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The increasing prevalence of dementia in the next decades is accompanied by various societal and economic problems. Previous studies have suggested that physical activity positively affects motor and cognitive skills in individuals with dementia (IWD). However, there is insufficient evidence probably related to several methodological limitations. Moreover, to date adequate physical activity interventions specifically developed for IWD are lacking.
This study aims to investigate the effectiveness of a multimodal exercise program (MEP) on motor and cognitive skills in IWD in a high-quality multicenter trial.
A multicenter randomized controlled trial with baseline and postassessments will be performed. It is planned to enroll 405 participants with dementia of mild to moderate stage, aged 65 years and older. The intervention group will participate in a 16-week ritualized MEP especially developed for IWD. The effectiveness of the MEP on the primary outcomes balance, mobility, and gait will be examined using a comprehensive test battery. Secondary outcomes are strength and function of lower limbs, activities of daily living, and cognition (overall cognition, language, processing speed, learning and memory, and visual spatial cognition).
Enrollment for the study started in May 2015. It is planned to complete postassessments by the beginning of 2017. Results are expected to be available in the first half of 2017.
This study will contribute to enhancing evidence for the effects of physical activity on motor and cognitive skills in IWD. Compared to previous studies, this study is characterized by a dementia-specific intervention based on scientific knowledge, a combination of motor and cognitive tasks in the intervention, and high standards regarding methodology. Findings are highly relevant to influence the multiple motor and cognitive impairments of IWD who are often participating in limited physical activity.
German Clinical Trials Register DRKS00010538; https://drks-neu.uniklinik-freiburg.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00010538 (Archived by WebCite at http://www.webcitation.org/6oVGMbbMD)
Dementia is one of the most frequently occurring diseases in the elderly [
Dementia is a syndrome which comprises several different types of usually chronic and progressive diseases of the brain (eg, Alzheimer disease or vascular dementia) [
To date, there is no cure for dementia, and commonly used medications for treating the symptoms of dementia have side effects emphasizing the urgent need for nonpharmacological interventions [
Reviews and meta-analyses examining the effects of physical activity on cognitive skills in IWD mainly assess overall cognition. Of 6 reviews and meta-analyses, 3 found no evidence for the benefit of physical activity on cognition in IWD [
Most of the systematic reviews and meta-analyses suggest even if evidence is lacking that physical activity positively affects IWD, for example, in balance, mobility, and cognition. Their conclusions are that there is an urgent need for high-quality intervention studies [
This study will investigate the effects of a physical activity intervention on motor and cognitive skills. The intervention focuses on dementia-specific motor deficits and aims to influence the underlying motor performance, which depends on complex cognitive processes like integrating sensory information, central processing, or efferent motor output [
Aiming to overcome the above mentioned methodological limitations, we will realize a high-quality multicenter trial with a sustainable intervention close to everyday life. The following aims will be addressed.
Primary aim: to determine the effect of a multimodal exercise program (MEP) compared to conventional treatment (eg, medication, care, therapeutic applications) on balance, mobility, and gait. We hypothesize that a 16-week MEP in addition to conventional treatment affects balance, mobility, and gait in IWD more than the conventional treatment. Additionally, we will compare different subgroups (eg, according to sex, stage of dementia, or attendance).
Secondary aim: to investigate the influence of mediator and moderator variables on primary outcome measures. We assume that the effects of physical activity on balance, mobility, and gait are caused or influenced by changes in underlying motor and cognitive skills.
Comparably, we will investigate the effect of MEP on the secondary outcomes strength and function of lower limbs, ADL, and cognition as well as the effect of mediator and moderator variables on ADL. By addressing these aims, this study contributes to enhancing evidence concerning the effects of physical activity on motor and cognitive skills in IWD.
The study design has been primarily defined to address the primary aim of the study on the effectiveness of a 16-week MEP. For this reason, we will perform a multicenter randomized controlled trial with baseline and postassessments and an allocation ratio of 2:1 for intervention (IG) and control group (CG), respectively. Ethical approval has been obtained from the ethics commission of the Karlsruhe Institute of Technology. The study is retrospectively registered in the German National Register of Clinical Trials [DRKS00010538]. This study protocol considers guidelines and recommendations of the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) [
Participants for this study will be recruited in public, private, and charitable care facilities in southwestern Germany, in particular in the metropolitan region Rhein-Neckar and the district around Karlsruhe. All randomly selected care facilities offer inpatient care for approximately 60 to 300 residents and provide a common room where the intervention will be performed. A total of 3 recruitment periods with consecutive sampling within each care facility are planned.
Employees of care facilities will identify possible participants with the purpose to fulfill selection criteria.
Inclusion criteria include (1) diagnosis of dementia or suspected dementia (based on the assessment of the objective ICD-10 criteria by employees and the examination of cognitive abilities with Mini-Mental State Examination [MMSE][
Exclusion criteria include (1) secondary dementia (all types resulting from organic illness or injury: eg, toxic substances or brain injuries [
Potential participants will receive a comprehensive information letter and an informed consent form, which will be signed by individuals or their legal guardians prior to the study. The informed consent along with clearance of participant’s general practitioner allow scheduling of baseline assessments where eligibility will be verified according to the inclusion and exclusion criteria. Flow of participants is illustrated in
Flow of participants.
The intervention is specifically developed for this study based on theoretical considerations, results of a pilot study [
The MEP will be guided by 2 skilled instructors with experience in sports science and performed as group training mainly in a seated position. A group will consist of a maximum of 12 participants and will be joined by familiar caregivers to support the instructors if needed. The underlying didactic concept focuses on specific needs and characteristics of IWD and includes increased supervision realized by 2 instructors, adaptation to the cognitive level of participants, adjusted communication (eg, simple language, nonverbal aspects), ritualization to give orientation and familiarity, and adequate complexity by simple and well-structured cognitive and motor tasks.
To ensure high standards and comparability, each session is planned in detail and all instructors participate in a special training focusing on structure and contents of MEP as well as special demands resulting from the characteristics of IWD. A detailed training manual is provided for instructors, and the adherence to this manual will be emphasized. To ensure standardization, all tasks are described precisely and photographs are provided.
Providing a sense of security is an important aspect realized by ritualization. To satisfy this ritualization, the general sequence is identical for all sessions including an imagination of experienced journeys. Each session is divided into 3 parts: arrival, destination, and departure. Whereas arrival and departure remain consistent over the whole intervention period, a new travel destination is selected every time. A total sample session of MEP is found in
The arrival as beginning ritual of each training session takes about 5 to 7 minutes and aims to prepare participants for the following main part. Tasks for mobilization and stimulation of the cardiovascular system are linked to cognitive activation.
The main part of MEP is the destination (about 35 minutes) which includes tasks for strength (43%), balance (25%), endurance (16%), flexibility (13%), and not further specified tasks (3%) (see
Examples of motor and cognitive tasks of the multimodal exercise program and their progression.
Simple performance | Progressive performance developed within the 16 weeks | ||
Imagination/journey | Mediterranean cruise – aquafitness on the deck of the ship | Circus – task after tightrope dance | |
Starting position | Seated, arms stretched above head | Standing upright behind chair, arms stretched above head | |
Motor task | Lateral flexion with pool noodle | Lateral flexion with rope | |
Sets and repetitions | 3 sets with 2 repetitions for each side | 2 sets with 3 repetitions for each side | |
Muscle activity | Upper limbs and core | Upper limbs, core, and lower limbs | |
Cognitive task | No additional cognitive task | Answering questions about circus performances (eg, Have you ever been to a circus? If yes: Which was the best circus act? If no: What do you think would be the most interesting thing if you visited a circus?) | |
Imagination/journey | Safari in Namibia – washing an elephant | World trip – washing an elephant | |
Starting position | Seated, 1 arm is horizontally stretched, flexion in hip joint to shift body weight forward | Standing upright behind chair, one arm is horizontally stretched, flexion in hip joint to shift body weight forward | |
Motor task | Slow and large arm movements in horizontal plane holding a small sandbag while leaning to left and right sides | Slow and large arm movements in horizontal plane holding a small sandbag while leaning to left and right sides | |
Cognitive task | Answering questions about elephants (eg, Have you ever seen an elephant? Are there different kinds of elephants? What are the differences?) | Counting to 180 in steps of 6 (change hands at 90) | |
Duration/repetitions | 1 minute/approximately 10 repetitions per side | Approximately 1:30 minutes/15 repetitions per side | |
Imagination/journey | Soccer World Cup – walking to the soccer training | On a treasure island – walking downhill through the jungle | |
Starting position | Seated | Standing upright behind chair | |
Motor task | “Walking” in seated position – lifting legs with active use of arms | “Walking” on the spot – lifting legs with active use of arms (if possible) | |
Duration | 1 minute | 3 minutes | |
Cognitive task | Answering questions about soccer and its rules (eg, Who knows some soccer rules? Do you know how many referees there are during a game?) | Naming animals living in the jungle. If a participant repeats an animal he or she is asked to name another one | |
Imagination/journey | Safari in Namibia – wood chopping for a campfire | Olympic Games – laola wave of the audience | |
Starting position | Seated | Standing upright behind chair | |
Motor task | Extention and flexion of the trunk, bringing arms in extention with maximal personal range of motion | Extention and flexion of the trunk, bringing arms in extention with maximal personal range of motion (try to increase range of motion) | |
Set and repetitions/duration | 3 sets with 10 repetitions (5 repetitions slow, 5 repetitions fast) | No repetitions defined, duration 3 minutes | |
Cognitive task (example) | Performing in the same rhythm synchronous with other participants, 5 slow hits, 5 faster hits | Learning 3 different signals: 1= moving fast, 2= moving slow, 3= change direction of laola wave, performing according to signals |
The departure takes about 5 minutes and aims to cool down and relax the body while leading participants out of imagination and back into reality. Similarly to the arrival, instructors guide participants through fixed sequences.
The MEP takes place twice a week on nonconsecutive days over a period of 16 weeks. Each session lasts 60 minutes with motor and cognitive tasks taking about 45 minutes to ensure sufficient time for rests and explanations. Prior to the first session, a social gathering session is held aiming for an initial familiarization and information acquisition with regard to participants and care facilities. Attendance and adherence of participants will be documented by instructors for each session. Adherence will be assessed using a short formula to rate attention, participation, motivation, and behavior of each participant.
Conventional treatment comprising, for instance, medication, care, or therapeutic applications is individually tailored and will be continued in all included participants of CG as well as IG.
Distribution of motor qualities within the main parts of the multimodal exercise program.
Primary outcomes refer to the motor qualities balance, mobility, and gait. Secondary outcomes are other motor variables such as strength and function of lower limbs and ADL as well as cognitive variables assessing overall cognition, language, processing speed, learning and memory, and visual spatial cognition. All outcome parameters are listed in
Primary and secondary outcome parameters.
Outcome | Assessments (at baseline and 16-week postassessment) | |
Balance | Frailty and Injuries: Cooperative Studies of Intervention Techniques 4 (FICSIT-4) [ |
|
Mobility | ||
Timed Up and Go test [ |
||
6-meter walk test [ |
||
Gait | Gait analysis using GAITRite: temporal and spatial gait parameters (gait speed, cadence, cycle time, step length, step width, gait variability, single support, and double support) | |
- Walking with normal speed | ||
- Walking with normal speed and the task counting backwards from 50 | ||
- Walking with normal speed and the task naming animals | ||
Lower limb strength | Modified 30-second chair-stand test [ |
|
Lower limb function | Short physical performance battery [ |
|
Activities of daily living | ||
Barthel Index (German version according to Hamburger Einstufungsmanual [ |
||
Erlangen Test of Activities of Daily Living (E-ADL-Test) [ |
||
7-item physical performance test [ |
||
Overall cognition | Mini-Mental State Examination (MMSE) [ |
|
Language | ||
Verbal fluency “category animals” | ||
Phonemic fluency “S-words” | ||
Processing speed | Trail Making Test A [ |
|
Learning and memory | ||
California Verbal Learning Test, short version 1 [ |
||
Digit span forward and backward [ |
||
Visual spatial cognition | Clock drawing test [ |
The primary and secondary outcomes have been discussed in an international expert panel consisting of 14 scientists from 7 institutions in 3 countries (Germany, Australia, and Netherlands) with the disciplines sports science (especially focusing on locomotion research, sports therapy, kinesiology, biomechanics, training science, physical education and health, diagnostics, evaluation, and sports psychology), geriatrics/gerontology, psychology, and physiology. Among these experts, a standardized testing procedure has been determined focusing on relevance of outcomes as well as validity, reliability, objectivity, and feasibility of recording methods. The selected outcomes and recording methods are common in geriatric assessments and have been frequently used in previous studies examining IWD. However, it must be pointed out that most of recording methods regarding the motor qualities have not been developed for IWD. Feasibility of the test battery and recording procedure was tested in a sample of 20 participants prior to the current study. This pilot study proved feasibility of planned assessments in IWD.
Trained investigators with experience in sports science guide the baseline and postassessments in the care facilities. Prior to assessments, investigators participate in a special course to get detailed information about testing procedure and measurements. To standardize testing procedure and ensure comparability, a detailed testing manual is provided to which investigators are urged to strictly adhere. Accordingly, a detailed description of performing each assessment is given in
Static balance will be determined using the Frailty and Injuries: Cooperative Studies of Intervention Techniques 4 scale (FICSIT-4) [
Temporal and spatial gait parameters will be analyzed using the electronic gait analysis system GAITRite (CIR Systems Inc, Franklin, NJ) with an active length of 4.88 meters, a spatial resolution of 1.27 centimeters, and a scan rate of 120 hertz. The following parameters are of special interest: gait speed, cadence, cycle time, step length, step width, gait variability, single support, and double support (as percentage of cycle time). Gait parameters are recorded for 3 different conditions: walking with normal speed, walking with normal speed and the task of counting backwards from 50, and walking with normal speed and the task of naming animals.
Changes in gait parameters caused by dual task will be calculated using the equation seen in
Calculation of changes in gait parameters caused by dual task.
Strength of lower limbs will be determined by modified 30-second chair-stand test. In this modified version participants are allowed to use their arms [
ADL will be determined using the Barthel Index (German version according to Hamburger Einstufungsmanual [
Cognitive outcomes will be assessed using some subtests of the neuropsychological test battery Consortium to Establish a Registry for Alzheimer's Disease–Plus (CERAD-Plus) [
Moreover, body mass and height will be measured using a Seca 813 Robusta scale and Seca 213 stadiometer (Seca, Hamburg, Germany) with an accuracy of 0.1 kilogram and 0.1 centimeter, respectively.
Further possible influencing variables including age, medication, or other diseases are recorded chronologically close to baseline assessments. Employees of the care facilities will be asked to complete the health and demographic data questionnaire and the Cumulative Illness Rating Scale [
The required sample size was calculated via G*Power version 3.1.9.2 (Heinrich Heine University of Dusseldorf) [
We assume 3 reasons for dropout: (1) withdrawal from the study, (2) missing data, and (3) low attendance or adherence to MEP. Possible reasons for withdrawal are death, hospitalization, serious deterioration in state of health, refusal to participate, etc. Based on the literature review of Blankevoort et al [
All participants will be asked at least twice if they are willing to participate in the assessments to reduce missing data. A familiar caregiver is asked to invite the participant if appropriate. If participants are not willing to complete all measures they are offered to choose assessments they are willing to complete. Moreover, all possible participants will be included in the data collection regardless of whether they discontinued or deviate from the intervention protocol. Caregivers will be asked to support the participants to get to training sessions to improve attendance. If participants miss a session, they are personally invited to the next training session.
Group allocation to IG and CG will be performed by minimization to obtain randomized groups with minimum group differences. Subjects rather than care facilities will be randomized to avoid confounding effects of the geographic location, and minimization will be done separately for each care facility based on the baseline criteria MMSE, sex, age, and baseline performance of modified 30-second chair-stand test. Minimization will be performed with the program MinimPy version 0.3 [
Investigators will be blinded to allocation wherever possible. It is not possible to blind participants or employees of care facilities regarding group allocation.
All data is stored in a strictly pseudonymous form. This is achieved by separating personally identifiable information of participants from data collected during baseline and postassessments. Collation of data is only possible with considerable effort at any time of the study. Thus, individual confidentiality will be ensured before, during, and after the study. Only selected team members have access to coded data.
All statistical analysis will be done with SPSS version 23 (IBM Corp). Trained and experienced investigators will evaluate and enter data. Investigators evaluating and entering data are not the same as investigators assessing outcomes. The number of investigators is limited to 2 per assessment method. Prior to actual analysis, interrater reliability (Cohen kappa [
Because of expected large dropout rate, which can lead to a critical amount of missing data, 2 separate analysis sets are planned: an intention-to-treat analysis and a per-protocol analysis. In the intention-to-treat analysis, all randomized participants regardless of protocol adherence will be included and missing data will be substituted by multiple imputation. Participants with sufficient attendance and adherence to the intervention as well as complete assessments of primary outcomes will be included in the per-protocol analysis, where missing data will not be considered.
Baseline values of participant characteristics will be compared between IG and CG using chi-square tests for categorical data, Mann-Whitney-U tests for nonparametric variables, and
Enrollment for the study started in May 2015. It is planned to complete postassessments by the beginning of 2017. Results are expected to be available in the first half of 2017.
Previous studies have discussed the use of physical activity as additional therapy strategy, and predominately positive effects have been reported. However, the results of these studies are not consistent and they have several methodological limitations. With respect to these limitations, the current study has been carefully designed and thus reflects the following strengths.
The overall strength is the strong effort to conduct a high-quality trial characterized by a standardized study design, theoretical considerations, an intervention specially designed for IWD, assessments adequate for IWD, a large sample size, and detailed and accurate reporting of methods according to the CONSORT [
The MEP, which is characterized through dementia-specific methodology and a combination of motor and cognitive tasks, is a major strength of this study. Because of its theoretical foundation and based on primary recommendations of the review by Scharpf et al [
Bearing in mind that most motor assessments are not developed for IWD and their psychometric properties have hardly been systematically established in this specific population [
This study is designed as a multicenter trial with a sustainable intervention close to everyday life. For instance, the MEP is established on everyday activities such as getting up, walking, or picking things up (see
There are several challenges in performing intervention studies in IWD. These are related to the selected study design as well as its target group and thus cannot be avoided. However, it is important to deal with these challenges to minimize their impact.
A big challenge in performing intervention studies with IWD is maintaining blinding to group allocation. Although all investigators will be blinded to group allocation, there is a potential risk that participants will disclose their group allocation during assessments. To minimize this risk, investigators will be asked not to talk about the intervention during assessments.
Working with IWD entails several general challenges as they are often suffering from frailty and multimorbidity. According to different motor and cognitive impairments in IWD, it is not possible to develop an intervention completely suitable for all participants. Hence, some adaptions of the intervention cannot be avoided. However, instructors are asked to minimize such adaptions and adhere to the manual as strictly as possible. Besides this, IWD are vulnerable in relation to attendance, adherence, and missing data. For instance, multiple motor and cognitive impairments partially prevent IWD from participating in all subassessments. Thus, attempts to enhance attendance and adherence as personal communication, support, or repeated invitation are planned.
Further challenges are seen in cooperation with care facilities. Employees assume important responsibilities, such as suggesting potential participants, assessing ADL and state of health, or supporting assessments and intervention. Restricted time or missing expertise is a potential risk for limitations. To reduce such limitations, employees will be provided detailed information on how to report required data and support for further problems.
Findings of this study will be disseminated through publications and presentations (including information about important protocol modifications). Improving the defined primary outcomes is highly relevant considering the consequences of dementia-related motor deficits as stated in the introduction [
This study will contribute to enhance scientific evidence and takes a first look at relations between motor and cognitive skills in IWD. The findings can also be directive for further investigations in the field of prevention, diagnosis, and therapy of dementia.
There is a clear need for high-quality studies investigating the effectiveness of physical activity on motor and cognitive skills in IWD. Our study is mainly characterized by a dementia-specific intervention based on scientific knowledge, the combination of motor and cognitive tasks, and a large sample. Findings are highly relevant to influence the multiple motor and cognitive impairments of IWD often participating in limited physical activity. If the MEP proves to be effective, positive influences on everyday life are expected justifying its permanent implementation in care facilities.
Sample session of the multimodal exercise program.
Description of assessments.
Alzheimer Disease Assessment Scale–Cognitive Subscale
activities of daily living
analysis of variance
Consortium to Establish a Registry for Alzheimer's Disease
Consolidated Standards of Reporting Trials
control group
Erlangen Test of Activities of Daily Living
Frailty and Injuries: Cooperative Studies of Intervention Techniques 4
International Statistical Classification of Diseases and Related Health Problems, Tenth Edition
intervention group
individuals with dementia
multimodal exercise program
Mini-Mental State Examination
Standard Protocol Items: Recommendations for Interventional Trials
All authors are members of the research team and participated in the implementation of the study. AW conceived the idea of this study along with ST and AS. All authors contributed to the conception and design of the study. ST coordinates the study under direct supervision of AW. ST and AS are responsible for the implementation of the study. AS developed and supervises the multimodal exercise program. All authors were involved in planning and writing the study protocol. ST and BB wrote the study protocol. AS and CN helped draft this manuscript. All authors provided critical feedback and approved the final manuscript.
This project is financially supported by the Dietmar Hopp Stiftung (St. Leon-Rot, Germany). The sponsor does not have any role in the design of the study; its execution, data collection, analysis, or interpretation; the decision to submit results; or the writing of the report.
Ethical approval has been obtained from the ethics commission of the Karlsruhe Institute of Technology (11.03.2015, reference number: 7712.14-0508-0). An informed consent will be signed by participants or their legal guardians prior to the study.
We are grateful to all participating in the study and to our research stuff. We thank Luisa Appelles for the coordination of fieldwork, Dr Annegret Mündermann for her writing assistance on behalf of the authors, Dr Doris Oriwol for the statistical consulting, and all participants of the expert panel for developing the test battery. We acknowledge support by Deutsche Forschungsgemeinschaft and the Open Access Publishing Fund of Karlsruhe Institute of Technology.
None declared.