Efficacy and safety of pharmacotherapy for Alzheimer's disease and for behavioural and psychological symptoms of dementia in older patients with moderate and severe functional impairments: a systematic review of controlled trials.

BACKGROUND: Many patients with Alzheimer's disease (AD) are physically frail or have substantial functional impairments. There is growing evidence that such patients are at higher risk for medication-induced adverse events. Furthermore, frailty seems to be more predictive of poor clinical outcomes than chronological age alone. To our knowledge, no systematic review of clinical trials examining drug therapy of AD or behavioural and psychological symptoms of dementia (BPSD) has specifically focused on the topic of physical frailty. Our objective was to evaluate the efficacy and safety of pharmacotherapy in AD patients with frailty or significant functional impairments. METHODS: We performed a systematic literature search in MEDLINE, Embase and the Cochrane Central Register of Controlled Trials (CENTRAL) for randomized controlled trials (RCTs) of drug therapy of AD and BPSD in patients with significant functional impairments according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement and Cochrane research criteria. Significant functionally impaired patient populations were identified using the recommendations of the Medication and Quality of Life in frail older persons (MedQoL) Research Group. Screening, selection of studies, data extraction and risk of bias assessment were performed independently by two reviewers. Outcomes including functional status, cognitive function, changes in BPSD symptoms, clinical global impression and quality of life were analysed. For assessing harm, we assessed adverse events, drop-outs as a proxy for treatment tolerability and death. Results were analysed according to Cochrane standards and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. RESULTS: Of 45,045 search results, 38,447 abstracts and 187 full texts were screened, and finally, 10 RCTs were included in the systematic review. Selected articles evaluated pharmacotherapy with acetylcholinesterase-inhibitors (AChEI), anticonvulsants, antidepressants and antipsychotics. Studies of AChEIs suggested that patients with significant functional impairments had slight but significant improvements in cognition and that AChEIs were generally well tolerated. Studies of antidepressants did not show significant improvements in depressive symptoms. Antipsychotics and anticonvulsants showed small effects on some BPSD items but also higher rates of adverse events. However, due to the very small number of identified trials, the quality of evidence for all outcomes was low to very low. Overall, the small number of eligible studies demonstrates that significantly functional impaired older patients have not been adequately taken into consideration in most clinical trials investigating drug therapy of AD and BPSD. CONCLUSION: Due to lack of evidence, it is not possible to give specific recommendations for drug therapy of AD and BSPD in frail older patients or older patients with significant functional impairments. Therefore, clinical trials focussing on frail older adults are urgently required. A standardized approach to physical frailty in future clinical studies is highly desirable.

Addressing COVID-19 challenges in a randomised controlled trial on exercise interventions in a high-risk population.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic is a threat to ongoing clinical trials necessitating regular face-to-face, in-person meetings, particularly in participants with a high risk of complications. Guidance on how to handle and safely continue such trials is lacking. Chronically ill elderly individuals require-in addition to protection from infection-regular physical exercise and social contact to remain healthy. Solutions on how to handle these conflicting necessities are needed. The ENTAIER-randomised controlled trial was investigating the influence of mindful movements on fall risk, fear of falling, mobility, balance, life quality, and other outcomes. The study population was planned to comprise of 550 chronically ill elderly individuals with a high risk of falling. The movements were regularly performed in coached groups over 6 months. After the trial began, COVID-19 lockdowns stopped all in-person meetings, and it was expected that the limitations of this pandemic would continue for a long term. Therefore, the exercise programme, which involved complex movements and was typically conducted face-to-face in groups, had to be substituted by a telemedicine programme within a short timeframe. The objectives, therefore, were to identify challenges and tasks that could to be resolved and steps that could to be taken to achieve high-quality, efficacy, safety, and enable human encounter and motivation. METHODS: We proceeded with four steps: 1) A literature review on the quality and feasibility issues of telemedicine in general, and specifically, in exercise training in elderly individuals. 2) Participation in two international telemedicine task forces on integrative medicine, particularly, mind-body medicine. 3) Interviews with study therapists, (for practical purposes, eurythmy therapists and Tai Chi teachers are summarized here as therapists) personnel, and international experts on providing mindful movement exercises and other physiotherapies via live telecommunication technology, and with scientists and patient representatives. 4) Final evaluation by the core trial team and subsequent planning and implementation of changes in the trial organisation. RESULTS: Various tasks and challenges were identified: for the technical equipment for therapists and patients; for the ability of therapists and trial participants to adequately manage the technology and telemedicine intervention; the reservations and concerns about the technology among therapists and participants; safety and data protection in using the technology; and study design. The two major options found on how to continue the trial in the COVID-19 situation were a complete switch to telemedicine and a partial switch in the form of risk management implemented into the former design. CONCLUSIONS: The management of an ongoing clinical trial in a national or international crisis with a minimum of available time and extra financial resources, alongside with two checklists on steps and procedures for trial continuation and telemedicine implementation, may be informative for other researchers or healthcare providers faced with similar challenges and making similar decisions in the current situation or similar future scenarios. TRAIL REGISTRATION: www.drks.de . DRKS00016609. Registered July 30, 2019.

A multi-centre, parallel-group, randomised controlled trial to assess the efficacy and safety of eurythmy therapy and tai chi in comparison with standard care in chronically ill elderly patients with increased risk of falling (ENTAiER): a trial protocol.

BACKGROUND: In elderly poeple, multimorbidity and polypharmacy increase while sensory, motor and cognitive functions decrease. Falls occur in 30% of people aged 65 years and older at least once per year, with injuries at 10-20%. Reducing falls and enhancing physical, emotional and cognitive capacities are essential for healthy aging despite chronic disease. Eurythmy therapy (EYT) and Tai Chi train balance, mobility and concentrative and sensory capacities. METHODS: In eight trial sites (academic or community hospitals), 550 outpatients aged 65 years and older with chronic disease and increased risk of falling (history of imbalance, Berg Balance Scale (BBS) score ≤ 49) will be randomly assigned (1:1:1) to receive either EYT or Tai Chi (each provided in one-hour group sessions, twice, later once per week plus practice at home, for over 24 weeks) added to standard care or standard care alone. Standard care includes a detailed written recommendation on fall prevention and the visit of a primary care doctor. Seniors living a reclusive life or economically disadvantaged elderly will be particularly addressed. A motivation and communication concept supports the trial participants' compliance with trial procedures and practicing. Public and patient representatives are involved in the planning and conduction of the trial. Falls will be documented daily in a diary by the participants. These falls as well as injuries and complications will be ascertained during monthly phone visits. The falls efficacy scale, BBS, cognition (MoCA), Mood (GDS-15), quality of life (SF12), instrumental activities of daily living (IADL), use of medical and non-medical services (FIMA) and adherence will be assessed at months 3, 6, and 12 and inner correspondence with practices (ICPH) at month 6. The trial is funded by the Federal Ministry of Education and Research (BMBF 01GL1805). DISCUSSION: This study will determine whether EYT and Tai Chi reduce falls, injurious falls, fear of falling and healthcare utilisation and improve mobility, cognition, mood, quality of life and functional independence. A reduction of fall risk and fear of falling and an improvement of mobility, autonomy, quality of life, mood, and cognition are highly relevant for older people to cope with aging and diseases and to reduce healthcare costs. TRAIL REGISTRATION: www.drks.de. DRKS00016609. Registered 30th July 2019.

[Comment on the TIDier Checklist]. / Kommentar zur TIDieR Checkliste.

This comment focuses on the need for and possible impact of the TIDieR reporting guideline.

Occupational therapy for elderly. Evidence mapping of randomised controlled trials from 2004-2012.

OBJECTIVE: Previous systematic reviews on occupational therapy for elderly included studies until 2003. The present evidence mapping summarizes recent evidence for the efficacy of occupational therapy with older persons based on randomised controlled trials from 2004-2012. METHOD: An electronic search in Cochrane and Medline databases identified publications of randomised controlled trials on occupational therapy interventions for persons≥65 years old. Two raters independently extracted data and analysed the quality of samples, interventions and outcome evalutations according to PRISMA criteria. RESULTS: In all, 136 abstracts were identified and 48 studies analysed, from these 12 on stroke, 15 on falls and mobility, 7 on dementia, 4 on prevention and 10 on other conditions. Reports of adverse events and evaluations of costs and long-term outcomes are frequently lacking. CONCLUSION: The most promising fields for further research are primary and secondary prevention in persons with stroke, falls or mobility problems and tertiary prevention in persons with dementia. Future trials should be conducted and reported according to consented reporting guidelines of the equator network.

Dementia quality of life instrument--construct and concurrent validity in patients with mild to moderate dementia.

BACKGROUND AND PURPOSE: To translate the Dementia quality of life instrument (DQoL) into German and assess its construct and concurrent validity in community-dwelling people with mild to moderate dementia. METHODS: Dementia quality of life instrument data of two pooled samples (n=287) were analysed regarding ceiling and floor effects, internal consistency, factor reliability and correlations with corresponding scales on quality of life (Quality of Life in Alzheimer's Disease and SF-12), cognition (Mini-Mental State Examination, Alzheimer's Disease Assessment Scale - cognitive), depression (Cornell Scale for Depression in Dementia) and activities of daily living (Interview of Deterioration in Daily Living Activities in Dementia). RESULTS: We found no floor effects (<2%), minor ceiling effects (1-11%), moderate to good internal consistency (Cronbach's α: 0.6-0.8) and factor reliability (0.6-0.8), moderate correlations with self-rated scales of quality of life (Spearman coefficient: 0.3-0.6) and no or minor correlations with scores for cognition, depression or activities of daily living (r<0.3). The original five-factor model could not be confirmed. CONCLUSION: The DQoL can be used in dementia research for assessing positive and negative affect, feelings of belonging and self-esteem. The findings suggest further research to improve the structure of the scales aesthetics, feelings of belonging and self-esteem.

[Nonmedical treatment of dementia]. / Nichtpharmakologische Behandlungsmethoden bei Demenzen.

Dementia is a highly prevalent condition. While randomized clinical trials of high quality provide strong evidence for newly developed drugs for dementia, nonpharmacological treatments are investigated mostly in smaller, lower-quality studies although they show promise and are being intensively studied in Europe and the USA. There are indications that programmes based on psychotherapy and neuropsychology can be effective in the early stages of dementia. Ergotherapy during the early and middle stages can delay the loss of abilities for daily living. Validation can ease problems presented by "challenging" behaviour for family members and care personnel. Education of family members has great potential for delaying insitutionalisation and should be integral to every treatment for dementia.

[Speech therapy assessment: field study on psychometric properties, practicability, acceptance and process quality]. / Das logopädische Assessment: Feldversuch zu psychometrischen Eigenschaften, Praktikabilität, Akzeptanz und Prozessqualität.

OBJECTIVE: to investigate the internal consistency, responsiveness, discriminative validity, practicability, acceptance and process quality of a recently developed Speech Therapy Assessment (STA) under routine work conditions of speech and language therapists in German speaking countries. Since standardised, generic and ICF-oriented assessment tools for documentation and evaluation of speech therapy interventions for adult clients are missing in German speaking countries and existing tests cover only sub-areas, the STA has been developed in the years 1995 to 2002. By means of different domains, speech and language therapists assess client (1) communication, (2) aphasia, (3) speech apraxia, (4) dysarthria and (5) dysphagia as well as (6) her or his dealing with corresponding disabilities. METHODS: 17 therapists from 14 institutions applied the STA to 260 adult clients with language, speaking or swallowing disorders. The clients were included in the study consecutively over a period of 7 month. After this period, the therapists completed a questionnaire regarding the benefit and practicability of the STA. Cronbach alpha was calculated as indicator for internal consistency, effect sizes (standardised response means) for responsiveness and ROC values for discriminative validity. The answers of the questionnaire about the benefit of the STA were evaluated both, quantitatively and qualitatively. RESULTS: The internal consistency and discriminative validity were high (Cronbach alpha: 0.79 to 0.95; ROC-values: 0.84 to 0.98). Effect sizes regarding responsiveness were moderate (standardised response means: 0.46 to 0.78). On a 5-step Likert scale (1 = very good, 5 = inadequate), the therapists rated the average (standard deviation) benefit of the STA with: practicability 2.6 (1.2), acceptance 2.8 (1.3), impact on diagnostics 2.8 (1.3), impact on finding therapeutic goals 3.5 (1.2), impact on communication with other rehabilitation partners 2.7 (1.5) and overall judgement 2.6 (0.9). CONCLUSION: The STA fulfils essential quality criteria of the classical test theory. The involved therapists assessed the benefit of the STA as satisfactory. In addition, they pointed out concrete improvement potential for the implementation in practice. It is planed to investigate a refined version of the STA in a multi centre validation study.

[Controlled trials on the efficacy of occupational therapy with elderly. Part I: Research question, search strategy and methodological quality of trials]. / Kontrollierte Studien zur Wirksamkeit von Ergotherapie bei Alteren. Teil I: Fragestellung, Recherche-Strategie und methodische Qualität der Studien.

OBJECTIVE: To investigate how far controlled trials give evidence for the assumption that occupational therapy treatment improves or stabilises the competence, autonomy or satisfaction of elderly while performing every day activities. METHOD: Clinical trials with randomised, quasi-experimental or crossover control group design and "occupational therapy" as the main subject were identified by an electronic search of the medline database. The criteria for the analysis were derived from the CONSORT-Statement and adapted for occupational therapy. They relate to the quality of sample, intervention, measurement and data analysis. RESULTS: The 31 identified studies (RCT, n=23; quasi-experimental, n=2; crossover, n=6) were mainly conducted in Great Britain, USA and Canada, but not in Germany. They are heterogeneous regarding the characteristics and size of samples, the outcome variables and treatment approaches. They give evidence for a significant efficacy of occupational therapy with elderly, but also show some methodological shortcomings. CONCLUSION: While on an international level the positive potential of occupational therapy for the elderly is evident, there is a strong need for further studies in Germany. Therefore a methodological harmonization and a co-operation with occupational therapy research and occupational science emerging currently in Europe are recommended.

[Controlled trials on the efficacy of occupational therapy with elderly. Part II: Evidence for prioritized diseases and disabilities]. / Kontrollierte Studien zur Wirksamkeit von Ergotherapie bei Alteren. Teil II: Evidenz bei priorisierten Krankheiten und Behinderungen.

OBJECTIVE: To identify the evidence for the efficacy of occupational therapy on prioritized diseases and disabilities of the elderly. METHOD: Reviews, meta-analyses and clinical trials with control group design regarding "occupational therapy" were identified by an electronic search of pubmed and reviewed based on the CONSORT-Statement. The study results were summarised in regard to diseases and commented considering further literature. RESULTS: A total of 31 studies were identified: 10 on stroke, 6 on dementia, 5 on prevention of falls, growing loneliness or inactivity, 4 on need of nursing care, and 6 on other diseases or disabilities. There is evidence for a positive efficacy of occupational therapy on the level of several controlled trials or reviews. CONCLUSION: Especially in Germany, further research specific to occupational therapy is needed in the fields of depression, diabetes mellitus and nursing care in the community.

[The occupational therapy assessment: implementation in practice]. / Das Ergotherapeutische Assessment: Implementierung in der Routine.

The "Ergotherapeutische Assessment" (EA, occupational therapy assessment instrument) is designed as a generic instrument assessing disabilities with consequences on everyday life. It is tested for its practicability and measurement properties and suitable for adult patients treated with occupational therapy. It can be used for routine documentation, as a result-indicator for data based quality management and in outcome research. The EA is integrated in an assessment network currently in development intended for occupational therapy, physiotherapy, speech therapy and, optionally, for further professions. The profession-specific approach should enhance the intrinsic motivation for self-evaluation and thus the learning organisation.

[Psychometric analyses of occupational therapy assessment]. / Psychometrische Testung des Ergotherapeutischen Assessments.

PURPOSE: In German-speaking countries standardised assessments measuring the specific aspects of occupational therapy in adults are missing. The Occupational Therapy Assessment (OTA) was introduced by the authors during 2000 in the context of a field study regarding acceptance, practicability and the influence of the instrument on process quality. The purpose of this study was to test the psychometric properties of the OTA. METHODS: : OTA was applied by 76 occupational therapists from 44 institutions to 833 consecutive patients. Additionally, the Mini Mental State Examination (MMSE) was applied. Patients completed established German instruments measuring functional capacity (Funktionsfragebogen Hannover - polyartikuläre Erkrankungen; FFbH-P), body complaints (Beschwerdenliste; BL) and general health (Indikatoren des Reha-Status; IRES). 59 randomly selected patients were assessed independently by two therapists. 42 randomly selected patients were assesses twice for test-retest reliability. RESULTS: : For the domains 'activities of physical self-supply', 'activities of independent living', and the three domains 'consequences of sensomotor/neuropsychological/psychosocial functioning on everyday life' internal consistency (Cronbach alpha: 0.90-0.97), test-retest reliability (intraclass correlation coefficient: 0.93-0.99) and interrater reliability (kappa: 0.72-0.82) were high. Overall, the concurrent validity of the domains with corresponding scales or subscales of the MMSE, FFbH-P and IRES is satisfactory. In addition, the domains are sensitive to change. CONCLUSION: : The OTA is a standardised assessment measuring the specific aspects of occupational therapy reliably, valid, sensitive to change and sufficiently comprehensive.

[Ergotherapy assessment: field study of acceptance, practicability and process quality]. / Das Ergotherapeutische Assessment: Feldstudie zu Akzeptanz, Praktikabilität und Prozessqualität.

There is need for comprehensive assessment of patients suitable for occupational therapy. The "Ergotherapeutische Assessment" (EA) occupational therapy assessment instrument has been developed recently by a group of experts in the field. Its main purpose is to significantly support occupational therapists in diagnostics, planning, communication and evaluation of therapeutic outcome. In a first step, EA was tested in a field study with regard to practicability, acceptance, and its effects on process quality. The EA was applied in 329 patients by 22 occupational therapists (office, institution) who had been specially trained (handbook, instruction session) prior to the study. In addition, participants had to answer standardized evaluation forms with respect to the general therapeutic success, relevant functional changes possibly not covered by the EA, and professional benefit in the areas under investigation. In summary, the value for practicability as described using a 10-point scale was 5.8, and 7.6 for acceptance. With regard to process quality, the ratings were 7.3 for diagnostic effect, 6.0 for definition of therapeutic aims, and 6.8 for improvement of communication between members of the rehabilitation team. The internal consistency of the five individual modules of the instrument as calculated by Cronbachs alpha was between 0.72 and 0.95. Changes considered relevant by the participants and not reflected by the instrument accounted for 9% only. The correlation coefficient for the evaluated general success of the patients and category changes found on the basis of EA severity ratings was 0.48.