosis, the study was not powered to do so. In this study, we only recruited participants who were able to read and write English and this may have introduced sampling bias and undermined the representativeness of the study. It was difficult to control for this however as there were no validated versions of the questionnaires we used available in the languages needed. Another possible source of sampling bias is the geographical limitations of our catchment area. In general however our sample s baseline demographics do seem similar to data presented from other dementia trials and our catchment area included a population of around 15,000,000 (ONS, 2005). The heterogeneity of the sample is a hallmark of pragmatic clinical trial design (Gartlehner et al., 2006). The importance of early intervention in the management of dementia is clear and there is a need for a safe, effective treatment that could slow down the progression of dementia and that can be used at an early stage of the disease, in a community setting. This, combined with a desire among the public to embrace complementary and alternative therapies explains the enduring interest in Ginkgo. However we are not sure whether this interest is warranted. Although Ginkgo appears safe in use we found no evidence that it provides a clinically significant benefit and we do not recommend its use in routine dementia care. CONFLICT OF INTEREST Robbert van Haselen provided some consultancy services to Schwabe Pharma in 2005, unrelated to this research. All the other authors have no conflicts of interest. ACKNOWLEDGEMENTS This study was funded by the Alzheimer s Society (grant ref: QRD/2001/01/07). Our thanks go to the following for their invaluable input into the project: Jean Barton, Patricia Best and Angela Clayton-Turner (consumer representatives of the Alzheimer s Society s Quality Research in Dementia (QRD) group); Susanne Sorensen (head of research, QRD) and Richard Harvey (former director of research, QRD); Cassie Richardson, Charmie Kodituwakku and Toria Maybey (members of the research team). REFERENCES American Psychiatric Association Diagnostic and Statistical Manual of Mental Disorders DSM-IV-TR (Text Revision), 4th edn. American Psychiatric Press: Washington, DC. Bedard M, Molloy D, Squire L, et al The Zarit Burden Interview: a new short version and screening version. Gerontologist 41(5): Birks J, Grimley EV, Van Dongen M Ginkgo biloba for cognitive impairment and dementia. Cochrane Database of Systematic Reviews 4: CD Cummings J, Mega M, Gray K, et al The Neuropsychiatric Inventory: comprehensive assessment of psychopathology in dementia. Neurology 44(12): Erkinjuntti T, Kurz A, Gauthier S, et al Efficacy of galantamine in probable vascular dementia and Alzheimer s disease combined with cerebrovascular disease: a randomised trial. Lancet 359(9314): Folstein M, Folstein S, McHugh P Mini-Mental State : a practical method for grading the cognitive state of patients for the clinician. J Psychiatric Res 12: Gartlehner G, Hansen R, Nissman D, et al A simple and valid tool distinguished efficacy from effectiveness studies. J Clin Epidemiol 59: ICH International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) adopts Consolidated Guideline on Good Clinical Practice in the Conduct of Clinical Trials on Medicinal Products for Human Use. Int Digest Health Legislation 48(2): Kayne S Ginkgo biloba: potential concern. Good Clin Pract J 8(11): Lexchin J, Bero LA, Djulbegovic B, Clark O Pharmaceutical industry sponsorship and research outcome and quality: systematic review. BMJ 326(7400): Logsdon R, Gibbons L, McCurry S, et al Quality of life in Alzheimer s disease: patient and caregiver reports. J Mental Health Ageing 5: McCarney R, Warner J Ginkgo biloba. In Therapeutic Strategies in Dementia, Ritchie C et al. (ed). Clinical Publishing: Oxford; McCarney R, Warner J, Iliffe S, et al The Hawthorne Effect: a randomised, controlled trial. BMC Medic Res Methodol 7(30). McKhann G, Drachman D, Folstein M, et al Clinical diagnosis of Alzheimer s disease: report of the NINCDS-ADRDA Work Group under the auspices of Department of Health and

9 1230 r. mccarney ET AL. Human Services Task Force on Alzheimer s Disease. Neurology 34: National Institute for Clinical Excellence Donepezil, Galantamine, Rivastigmine (Review) and Memantine for the Treatment of Alzheimer s Disease. NICE: London. ODPM Indices of Multiple Deprivation, Office of the Deputy Prime Minister: London. ONS Mid-2004 Population Estimates: Quinary Age Groups and Sex for Local Authorities in England and Wales; Estimated Resident Population. Office for National Statistics: London. Perlis RH, Perlis CS, Wu Y, et al Industry sponsorship and financial conflict of interest in the reporting of clinical trials in psychiatry. Am J Psychiatry 162(10): Raskind MA, Peskind ER, Wessel T, Yuan W Galantamine in AD: A 6-month randomized, placebo-controlled trial with a 6-month extension. The Galantamine USA-1 Study Group. Neurology 54(12): Rosen W, Mohs R, Davis K A new rating scale for Alzheimer s disease. Am J Psychiatry 141: Rubin DB, Schenker N Multiple imputation in health-care databases: an overview and some applications. Stat Med 10(4): Schwartz G Development and validation of the Geriatric Evaluation by Relative s Rating Instrument (GERRI). Psychologic Rep 53: The EuroQol Group EuroQol-a new facility for the measurement of health-related quality of life. Health Policy 16(3): Vale S Subarachnoid haemorrhage associated with Ginkgo biloba. Lancet 352(9121): 36. van Dongen MC, van Rossum E, Kessels AG, et al The efficacy of ginkgo for elderly people with dementia and age-associated memory impairment: new results of a randomized clinical trial. J Am Geriatr Soc 48(10):

10

RESEARCH AND PRACTICE IN ALZHEIMER S DISEASE VOL 10 EADC OVERVIEW B. VELLAS & E. REYNISH

RESEARCH AND PRACTICE IN ALZHEIMER S DISEASE VOL 10 EADC OVERVIEW B. VELLAS & E. REYNISH EADC BRUNO VELLAS 14/01/05 10:14 Page 1 EADC OVERVIEW B. VELLAS & E. REYNISH (Toulouse, France, EU) Bruno Vellas: The European Alzheimer's Disease Consortium is a European funded network of centres of

More information

K. Kahle-Wrobleski 1, J.S. Andrews 1, M. Belger 2, S. Gauthier 3, Y. Stern 4, D.M. Rentz 5, D. Galasko 6

K. Kahle-Wrobleski 1, J.S. Andrews 1, M. Belger 2, S. Gauthier 3, Y. Stern 4, D.M. Rentz 5, D. Galasko 6 The Journal of Prevention of Alzheimer s Disease - JPAD Volume 2, Number 2, 2015 Clinical and Economic Characteristics of Milestones along the Continuum of Alzheimer s Disease: Transforming Functional

More information

Dementia of the Alzheimer Type: the Drug Treatment Debate

Dementia of the Alzheimer Type: the Drug Treatment Debate Dementia of the Alzheimer Type: the Drug Treatment Debate I have no financial conflict of interest. Many years ago I was given a trip to San Fran and taught to use a slide set from the drug company. I

More information

ClinicalTrials.gov "Basic Results" Data Element Definitions (DRAFT)

ClinicalTrials.gov Basic Results Data Element Definitions (DRAFT) ClinicalTrials.gov "Basic Results" Data Element Definitions (DRAFT) January 9, 2009 * Required by ClinicalTrials.gov [*] Conditionally required by ClinicalTrials.gov (FDAAA) May be required to comply with

More information

EBM Journal Club: Does Ginkgo Biloba improve memory in elder group

EBM Journal Club: Does Ginkgo Biloba improve memory in elder group EBM Journal Club: Does Ginkgo Biloba improve memory in elder group R2 0 Memory loss in elder >> Dementia Defination Diagnosis Prognosis 1 Why so serious? 2 Any way to improve memory in elder??? 3 Any way

More information

Gerardo Machnicki 1, Ricardo F. Allegri 1,2 *, Carol Dillon 1, Cecilia M. Serrano 1,2 and Fernando E Taragano 2 SUMMARY INTRODUCTION

Gerardo Machnicki 1, Ricardo F. Allegri 1,2 *, Carol Dillon 1, Cecilia M. Serrano 1,2 and Fernando E Taragano 2 SUMMARY INTRODUCTION INTERNATIONAL JOURNAL OF GERIATRIC PSYCHIATRY Int J Geriatr Psychiatry (2008) Published online in Wiley InterScience (www.interscience.wiley.com).2133 Cognitive, functional and behavioral factors associated

More information

IQWiG Reports - Commission No. A05-19B. Executive Summary

IQWiG Reports - Commission No. A05-19B. Executive Summary IQWiG Reports - Commission No. A05-19B Ginkgo in Alzheimer s disease 1 Executive Summary 1 Translation of the executive summary of the final report Ginkgohaltige Präparate bei Alzheimer Demenz (Version

More information

Ian McKeith MD, F Med Sci, Professor of Old Age Psychiatry, Newcastle University

Ian McKeith MD, F Med Sci, Professor of Old Age Psychiatry, Newcastle University Ian McKeith MD, F Med Sci, Professor of Old Age Psychiatry, Newcastle University Design of trials in DLB and PDD What has been learnt from previous trials in these indications and other dementias? Overview

More information

Supplementary Appendix

Supplementary Appendix Supplementary Appendix This appendix has been provided by the authors to give readers additional information about their work. Supplement to: Howard R, McShane R, Lindesay J, et al. Donepezil and memantine

More information

Prevention, health promotion & early intervention in dementia

Prevention, health promotion & early intervention in dementia Prevention, health promotion & early intervention in dementia Alzheimer New Zealand Conference 2014 Steve Iliffe Professor of Primary Care & Older People University College London Rotorua, New Zealand

More information

Clinical Trial Designs for RCTs focussing on the Treatment of Agitation in people with Alzheimer s disease

Clinical Trial Designs for RCTs focussing on the Treatment of Agitation in people with Alzheimer s disease Clinical Trial Designs for RCTs focussing on the Treatment of Agitation in people with Alzheimer s disease Professor Clive Ballard Dr Byron Creese University of Exeter, UK Guardian guide for 2018: Top

More information

SHARED CARE PROTOCOL CHOLINESTERASE INHIBITORS IN ALZHEIMER S DEMENTIA

SHARED CARE PROTOCOL CHOLINESTERASE INHIBITORS IN ALZHEIMER S DEMENTIA SHARED CARE PROTOCOL CHOLINESTERASE INHIBITORS IN ALZHEIMER S DEMENTIA Introduction Alzheimer s disease is the most common cause of dementia. It is characterised by an insidious onset of global mental

More information

MedDRA Overview A Standardized Terminology

MedDRA Overview A Standardized Terminology MedDRA Overview A Standardized Terminology Patrick Revelle Director, MedDRA MSSO 6 May 2010 MedDRA is a registered trademark of the International Federation of Pharmaceutical Manufacturers and Associations

More information

Cholinesterase inhibitors for Alzheimer s disease (Review)

Cholinesterase inhibitors for Alzheimer s disease (Review) Birks J This is a reprint of a Cochrane review, prepared and maintained by The Cochrane Collaboration and published in The Cochrane Library 2008, Issue 3 http://www.thecochranelibrary.com 1 T A B L E O

More information

Evidence-based pharmacotherapy of Alzheimer s disease

Evidence-based pharmacotherapy of Alzheimer s disease International Journal of Neuropsychopharmacology (2004), 7, 351 369. Copyright f 2004 CINP DOI: 10.1017/S1461145704004444 Evidence-based pharmacotherapy of Alzheimer s disease SPECIAL SERIES John Grimley

More information

PATCH Analysis Plan v1.2.doc Prophylactic Antibiotics for the Treatment of Cellulitis at Home: PATCH Analysis Plan for PATCH I and PATCH II Authors: Angela Crook, Andrew Nunn, James Mason and Kim Thomas,

More information

The audit is managed by the Royal College of Psychiatrists in partnership with:

The audit is managed by the Royal College of Psychiatrists in partnership with: Background The National Audit of Dementia (NAD) care in general hospitals is commissioned by the Healthcare Quality Improvement Partnership on behalf of NHS England and the Welsh Government, as part of

More information

As people age, changes to the structure

As people age, changes to the structure CMAJ Guidelines CME Recommendations on screening for cognitive impairment in older adults Canadian Task Force on Preventive Health Care* CMAJ podcasts: author interview at https://soundcloud.com/cmajpodcasts/141165-guide

More information

Psychological therapies for people with dementia who have associated depression [New 2015].

Psychological therapies for people with dementia who have associated depression [New 2015]. Psychological therapies for people with dementia who have associated depression [New 2015]. SCOPING QUESTION: For people with dementia and comorbid depression, do psychological interventions (including

More information

A report for the UK National Screening Committee

A report for the UK National Screening Committee Screening for dementia: Can screening bring benefits to those with unrecognised dementia, their carers and society? An appraisal against UKNSC criteria A report for the UK National Screening Committee

More information

The course of neuropsychiatric symptoms in dementia. Part II: relationships among behavioural sub-syndromes and the influence of clinical variables

The course of neuropsychiatric symptoms in dementia. Part II: relationships among behavioural sub-syndromes and the influence of clinical variables INTERNATIONAL JOURNAL OF GERIATRIC PSYCHIATRY Int J Geriatr Psychiatry 2005; 20: 531 536. Published online in Wiley InterScience (www.interscience.wiley.com). DOI: 10.1002/gps.1317 The course of neuropsychiatric

More information

TRANSPARENCY COMMITTEE

TRANSPARENCY COMMITTEE The legally binding text is the original French version TRANSPARENCY COMMITTEE Opinion 18 December 2013 EXELON 13.3 mg/24 hours, transdermal patch B/30 sachets (CIP: 34009 268 908 1 0) Applicant: NOVARTIS

More information

HOW TO PREVENT COGNITIVE DECLINE.AT MCI STAGE?

HOW TO PREVENT COGNITIVE DECLINE.AT MCI STAGE? EAMA CORE CURRICULUM HOW TO PREVENT COGNITIVE DECLINE.AT MCI STAGE? Sofia Duque Orthogeriatric Unit São Francisco Xavier Hospital Occidental Lisbon Hospital Center University Geriatric Unit, Faculty of

More information

PROSPERO International prospective register of systematic reviews

PROSPERO International prospective register of systematic reviews PROSPERO International prospective register of systematic reviews The effect of probiotics on functional constipation: a systematic review of randomised controlled trials EIRINI DIMIDI, STEPHANOS CHRISTODOULIDES,

More information

NEUROPSYCHOMETRIC TESTS

NEUROPSYCHOMETRIC TESTS NEUROPSYCHOMETRIC TESTS CAMCOG It is the Cognitive section of Cambridge Examination for Mental Disorders of the Elderly (CAMDEX) The measure assesses orientation, language, memory, praxis, attention, abstract

More information

Safinamide (Addendum to Commission A15-18) 1

Safinamide (Addendum to Commission A15-18) 1 IQWiG Reports Commission No. A15-41 Safinamide (Addendum to Commission A15-18) 1 Addendum Commission:A15-41 Version: 1.1 Status: 29 October 2015 1 Translation of addendum A15-41 Safinamid (Addendum zum

More information

Technology appraisal guidance Published: 23 March 2011 nice.org.uk/guidance/ta217

Technology appraisal guidance Published: 23 March 2011 nice.org.uk/guidance/ta217 Donepezil, galantamine, rivastigmine and memantine for the treatment of Alzheimer's disease Technology appraisal guidance Published: 23 March 2011 nice.org.uk/guidance/ta217 NICE 2017. All rights reserved.

More information

Nutritional intervention in early Alzheimer s disease. Sasha Newsam, PhD Global Medical Affairs Manager Nutricia

Nutritional intervention in early Alzheimer s disease. Sasha Newsam, PhD Global Medical Affairs Manager Nutricia Nutritional intervention in early Alzheimer s disease Sasha Newsam, PhD Global Medical Affairs Manager Nutricia Agenda Nutrition and brain function Single nutrient intervention Diet and risk of Alzheimer

More information

Chapter 6 Psychoeducation for depression, anxiety and psychological distress: a meta-analysis

Chapter 6 Psychoeducation for depression, anxiety and psychological distress: a meta-analysis Chapter 6 Psychoeducation for depression, anxiety and psychological distress: a meta-analysis Published: Donker, T., Griffiths, K.M., Cuijpers, P., Christensen, H., 2009. Psychoeducation for depression

More information

Medications for treating people with dementia: summary of evidence on cost-effectiveness

Medications for treating people with dementia: summary of evidence on cost-effectiveness Medications for treating people with dementia: summary of evidence on cost-effectiveness Martin Knapp, A-La Park and Alistair Burns PSSRU, London School of Economics and Political Science v4 23 July 2017

More information

Surveillance report Published: 17 March 2016 nice.org.uk

Surveillance report Published: 17 March 2016 nice.org.uk Surveillance report 2016 Ovarian Cancer (2011) NICE guideline CG122 Surveillance report Published: 17 March 2016 nice.org.uk NICE 2016. All rights reserved. Contents Surveillance decision... 3 Reason for

More information

Linagliptin Renewed benefit assessment according to 35a Paragraph 5b Social Code Book V 1

Linagliptin Renewed benefit assessment according to 35a Paragraph 5b Social Code Book V 1 IQWiG Reports Commission No. A12-11 Linagliptin Renewed benefit assessment according to 35a Paragraph 5b Social Code Book V 1 Extract 1 Translation of Sections 2.1 to 2.6 of the dossier assessment ( Linagliptin

More information

Surveillance report Published: 13 April 2017 nice.org.uk. NICE All rights reserved.

Surveillance report Published: 13 April 2017 nice.org.uk. NICE All rights reserved. Surveillance report 2017 Antisocial behaviour and conduct disorders in children and young people: recognition and management (2013) NICE guideline CG158 Surveillance report Published: 13 April 2017 nice.org.uk

More information

Technology appraisal guidance Published: 30 August 2017 nice.org.uk/guidance/ta471

Technology appraisal guidance Published: 30 August 2017 nice.org.uk/guidance/ta471 Eluxadoline for treating irritable bowel syndrome with diarrhoea Technology appraisal guidance Published: 30 August 2017 nice.org.uk/guidance/ta471 NICE 2017. All rights reserved. Subject to Notice of

More information

Enhanced Service for people with dementia in Primary Care

Enhanced Service for people with dementia in Primary Care Enhanced Service for people with dementia in Primary Care Alistair Burns and Laurence Buckman September 2013 1 Summary The Enhanced Service for dementia, introduced in April 2013, is based in Primary Care

More information

Critical Appraisal. Dave Abbott Senior Medicines Information Pharmacist

Critical Appraisal. Dave Abbott Senior Medicines Information Pharmacist Critical Appraisal Dave Abbott Senior Medicines Information Pharmacist Aims Identify key components of clinical trial design and apply these to a critical appraisal of the literature Be able to work out

More information

LTC Research Influencing Practice

LTC Research Influencing Practice LTC Research Influencing Practice David A. Nace, MD, MPH Division of Geriatric Medicine naceda@upmc.edu PGS Clinical Update April 6, 2017 Conflicts of Interest Dr. Nace does not have any current conflicts

More information

Mental Health Policy Group Institute of Mental Health

Mental Health Policy Group Institute of Mental Health Well-being of the Singapore Elderly Survey April 2011 March 2014 Mental Health Policy Group Institute of Mental Health WiSE Study Team Principal Investigator (PI) Prof. Chong Siow Ann (IMH) CGH Dr Ng Li

More information

Delirium. Quick reference guide. Issue date: July Diagnosis, prevention and management

Delirium. Quick reference guide. Issue date: July Diagnosis, prevention and management Issue date: July 2010 Delirium Diagnosis, prevention and management Developed by the National Clinical Guideline Centre for Acute and Chronic Conditions About this booklet This is a quick reference guide

More information

Randomized controlled trial of physical activity counseling as an aid to smoking cessation: 12 month follow-up

Randomized controlled trial of physical activity counseling as an aid to smoking cessation: 12 month follow-up Addictive Behaviors 32 (2007) 3060 3064 Short communication Randomized controlled trial of physical activity counseling as an aid to smoking cessation: 12 month follow-up Michael Ussher a,, Robert West

More information

Anosognosia, or loss of insight into one s cognitive

Anosognosia, or loss of insight into one s cognitive REGULAR ARTICLES Anosognosia Is a Significant Predictor of Apathy in Alzheimer s Disease Sergio E. Starkstein, M.D., Ph.D. Simone Brockman, M.A. David Bruce, M.D. Gustavo Petracca, M.D. Anosognosia and

More information

Treatment changes in cancer clinical trials: design and analysis

Treatment changes in cancer clinical trials: design and analysis Treatment changes in cancer clinical trials: design and analysis Ian White Statistical methods and designs in clinical oncology Paris, 9 th November 2017 Plan 1. Treatment changes

More information

words excluding references

words excluding references Psychological problems in New Zealand primary health care: A report on the pilot phase of the Mental Health and General Practice Investigation (MaGPIe) NZ Med J 2001; 114, 11-13 The MaGPIe Research Group

More information

NeuRA Schizophrenia diagnosis May 2017

NeuRA Schizophrenia diagnosis May 2017 Introduction Diagnostic scales are widely used within clinical practice and research settings to ensure consistency of illness ratings. These scales have been extensively validated and provide a set of

More information

Incident dementia and blood pressure lowering in the Hypertension in the Very Elderly Trial [HYVET] R. Peters

Incident dementia and blood pressure lowering in the Hypertension in the Very Elderly Trial [HYVET] R. Peters Incident dementia and blood pressure lowering in the Hypertension in the Very Elderly Trial [HYVET] R. Peters ClinicalTrials.gov: NCT00122811 Backgound The prevalence of dementia rises with increasing

More information

CURRICULUM VITAE. University of Columbia Missouri Department of Psychiatry and Neurology

CURRICULUM VITAE. University of Columbia Missouri Department of Psychiatry and Neurology CURRICULUM VITAE Rubén Bravo Valverde, M.D. Forensic and Geriatric Psychiatrist Centro Especializado de Psiquiatría 1995 Road 2 Suite 1209-1210 Bayamón, Puerto Rico 00959-1201 Telephones: (787) 786-0575/780-3752

More information

EPF s response to the European Commission s public consultation on the "Summary of Clinical Trial Results for Laypersons"

EPF s response to the European Commission s public consultation on the Summary of Clinical Trial Results for Laypersons EPF s response to the European Commission s public consultation on the "Summary of Clinical Trial Results for Laypersons" August 2016 This document received funding under an operating grant from the European

More information

Pharmacological Treatment of Behavioural and Psychological Symptoms of Dementia (BPSD) Gurdeep K Major St. Charles Hospital

Pharmacological Treatment of Behavioural and Psychological Symptoms of Dementia (BPSD) Gurdeep K Major St. Charles Hospital Pharmacological Treatment of Behavioural and Psychological Symptoms of Dementia (BPSD) Gurdeep K Major St. Charles Hospital with thanks to Jonathan Cavan for his input Aims Define BPSD and common symptoms

More information

Dementia data harmonisation: South of England Protocol

Dementia data harmonisation: South of England Protocol Dementia data harmonisation: South of England Protocol Background 1. In 2013 an aspiration was agreed between the Department of Health and the new-look NHS England that by 2015 two-thirds of people with

More information

Evidence-Based Interventions to Improve Caregiver and Patient Outcomes in Dementia

Evidence-Based Interventions to Improve Caregiver and Patient Outcomes in Dementia Evidence-Based Interventions to Improve Caregiver and Patient Outcomes in Dementia Alan B. Stevens, PhD Professor, Department of Medicine Vernon D. Holleman-Lewis M. Rampy Centennial Chair in Gerontology

More information

Burden of behavioral and psychiatric symptoms in people screened positive for dementia in primary care results of the DelpHi-study René Thyrian

Burden of behavioral and psychiatric symptoms in people screened positive for dementia in primary care results of the DelpHi-study René Thyrian Burden of behavioral and psychiatric symptoms in people screened positive for dementia in primary care results of the DelpHi-study René Thyrian German Center for Neurodegenerative Diseases (DZNE), site

More information

Drug Class Literature Scan: Pancreatic Enzymes

Drug Class Literature Scan: Pancreatic Enzymes Copyright 2012 Oregon State University. All Rights Reserved Drug Use Research & Management Program Oregon State University, 500 Summer Street NE, E35 Salem, Oregon 97301-1079 Phone 503-947-5220 Fax 503-947-1119

More information

inserm , version 1-3 May 2011 Corresponding author:

inserm , version 1-3 May 2011 Corresponding author: Author manuscript, published in "The journal of nutrition, health & aging 0;():-" inserm-000, version - May 0 0 0 0 Diagnosis of Alzheimer s disease patients with Rapid Cognitive Decline in clinical practice:

More information

SYNOPSIS. Risperidone-R064766: Clinical Study Report RIS-AUS-5 (FOR NATIONAL AUTHORITY USE ONLY)

SYNOPSIS. Risperidone-R064766: Clinical Study Report RIS-AUS-5 (FOR NATIONAL AUTHORITY USE ONLY) SYNOPSIS Protocol No.: RIS-AUS-5 Psychosis in Alzheimer s disease (PAD) analysis Title of Study: Risperidone in the treatment of behavioral and psychological symptoms in dementia: a multicenter, double-blind,

More information

Prevalence of Premenstrual Syndrome in Autism: a Prospective Observer-rated Study

Prevalence of Premenstrual Syndrome in Autism: a Prospective Observer-rated Study The Journal of International Medical Research 2008; 36: 268 272 Prevalence of Premenstrual Syndrome in Autism: a Prospective Observer-rated Study H OBAYDI 1 AND BK PURI 2 1 Hertfordshire Partnership Foundation

More information

Technology appraisal guidance Published: 23 May 2012 nice.org.uk/guidance/ta256

Technology appraisal guidance Published: 23 May 2012 nice.org.uk/guidance/ta256 Rivaroxaban for the prevention ention of stroke and systemic embolism in people with atrial fibrillation Technology appraisal guidance Published: 23 May 2012 nice.org.uk/guidance/ta256 NICE 2018. All rights

More information

Of those with dementia have a formal diagnosis or are in contact with specialist services. Dementia prevalence for those aged 80+

Of those with dementia have a formal diagnosis or are in contact with specialist services. Dementia prevalence for those aged 80+ Dementia Ref HSCW 18 Why is it important? Dementia presents a significant and urgent challenge to health and social care in County Durham, in terms of both numbers of people affected and the costs associated

More information

Resource Utilisation and Cost Analysis of Memantine in Patients with Moderate to Severe Alzheimer s Disease

Resource Utilisation and Cost Analysis of Memantine in Patients with Moderate to Severe Alzheimer s Disease ORIGINAL RESEARCH ARTICLE Pharmacoeconomics 2003; 21 (5): 1 1170-7690/03/0099-0001/$30.00/0 Adis International Limited. All rights reserved. Resource Utilisation and Cost Analysis of Memantine in Patients

More information

The Pleasant Events Schedule-AD: Psychometric Properties and Relationship to Depression and Cognition in Alzheimer's Disease Patients 1

The Pleasant Events Schedule-AD: Psychometric Properties and Relationship to Depression and Cognition in Alzheimer's Disease Patients 1 Copyright 1997 by The Cerontological Society of America The Cerontologist Vol.37, No. 1,40-45 The Pleasant Events Schedule-AD (PES-AD) has been described as a useful tool for identifying pleasant activities

More information

SYNOPSIS. Risperidone-R064766: Clinical Study Report RIS-INT-24 (FOR NATIONAL AUTHORITY USE ONLY)

SYNOPSIS. Risperidone-R064766: Clinical Study Report RIS-INT-24 (FOR NATIONAL AUTHORITY USE ONLY) SYNOPSIS Protocol No.: RIS-INT-24 Psychosis in Alzheimer s disease (PAD) analysis Title of Study: Risperidone in the treatment of behavioral disturbances in demented patients: an international, multicenter,

More information

Summary of funded Dementia Research Projects

Summary of funded Dementia Research Projects Summary of funded Dementia Research Projects Health Services and Delivery Research (HS&DR) Programme: HS&DR 11/2000/05 The detection and management of pain in patients with dementia in acute care settings:

More information

MODIFIED INFORMANT QUESTIONNAIRE ON COGNITIVE DECLINE IN THE ELDERLY (IQCODE) AS A SCREENING TEST FOR DEMENTIA FOR THAI ELDERLY

MODIFIED INFORMANT QUESTIONNAIRE ON COGNITIVE DECLINE IN THE ELDERLY (IQCODE) AS A SCREENING TEST FOR DEMENTIA FOR THAI ELDERLY MODIFIED IQCODE FOR DEMENTIA SCREENING MODIFIED INFORMANT QUESTIONNAIRE ON COGNITIVE DECLINE IN THE ELDERLY (IQCODE) AS A SCREENING TEST FOR DEMENTIA FOR THAI ELDERLY Sukhontha Siri 1, Kamolnetr Okanurak

More information

Pharmacological Treatment of Dementia

Pharmacological Treatment of Dementia Pharmacological Treatment of Dementia Measure Description Percentage of patients with dementia or their caregivers with whom available guideline-appropriate pharmacological treatment options and nonpharmacological

More information

Surveillance report Published: 8 June 2017 nice.org.uk. NICE All rights reserved.

Surveillance report Published: 8 June 2017 nice.org.uk. NICE All rights reserved. Surveillance report 2017 Antenatal and postnatal mental health: clinical management and service guidance (2014) NICE guideline CG192 Surveillance report Published: 8 June 2017 nice.org.uk NICE 2017. All

More information

This information explains the advice about supporting people with dementia and their carers that is set out in NICE SCIE clinical guideline 42.

This information explains the advice about supporting people with dementia and their carers that is set out in NICE SCIE clinical guideline 42. Supporting people with dementia and their carers Information for the public Published: 1 November 2006 nice.org.uk About this information NICEclinicalguidelinesadvisetheNHSoncaringforpeoplewithspe cificconditionsordiseasesandthetreatmentstheyshouldreceive.

More information

A study about how parts of the brain work in people with Down syndrome

A study about how parts of the brain work in people with Down syndrome A study about how parts of the brain work in people with Down syndrome Our names are Carla Startin, Sarah Hamburg and Ros Hithersay. We are researchers working at University College London. We are carrying

More information

ASH 2011: Clinically Relevant Highlights Regarding Venous Thromboembolism and Anticoagulation

ASH 2011: Clinically Relevant Highlights Regarding Venous Thromboembolism and Anticoagulation ASH 2011: Clinically Relevant Highlights Regarding Venous Thromboembolism and Anticoagulation Stephan Moll Department of Medicine, Division of Hematology-Oncology, University of North Carolina School of

More information

Primary Care Prescribing Protocol to Support the Diagnosis and Management of People with Dementia

Primary Care Prescribing Protocol to Support the Diagnosis and Management of People with Dementia Primary Care Prescribing Protocol to Support the Diagnosis and Management of People with Dementia This prescribing guideline provides the necessary information and guidance to support clinicians in the

More information

Evidence Based Medicine

Evidence Based Medicine Course Goals Goals 1. Understand basic concepts of evidence based medicine (EBM) and how EBM facilitates optimal patient care. 2. Develop a basic understanding of how clinical research studies are designed

More information

Technology appraisal guidance Published: 26 September 2012 nice.org.uk/guidance/ta264

Technology appraisal guidance Published: 26 September 2012 nice.org.uk/guidance/ta264 Alteplase for treating acute ischaemic stroke Technology appraisal guidance Published: 26 September 2012 nice.org.uk/guidance/ta264 NICE 2018. All rights reserved. Subject to Notice of rights (https://www.nice.org.uk/terms-and-conditions#notice-ofrights).

More information

What is dementia? alzheimers.org.uk

What is dementia? alzheimers.org.uk alzheimers.org.uk What is dementia? If you, or a friend or relative, have been diagnosed with dementia, you may be feeling anxious or confused. You may not know what dementia is. This factsheet should

More information

Shire Pharmaceuticals/Johnson & Johnson 16 December 2005

Shire Pharmaceuticals/Johnson & Johnson 16 December 2005 Shire Pharmaceuticals/Johnson & Johnson 16 December 2005 Comments on Addenda to MRC report on clinical efficacy and NICE Technical Report 2; Drugs for the Treatment of Alzheimer s Disease (review) Executive

More information

NIH Public Access Author Manuscript Metab Brain Dis. Author manuscript; available in PMC 2011 October 24.

NIH Public Access Author Manuscript Metab Brain Dis. Author manuscript; available in PMC 2011 October 24. NIH Public Access Author Manuscript Published in final edited form as: Metab Brain Dis. 2006 September ; 21(2-3): 235 240. doi:10.1007/s11011-006-9017-2. Risk factors for incident Alzheimer s disease in

More information

Diagnostic Disclosure of Mild Cognitive Impairment: what is told to the patient?

Diagnostic Disclosure of Mild Cognitive Impairment: what is told to the patient? Chapter 5 Diagnostic Disclosure of Mild Cognitive Impairment: what is told to the patient? Els Derksen Maud Graff Pieter-Jelle Visser Marcel Olde Rikkert Myrra Vernooij-Dassen 1 ABSTRACT Objective: To

More information

Alzheimer Europe Conference Berlin, 2-4 October Special Symposium 4 October, , Room II. Eli Lilly and Company

Alzheimer Europe Conference Berlin, 2-4 October Special Symposium 4 October, , Room II. Eli Lilly and Company ENGAGING WITH PATIENT ORGANISATIONS WITHIN IMI CONSORTIA TO INFORM QUALITY, RELEVANCE AND VALUE IN ALZHEIMER S RESEARCH INSIGHTS FROM MOPEAD, EPAD AND ROADMAP Alzheimer Europe Conference Berlin, 2-4 October

More information

The Sleep Disorders Inventory: an instrument for studies of sleep disturbance in persons with Alzheimer s disease

The Sleep Disorders Inventory: an instrument for studies of sleep disturbance in persons with Alzheimer s disease J. Sleep Res. (2003) 12, 331 337 The Sleep Disorders Inventory: an instrument for studies of sleep disturbance in persons with Alzheimer s disease ROCHELLE E. TRACTENBERG 1, CLIFFORD M. SINGER 2, JEFFREY

More information

Aricept, Exelon and Reminyl the new drugs for Alzheimer s disease

Aricept, Exelon and Reminyl the new drugs for Alzheimer s disease PBO 930022142 NPO 049-191 Aricept, Exelon and Reminyl the new drugs for Alzheimer s disease Aricept, Exelon and Reminyl are not cures for Alzheimer s disease. However, they can temporarily slow down the

More information

A 24-Week, Open-Label Extension Study to Investigate the Long-Term Safety,

A 24-Week, Open-Label Extension Study to Investigate the Long-Term Safety, 1 A 24-Week, Open-Label Extension Study to Investigate the Long-Term Safety, Tolerability, and Efficacy of 13.3 mg/24 h Rivastigmine Patch in Patients with Severe Alzheimer s Disease Martin R. Farlow,

More information

COGNOS. Care for people with Cognitive dysfunction A National Observational Study. Professor Dr Jan De Lepeleire COGNOS members

COGNOS. Care for people with Cognitive dysfunction A National Observational Study. Professor Dr Jan De Lepeleire COGNOS members COGNOS Care for people with Cognitive dysfunction A National Observational Study Professor Dr Jan De Lepeleire COGNOS members Luxembourg Alzheimer Europe 2010 The Careplan in Belgium Requirements for reimbursement

More information

Dementia in Taiwan area

Dementia in Taiwan area Translational Neuroscience and Clinics ISSN print edition: 2096-0441 ISSN electronic edition: 2096-0670 CN print edition: 10-1319/R CN electronic edition: 11-6030/R DOI Vol. 2, No. 1, March 2016, pp 38

More information

One-off assessments within a community mental health team

One-off assessments within a community mental health team Primary Care Mental Health 2007;4:00 00 # 2007 Radcliffe Publishing International research One-off assessments within a community mental health team Linda Heaney Consultant Psychiatrist, Avon and Wiltshire

More information

rosuvastatin, 5mg, 10mg, 20mg, film-coated tablets (Crestor ) SMC No. (725/11) AstraZeneca UK Ltd.

rosuvastatin, 5mg, 10mg, 20mg, film-coated tablets (Crestor ) SMC No. (725/11) AstraZeneca UK Ltd. rosuvastatin, 5mg, 10mg, 20mg, film-coated tablets (Crestor ) SMC No. (725/11) AstraZeneca UK Ltd. 09 September 2011 The Scottish Medicines Consortium (SMC) has completed its assessment of the above product

More information

This booklet has been published by CREST (the Clinical Resource Efficiency Support Team).

This booklet has been published by CREST (the Clinical Resource Efficiency Support Team). This booklet has been published by CREST (the Clinical Resource Efficiency Support Team). CREST is a small committee of health care professionals established under the auspices of the Central Medical Advisory

More information

Evidence profile: cognitive impairment

Evidence profile: cognitive impairment Integrated care for older people (ICOPE) Guidelines on community-level interventions to manage declines in intrinsic capacity Evidence profile: cognitive impairment Scoping question: Does cognitive stimulation,

More information

Critical Appraisal of RCT

Critical Appraisal of RCT Critical Appraisal of RCT What is critical appraisal? Definition Process of systematically examining research evidence to assess its reliability (validity/internal validity), results and relevance (external

More information

Surr et al. Trials (2016) 17:300 DOI /s z

Surr et al. Trials (2016) 17:300 DOI /s z Surr et al. Trials (2016) 17:300 DOI 10.1186/s13063-016-1416-z STUDY PROTOCOL Evaluating the effectiveness and cost-effectiveness of Dementia Care Mapping to enable person-centred care for people with

More information

ORIGINAL CONTRIBUTION. Response of Patients With Alzheimer Disease to Rivastigmine Treatment Is Predicted by the Rate of Disease Progression

ORIGINAL CONTRIBUTION. Response of Patients With Alzheimer Disease to Rivastigmine Treatment Is Predicted by the Rate of Disease Progression ORIGINAL CONTRIBUTION Response of Patients With Alzheimer Disease to Rivastigmine Treatment Is Predicted by the Rate of Disease Progression Martin R. Farlow, MD; Ann Hake, MD; John Messina, PharmD; Richard

More information

An occupational therapy intervention for residents with stroke related disabilities in UK care homes (OTCH): cluster randomised controlled trial

An occupational therapy intervention for residents with stroke related disabilities in UK care homes (OTCH): cluster randomised controlled trial open access An occupational therapy intervention for residents with stroke related disabilities in UK care homes (OTCH): cluster randomised controlled trial Catherine M Sackley, 1 Marion F Walker, 2 Christopher

More information

PRESCRIBING FOR PEOPLE WITH DEMENTIA; SELECTED FINDINGS FROM POMH-UK QUALITY IMPROVEMENT PROGRAMMES (QIPS)

PRESCRIBING FOR PEOPLE WITH DEMENTIA; SELECTED FINDINGS FROM POMH-UK QUALITY IMPROVEMENT PROGRAMMES (QIPS) PRESCRIBING FOR PEOPLE WITH DEMENTIA; SELECTED FINDINGS FROM POMH-UK QUALITY IMPROVEMENT PROGRAMMES (QIPS) The Prescribing Observatory for Mental Health (POMH-UK) is a national initiative to improve the

More information

The National Paediatric Diabetes Audit

The National Paediatric Diabetes Audit Introduction The National Paediatric Diabetes Audit (NPDA) for and is commissioned by the Healthcare Quality Improvement Partnership (HQIP) as part of the National Clinical Audit and Patient Outcomes Programme

More information

Dementia: Rethinking our approach to behaviour

Dementia: Rethinking our approach to behaviour Dementia: Rethinking our approach to behaviour Dr Kathryn Lord Research Fellow 1 A bit about me: The 3 P s! Psychology Psychiatry Person centredcare 2 Challenging behaviours in Challenging behaviours dementia

More information

This clinical study synopsis is provided in line with Boehringer Ingelheim s Policy on Transparency and Publication of Clinical Study Data.

This clinical study synopsis is provided in line with Boehringer Ingelheim s Policy on Transparency and Publication of Clinical Study Data. abcd Clinical Study for Public Disclosure This clinical study synopsis is provided in line with s Policy on Transparency and Publication of Clinical Study Data. The synopsis which is part of the clinical

More information

The comparison or control group may be allocated a placebo intervention, an alternative real intervention or no intervention at all.

The comparison or control group may be allocated a placebo intervention, an alternative real intervention or no intervention at all. 1. RANDOMISED CONTROLLED TRIALS (Treatment studies) (Relevant JAMA User s Guides, Numbers IIA & B: references (3,4) Introduction: The most valid study design for assessing the effectiveness (both the benefits

More information

UK Liver Transplant Audit

UK Liver Transplant Audit November 2012 UK Liver Transplant Audit In patients who received a Liver Transplant between 1 st March 1994 and 31 st March 2012 ANNUAL REPORT Advisory Group for National Specialised Services Prepared

More information

BEST PRACTICES FOR IMPLEMENTATION AND ANALYSIS OF PAIN SCALE PATIENT REPORTED OUTCOMES IN CLINICAL TRIALS

BEST PRACTICES FOR IMPLEMENTATION AND ANALYSIS OF PAIN SCALE PATIENT REPORTED OUTCOMES IN CLINICAL TRIALS BEST PRACTICES FOR IMPLEMENTATION AND ANALYSIS OF PAIN SCALE PATIENT REPORTED OUTCOMES IN CLINICAL TRIALS Nan Shao, Ph.D. Director, Biostatistics Premier Research Group, Limited and Mark Jaros, Ph.D. Senior

More information

The physiofirst pilot study: A pilot randomised clinical trial for the efficacy of a targeted physiotherapy intervention for

The physiofirst pilot study: A pilot randomised clinical trial for the efficacy of a targeted physiotherapy intervention for The physiofirst pilot study: A pilot randomised clinical trial for the efficacy of a targeted physiotherapy intervention for Click to edit Master title style femoroacetabular impingement syndrome (FAIS)

More information

Time Series Analysis for selected clinical indicators from the Quality and Outcomes Framework

Time Series Analysis for selected clinical indicators from the Quality and Outcomes Framework Time Series Analysis for selected clinical indicators from the Quality and Outcomes Framework 21-26 Title Document Type Time Series Analysis for selected clinical indicators from the Quality and Outcomes

More information

Diversity and Dementia

Diversity and Dementia Diversity and Dementia Kala M. Mehta, DSc, MPH January 17, 2012 Overview Background Incidence and Prevalence of Dementia Why are these differences found? What s important for diverse dementia patients

More information

The prevalence and history of knee osteoarthritis in general practice: a case control study

The prevalence and history of knee osteoarthritis in general practice: a case control study The Author (2005). Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oupjournals.org doi:10.1093/fampra/cmh700 Family Practice Advance Access

More information

Annex I. List of medicinal products and presentations

Annex I. List of medicinal products and presentations Annex I List of medicinal products and presentations Member State EU/EEA Applicant (Invented) Name INN + Strength Pharmaceutical form 4 Route of administration 5 Austria Ibucomb 500mg/150mg film Belgium

More information