Kingshill Research Center

Swindon, United Kingdom

Kingshill Research Center

Swindon, United Kingdom
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Robert P.H.,University of Nice Sophia Antipolis | Robert P.H.,Nice University Hospital Center | Konig A.,University of Nice Sophia Antipolis | Konig A.,Maastricht University | And 22 more authors.
Frontiers in Aging Neuroscience | Year: 2014

Alzheimer's disease and other related disorders (ADRD) represent a major challenge for health care systems within the aging population. It is therefore important to develop better instruments to assess the disease severity and progression, as well as to improve its treatment, stimulation, and rehabilitation. This is the underlying idea for the development of Serious Games (SG). These are digital applications specially adapted for purposes other than entertaining; such as rehabilitation, training and education. Recently, there has been an increase of interest in the use of SG targeting patients with ADRD. However, this field is completely uncharted, and the clinical, ethical, economic and research impact of the employment of SG in these target populations has never been systematically addressed. The aim of this paper is to systematically analyze the Strengths, Weaknesses, Opportunities, and Threats (SWOT) of employing SG with patients with ADRD in order to provide practical recommendations for the development and use of SG in these populations. These analyses and recommendations were gathered, commented on and validated during a 2-round workshop in the context of the 2013 Clinical Trial of Alzheimer's Disease (CTAD) conference, and endorsed by stakeholders in the field. The results revealed that SG may offer very useful tools for professionals involved in the care of patients suffering from ADRD. However, more interdisciplinary work should be done in order to create SG specifically targeting these populations. Furthermore, in order to acquire more academic and professional credibility and acceptance, it will be necessary to invest more in research targeting efficacy and feasibility. Finally, the emerging ethical challenges should be considered a priority. © 2014 Robert, König, Amieva, Andrieu, Bremond, Bullock, Ceccaldi, Dubois, Gauthier, Kenigsberg, Nave, Orgogozo, Piano, Benoit, Touchon, Vellas, Yesavage and Manera.


Emre M.,Istanbul University | Bernabei R.,Catholic University of the Sacred Heart | Blesa R.,Hospital Of La Sta Creu I Sant Pau | Bullock R.,Kingshill Research Center | And 12 more authors.
CNS Neuroscience and Therapeutics | Year: 2010

Cholinesterase inhibitors constitute one of the mainstays of treatment of Alzheimer disease (AD). Gastrointestinal side effects, difficulty accessing therapeutic doses and poor patient compliance have been identified as barriers to effective treatment with these substances. The rivastigmine transdermal patch provides continuous delivery of drug through the skin into the bloodstream, avoiding the fluctuations in plasma concentration associated with oral administration. This pharmacokinetic profile is associated with reduced side effects, resulting in easier access to expected target doses. These benefits, along with other practical advantages of the transdermal patch, may contribute to enhanced patient compliance. Here, we present a review of the current literature on rivastigmine patch, and offer advice based on our own collective clinical experience. Rivastigmine patch provides an efficient option for managing patients with AD, to be considered among the first line therapies for the disease. © 2010 Blackwell Publishing Ltd.


Sikkes S.A.M.,VU University Amsterdam | Visser P.J.,VU University Amsterdam | Visser P.J.,Maastricht University | Tsolaki M.,Aristotle University of Thessaloniki | And 17 more authors.
Journal of the American Geriatrics Society | Year: 2011

Objectives To investigate whether problems in instrumental activities of daily living (IADL) can add to conventionally used clinical measurements in helping to predict a diagnosis of dementia at 1- and 2-year follow-up. Design Multicenter prospective cohort study. Setting Memory clinics in Europe. Participants Individuals aged 55 and older without dementia. Measurements IADLs were measured using pooled activities from five informant-based questionnaires. Structural equation modeling (SEM) was used to investigate the relation between IADLs and dementia. Age, sex, education, depression, and cognitive measures (Mini-Mental State Examination and verbal memory) were included in the model. Results Five hundred thirty-one participants had baseline and 1-year follow-up assessments; 69 (13.0%) of these had developed dementia at 1-year follow-up. At 2-year follow-up, 481 participants were seen, of whom 100 (20.8%) had developed dementia. Participants with IADL disabilities at baseline had a higher conversion rate (24.4%) than participants without IADL disabilities (16.7%) (chi-square = 4.28, degrees of freedom = 1, P =.04). SEM showed that IADL disability could help predict dementia in addition to the measured variables at 1-year follow-up (odds ratio (OR) = 2.20, 95% confidence interval (CI) = 1.51-3.13) and 2-year follow-up (OR = 2.11, 95% CI = 1.33-3.33). Conclusion IADL disability is a useful addition to the diagnostic process in a memory clinic setting, indicating who is at higher risk of developing dementia at 1- and 2-year follow-up. © 2011, Copyright the Authors.


Lindesay J.,University of Leicester | Bullock R.,Kingshill Research Center | Daniels H.,Memory Clinic | Emre M.,Istanbul University | And 7 more authors.
International Journal of Clinical Practice | Year: 2010

Summary The prevalence of dementia is reaching epidemic proportions globally, but there remain a number of issues that prevent people with dementia, their families and caregivers, from taking control of their condition. In 2008, Alzheimer's Disease International (ADI) launched a Global Alzheimer's Disease Charter, which comprises six principles that underscore the urgency for a more ambitious approach to diagnosis, treatment and care. This review highlights some of the most important aspects and challenges of dementia diagnosis and treatment. These issues are reviewed in light of the six principles of the recent ADI Charter: promoting dementia awareness and understanding; respecting human rights; recognizing the key role of families and caregivers; providing access to health and social care; stressing the importance of optimal diagnosis and treatment; and preventing dementia through improvements in public health. The authors continue to hope that, one day, a cure for Alzheimer's disease will be found. Meanwhile, healthcare professionals need to unite in rising to the challenge of managing all cases of dementia, using the tools available to us now to work toward improved patient care. © 2010 Blackwell Publishing Ltd.


Hanney M.,King's College London | Prasher V.,Birmingham Community Healthcare National Health Service Trust | Williams N.,Center for Statistics in Medicine | Jones E.L.,King's College London | And 9 more authors.
The Lancet | Year: 2012

Background: Prevalence of Alzheimer's disease in people with Down's syndrome is very high, and many such individuals who are older than 40 years have pathological changes characteristic of Alzheimer's disease. Evidence to support treatment with Alzheimer's drugs is inadequate, although memantine is beneficial in transgenic mice. We aimed to assess safety and efficacy of memantine on cognition and function in individuals with Down's syndrome. Methods: In our prospective randomised double-blind trial, we enrolled adults (>40 years) with karyotypic or clinically diagnosed Down's syndrome, with and without dementia, at four learning disability centres in the UK and Norway. We randomly allocated participants (1:1) to receive memantine or placebo for 52 weeks by use of a computer-generated sequence and a minimisation algorithm to ensure balanced allocation for five prognostic factors (sex, dementia, age group, total Down's syndrome attention, memory, and executive function scales [DAMES] score, and centre). The primary outcome was change in cognition and function, measured with DAMES scores and the adaptive behaviour scale (ABS) parts I and II. We analysed differences in DAMES and ABS scores between groups with analyses of covariance or quantile regression in all patients who completed the 52 week assessment and had available follow-up data. This study is registered, number ISRCTN47562898. Findings: We randomly allocated 88 patients to receive memantine (72 [82] had DAMES data and 75 [85] had ABS data at 52 weeks) and 85 to receive placebo (74 [87] and 73 [86]). Both groups declined in cognition and function but rates did not differ between groups for any outcomes. After adjustment for baseline score, there were non-significant differences between groups of -4·1 (95 CI -13·1 to 4·8) in DAMES scores, -8·5 (-20·1 to 3·1) in ABS I scores, and 2·0 (-7·2 to 11·3) in ABS II scores, all in favour of controls. 10 (11) of 88 participants in the memantine group and six (7) of 85 controls had serious adverse events (p=0·33). Five participants in the memantine group and four controls died from serious adverse events (p=0·77). Interpretation: There is a striking absence of evidence about pharmacological treatment of cognitive impairment and dementia in people older than 40 years with Down's syndrome. Despite promising indications, memantine is not an effective treatment. Therapies that are effective for Alzheimer's disease are not necessarily effective in this group of patients. Funding: Lundbeck. © 2012 Elsevier Ltd.


Rinne J.O.,Clinical Research Services Turku | Brooks D.J.,Medical Research Council Clinical science Center | Rossor M.N.,University College London | Fox N.C.,University College London | And 13 more authors.
The Lancet Neurology | Year: 2010

Background: Carbon-11-labelled Pittsburgh compound B (11C-PiB) PET is a marker of cortical fibrillar amyloid-β load in vivo. We used 11C-PiB PET to investigate whether bapineuzumab, a humanised anti-amyloid-β monoclonal antibody, would reduce cortical fibrillar amyloid-β load in patients with Alzheimer's disease. Methods: Patients with mild-to-moderate Alzheimer's disease were randomly assigned to receive intravenous bapineuzumab or placebo in a ratio of seven to three in three ascending dose groups (0·5, 1·0, or 2·0 mg/kg). Each dose group was enrolled after safety review of the previous group. Randomisation was by interactive voice response system; masking was achieved with numbered kit allocation. Patients, investigators, study site personnel, sponsor staff, and carers were masked to treatment. Patients received up to six infusions, 13 weeks apart, and had 11C-PiB PET scans at baseline and at weeks 20, 45, and 78. The primary outcome was the difference between the pooled bapineuzumab group and the pooled placebo group in mean change from screening to week 78 in 11C-PiB cortical to cerebellar retention ratio averaged across six cortical regions of interest. Analysis was by modified intention to treat. This study is registered with EudraCT, number 2004-004120-12; ISRCTN17517446. Findings: 28 patients were assigned to bapineuzumab (n=20) or placebo (n=8). 19 patients in the bapineuzumab group and seven in the placebo group were included in the modified intention-to-treat analysis. Estimated mean 11C-PiB retention ratio change from baseline to week 78 was -0·09 (95% CI -0·16 to -0·02; p=0·014) in the bapineuzumab group and 0·15 (95% CI 0·02 to 0·28; p=0·022) in the placebo group. Estimated mean difference in 11C-PiB retention ratio change from baseline to week 78 between the bapineuzumab group and the placebo group was -0·24 (95% CI -0·39 to -0·09; p=0·003). Differences between the bapineuzumab group and the placebo group in the individual regions of interest were similar to the overall mean difference. Adverse events were typically mild to moderate in severity and transient. Two patients in the 2·0 mg/kg bapineuzumab group had transient cerebral vasogenic oedema. Interpretation: Treatment with bapineuzumab for 78 weeks reduced cortical 11C-PiB retention compared with both baseline and placebo. 11C-PiB PET seems to be useful in assessing the effects of potential Alzheimer's disease treatments on cortical fibrillar amyloid-β load in vivo. Funding: Elan Pharmaceuticals and Wyeth Research. © 2010 Elsevier Ltd. All rights reserved.


Small G.,University of California at Los Angeles | Bullock R.,Kingshill Research Center
Alzheimer's and Dementia | Year: 2011

Despite growing recognition that Alzheimer's disease (AD) represents a global public health and social care crisis, diagnosis is frequently slow and many patients still receive no treatment at all. Of those who do receive treatment, many remain on lower than recommended doses. The Alzheimer's disease International Global Charter promotes awareness and understanding of AD, stressing the importance of optimal treatment. However, the definition of "optimal treatment" is unclear. Since cholinesterase inhibitors became available nearly 20 years ago, clinicians have developed a variety of protocols on the basis of clinical experiences. This review considers what is optimal for several aspects of cholinesterase inhibitor therapy, taking into account initiation strategies, dosages, modes of drug delivery (e.g., oral vs. transdermal), and treatment durations. Regardless of management approach, individuals with AD, their families, and caregivers have a right to a timely diagnosis and access to best available treatment. © 2011 The Alzheimer's Association. All rights reserved.


Damian M.,University of Heidelberg | Hausner L.,University of Heidelberg | Jekel K.,University of Heidelberg | Jekel K.,Ludwig Maximilians University of Munich | And 26 more authors.
Dementia and Geriatric Cognitive Disorders | Year: 2013

Background/Aims: To identify prodromal Alzheimer's disease (AD) subjects using a data-driven approach to determine cognitive profiles in mild cognitive impairment (MCI). Methods: A total of 881 MCI subjects were recruited from 20 memory clinics and followed for up to 5 years. Outcome measures included cognitive variables, conversion to AD, and biomarkers (e.g. CSF, and MRI markers). Two hierarchical cluster analyses (HCA) were performed to identify clusters of subjects with distinct cognitive profiles. The first HCA included all subjects with complete cognitive data, whereas the second one selected subjects with very mild MCI (MMSE ≥28). ANOVAs and ANCOVAs were computed to examine whether the clusters differed with regard to conversion to AD, and to AD-specific biomarkers. Results: The HCAs identified 4-cluster solutions that best reflected the sample structure. One cluster (aMCIsingle) had a significantly higher conversion rate (19%), compared to subjective cognitive impairment (SCI, p < 0.0001), and non-amnestic MCI (naMCI, p = 0.012). This cluster was the only one showing a significantly different biomarker profile (Aβ42, t-tau, APOE ε4, and medial temporal atrophy), compared to SCI or naMCI. Conclusion: In subjects with mild MCI, the single-domain amnestic MCI profile was associated with the highest risk of conversion, even if memory impairment did not necessarily cross specific cut-off points. A cognitive profile characterized by isolated memory deficits may be sufficient to warrant applying prevention strategies in MCI, whether or not memory performance lies below specific z-scores. This is supported by our preliminary biomarker analyses. However, further analyses with bigger samples are needed to corroborate these findings. Copyright © 2013 S. Karger AG, Basel.


Baker N.L.,Pfizer | Cook M.N.,Pfizer | Arrighi H.M.,LLC Epidemiology | Bullock R.,Kingshill Research Center
Age and Ageing | Year: 2011

Background: hip fractures result in a significant burden to the patient, their caregivers and the health care system. Patients with Alzheimer's disease (AD) have a higher incidence of hip fracture compared with other older people without AD, although it is not clear if AD is an independent risk factor for hip fracture. Methods: a retrospective cohort study was conducted using anonymised electronic medical records from primary care practices in the United Kingdom. Proportional hazards regression modelling with adjustment for potential confounders was used to evaluate AD as an independent risk factor for predicting hip fractures. Results: the incidence of hip fracture among patients with and without AD was 17.4 (95% CI, 15.7-19.2) and 6.6 (95% CI, 5.8-7.6) per 1,000 person years, respectively. Patients with AD had a hazard that was 3.2 (95% CI, 2.4-4.2) times that of non-AD patients after controlling for potential confounders. AD patients who experienced a hip fracture also had an increased mortality rate compared with non-AD patients who experienced a hip fracture (hazard ratio = 1.5; 95% CI, 1.1-1.9). Conclusion: patients with AD and their caregivers should be advised on how to prevent hip fractures and more attention should be given to AD patients who are undergoing rehabilitation following a hip fracture. © The Author 2010. Published by Oxford University Press on behalf of the British Geriatrics Society. All rights reserved.


PubMed | Kingshill Research Center
Type: Journal Article | Journal: Dementia (London, England) | Year: 2014

Primary care is ideally placed to recognise and manage dementia and yet dementia can be overlooked or misattributed by primary care practitioners and is underdiagnosed. This might be explained by a lack of formal training in the diagnosis of dementia combined with a reluctance to diagnose due to its associated stigma. This paper describes focus group work with service users, carers and health professionals, conducted to develop an educational intervention for primary care promoting person-centred responses to people experiencing cognitive decline and dementia. Data was analysed thematically and four themes emerged: Reframing dementia as cognitive decline (Individual level); triggers for the recognition of dementia (Practitioner level); engaging the whole primary care team (Practice level); the relationship between primary and secondary care (Service level). Findings are discussed in the context of their contribution to challenging attitudes to dementia in primary care and the positive aspects of person-centred primary care for dementia.

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