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Abstract
Introduction The prevalence of dementia is increasing, both worldwide and in China. This disease is associated with numerous restrictions for those affected but also for caregivers and society. Due to the limited effectiveness of pharmacological interventions, more research on non-pharmacological interventions is needed. For the non-pharmacological multimodal MAKS (M: motor training, A: activities of daily living training, K: cognitive training, S: social-communicative setting) intervention, positive effects on cognition, activities of daily living, and the occurrence of behavioural and psychological symptoms of dementia were identified in two randomised controlled trials in different settings in Germany. Thus, the German MAKS intervention was culturally adapted for China and will now be tested for its efficacy in Chinese nursing homes in a randomised controlled trial.
Methods and analysis Participants will be residents of Chinese nursing homes in Shenyang, Nanjing and Dalian, fulfilling the ICD-10 criteria for Alzheimer’s dementia, the psychometric criteria for mild to moderate dementia (MMSE 10–23) and none of the exclusion criteria. With n=200, effects with an effect size of Cohen’s d=0.45 and a power of 1-β = 0.80 can be detected. Screening and data collection at baseline, t6 and t12 will be conducted via face-to-face contact by proxy raters in the nursing homes (i.e., trained nursing staff not involved in the intervention) and master students as external testers for the performance tests on cognition and activities of daily living. Participants will be randomly allocated to the intervention or control group. SinoMAKS (i.e., the Chinese version of the MAKS intervention) will be conducted at least three times a week for six months by trained MAKS therapists. The control group will receive care as usual for 12 months after baseline. Thus, the treatment phase is six months with follow-ups after six and 12 months after baseline. In the open phase, from t6 to t12, the nursing homes are free to offer SinoMAKS to the intervention group residents. In line with international guidelines, the primary population for analysis is the intention-to-treat sample. Global cognition (measured with the Addenbrooke’s Cognitive Examination-III) is the primary outcome. The hypotheses will be analysed using multiple linear regression with the outcome variables as dependent variables.
Ethics and dissemination All procedures were approved by the Ethics Committee of the Medical Faculty of the Friedrich-Alexander-Universität Erlangen-Nürnberg (Ref. 24–162-B) and the Ethics Committee of the China Medical University (Ref. [2024]181). Written informed consent will be obtained from all participants or—if applicable—their legal representatives. Results will be published in peer-reviewed scientific journals and conference presentations.
Trial registration number ISRCTN10262531.
- Dementia
- Cognition
- Nursing Homes
- Randomized Controlled Trial
- Clinical Protocols
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STRENGTHS AND LIMITATIONS OF THIS STUDY
The internal validity of the study results will be high due to the use of a standardised manualised treatment and the random allocation of the participants to the intervention and control groups, stratified by cognitive status (MMSE 10–17 vs MMSE 18–23).
The external validity of the results will be high due to the ‘naturalistic setting’ in everyday practice in Chinese nursing homes and the recruitment of nursing homes from different cities and regions in China.
Longitudinal data collection across 12 months will enable an examination of the facilities’ adherence to the SinoMAKS intervention in the open phase of the study and the sustainability of effects.
The external testers of the performance tests will be blinded, but not the proxy raters, as they must necessarily be members of the nursing homes’ staff.
As the study will take place only in nursing homes in Chinese cities, no conclusions can be drawn about community-dwelling people with dementia or about people in rural regions.
Introduction
Dementia is one of the most common causes of health impairments in older people. The prevalence of dementia has risen worldwide in recent years, and the increase will continue.1 2 At least 50 million people worldwide are currently living with dementia, and the number is rising.3 In China today, around 10–15 million people are living with dementia.4 5 Current forecasts predict a tripling of the global prevalence figures by 2050.6 In China, too, the rise in prevalence rates is due to demographic changes and the associated increase in life expectancy, as the risk of developing dementia increases with age.7 The progression of dementia is accompanied by behavioural and psychological symptoms of dementia (BPSD).8 These include agitated and aggressive behaviour in people with dementia. These BPSD pose a major challenge for both those affected and their caregivers,9 10 lead to institutionalisation, reduce social participation and have negative consequences on mental, cognitive and physical abilities.11–13 Effective psychosocial interventions are therefore needed to prevent the progression of dementia with respect to BPSD in addition to the obligatory symptoms of dementia: cognitive impairment and limitations in activities of daily living (ADLs).
With regard to therapeutic interventions for dementia, a distinction can be made between pharmacological and non-pharmacological interventions. To date, there is only limited evidence for the effectiveness of pharmacological therapies.14 By contrast, non-pharmacological, psychosocial interventions have been shown to be effective for people with dementia, especially for the treatment of BPSD.15 16 A recently published systematic review by Yorozuya et al17 confirmed the efficacy of various multimodal psychosocial interventions, including the MAKS intervention, in improving cognition. In particular, the combination of cognitive training, physical training and exercises for ADLs was seen as beneficial for improving global cognition in dementia patients living in nursing homes.
The MAKS intervention18 includes four components of a non-pharmacological, multimodal intervention, which comprises components also recommended by Yorozuya et al.17 MAKS is a group intervention consisting of four components for up to 12 participants.18 19 It consists of motor exercises (M, for example, bowling, balance exercises), exercises for ADLs (A, for example, handcrafts, preparing a drink) and cognitive exercises (K, for example, memory, picture puzzles) in a social-communicative setting to strengthen group cohesion (S, for example, meditation, group interaction). The programme is conducted by two trained MAKS therapists who follow a digital manual. The MAKS intervention has already demonstrated efficacy in two large randomised controlled trials for people with mild to moderate dementia in Germany. In nursing homes18 and day care facilities,19 MAKS showed significant positive effects on the global cognition and ADL performance of people with dementia. Beyond these effects, positive effects on BPSD have also been found in nursing homes.20
However, psychosocial interventions are based on culturally known and accepted exercise content, meaning that, when transferred to another culture, the concept can be adopted but not the content of the individual exercises, which must be culturally adapted. This process of adapting the content of the exercises to the Chinese culture resulted in SinoMAKS. As the content of the therapy has now been adapted, we cannot ensure the efficacy of the cultural adaption. Thus, this study will aim to test the efficacy of SinoMAKS with regard to cognitive abilities in people with mild to moderate dementia in Chinese nursing homes in a randomised controlled trial. In addition to cognition, we will also evaluate three secondary outcomes: ADLs, BPSD and clinical global impression (CGI). This manuscript describes the study protocol while following the evidence-based reporting guidelines of the SPIRIT statement.21
Methods and analyses
Aims and hypotheses
Aims
The main aim of the project will be to test the efficacy of the culturally adapted MAKS intervention in Chinese nursing homes. Specifically, the aim will be to investigate whether SinoMAKS has positive effects on the cognitive abilities, ADLs, BPSD and CGI of people with mild to moderate dementia in Chinese nursing homes.
Research hypotheses
Primary hypothesis
Compared with the control group (care as usual), people with dementia in the intervention group will have significantly better cognitive abilities 6 months after the baseline data are collected.
Secondary hypothesis I
Compared with the control group, people with dementia in the intervention group will have significantly less aggression and agitation (part of BPSD) 6 months after the baseline data are collected.
Secondary hypothesis II
Compared with the control group, people with dementia in the intervention group will have significantly fewer limitations in ADLs 6 months after the baseline data are collected.
Secondary hypothesis III
Compared with the control group, people with dementia in the intervention group will have significantly better CGI 6 months after the baseline data are collected.
Exploratory study question
Are there changes in the cognitive abilities, ADLs, BPSD and CGI of people with mild to moderate dementia in Chinese nursing homes during the 12-month observation period?
Study design and setting
We will conduct a prospective randomised controlled trial with three assessment points to test the abovementioned hypotheses. The overall start date of the study was 1 July 2022. Recruitment will begin on 14 October 2024 and will continue until 31 October 2024.
The randomised controlled trial will be conducted in about 17 nursing homes in Shenyang, Nanjing and Dalian in China. In these participating nursing homes, 200 individuals with mild to moderate dementia will be recruited for the project. The study coordination centre will be the China Medical University, School of Nursing, Shenyang; whereas, the headquarters for the entire study will be at the Centre for Health Services Research in Medicine, Department of Psychiatry and Psychotherapy, Uniklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Germany.
Each participating nursing home will appoint a monitor who will act as a contact person between the study coordination centre in China and the nursing home. Additionally, monitors will supervise the implementation of the MAKS intervention in the nursing home and the completion and shipping of the proxy ratings and questionnaires. Before the study begins, this monitor will be comprehensively trained by the study coordination centre in China in the study procedures and in their specific tasks.
At baseline, all participants will be randomly assigned to one of the two groups within their nursing home. At least four employees will be trained in SinoMAKS in each nursing home, so that at all times (e.g., even in the case of sickness, vacations), at least two MAKS therapists will be able to carry out SinoMAKS in a manner that is standardised according to the manual three times a week in a group of a maximum of 12 dementia patients. The treatment phase is 6 months with a 6-month follow-up period (open phase) in which SinoMAKS can, but does not have to, be offered to the intervention group (IG). In the treatment phase, participants in the IG will receive SinoMAKS; whereas, participants in the control group (CG) will not receive a project-specific additional intervention but will continue to receive care as usual. No therapy or care services that are part of standard care will be withheld from the CG. They will simply not be given SinoMAKS. The CG participants will therefore be blocked from SinoMAKS for the duration of the study (12 months, from t0 to t12). Aim of the open phase is to identify long-time effects of the SinoMAKS intervention. Open phase means that there is no obligation to carry out SinoMAKS. If nursing homes decide to carry it out, they record the implementation frequency of SinoMAKS. Further, there are no fixed daily plans and the therapists of the IG are free in the choice of the tasks of each component, which allows us to test whether the intervention is also effective in a non-strictly implemented RCT design. Afterward, the nursing homes will be free to decide whether they will offer SinoMAKS to all nursing home residents, including the CG, or not. The two groups are visualised in figure 1.
Course of the study in the IG and CG. CG, control group; IG, intervention group.
Data will be collected at baseline and after six (t6) and 12 (t12) months. The treatment phase is from t0 to t6; the open phase is from t6 to t12. Table 1 presents the trial registration data.
Trial registration data
Data will be collected by means of psychometric tests and proxy rating questionnaires. Psychometric tests evaluating cognitive abilities (ACE-III) and ADLs (E-ADL-CN) will be collected by trained student assistants who are blinded (ie, they have no knowledge of group allocation at any time). Proxy rating questionnaires—especially regarding information on BPSD (CMAI-SF) and the CGI (CGI-S and CGI-I)—will be filled out by nursing staff in the nursing homes who are not involved in the SinoMAKS intervention.
Sample size estimation
The calculation of the sample size was based on an effect size of Cohen’s d=0.45, which was identified in the MAKS study (evaluation of MAKS intervention in German nursing homes) by Graessel et al18 for the primary outcome global cognition. Assuming this effect size, a statistical power of 0.80, and a significance level of 0.05 (two-sided), 158 individuals are needed in a two-armed trial with 1:1 allocation (i.e., 79 in each group). With an assumed dropout of 20%, mainly due to participants becoming bedridden or dying between t0 and t6,18 200 individuals will be recruited to compensate. Therefore, the final sample size is n=200.
Recruitment strategies
The recruitment of participating nursing facilities will be conducted by contacting them directly through the project manager, Dr. Jian Su, and the head of the Chinese study coordination centre, Prof. Dr. Yu Liu. For this purpose, letters containing information about the study will be sent via postal mail and email to the nursing homes in the metropolitan areas of Shenyang, Nanjing and Dalian in China.
Participant eligibility
All individuals in the participating nursing homes will be tested for fulfilment of inclusion criteria unless they meet one of the exclusion criteria. Individuals who fulfil the criteria for inclusion will be informed about the study, and informed consent will be obtained.
Criteria for inclusion are: (a) criteria of the dementia syndrome according to International Classification of Diseases, 10th Revision (F00), (b) psychometric verification of mild to moderate dementia—Mini-Mental State Examination (MMSE) score of ≥10 and ≤23,22–26 (c) basic language skills as well as reading and spelling skills in Chinese and (d) informed consent.
Criteria for exclusion are (a) completely blind, (b) completely deaf, (c) permanently immobile, (d) elementary school not completed (ie, less than 6 years of school), (e) unable to communicate (does not respond to simple closed questions), (f) other psychiatric or neurologically diagnosed diseases (checklist): more than one stroke, Parkinson’s disease, multiple sclerosis, other severe brain disease (especially brain tumour, brain injury, hydrocephalus), major depression, psychosis (schizophrenia, mania, bipolar psychosis), alcohol abuse/drug abuse (addiction) and (g) concrete plans/vision to move out of the nursing home.
Randomization
The randomised allocation of participants to the IG or CG will take place within the nursing homes using a method similar to Graessel et al,18 stratified by cognitive status (MMSE 10–17 vs MMSE 18–23). For this purpose, the responsible and trained monitor person in each participating nursing home will list the names of residents who are suitable for participation on the basis of screening criteria and who consent to participate in the study. This list will be anonymised from the leading coordinating centre of the study in China at the China Medical University and sent to the study headquarters in Germany. There, the Institute of Medical Informatics, Biometry, and Epidemiology of the Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU) will conduct the randomisation within the nursing homes. Thereby, the nursing home residents who are suitable for participation according to the screening and who agree to participate in the study will be randomly allocated to the IG or CG in a 1:1 ratio. The allocation will be stratified by the severity of the dementia. Participants living in the same room will be allocated to the same group. Afterward, the lists for each nursing home will be provided to the lead coordinating centre of the study in China. In the final step, the nursing homes will receive a list with the residents’ names and their allocation to the IG and CG.
Intervention – SinoMAKS
SinoMAKS is a version of the multimodal psychosocial MAKS intervention for individuals with mild or moderate dementia culturally adapted for China. The MAKS intervention is a group intervention consisting of four components for up to 12 participants. These four components (M: motor training, A: ADL training, K: cognitive training, S: social-communicative setting) form an intervention session lasting approximately 2 hours and are always carried out in the same order: S–M–K–A. The entire MAKS intervention is manualised, meaning it is implemented by two trained MAKS therapists on the basis of a digital manual. The daily session begins with a 10 min social-communicative ‘get together’ (e.g., welcome round). The following motor training session (approximately 30 min) focuses on improving general mobility, gross and fine motor skills, balance, and sensory perception through relaxation exercises, movement games, and various sports and activities. After a break, the cognitive training session (approximately 30 min) focuses on memory, recognition, association and specific cognitive abilities (e.g., language comprehension and logical thinking) through paper-and-pencil exercises and projector-based exercises. The final 40-min session of ADL training (which also includes creative or handcrafting activities) promotes ADLs, especially the associated gross and fine motor skills, mobility and particularly procedural memory.27 The background for the development of a multicomponent intervention such as MAKS is results that multicomponent interventions have a greater effect size than their individual components—as shown, for example, for cognitive and (sensory) motor training by Oswald et al.28 In addition, the four components of MAKS therapy are based on the biopsychosocial health model of dementia, with focus on the biopsychosocial factors, in which physical activity, cognitive stimulation, social interaction and active participation in everyday life are seen as relevant approaches to dementia treatment.29
In the IG, the MAKS intervention will be conducted for 6 months, three times a week, on Mondays, Wednesdays and Fridays. The other services provided by the nursing homes and participants’ medication will not be affected by the study.
Cultural adaption
To implement the MAKS intervention in Chinese nursing homes, a comprehensive culturally specific adaptation of the MAKS intervention was conducted, resulting in the intervention called SinoMAKS. The first cultural adaptation was implemented from November 2021 to January 2022 by three rehabilitation therapists from Nanjing Brain Hospital, with a total of four meetings to check the cultural translation of the content of the exercises. From October 2022 to February 2023, nursing staff from two nursing homes were asked to do the second cultural adaptation. The participants were one social worker from the nursing home, one nurse and two volunteers (master students in social work), who checked the feasibility of the adaption. Three meetings were held during this period. In 2023, Jiangsu Provincial People’s Hospital (JPH) put MAKS on trial for 5 months (from June to November) in one nursing home. Afterward, a third cultural adaptation was carried out from December 2023 to February 2024 by a social worker, a nurse and two volunteers from JPH. In this step, the usability was demonstrated. During this period, another three meetings were held to discuss qualitative feedback and adaption. In addition, nursing home residents with dementia evaluated the complexity and feasibility of single exercises from the SinoMAKS intervention during the process of the cultural adaption.
For example, the previous images used in the digital cognitive exercise picture puzzles were replaced with images of landscapes and landmarks known in China. The motor exercises (M) were modified to reflect the typical movement games and dances in China. In the area of ADLs (A), care was taken to adapt these activities to Chinese festivals and holidays, and appropriate traditional dishes were used in cooking activities. Table 2 presents an example weekly plan for SinoMAKS.
Example of a weekly plan for the SinoMAKS intervention
Measures
The data will be collected at baseline and follow-up by proxy raters (nursing home staff) and student assistants. The measures that will be used at the different measurement points are shown in figure 2 and described in the following.
Overview of data collection instruments and measurement points.
Primary outcome measure
Addenbrooke’s Cognitive Examination-III (ACE-III).30 31The primary outcome measure is the Chinese version of Addenbrooke’s Cognitive Examination-III (ACE-III),30 administered in a face-to-face setting. The ACE-III31 is a brief neuropsychological test battery with a duration of approximately 20 min, designed to assess cognitive impairments. The test serves as a more comprehensive dementia screening compared with the widely used MMSE and is intended to be freely and readily accessible.32 In 19 tasks, the five cognitive dimensions—attention, memory, verbal fluency, language and visuospatial abilities—are examined. Scores range from 0 to 100 points, with higher scores indicating better global cognitive function. The ACE-III has been internationally validated,31 33–35 including in China.30
Secondary outcome measures
Cohen-Mansfield Agitation Inventory – Short Form (CMAI-SF).36 37 To assess BPSD, particularly agitation and aggression, the Chinese version of the Cohen-Mansfield Agitation Inventory-Short Form (CMAI-SF)37 will be used. This inventory, originally from the USA, comprises 14 items and is a caregiver-rated assessment tool,38 derived from the longer version of the CMAI containing 29 items.36 Caregivers rate the frequency of agitated and aggressive behaviours described in the items during the past week on a 5-point scale, resulting in scores ranging from 14 to 70. Higher scores indicate more pronounced agitation or aggression. The CMAI is one of the most widely used instruments for assessing agitation and aggression in individuals with dementia.39 The reliability and validity of the CMAI-SF have been demonstrated in several international studies.37 40 41
E-ADL-CN – Erlangen Test of Activities of Daily Living, Chinese version (actually under validation). To assess ADLs, a culturally adapted Chinese version of the Erlangen Test of Activities of Daily Living (E-ADL Test) 42 will be used. The E-ADL Test is a compact, time-efficient test (administration: <10 min) designed to measure ADL abilities. In this test, nursing home residents are asked to perform five basic ADL tasks: making honey water, peeling eggs, handling finances, dealing with a pill organiser, and folding clothes. The administering person assesses the individual’s ADL ability on a multistage scale, with ratings made independently of any causes of impairment (0 to 6 points for each item). A higher total score (range 0 to 30) indicates better ADL abilities in the individual. The E-ADL Test has demonstrated high reliability and validity.42 This test is being adapted to Chinese culture in collaboration with the Chinese Medical University School of Nursing and is actually under validation.
CGI – Clinical Global Impression.43 To assess participants’ CGI, the CGI Severity Score (CGI-S) and the CGI Improvement Score (CGI-I)43 will be used to measure the symptom severity and the efficacy of treatments in intervention studies. The CGI-S and CGI-I consist each of one item, are change-sensitive, widely used and validated scales for evaluating the overall clinical impression through clinical observation.44 The CGI-S score ranges from 1 to 8, with a higher score indicating greater severity of the condition. The CGI-I score ranges from 1 to 8 (1=not assessable, 2=much better, 8=much worse).
Other variables
Sociodemographic and health-related data questionnaire. Sociodemographic data (age, sex, education) from a standardised questionnaire will be recorded by the proxy raters in the nursing homes at baseline. Additionally, proxy raters will also collect health-related data (medication, medical diagnoses from medical records, injury-related falls, duration and cause of hospitalisation, permanent bedridden status, care level).
NPI-NH - Neuropsychiatric Inventory – Nursing Home.45 46 To assess anxiety and depression as part of BPSD, the corresponding two items from the Neuropsychiatric Inventory-Nursing Home (NPI-NH)46 will be used. The NPI-NH is a standardised and internationally validated proxy rating instrument for assessing neuropsychiatric symptoms.47 A validated Chinese version is also available.45
Structured questionnaire - nursing homes. The structured questionnaire for nursing homes captures the following information: location of nursing home; construction date of the nursing home; total number of beds in the nursing home; distribution of residents by care levels; participation in a protected area (yes/no); garden use (square metres); possibility of one’s own furniture; star rating of the nursing home; number and qualification of caregivers in the nursing home.
Data collection
The data will be collected at baseline (t0), after 6 months (t6) and after 12 months (t12; see figure 1). All data will be captured via paper and pencil.
At each assessment point, cognitive abilities (ACE-III), aggression/agitation (CMAI-SF), ADLs (E-ADL-CN) and CGI (CGI-I and CGI-S) will be measured. Master students will assess cognitive abilities and ADLs (E-ADL-CN) on site. These assessors will be blinded to participants’ group allocation. To ensure this blinding, each nursing home will be instructed not to inform the master students about whether the person being tested belongs to the IG or CG prior to their cognitive and ADL assessments. The two secondary outcomes (i.e., agitation and aggression) will be assessed with the CMAI-SF. CGI will be assessed with the CGI-I/CGI-S. The evaluations will be conducted by trained individuals from the nursing homes who are not involved in the intervention (proxy raters). Blinding is inherently not feasible, as the assessors must observe the participants in their daily routines and must therefore be members of the nursing home staff.
As part of the confounding variables, in addition to sociodemographic data, health-related data (medications, medical diagnoses from medical records, hospitalisations) will be collected in the nursing home. These data will be obtained from the nursing documentation for the study participants in the nursing home. The two psychological confounding variables, anxiety and depression, will also be assessed via proxy rating (NPI-NH items). Again, the assessment will be conducted by trained nursing home personnel who are not involved in the intervention (proxy raters).
Data quality management and data protection
The student assistants and proxy raters from the nursing home involved in data collection have been thoroughly trained for their tasks by the study coordination centre in China. The quality of the data will be guaranteed by strict data monitoring at the study coordination centre for the total study period. Plausibility checks and logical considerations of the relationships between the associated variables will be performed. To ensure a standardised process of study procedures within the collaborating nursing homes, one monitor per nursing home will be trained in all relevant study procedures. This monitor will supervise other staff in the nursing home during the screening, data collection and implementation of the MAKS intervention. Additionally, they will act as a contact person between the nursing home and the study headquarters.
Furthermore, both the MAKS therapists (trained by the cooperating partner ClarCert GmbH, a German certification institute) and the individuals conducting the data collection and screening will receive standardised and comprehensive training, including written informational material.
A data protection concept was developed, reviewed and approved by the data protection officer of the study coordination centre in China (China Medical University, School of Nursing, Shenyang). All paper-pencil documents are kept in a locked filing cabinet. Electronic data are stored on an encrypted computer provided specifically for data collection, which is not connected to the Internet, and are protected by a secure and complex password access control mechanism.
Patient and public involvement
The patients and the public were not involved in the development of hypotheses or design of the study, as the study is based on previous studies investigating the MAKS intervention. Nevertheless, the curriculum of the MAKS therapist training fully complies with the principles of the German Alzheimer Society (letter from 6 April 2024). Additionally, as part of the process of culturally adapting the MAKS intervention to China, several pretests and experience exchanges were conducted with the care staff and nursing home residents. Furthermore, nursing home staff was involved in modifying the culturally adapted MAKS. In addition, nursing home residents with dementia evaluated the complexity and feasibility of single exercises from the SinoMAKS intervention during the process of the cultural adaption.
Data analysis
All relevant data (ie, sociodemographic, health-related, and primary and secondary outcome variables) will be reported descriptively. The primary hypothesis and the three secondary hypotheses (dependent variables are metric) will be tested with multiple linear regression analyses with the outcome variables as dependent variables. For the primary hypothesis, the final multivariate regression model will include the ACE-III at t6 as dependent variable and the ACE-III at t0, the group allocation (intervention vs control) as well as the secondary outcomes at t0 (ie, CMAI-SF, E-ADL-CN, CGI) and other variables at t0 (ie, sociodemographic and health-related data, NPI-NH anxiety and depression items) as independent variables that were significantly (p<0.05) correlated with the dependent variable at t6 in the previously calculated bivariate statistical analyses. An analogous procedure is used for the secondary hypotheses: the respective secondary outcome at t6 (E-ADL-CN, CMAI-SF, CGI) is included as the dependent variable in the multivariate regression model, and the respective secondary outcome at t0, the group assignment (intervention vs control) and the other variables that were significantly (p<0.05) related to the dependent variable at t6 in previously calculated bivariate analyses are included as independent variables.
In line with international guidelines, the primary population for analysis will be the intention-to-treat (ITT) sample, with individuals who pass away between t0 and t6 excluded from the ITT analysis.
As a sensitivity analysis, per protocol (PP) analyses will also be conducted because the intervention might not unfold its effect when a dementia patient drops out. The three criteria for the PP sample are participation in (a) at least one intervention session in the last week before t6 data collection, (b) at least 50% of intervention sessions in the last 4 weeks before data collection and (c) at least 66.6% of intervention sessions (2 out of 3 per week) throughout the intervention period between t0 and t6. These decisions are based on experiences with previous studies on the efficacy of the MAKS intervention.18 19 Additionally, clinical outliers will be excluded from the PP analysis. These are statistical outliers with a clear clinical reason for the outlier value, according to the European Medicine Agency’s guidelines48 (e.g., severe infections, falls leading to immobility, and the mentioned exclusion criteria). The significance level will be defined as α=0.05. The data analyses will be performed using the IBM SPSS statistics software, V. 28.
Ethics and dissemination
Ethical considerations
All procedures were approved by the Ethics Committee of the Medical Faculty of the Friedrich-Alexander-Universität Erlangen-Nürnberg (Ref. 24–162-B) and the Ethics Committee of the China Medical University (Ref. [2024]181).
Participation will be voluntary, and participants will be free to leave the study at any time. All legal matters, such as voluntary participation, right of revocation and General Data Protection Regulation, are considered. All described studies in humans are being conducted with the approval of the responsible ethics committee, in accordance with the national law and the Declaration of Helsinki of 1975 (in the current revised version). Written informed consent to participate will be obtained from all participants by the trained nursing staff conducting the screening (see online supplemental files 1 and 2). All participants will be informed about the study after they are screened for eligibility. This information contains all legal aspects, especially the voluntary participation, right to withdraw without any disadvantages, and data protection (according to the valid relevant data protection regulations). Every participant is considered capable of giving consent as long as they do not have a legal representative or the person obtaining the informed consent does not gain the impression that the person being informed is unable to understand what is important to them in the current situation. In the course of the study, ongoing consent is observed, which may also take into account non-verbal statements made by people with dementia about refusing to participate. If potential study participants have a legal representative, they have to consent to the participation. In all other cases, the decision of the dementia patient is to accept. In order to place informed consent on a broader basis, relatives are also informed in these cases and must give their consent for the person with dementia to participate in the study. Nevertheless, the participation of this participant group is necessary and justified in accordance with Article 20 of the Declaration of Helsinki, as the non-pharmacological intervention aims to improve the cognitive abilities of the study participants, reduce BPSD and increase ADLs.
Supplemental material
Supplemental material
A participant information sheet including important information about participation (e.g., intervention, randomisation, data protection, data storage) will be given to every participant. The opportunity to ask questions will be granted at any time. Participants will not be offered any financial incentive to participate. The external funder, Jiangsu Jicui Aging Technology Research Institute (JITRI ageing), is continuously being informed about the progress of the study. In the case of important protocol modifications, we will inform the Ethics Committee, the funder and the trial registry platform ISRCTN.
Data handling
After the data are collected, a research assistant from the School of Nursing, China Medical University, will enter the data into an Excel spreadsheet on a computer specifically provided for data collection and not connected to the Internet. Only the head of the study coordination centre in China (Prof. Dr. Yu Liu) and the research assistant have access to the data. As part of the study, no personally identifiable information (eg, participants’ names, ID numbers and case numbers) will be entered into the electronic database. However, because it is a longitudinal study, the names and admission numbers of the participants’ nursing homes must be recorded. These identifying personal details will be kept in a separate sheet, apart from the study data, and will be coded. The sheet containing the personal information will be locked in Prof. Liu’s filing cabinet, separated from the data sheets. Only the School of Nursing research team at China Medical University will have access to the key file that links the participants’ real names with the codes.
The transfer or sharing of data will occur between the cooperating partners only in pseudonymised form. Data sharing with third parties (e.g., other research groups) is not intended. Cross-border data transfers must pass a security review organised by China’s National Netcom Department, be certified for the protection of personal data according to the regulations of the National Netcom Department and be concluded with recipients abroad according to a standard contract specified by the National Netcom Department.
The data will be retained for at least 3 years in accordance with Chinese data protection regulations.
Results of the study for scientific or other publications will be published only in aggregate form (e.g., mean values). No published material will contain patient-identifying information.
Safety considerations
No negative consequences or risks from conducting the culturally adapted MAKS intervention are anticipated on the basis of experience in previous studies investigating the MAKS intervention.18–20 49 By contrast, there is an opportunity to develop a culturally adapted, psychosocial intervention for dementia that is effective, particularly in preserving cognitive abilities, ADLs, and therefore, individual independence. This is because the MAKS intervention is a scientifically grounded and demonstrated multimodal, non-pharmacological intervention for people with dementia.18–20 49 All examinations in the project are non-invasive. Insights into the efficacy of a non-pharmacological, multimodal intervention that is feasible for nursing homes in different countries and regions of the world would broaden the methodological spectrum of current non-pharmacological treatments at an international level. Because only positive consequences are expected, the risk-benefit balance is entirely positive.
Dissemination plan
The research group intends to publish the data generated from this study in peer-reviewed journals. In addition, results will be communicated at international conferences, national conventions with the funders, and the press.
Trial status
Protocol version 1.0, 10/09/2024. The overall start date of the study was 1 July 2022. Recruitment will begin on 14 October 2024 and will continue until 31 October 2024.
Ethics statements
Patient consent for publication
Acknowledgments
We would like to thank our student assistants Malin Förstel, Romi Kuntscher and Katja Ablaßmeier for their support and commitment. We would like to thank JITRI ageing for funding the study. Many thanks also to our professional English-language editor, Dr. Jane Zagorski.
References
Footnotes
Contributors J-SS contributed to the design of the study, is contributing to the implementation of the study and drafted the manuscript. PS contributed to the design of the study, is contributing to the implementation of the study and drafted parts of the manuscript. YL, YD and JL are contributing to the implementation of the study and drafted parts of the manuscript. MZ initiated the study, contributed to the design of the study and is contributing to the implementation of the study. JS initiated the study, contributed to the design of the study and is contributing to the implementation of the study. OG contributed to the design of the study and drafted parts of the manuscript. EG initiated the study, contributed to the design of the study, is supervising the study and drafted parts of the manuscript. AK initiated the study, contributed to the design of the study, is supervising the study and drafted parts of the manuscript. All authors read and approved the final version of the manuscript. JSS and PS are sharing first authorship. EG and AK are sharing last authorship. All authors read and approved the final version of the manuscript. Guarantor: EG.
Funding This work is financially supported by Jiangsu Jicui Aging Technology Research Institute (JITRI ageing; 15th Floor, Kechuang Building, 50 Futian Road, Lishui District, Nanjing, Jiangsu, P. R. China); grant number n.a.
Disclaimer The funding body has not played and will not play any role in the study design, the collection, analysis, or interpretation of the data, or in writing the manuscript.
Competing interests MZ, JS and EG are involved in a Chinese company (Nanjing Nande Cognitive Health Technology Ltd, Co.) that aims to disseminate non-pharmacological therapies—involving the MAKS concept—in China. All the other authors report no conflicts of interest.
Patient and public involvement Patients and/or the public were involved in the design, or conduct, or reporting, or dissemination plans of this research. Refer to the Methods section for further details.
Provenance and peer review Not commissioned; externally peer reviewed.
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