Clinical Dementia Research Research Articles

Importing implementation methods in clinical dementia research

AbstractBackgroundBringing clinical innovation from dementia research to health‐care requires implementing new courses of action. Implementation science methods can help bridge the gap between biomedical research and clinical practice. We imported implementation methods to perform a feasibility analysis for implementing the clinician’s Uniform Dataset‐cUDS as a standard cognitive assessment in two contexts: European academic memory clinics and Italian academic and non‐academic memory clinics.Method33 questions, addressing centers' contextual factors, mechanisms of impact, acceptability, hurdles and facilitators were posed to academic and non‐academic memory clinics. The Process Evaluation framework was used as a guidance to evaluate implementation feasibility. Mixed‐methods analyses were performed with SPSS and MAXQDA. We labelled open answers into categories and performed proportion tests for each hurdle and facilitator in both contexts.Result46 EADC (European Alzheimer’s' Disease Consortium) academic and 62 SINDem (Italian Society of Neurology on Dementia)(30 academic, 32 non‐academic) clinicians answered the survey. Acceptability towards implementation of cUDS was 65% among EADC and 95% among SINDem responders (p = .134,ɑ = .05). A statistically significant (p = .01) proportion of SINDem clinicians (47%) reported to envision no barrier to the implementation, as compared to EADC clinicians (11%). 59% of EADC centers reported to receive full reimbursement for cognitive assessment versus only 10% in Italian academic centers(p = .58). Qualitative analysis showed similar barriers as the unavailability of material (e.g., local norms) and finances (e.g., insurance, salary) in both EADC‐SINDem centers. Despite non‐statistical significant differences, compared to EADC, SINDem clinicians showed a trend towards greater need of neuropsychologists/specialized staff (EADC: 6%; SINDem: 14‐25%),in particular among non‐academic centers. On the other hand, EADC clinicians seemed more concerned with logistics (EADC: 15%; SINDem: 3%).ConclusionOur analysis revealed a good level of feasibility and acceptability for cUDS in Europe, especially in Italy which has no prior local standard as compared to other European countries (e.g., Germany, Netherlands). Similar barriers were identified among Europe and Italy, however, facilitators seemed to be more specific of the country and setting of implementation. This data also revealed structural hurdles, like heterogeneous reimbursement levels for cognitive assessment. Overall, country‐based feasibility analysis are necessary before proceeding into implementation.

Methodological gaps in clinical dementia research

AbstractBackgroundEvidence‐based decisions allow to compile clinical guidelines, or to approve or refund new treatments or diagnostic procedures. Different evidence‐to‐decision (EtD) procedures exist to define recommendations based on evidence. However, often data are not eligible to such EtDs due to faults in the methodology that generated them. This is a relevant and upstream problem hurdling the transfer of knowledge. Aim of this work is to outline these methodological problems to help overcoming such concrete hurdle to knowledge transfer.MethodA range of methodological issues hampering eligibility of data to EtD was searched across different evidence assessment initiatives, based on the methodological requirements defined by the main steps of formal methodologies for the validation of diagnostic biomarkers, namely analytical validity, clinical validity, and clinical utility.ResultMethodological gaps involve all these main development phases. The main issues at the analytical validity phase consist in limited use of standard operating procedures. This causes exceedingly large variability of data that cannot be amended post hoc. Such variability thus propagates to all downstream validation studies and final data cannot support any decision, not in favor nor against clinical recommendations. At the phase of clinical utility, many studies do not use either proper gold‐ or reference‐standards, or study designs able to address the target question. At the clinical utility phase, implementation methods are still not systematically imported and adapted to the dementia field, and the assessed outcomes are mainly defined by researchers, with limited participation of other relevant stakeholders (e.g., regulators; patients or caregivers).ConclusionWith such gaps along the translational continuum, published data cannot support evidence‐based decision‐making. To improve implementation, attention should not only target the latest adoption steps, but many more upstream steps that eventually prevent the formal approval and refund of new diagnostic procedures or of other innovation.

Mini research projects as a mechanism to improve the quality of dementia care

Several models have been proposed to connect academia and practice in order to improve long-term care. In this paper we propose and describe the “Mini-Research Group” as an alternative model of such collaboration. The formation of mini-research groups was the unplanned by-product of a longitudinal action research project headed by the late Prof. Rebecca Bergman, a prominent nursing leader from the Department of Nursing at Tel-Aviv University. It involved a two-stage project aimed at developing, and later implementing, a specific tool to evaluate the quality of care provided in geropsychiatric units and to design a nursing intervention which entailed an improved model for care in specialized geropsychiatric units for persons with dementia. Initially, this article describes the projects that led to the development of mini-research groups, and then continues to describe several mini-research projects, focusing on the research questions which emerged from practice as well as the variety of methodologies used. Finally, we discuss the ways in which mini- research groups contributed to the quality of care for persons with dementia, benefited their families, professional staff, faculty participants, and advanced policy development. We argue that in light of the present array of ethical and legal restrictions which inhibit the recruitment of participants, using mini-research groups combined of practitioners and researchers, can provide a pragmatic solution, not only to overcome these barriers, but to improve the quality of care, stimulate clinical dementia research, and promote new insights into the lives of persons with dementia.

AN INNOVATIVE APPROACH TO ENHANCE THE INFORMED CONSENT PROCESS FOR PEOPLE WITH DEMENTIA: THE ENSURE PROJECT

People with dementia have the right to decide whether or not they want to participate in clinical research and to give their free, prior and informed consent. However, as dementia progresses, they can lose their ability to give informed consent to complex medical research because of an increasing loss of cognitive functions. At first sight, it seems ethically problematic to involve dementia patients in research, as people with impaired mental capacity must be protected against the risks of research participation. In contrast to informed consent to medical treatment, an individual benefit from participation in research can rarely be taken for granted. However, people with dementia also have a right to benefit from medical research in particular, so their categorical exclusion would appear to be ethically problematic too. The international, interdisciplinary ENSURE project (Enhancing the informed consent process: Supported decision-making and capacity assessment in clinical dementia research) aims to provide interdisciplinary recommendations to support the development of an action model of an informed consent process in clinical dementia research that 1) enhances the capacity to consent of people with dementia, 2) improves the assessment of decision-making capacity, 3) protects those who do not have the capacity to consent, and 4) guarantees the ethically justified inclusion of research subjects in clinical dementia research. To achieve this, four international project partners cooperate on four interdisciplinary interlinked subprojects. The disciplines involved are gerontology, ethics and law. A flow-chart of ENSURE and an overview of the first results of the subprojects will be presented. Implications for practical use in informed consent procedures will be discussed.

Alzheimer's Therapeutic Research Institute

The Alzheimer's Therapeutic Research Institute (ATRI) was established in 2015 after ATRI director, Paul Aisen, and his fellow experts in therapeutic interventions for Alzheimer's disease (AD) moved from the Alzheimer's Disease Cooperative Study (ADCS) at the University of California to the Keck School of Medicine of the University of Southern California. The National Institute on Aging (NIA) decided to commit $14 million to the ATRI via an Alzheimer's Clinical Trials Consortium (ACTC). The ATRI supports various studies such as the Anti-Amyloid Treatment in Asymptomatic Alzheimer's study ("A4 study"), Alzheimer's Disease Neuroimaging Initiative 3 (ADNI3), Longitudinal Evaluation of Amyloid Risk and Neurodegeneration (LEARN), and The Alzheimer's Disease Neuroimaging Initiative-Depression Project (ADNI-D). The ATRI will share all relevant data and materials with the academic community, corporations, and government organizations. The ATRI is overseen by a Data and Safety Monitoring Board (DSMB), which comprises of leading experts in the field of Alzheimer's research and acts independently. The ATRI is slated to play a central role in clinical dementia research in the US in near future.

When Does Therapeutic Misconception Affect Surrogates' or Subjects' Decision Making about Whether to Participate in Dementia Research?

"Therapeutic misconception" (TM) refers to inappropriate assumptions and beliefs on the part of research participants regarding key distinctions between the purpose, methods, intended benefits, and potential disadvantages of research compared to those of clinical care. Despite an extensive literature describing TM across varied types of research and populations, minimal work has addressed TM in the context of dementia research. This is a serious gap, for several reasons: people with dementia are at significant risk of diminished capacity; surrogate decision makers are typically asked to provide consent on behalf of the person with dementia; and available treatments for dementia are quite limited. More research is needed on the prevalence, nature, and impact of TM in the context of clinical dementia research.

Interview: Unraveling the Neuropsychiatric Symptoms of Parkinson’s and Alzheimer’s Disease: Current and Future Progress

Dag Aarsland, MD, PhD, is Professor of Clinical Dementia Research at the Alzheimer’s Disease Research Centre (Karolinska Institutet, Stockholm, Sweden) and Research Director at the Centre for Age-Related Medicine (Stavanger University Hospital, Stavanger, Norway). He is a psychiatrist and has worked as a senior consultant in geriatric psychiatry for most of his career. His main research interest is the neurospychiatric aspects of patients with neurodegenerative diseases.

Dag Aarsland: moving Parkinson's disease forward

Dag Aarsland: moving Parkinson's disease forward

CATIE'S LESSONS

CATIE'S LESSONS

Dementia: finding the signals in the noise

Clinical dementia research is dependent on measurements that can detect variable signals amid the noise of clinical variation and uncertainty. In the past year, we have seen attempts to define these signals for the diagnosis and prediction of dementia, measurement of outcomes in clinical trials, and definition of important risk factors in epidemiological studies. Advances in each of these areas have come through the development of new technologies or through the study of large groups of patients with new approaches.

2nd Asia-Pacific regional meeting of the International Working Group on Harmonization of Dementia Drug Guidelines: meeting report.

The 2nd Asia-Pacific regional meeting of the International Working Group on Harmonization of Dementia Drug Guidelines (IWGH) was held in Beijing, China in late 2002. Representatives from over a dozen countries convened to present data on dementia within the region and to share information on locally adapted outcome measures for use in dementia clinical trials. The IWGH recognized the competency and capability of many Asian sites and endorsed their inclusion in future multicenter clinical dementia research activities.

BEHAVIORAL SYMPTOMS IN ALZHEIMER's DISEASE AMONG ETHNIC MINORITIES

Background and Objective: Behavioral disturbances in patients with Alzheimer's disease are a major determinant of need for psychiatric services among elderly persons. Despite the disproportionate growth of the older minority population and the anticipated rapid rise in prevalence of dementia, participation of ethnic minorities in behavioral research on AD has been limited by language and cultural barriers. This descriptive study examined behavioral symptoms in an ethnolinguistically heterogeneous group of minority elderly with AD, as a starting point for the design of culturally congruent dementia services. Method: Potential subjects were identified in collaboration with community social services agencies serving ethnic minorities and enrolled in a multi-ethnic registry of the University of Washington ADRC. One hundred nineteen (91 women, 28 men) met NINCDS-ADRDA diagnostic criteria for probable or possible AD and DSM-IV criteria for AD. Ethnicities included African American (n=35), Asian-Pacific Islander (n= 62; Chinese, Korean, and Filipino), Hispanic (n=15), and Native American (n=7). Half spoke a language other than English. Behavioral symptoms were rated by caregiver interview using the BEHAVE-AD and dementia was staged using the CDR. Results: The mean BEHAVE-AD total score was 13.1 ± 8.3 and no significant differences between ethnic groups were observed. One or more symptoms occurred in 114 (96%) of this sample. Most occurred during CDR stage 1 to 3, with the peak at stage 3. Behavioral symptoms were less frequent in CDR stage 4 and 5. Conclusion: In this sample, ethnic minorities demonstrated levels of AD-associated psychopathology comparable to those previously reported in whites and at similar levels of disease severity. These data emphasize the need for development of geropsychiatric services accessible to older minorities, many of whom do not speak English, and the potential of University-community collaborations to bring older minorities into clinical dementia research.

Advance directives for non-therapeutic dementia research: some ethical and policy considerations.

This paper explores the use of advance directives in clinical dementia research. The focus is on advance consent to participation of demented patients in non-therapeutic research involving more than minimal...

Alzheimer's disease: clinical Features

The last decade of clinical dementia research has led to the development of standardized criteria for the diagnosis of Alzheimer's disease (AD) and to the rediscovery of ‘non-cognitive’ features of AD. This review will discuss some of the diagnostic problems caused by the lack of reliable diagnostic markers and by the heterogeneity of AD's clinical manifestations, and it will focus on the ‘non-cognitive’ features which are responsible for a large part of the clinical diversity of AD: hallucinations, delusions, delusional misidentifications, depressive symptoms, behavioural disturbance and neurological disorders. These features are of particular interest, because they may aggravate cognitive impairment, influence the course of illness, increase the patients' and their families' stress, and because some of them may be accessible to treatment