Stigma and GPs’ perceptions of dementia

YesObjectives: General practitioners (GPs) are crucial to improving timely diagnosis, but little is reported about how they perceive dementia, and whether their perceptions display any elements of stigma. The aim of this study was to explore how GPs’ perceptions of dementia map onto current conceptualizations of stigma and whether GPs feel that stigma affects timely diagnosis. Methods: Twenty-three GPs from England were interviewed by telephone. Data were analyzed by means of content analysis. This involved open coding followed by the application of a coding framework derived from the literature to explore how and to what extent their perceptions relate to stigma as well as the unique nature of their perceptions. Results: Three themes emerged from the analysis: (1) ‘making sense of dementia’, (2) ‘relating perceptions of dementia to oneself’ and (3) ‘considering the consequences of dementia’. GPs’ perceptions of dementia mapped onto current conceptualizations of stigma. Perceptions about dementia that were linked to their own existential anxiety and to a perceived similarity between people with dementia and themselves were particularly salient. GPs perceived dementia as a stigma which was gradually being overcome but that stigma still hindered timely diagnosis. They provided examples of structural discrimination within the health service, including lack of time for patients and shortcomings in training that were to the detriment of people with dementia. Conclusion: Measures to involve GPs in tackling stigma should include training and opportunities to explore how they perceive dementia, as well as support to address structural discrimination.The study was funded by Alzheimer Europe (Luxembourg) in the form of tuition fees for Dianne Gove for her PhD study

Neuropsychological predictors of conversion from mild cognitive impairment to Alzheimer’s disease: a feature selection ensemble combining stability and predictability

Background Predicting progression from Mild Cognitive Impairment (MCI) to Alzheimer’s Disease (AD) is an utmost open issue in AD-related research. Neuropsychological assessment has proven to be useful in identifying MCI patients who are likely to convert to dementia. However, the large battery of neuropsychological tests (NPTs) performed in clinical practice and the limited number of training examples are challenge to machine learning when learning prognostic models. In this context, it is paramount to pursue approaches that effectively seek for reduced sets of relevant features. Subsets of NPTs from which prognostic models can be learnt should not only be good predictors, but also stable, promoting generalizable and explainable models. Methods We propose a feature selection (FS) ensemble combining stability and predictability to choose the most relevant NPTs for prognostic prediction in AD. First, we combine the outcome of multiple (filter and embedded) FS methods. Then, we use a wrapper-based approach optimizing both stability and predictability to compute the number of selected features. We use two large prospective studies (ADNI and the Portuguese Cognitive Complaints Cohort, CCC) to evaluate the approach and assess the predictive value of a large number of NPTs. Results The best subsets of features include approximately 30 and 20 (from the original 79 and 40) features, for ADNI and CCC data, respectively, yielding stability above 0.89 and 0.95, and AUC above 0.87 and 0.82. Most NPTs learnt using the proposed feature selection ensemble have been identified in the literature as strong predictors of conversion from MCI to AD. Conclusions The FS ensemble approach was able to 1) identify subsets of stable and relevant predictors from a consensus of multiple FS methods using baseline NPTs and 2) learn reliable prognostic models of conversion from MCI to AD using these subsets of features. The machine learning models learnt from these features outperformed the models trained without FS and achieved competitive results when compared to commonly used FS algorithms. Furthermore, the selected features are derived from a consensus of methods thus being more robust, while releasing users from choosing the most appropriate FS method to be used in their classification task.PTDC/EEI-SII/1937/2014; SFRH/BD/95846/2013; SFRH/BD/118872/2016info:eu-repo/semantics/publishedVersio

Presenilin Is the Molecular Target of Acidic γ-Secretase Modulators in Living Cells

The intramembrane-cleaving protease γ-secretase catalyzes the last step in the generation of toxic amyloid-β (Aβ) peptides and is a principal therapeutic target in Alzheimer's disease. Both preclinical and clinical studies have demonstrated that inhibition of γ-secretase is associated with prohibitive side effects due to suppression of Notch processing and signaling. Potentially safer are γ-secretase modulators (GSMs), which are small molecules that selectively lower generation of the highly amyloidogenic Aβ42 peptides but spare Notch processing. GSMs with nanomolar potency and favorable pharmacological properties have been described, but the molecular mechanism of GSMs remains uncertain and both the substrate amyloid precursor protein (APP) and subunits of the γ-secretase complex have been proposed as the molecular target of GSMs. We have generated a potent photo-probe based on an acidic GSM that lowers Aβ42 generation with an IC50 of 290 nM in cellular assays. By combining in vivo photo-crosslinking with affinity purification, we demonstrated that this probe binds the N-terminal fragment of presenilin (PSEN), the catalytic subunit of the γ-secretase complex, in living cells. Labeling was not observed for APP or any of the other γ-secretase subunits. Binding was readily competed by structurally divergent acidic and non-acidic GSMs suggesting a shared mode of action. These findings indicate that potent acidic GSMs target presenilin to modulate the enzymatic activity of the γ-secretase complex

WHEDA study: Effectiveness of occupational therapy at home for older people with dementia and their caregivers - the design of a pragmatic randomised controlled trial evaluating a Dutch programme in seven German centres

Contains fulltext : 80941.pdf (publisher's version ) (Open Access)BACKGROUND: A recent Dutch mono-centre randomised controlled trial has shown that occupational therapy improves daily functioning in dementia. The aim of this present study is to compare the effects of the Dutch community occupational therapy programme with a community occupational therapy consultation on daily functioning in older people with mild or moderate dementia and their primary caregivers in a German multi-centre context. METHODS/DESIGN: A multi-centre single blind randomised controlled trial design is being used in seven health care centres (neurological, psychiatric and for older people) in urban regions. Patients are 1:1 randomised to treatment or control group. Assessors are blind to group assignment and perform measurements on both groups at baseline, directly after intervention at 6 weeks and at 16, 26 and 52 weeks follow-up. A sample of 140 community dwelling older people (aged >65 years) with mild or moderate dementia and their primary caregivers is planned. The experimental intervention consists of an evidence-based community occupational therapy programme including 10 sessions occupational therapy at home. The control intervention consists of one community occupational therapy consultation based on information material of the Alzheimer Society. Providers of both interventions are occupational therapists experienced in treatment of cognitively impaired older people and trained in both programmes. 'Community' indicates that occupational therapy intervention occurs in the person's own home. The primary outcome is patients' daily functioning assessed with the performance scale of the Interview for Deterioration in Daily Living Activities in Dementia and video tapes of daily activities rated by external raters blind to group assignment using the Perceive, Recall, Plan and Perform System of Task Analysis. Secondary outcomes are patients' and caregivers' quality of life, mood and satisfaction with treatment; the caregiver's sense of competence, caregiver's diary (medication, resource utilisation, time of informal care); and the incidence of long-term institutionalisation. Process evaluation is performed by questionnaires and focus group discussion. DISCUSSION: The transfer from the Dutch mono-centre design to the pragmatic multi-site trial in a German context implicates several changes in design issues including differences in recruitment time, training of interventionists and active control group treatment.The study is registered under DRKS00000053 at the German register of clinical trials, which is connected to the International Clinical Trials Registry Platform

Characterization of a Drosophila Alzheimer's Disease Model: Pharmacological Rescue of Cognitive Defects

Transgenic models of Alzheimer's disease (AD) have made significant contributions to our understanding of AD pathogenesis, and are useful tools in the development of potential therapeutics. The fruit fly, Drosophila melanogaster, provides a genetically tractable, powerful system to study the biochemical, genetic, environmental, and behavioral aspects of complex human diseases, including AD. In an effort to model AD, we over-expressed human APP and BACE genes in the Drosophila central nervous system. Biochemical, neuroanatomical, and behavioral analyses indicate that these flies exhibit aspects of clinical AD neuropathology and symptomology. These include the generation of Aβ40 and Aβ42, the presence of amyloid aggregates, dramatic neuroanatomical changes, defects in motor reflex behavior, and defects in memory. In addition, these flies exhibit external morphological abnormalities. Treatment with a γ-secretase inhibitor suppressed these phenotypes. Further, all of these phenotypes are present within the first few days of adult fly life. Taken together these data demonstrate that this transgenic AD model can serve as a powerful tool for the identification of AD therapeutic interventions

A randomised controlled trial to evaluate the impact of a human rights based approach to dementia care in inpatient ward and care home settings

BackgroundAlthough it is widely recognised that adopting a person-centred approach is beneficial in the care of people living with dementia, a gap remains between the rhetoric and the reality of quality care. Some widely adopted care practices can result in the personhood of this group being threatened and their human rights being undermined.ObjectivesTo evaluate the impact of applying a human rights based approach in dementia inpatient wards and care homes on the quality of care delivered and the well-being of the person living with dementia.DesignA cluster randomised design was employed to compare the impact of implementing a human rights based approach intervention (i.e. training, applying the ‘Getting It Right’ assessment tool and receiving booster sessions) at 10 intervention sites with 10 control sites.SettingEight NHS dementia inpatient wards and 12 care homes in the north-west of England.ParticipantsPeople living with dementia who were residing on dementia inpatient wards or in care homes, and staff working at these sites. The aim was to recruit 280 people living with dementia.InterventionsA sample of staff (an average of 8.9 per site) at each of the sites was trained in a human rights based approach to care, including the application of the ‘Getting It Right’ assessment tool. The tool was then introduced at the site and monthly booster sessions were delivered.Main outcome measuresThe primary outcome measure used in the research was the Quality of Life in Alzheimer’s Disease scale to assess the subjective well-being of the person with dementia. Secondary outcome measures included measures of the quality of care provided (dementia care mapping) and direct measures of the effectiveness of the training in increasing knowledge of and attitudes towards human rights. The study also included an economic evaluation utilising the EuroQol-5 Dimensions, three-level version, and the Adult Social Care Outcomes Toolkit measure.ResultsThe study recruited 439 people living with dementia: 213 to the intervention arm and 226 to the control arm. Primary outcome data were analysed using a linear mixed model. There were no significant differences found in the reported quality of life of residents between the control and intervention groups after the intervention [F(1,16.51) = 3.63;p = 0.074]. The mean difference between the groups was 1.48 (95% confidence interval –7.86 to 10.82).ConclusionsDespite the fact that the training increased staff knowledge of and positive attitudes towards human rights, and although there were some changes in staff decision-making strategies in clinical situations, there was no change in the quality of care provided or in the reported well-being of people living with dementia in these settings. This led to questions about the efficacy of training in bringing about cultural change and improving care practices.LimitationsThere was limited uptake of the training and booster sessions that were integral to the intervention.Future workFuture work could usefully focus on understanding the difficulty in translating change in attitude and knowledge into behaviour.Trial registrationCurrent Controlled Trials ISRCTN94553028.FundingThis project was funded by the National Institute for Health Research (NIHR) Health Services and Delivery Research programme and will be published in full inHealth Services and Delivery Research; Vol. 6, No. 13. See the NIHR Journals Library website for further project information.</jats:sec

Improving Nursing Home Care through Feedback On PerfoRMance Data (INFORM): Protocol for a cluster-randomized trial

Background Audit and feedback is effective in improving the quality of care. However, methods and results of international studies are heterogeneous, and studies have been criticized for a lack of systematic use of theory. In TREC (Translating Research in Elder Care), a longitudinal health services research program, we collect comprehensive data from care providers and residents in Canadian nursing homes to improve quality of care and life of residents, and quality of worklife of caregivers. The study aims are to a) systematically feed back TREC research data to nursing home care units, and b) compare the effectiveness of three different theory-based feedback strategies in improving performance within care units. Methods INFORM (Improving Nursing Home Care through Feedback On PerfoRMance Data) is a 3.5-year pragmatic, three-arm, parallel, cluster-randomized trial. We will randomize 67 Western Canadian nursing homes with 203 care units to the three study arms, a standard feedback strategy and two assisted and goal-directed feedback strategies. Interventions will target care unit managerial teams. They are based on theory and evidence related to audit and feedback, goal setting, complex adaptive systems, and empirical work on feeding back research results. The primary outcome is the increased number of formal interactions (e.g., resident rounds or family conferences) involving care aides – non-registered caregivers providing up to 80% of direct care. Secondary outcomes are a) other modifiable features of care unit context (improved feedback, social capital, slack time) b) care aides’ quality of worklife (improved psychological empowerment, job satisfaction), c) more use of best practices, and d) resident outcomes based on the Resident Assessment Instrument – Minimum Data Set 2.0. Outcomes will be assessed at baseline, immediately after the 12-month intervention period, and 18 months post intervention. Discussion INFORM is the first study to systematically assess the effectiveness of different strategies to feed back research data to nursing home care units in order to improve their performance. Results of this study will enable development of a practical, sustainable, effective, and cost-effective feedback strategy for routine use by managers, policy makers and researchers. The results may also be generalizable to care settings other than nursing homes. Trial registration ClinicalTrials.gov Identifier: NCT02695836 . Date of registration: 24 February 201