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Effect of physical activity training on dementia patients: A systematic review with a meta-analysis
Accepted Manuscript Effect of physical activity training on dementia patients: A systematic review with a meta-analysis Zi Zeng, Yong-Hong Deng, Ting Shuai, Hui Zhang, Yan Wang, Guo-Min Song PII:
S2095-7718(16)30094-9
DOI:
10.1016/j.cnre.2016.11.006
Reference:
CNR 72
To appear in:
Chinese Nursing Research
Received Date: 1 August 2016 Revised Date:
23 August 2016
Accepted Date: 9 September 2016
Please cite this article as: Zeng Z, Deng YH, Shuai T, Zhang H, Wang Y, Song GM, Effect of physical activity training on dementia patients: A systematic review with a meta-analysis, Chinese Nursing Research (2016), doi: 10.1016/j.cnre.2016.11.006. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT *Corresponding author. E-mail address: [email protected] (G. -M. Song). Peer review under the responsibility of Shanxi Medical Periodical Press.
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DOI: © 2016 Shanxi Medical Periodical Press. Publishing services by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). Cited information: Zeng Z, Deng YH, Shuai T, Zhang H, Wang Y, Song GM. Effect of physical activity training on dementia patients: a systematic review with a meta-analysis. Chin Nurs Res. 2016; 4: xx-xx.
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Original article Effect of physical activity training on dementia patients: a systematic review with a meta-analysis Zi Zeng a, Yong-Hong Deng a, Ting Shuai a, Hui Zhang a, Yan Wang b, Guo-Min Song c, * a
Graduate College, Tianjin University of Traditional Chinese Medicine, Tianjin 300193, China. b School of Nursing, Tianjin University of Traditional Chinese Medicine, Tianjin 300193, China. c Department of Nursing, Tianjin Hospital, Tianjin 300211, China.
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ARTI C LE I N FO Article history: Received 1 August 2016 Received in revised form 23 August 2016 Accepted 9 September 2016 Published 20 December 2016
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Keywords: Dementia Physical activity Training Meta-analysis Systematic review
ABSTRACT Background: Activity in a favorable environment excites the brain on a bodily and cognitive level and is beneficial for brain plasticity in dementia patients. Although dementia is an incurable disease, its progression can be slowed with exercise and some patient functionality may be improved through physical exercise. The objective of this meta-analysis was to assess the effect of physical exercise on patients with dementia.
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Methods: The Pubmed, EMbase, Web of Science, Cochrane Library, China National Knowledge Infrastructure (CNKI), VIP and Wan Fang databases were searched for randomized controlled trials (RCTs) through July 2016. References of eligible citations were also searched by hand. Articles were screened and data were extracted. The methodological quality was independently assessed by two reviewers. Then, a meta-analysis was performed by RevMan 5.3. Results: A total of 14 RCTs, involving 1546 participants, were included. The pooled results suggested that physical exercise effectively improved the Time up and go (seconds) [(MD = -2.87, 95%CI (-3.25, -2.5)], Function Reach (cm) [(MD = 4.25, 95%CI (3.52, 4.98)], Cadence, steps/min [(MD = 12.71, 95%CI (6.92, 18.51)], NPI-caregiver total score [(MD = 2.33, 95%CI (-3.65, -1.01)] and Berg Balance Scale [(MD = 3.62, 95%CI (1.51, 5.73)]. Conclusions: Physical activity training effectively improved the condition of dementia patients. Physical activity training effectively improved the condition of Time up and go (seconds), NPI-caregiver total score, Function Reach (cm), Cadence, steps/min and Berg Balance Scale. Hence, physical activity training offers many advantages for dementia patients, including improving their balance ability, athletic ability and relieve caregivers’ burden. © 2016 Shanxi Medical Periodical Press. Publishing services by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
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1. Introduction
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Dementia is a disease of mental deterioration in the setting of organic or functional problems, including Alzheimer’s disease, vascular dementia and other causes. Dementia patients have many different signs and symptoms, and medical workers should know more about these, which facilitates caring for them. 1 Physical activity involves performing various movements that are led by a professional and should assure patients’ safe, each training should take approximately 30 minutes. Physical exercise is a useful method for improving the condition of dementia patients. Physical exercise interventions help older individuals with dementia to improve their health and well-being. 2 Physical activity programs can help relieve or delay declines in activities of daily living (ADL) functioning for dementia patients who have mild to moderate conditions. 3 Physical activity has also been shown to help with cognitive improvement and overall functioning of the brain and its structures. One review indicated that physical activity can help improve balance, motor sequences, stride length and performance of activities of daily living, which are severely affected by Alzheimer’s disease. 4 Hence, it is imperative to identify the effect of physical activity on patients with dementia. Published studies have suggested that early physical exercise can improve the function of dementia patients. However, the conclusion remains equivocal and there are some drawbacks as a result of the variations in results across studies, such as the small sample size, which can lead to relatively low power regarding the effects of
ACCEPTED MANUSCRIPT physical activity for dementia patients. Lack of power may contribute to false-negative results. It is important that many RCTs have been completed on this topic; as a result, we undertook a meta-analysis to further evaluate the potential of physical exercise on the function of dementia patients. 2. Methods
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The Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) statement 5 and Cochrane Handbook for Systematic Reviews of Interventions are adopted as guidelines for performing this meta-analysis and systematic review. 6 Because all pooled analyses are originated from published studies, ethical approval and patient consent are not required. 2.1. Literature search We searched 6 electronic databases, including PubMed, EMbase, Web of Science, CNKI (China National Knowledge Infrastructure), Wan Fang and VIP, using combinations of Mesh and entry terms with words like ‘Dementia’, ‘Dementias’, ‘Amentia’, ‘Amentias’, ‘Senile Paranoid Dementia’, ‘Dementias, Senile Paranoid’, ‘Paranoid Dementia, Senile’, ‘Paranoid Dementias, Senile’, ‘Senile Paranoid Dementias’, ‘Familial Dementia’, ‘Dementia, Familial’, ‘Dementias, Familial’, ‘Familial Dementias’, exercise and random*. This search strategy can improve the effectiveness of the literature search. The references of included articles were manually searched to identify any new relevant studies. 2.2. Selection criteria According to the population, intervention, comparison, outcomes and study design in our selection criteria, we set the following as inclusion criteria: ① Population (P): all the patients who were diagnosed with dementia (including Alzheimer’s disease, vascular dementia and other types of dementia), by diagnostic criteria that were included in the article. ② Interventions (I): physical exercises. ③ Comparisons (C): comparing the efficacy of physical exercises program versus intervention or routine alone. ④ Outcomes (O): outcomes cannot be decided before including all necessary literature and read full-text. ⑤ Study design (S): RCTs with appropriate random sequence generation. Additionally, we only included methodologically sound articles if there are duplicates. 2.3. Literature screening and data extraction Searches were conducted and data were extracted by two independent investigators. Each trial was evaluated for the author, published year, number of participants, allocation method, blinding method, age of included patients, intervention measures, period of treatments, patient eligibility criteria, and baseline and outcome measures. Any disagreement between investigators on the eligibility of a trial was resolved through discussing or consulting with a third investigator. Initial screening was conducted after finding duplicates. All undetermined articles were screened by full text. 2.4. Assessing the risk of bias Quality assessment of trials included in the study was independently performed
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by two reviewers in accordance with Cochrane Handbook for Systematic Reviews of Interventions version 5.1.0. 7 The evaluation index included randomization sequence generation, allocation concealment, blinding of participants and study personnel, blinding of outcome assessors, incomplete outcome data, selective reporting and other biases. Based on the information extracted from primary studies, each domain was rated as “high risk”, “unclear risk” or “low risk”. Those domains, which are rated as having a high risk of bias, were obviously false. For those rated as having an unclear risk of bias, clear judgment could not be performed from the text. For those with a low risk of bias, the description was more correct for concluding there was a low risk of bias judgment. For example, the domain of randomization sequence generation was rated to have a low risk of bias if the text described the method used to generate the allocation sequence in sufficient detail. Studies with “low risk” in all domains were rated as grade A; one or more domains are were considered “unclear risk” but without “high risk” and were rated as grade B, with one or more terms were “high risk” and were rated as grade C. 2.5. Statistical analysis method All extracted data were entered into RevMan 5.3 (Copenhagen: The Nordic Cochrane Centre, The Cochrane Collaboration, 2013) for statistical analysis. Weighted mean differences (WMDs) or standard mean differences (SMDs) with a 95% confidence interval (CI) for continuous outcomes was selected to estimate the pooled effects size. The outcomes include the MMSE, Time up and go (seconds), NPI-caregiver total score, Function Reach (cm), Functional Independence Measure, Cadence (steps/min), Walking Speed, Barthel Index, Berg Balance Scale, Step length (cm) and Cornell depression in dementia scale. Heterogeneity in the included studies was evaluated using the Chi2 test, corresponding to a P value and I2 statistic. If I2 was ≥ 50%, the eligible studies were considered to be heterogeneous and a random effects model based on the Mantel-Haenszel (MH) or inverse variance (IV) statistical approach. If I2 was < 50%, the studies were considered to be homogeneous and a fixed-effect model was selected. Subgroup analysis was performed if there were any detectable heterogeneity resources present. Change data were selected to calculate the summary results according to the baseline and end-point data. (Calculation formula: S2effect 2 2 size=S baseline+S end-point-2*R*Sbaseline*Send-point; Meffect size=|Mbaseline-Mend-point|; R: 0.4 or 0.5). 8 Sensitivity analyses were performed to confirm the robustness of pooled results according to the change combination model. 3. Results
3.1. Study selection and trial characteristics A total of 958 trials were included in the initial literature retrieval. Then, 0 trials were added to the search result, and 14 trials, 9-22 which included 1546 patients, remained according to the inclusion and exclusion criteria with quantitative or qualitative analysis. The flow diagram of literature retrieval and selection is given in Fig. 1.
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770 of records after duplicates removed
749 of records excluded
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770 of records screened
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0 of additional records identified through other sources
958 of records identified through database searching
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14 of full-text articles assessed for eligibility
7 of full-text articles excluded 2 cannot get the full-text 3 inappropriate with included criteria 2 the same RCT with included ones
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14 of studies included in qualitative synthesis
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10 of studies included in quantitative synthesis (meta-analysis)
Fig. 1. Flow chart of literature retrieval and selection.
3.2. Assessment of risk of bias Two RCTs were Grade A, 10 RCTs were Grade B and 2 RCTs were Grade C. Most have problems with blinding. The methodological quality assessments of the included trials were revealed (Fig. 2).
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B Fig. 2. Percentage of the risk of bias: authors’ judgements regarding the risk of bias with respect to various parameters among all included studies; B. Risk of bias summary: authors’ judgements regarding the risk of bias with respect to various parameters for individual studies.
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3.3. Qualitative analysis 3.3.1. Meta-analysis on MMSE The MMSE, mini-mental state examination, which is a scale for testing cognitive impairment was evaluated. Four trials involving 437 participants reported the MMSE. 9-10, 13, 18
Heterogeneity was identified across the included studies [P＜0.0001, I2 =
88%]. A random-effect model was selected to summarize the mean effect size, which was not detected because the resources caused heterogeneity. This model indicates that all participants from the included trials were sampled from different populations. Pooled results suggested that physical exercise had no obvious effect on the MMSE (mini-mental state examination) [MD = 0.77, 95%CI (-0.84, 2.39), P=0.35] (Fig. 3).
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Fig. 3. Meta-analysis of the MMSE on physical activity and control groups.
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3.3.2. Meta-analysis on Time up and go (seconds) The time up and go test is a simple test used to evaluate a person’s mobility ability that requires both dynamic and static balance. Three trials, including 206 participants, were enrolled in the meta-analysis calculating the Time up and go (seconds). 10, 14, 21 We identified homogeneity in the three assessed studies [P = 0.34, I2 = 8%]. Therefore, a fixed-effect model of analysis was performed to calculate the mean effect size. This model indicates that all participants from the included trials were sampled from the same population. Pooled results indicated that the Time up and go (seconds) can be shortened by physical activity, and there was a significant difference [MD = -2.87, 95%CI (-3.25, -2.5), P<0.00001] (Fig. 4). As a result, physical activity can affect the Time up and go task in dementia patients and is worth clinical use.
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Fig. 4. Meta-analysis of Time up and go (seconds) on physical activity and control groups. 3.3.3. Meta-analysis on the NPI-caregiver total score The NPI-caregiver total score is the neuropsychiatric inventory for caregivers. Three hundred and ninety-seven dementia patients were involved in three trials, which were enrolled in the meta-analysis as identified by the NPI-caregiver total score. 9, 13, 18 There was homogeneity in the three studies [P = 0.25, I2 = 28%]. Therefore, a fixed-effect model of analysis was used. Pooled result showed physical exercise can greatly decrease the NPI-caregiver total score, and there was a statistically significant difference [MD =2.33, 95%CI (-3.65, -1.01), P=0.0005] (Fig. 5). As a result, physical activity has a positive effect on the NPI-caregiver total score for dementia patients.
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Fig. 5. Meta-analysis of the NPI-caregiver total score on physical activity and control groups.
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3.3.4. Meta-analysis on the Function Reach (cm) The function reach test can only be tested when the patient is standing, which is a new clinical measure of balance. Two trials of 80 patients provided the Function Reach (cm). 10, 21 Homogeneity was detected in the incorporated studies [P = 0.54, I2 = 0%]; then, a fixed-effect model of analysis was performed to calculate the mean effect size. Physical exercise can appropriately and significantly enhance the Function Reach (cm) [MD = 4.25, 95%CI (3.52, 4.98), P<0.00001] (Fig. 6).
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Fig. 6. Meta-analysis of Function Reach (cm) in the physical activity and control groups.
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3.3.5. Meta-analysis of the Functional Independence Measure (FIM) The functional independence measure (FIM) scale assesses physical and cognitive disability. Two of 14 trials, including 326 patients, were enrolled in the meta-analysis of the Functional Independence Measure (FIM). 11, 17 Heterogeneity was determined in the eligible studies [P<0.00001, I2 = 99%]. We chose a random-effect model to summarize the mean effect size. Pooled results revealed that physical activity cannot obviously improve the FIM [MD = 12.93, 95%CI (-9.8, 35.67), P=0.26] (Fig. 7).
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Fig. 7. Meta-analysis of Functional Independence Measure (FIM) on physical activity and control groups.
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Meta-analysis of Cadence (steps/min) One hundred and eighty-three dementia patients were involved in two trials and had been enrolled in the meta-analysis on the Cadence (steps/min). 14, 20 There was homogeneity in the two studies [P = 0.69, I2 = 0%]. Therefore, a fixed-effect model of analysis was used. The pooled result showed that physical exercise can significantly improve the Cadence [MD = 12.71, 95%CI (6.92, 18.51), P<0.0001] (Fig. 8).
Fig. 8. Meta-analysis of Cadence (steps/min) in the physical activity and control groups.
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3.3.6. Meta-analysis of the walking speed Two hundred and twenty-three dementia patients were involved in three trials; they were enrolled in the meta-analysis on the Walking speed. 14, 20-21 Heterogeneity was checked in eligible studies [P<0.00001, I2 = 99%]. We chose a random-effect model to summarize the mean effect size. The pooled result revealed that physical activity cannot adequately improve the Walking speed [MD = 13.21, 95%CI (-8.01, 34.43), P=0.22] (Fig. 9).
Fig. 9. Meta-analysis of walking speed in the physical activity and control groups.
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3.3.7. Meta-analysis of the Barthel Index (BI) BI is a scale used to measure performance in the activities of daily living (ADL). Two of 14 trials, involving 356 patients, which were enrolled in the meta-analysis reported the Barthel Index (BI). 17, 18 We identified homogeneity in the three studies that were assessed [P = 0.78, I2 =0%]. Therefore, a fixed-effect model of analysis was chosen to pool the mean effect size. Pooled results revealed that physical activity cannot appropriately improve the Barthel Index [MD = 0.67, 95%CI (-0.01, 1.35), P=0.05] (Fig. 10).
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Fig. 10. Meta-analysis of the Barthel Index on the physical activity and control groups.
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3.3.8. Meta-analysis of the Berg Balance Scale (BBS) The berg balance scale is a scale for measuring balance among older people with balance function impairment. Two trials, including 356 patients, provided the Berg Balance Scale (BBS). 17, 18 Homogeneity was detected in the incorporated studies [P = 0.32, I2 = 0%]; then, a fixed-effect model of analysis was performed to calculate the mean effect size. Physical exercise can significantly enhance the Berg Balance Scale (BBS) scores [MD = 3.62, 95%CI (1.51, 5.73), P=0.0008] (Fig. 11).
Fig. 11. Meta-analysis of the Berg Balance Scale in the physical activity and control groups. 3.3.9. Meta-analysis of the step length (cm) One hundred and sixty-two dementia patients in two trials identified the step length (cm). 14, 21 There was heterogeneity between the two studies [P = 0.16, I2 = 50%]. Therefore, a random effects model of analysis was used. The pooled result showed physical exercise I cannot improve the step length (cm), [MD = 3.85, 95%CI (-0.14, 7.85), P=0.06] (Fig. 12).
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Fig. 12. Meta-analysis of the step length (cm) in the physical activity and control groups.
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3.3.10. Meta-analysis of Cornell depression in the dementia scale One hundred and sixty-two dementia patients from two trials had Cornell depression according to the dementia scale. 15, 18 There was homogeneity in the two studies [P = 0.25, I2 = 24%]. Therefore, a fixed-effect model of analysis was used. Pooled results showed physical exercise cannot improve the Cornell depression in the dementia scale [MD = -0.40, 95%CI (-1.34, 0.53), P=0.40] (Fig. 13).
Fig. 13. Meta-analysis of Cornell depression in the dementia scale for the physical activity and control groups.
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3.4. Qualitative analysis Outcomes reported in one RCT cannot be pooled for comparative analysis. These outcomes included executive function and language ability, the waist/hip ratio, symbol digit modalities test, and move. Although these outcomes cannot be pooled, further studies should explore the potential of these outcomes for dementia patients. 3.5. Publication bias The funnel plot cannot be performed because all outcomes have few included RCTs. 4. Discussion 4.1. Reporting quality The evaluation index included randomization sequence generation, allocation concealment, blinding of participants and study personnel, blinding of outcome assessors, incomplete outcome data, selective reporting and other biases. In terms of the domain of blinding of participants and personnel, 10 included studies were judged
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with an unclear risk of bias and one had high risk. In blinding of the outcome assessment, three studies evaluated an unclear risk of bias, which may result from an inappropriate design for blinding, lack of obvious information on blinding of the outcome assessment in these studies, and evaluation bias. For association concealment, 9 studies were considered to have an unclear risk of bias, and specific explanations for this domain were not found. Because all outcomes were objective, they cannot influence the outcomes related to implementation of blinding for personnel. Overrated intervention effects may result from insufficient allocation concealment. Hence, we should carefully evaluate the reliability of pooled results. To draw a more reliable conclusion, we hope that researchers will emphasize blinding, allocation concealment and complete outcome data in further studies. Among 14 studies included in this research, only two studies were assessed as Grade A, and one study was a low level RCT. Low-quality studies have greater bias in quality control and will affect the results of this study to some extent. 4.2. Necessities Dementia is a disease that gradually develops and an appropriate exercise program can improve the condition of dementia patients. Exercise may improve the patient quality of life and delay dementia progression. The approach for improving safe, effective exercise methods for dementia patients is an important target for health care workers. 23-26 This meta-analysis showed that physical activity can effectively improve the condition of Time up and go (seconds), NPI-caregiver total score, Function Reach (cm), Cadence, steps/min and Berg Balance Scale. The successful exploration of physical activity and its operation process reflect the limitations of traditional care for dementia patients. We hope that clinical staff members can improve and update their old care manners and then use the direction of evidence-based nursing theory. Published studies have suggested that physical activity programs affect dementia patients and have many other advantages. 4.3. Limitations 4.3.1. Limitations to this meta-analysis This study only searched the PubMed, Web of Science, EMbase, CNKI, WanFang and VIP databases without including SpringerLink, Sciencedirect, Chinese Biomedical Literature Database (CBM) and other databases. As a result, there is a risk of incomplete study retrieval. In addition, this study only included English and Chinese studies because of language limitations, which may result in selection bias and affect the credibility of the pooled results in this study. 4.3.2. Limitations for included literature Physical activity is beneficial for dementia patients, but there remain some questions for clinical promotion. The positive function of physical exercise has achieved consensus, but the application of the form and intensity of it does not yet include unified regulations. Physical activity for those patients should be more standardized and systematic. As a result, more studies need to explore a standard operational approach. We hope researchers will perform more studies to provide more standardized, scientific, rationalized approaches for clinical use.
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In conclusion, physical activity can effectively improve the condition of dementia patients in the Time up and go (seconds), NPI-caregiver total score, Function Reach (cm), Cadence, steps/min and Berg Balance Scale tasks, making physical activity worthwhile for broad use in hospitals. Conflicts of interest
All of the contributing authors declare that they have no conflicts of interest.
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S2095-7718(16)30094-9
DOI:
10.1016/j.cnre.2016.11.006
Reference:
CNR 72
To appear in:
Chinese Nursing Research
Received Date: 1 August 2016 Revised Date:
23 August 2016
Accepted Date: 9 September 2016
Please cite this article as: Zeng Z, Deng YH, Shuai T, Zhang H, Wang Y, Song GM, Effect of physical activity training on dementia patients: A systematic review with a meta-analysis, Chinese Nursing Research (2016), doi: 10.1016/j.cnre.2016.11.006. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT *Corresponding author. E-mail address: [email protected] (G. -M. Song). Peer review under the responsibility of Shanxi Medical Periodical Press.
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DOI: © 2016 Shanxi Medical Periodical Press. Publishing services by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). Cited information: Zeng Z, Deng YH, Shuai T, Zhang H, Wang Y, Song GM. Effect of physical activity training on dementia patients: a systematic review with a meta-analysis. Chin Nurs Res. 2016; 4: xx-xx.
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Original article Effect of physical activity training on dementia patients: a systematic review with a meta-analysis Zi Zeng a, Yong-Hong Deng a, Ting Shuai a, Hui Zhang a, Yan Wang b, Guo-Min Song c, * a
Graduate College, Tianjin University of Traditional Chinese Medicine, Tianjin 300193, China. b School of Nursing, Tianjin University of Traditional Chinese Medicine, Tianjin 300193, China. c Department of Nursing, Tianjin Hospital, Tianjin 300211, China.
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ARTI C LE I N FO Article history: Received 1 August 2016 Received in revised form 23 August 2016 Accepted 9 September 2016 Published 20 December 2016
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Keywords: Dementia Physical activity Training Meta-analysis Systematic review
ABSTRACT Background: Activity in a favorable environment excites the brain on a bodily and cognitive level and is beneficial for brain plasticity in dementia patients. Although dementia is an incurable disease, its progression can be slowed with exercise and some patient functionality may be improved through physical exercise. The objective of this meta-analysis was to assess the effect of physical exercise on patients with dementia.
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Methods: The Pubmed, EMbase, Web of Science, Cochrane Library, China National Knowledge Infrastructure (CNKI), VIP and Wan Fang databases were searched for randomized controlled trials (RCTs) through July 2016. References of eligible citations were also searched by hand. Articles were screened and data were extracted. The methodological quality was independently assessed by two reviewers. Then, a meta-analysis was performed by RevMan 5.3. Results: A total of 14 RCTs, involving 1546 participants, were included. The pooled results suggested that physical exercise effectively improved the Time up and go (seconds) [(MD = -2.87, 95%CI (-3.25, -2.5)], Function Reach (cm) [(MD = 4.25, 95%CI (3.52, 4.98)], Cadence, steps/min [(MD = 12.71, 95%CI (6.92, 18.51)], NPI-caregiver total score [(MD = 2.33, 95%CI (-3.65, -1.01)] and Berg Balance Scale [(MD = 3.62, 95%CI (1.51, 5.73)]. Conclusions: Physical activity training effectively improved the condition of dementia patients. Physical activity training effectively improved the condition of Time up and go (seconds), NPI-caregiver total score, Function Reach (cm), Cadence, steps/min and Berg Balance Scale. Hence, physical activity training offers many advantages for dementia patients, including improving their balance ability, athletic ability and relieve caregivers’ burden. © 2016 Shanxi Medical Periodical Press. Publishing services by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
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1. Introduction
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Dementia is a disease of mental deterioration in the setting of organic or functional problems, including Alzheimer’s disease, vascular dementia and other causes. Dementia patients have many different signs and symptoms, and medical workers should know more about these, which facilitates caring for them. 1 Physical activity involves performing various movements that are led by a professional and should assure patients’ safe, each training should take approximately 30 minutes. Physical exercise is a useful method for improving the condition of dementia patients. Physical exercise interventions help older individuals with dementia to improve their health and well-being. 2 Physical activity programs can help relieve or delay declines in activities of daily living (ADL) functioning for dementia patients who have mild to moderate conditions. 3 Physical activity has also been shown to help with cognitive improvement and overall functioning of the brain and its structures. One review indicated that physical activity can help improve balance, motor sequences, stride length and performance of activities of daily living, which are severely affected by Alzheimer’s disease. 4 Hence, it is imperative to identify the effect of physical activity on patients with dementia. Published studies have suggested that early physical exercise can improve the function of dementia patients. However, the conclusion remains equivocal and there are some drawbacks as a result of the variations in results across studies, such as the small sample size, which can lead to relatively low power regarding the effects of
ACCEPTED MANUSCRIPT physical activity for dementia patients. Lack of power may contribute to false-negative results. It is important that many RCTs have been completed on this topic; as a result, we undertook a meta-analysis to further evaluate the potential of physical exercise on the function of dementia patients. 2. Methods
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The Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) statement 5 and Cochrane Handbook for Systematic Reviews of Interventions are adopted as guidelines for performing this meta-analysis and systematic review. 6 Because all pooled analyses are originated from published studies, ethical approval and patient consent are not required. 2.1. Literature search We searched 6 electronic databases, including PubMed, EMbase, Web of Science, CNKI (China National Knowledge Infrastructure), Wan Fang and VIP, using combinations of Mesh and entry terms with words like ‘Dementia’, ‘Dementias’, ‘Amentia’, ‘Amentias’, ‘Senile Paranoid Dementia’, ‘Dementias, Senile Paranoid’, ‘Paranoid Dementia, Senile’, ‘Paranoid Dementias, Senile’, ‘Senile Paranoid Dementias’, ‘Familial Dementia’, ‘Dementia, Familial’, ‘Dementias, Familial’, ‘Familial Dementias’, exercise and random*. This search strategy can improve the effectiveness of the literature search. The references of included articles were manually searched to identify any new relevant studies. 2.2. Selection criteria According to the population, intervention, comparison, outcomes and study design in our selection criteria, we set the following as inclusion criteria: ① Population (P): all the patients who were diagnosed with dementia (including Alzheimer’s disease, vascular dementia and other types of dementia), by diagnostic criteria that were included in the article. ② Interventions (I): physical exercises. ③ Comparisons (C): comparing the efficacy of physical exercises program versus intervention or routine alone. ④ Outcomes (O): outcomes cannot be decided before including all necessary literature and read full-text. ⑤ Study design (S): RCTs with appropriate random sequence generation. Additionally, we only included methodologically sound articles if there are duplicates. 2.3. Literature screening and data extraction Searches were conducted and data were extracted by two independent investigators. Each trial was evaluated for the author, published year, number of participants, allocation method, blinding method, age of included patients, intervention measures, period of treatments, patient eligibility criteria, and baseline and outcome measures. Any disagreement between investigators on the eligibility of a trial was resolved through discussing or consulting with a third investigator. Initial screening was conducted after finding duplicates. All undetermined articles were screened by full text. 2.4. Assessing the risk of bias Quality assessment of trials included in the study was independently performed
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by two reviewers in accordance with Cochrane Handbook for Systematic Reviews of Interventions version 5.1.0. 7 The evaluation index included randomization sequence generation, allocation concealment, blinding of participants and study personnel, blinding of outcome assessors, incomplete outcome data, selective reporting and other biases. Based on the information extracted from primary studies, each domain was rated as “high risk”, “unclear risk” or “low risk”. Those domains, which are rated as having a high risk of bias, were obviously false. For those rated as having an unclear risk of bias, clear judgment could not be performed from the text. For those with a low risk of bias, the description was more correct for concluding there was a low risk of bias judgment. For example, the domain of randomization sequence generation was rated to have a low risk of bias if the text described the method used to generate the allocation sequence in sufficient detail. Studies with “low risk” in all domains were rated as grade A; one or more domains are were considered “unclear risk” but without “high risk” and were rated as grade B, with one or more terms were “high risk” and were rated as grade C. 2.5. Statistical analysis method All extracted data were entered into RevMan 5.3 (Copenhagen: The Nordic Cochrane Centre, The Cochrane Collaboration, 2013) for statistical analysis. Weighted mean differences (WMDs) or standard mean differences (SMDs) with a 95% confidence interval (CI) for continuous outcomes was selected to estimate the pooled effects size. The outcomes include the MMSE, Time up and go (seconds), NPI-caregiver total score, Function Reach (cm), Functional Independence Measure, Cadence (steps/min), Walking Speed, Barthel Index, Berg Balance Scale, Step length (cm) and Cornell depression in dementia scale. Heterogeneity in the included studies was evaluated using the Chi2 test, corresponding to a P value and I2 statistic. If I2 was ≥ 50%, the eligible studies were considered to be heterogeneous and a random effects model based on the Mantel-Haenszel (MH) or inverse variance (IV) statistical approach. If I2 was < 50%, the studies were considered to be homogeneous and a fixed-effect model was selected. Subgroup analysis was performed if there were any detectable heterogeneity resources present. Change data were selected to calculate the summary results according to the baseline and end-point data. (Calculation formula: S2effect 2 2 size=S baseline+S end-point-2*R*Sbaseline*Send-point; Meffect size=|Mbaseline-Mend-point|; R: 0.4 or 0.5). 8 Sensitivity analyses were performed to confirm the robustness of pooled results according to the change combination model. 3. Results
3.1. Study selection and trial characteristics A total of 958 trials were included in the initial literature retrieval. Then, 0 trials were added to the search result, and 14 trials, 9-22 which included 1546 patients, remained according to the inclusion and exclusion criteria with quantitative or qualitative analysis. The flow diagram of literature retrieval and selection is given in Fig. 1.
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770 of records after duplicates removed
749 of records excluded
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770 of records screened
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0 of additional records identified through other sources
958 of records identified through database searching
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14 of full-text articles assessed for eligibility
7 of full-text articles excluded 2 cannot get the full-text 3 inappropriate with included criteria 2 the same RCT with included ones
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14 of studies included in qualitative synthesis
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10 of studies included in quantitative synthesis (meta-analysis)
Fig. 1. Flow chart of literature retrieval and selection.
3.2. Assessment of risk of bias Two RCTs were Grade A, 10 RCTs were Grade B and 2 RCTs were Grade C. Most have problems with blinding. The methodological quality assessments of the included trials were revealed (Fig. 2).
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B Fig. 2. Percentage of the risk of bias: authors’ judgements regarding the risk of bias with respect to various parameters among all included studies; B. Risk of bias summary: authors’ judgements regarding the risk of bias with respect to various parameters for individual studies.
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3.3. Qualitative analysis 3.3.1. Meta-analysis on MMSE The MMSE, mini-mental state examination, which is a scale for testing cognitive impairment was evaluated. Four trials involving 437 participants reported the MMSE. 9-10, 13, 18
Heterogeneity was identified across the included studies [P＜0.0001, I2 =
88%]. A random-effect model was selected to summarize the mean effect size, which was not detected because the resources caused heterogeneity. This model indicates that all participants from the included trials were sampled from different populations. Pooled results suggested that physical exercise had no obvious effect on the MMSE (mini-mental state examination) [MD = 0.77, 95%CI (-0.84, 2.39), P=0.35] (Fig. 3).
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Fig. 3. Meta-analysis of the MMSE on physical activity and control groups.
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3.3.2. Meta-analysis on Time up and go (seconds) The time up and go test is a simple test used to evaluate a person’s mobility ability that requires both dynamic and static balance. Three trials, including 206 participants, were enrolled in the meta-analysis calculating the Time up and go (seconds). 10, 14, 21 We identified homogeneity in the three assessed studies [P = 0.34, I2 = 8%]. Therefore, a fixed-effect model of analysis was performed to calculate the mean effect size. This model indicates that all participants from the included trials were sampled from the same population. Pooled results indicated that the Time up and go (seconds) can be shortened by physical activity, and there was a significant difference [MD = -2.87, 95%CI (-3.25, -2.5), P<0.00001] (Fig. 4). As a result, physical activity can affect the Time up and go task in dementia patients and is worth clinical use.
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Fig. 4. Meta-analysis of Time up and go (seconds) on physical activity and control groups. 3.3.3. Meta-analysis on the NPI-caregiver total score The NPI-caregiver total score is the neuropsychiatric inventory for caregivers. Three hundred and ninety-seven dementia patients were involved in three trials, which were enrolled in the meta-analysis as identified by the NPI-caregiver total score. 9, 13, 18 There was homogeneity in the three studies [P = 0.25, I2 = 28%]. Therefore, a fixed-effect model of analysis was used. Pooled result showed physical exercise can greatly decrease the NPI-caregiver total score, and there was a statistically significant difference [MD =2.33, 95%CI (-3.65, -1.01), P=0.0005] (Fig. 5). As a result, physical activity has a positive effect on the NPI-caregiver total score for dementia patients.
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Fig. 5. Meta-analysis of the NPI-caregiver total score on physical activity and control groups.
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3.3.4. Meta-analysis on the Function Reach (cm) The function reach test can only be tested when the patient is standing, which is a new clinical measure of balance. Two trials of 80 patients provided the Function Reach (cm). 10, 21 Homogeneity was detected in the incorporated studies [P = 0.54, I2 = 0%]; then, a fixed-effect model of analysis was performed to calculate the mean effect size. Physical exercise can appropriately and significantly enhance the Function Reach (cm) [MD = 4.25, 95%CI (3.52, 4.98), P<0.00001] (Fig. 6).
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Fig. 6. Meta-analysis of Function Reach (cm) in the physical activity and control groups.
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3.3.5. Meta-analysis of the Functional Independence Measure (FIM) The functional independence measure (FIM) scale assesses physical and cognitive disability. Two of 14 trials, including 326 patients, were enrolled in the meta-analysis of the Functional Independence Measure (FIM). 11, 17 Heterogeneity was determined in the eligible studies [P<0.00001, I2 = 99%]. We chose a random-effect model to summarize the mean effect size. Pooled results revealed that physical activity cannot obviously improve the FIM [MD = 12.93, 95%CI (-9.8, 35.67), P=0.26] (Fig. 7).
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Fig. 7. Meta-analysis of Functional Independence Measure (FIM) on physical activity and control groups.
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Meta-analysis of Cadence (steps/min) One hundred and eighty-three dementia patients were involved in two trials and had been enrolled in the meta-analysis on the Cadence (steps/min). 14, 20 There was homogeneity in the two studies [P = 0.69, I2 = 0%]. Therefore, a fixed-effect model of analysis was used. The pooled result showed that physical exercise can significantly improve the Cadence [MD = 12.71, 95%CI (6.92, 18.51), P<0.0001] (Fig. 8).
Fig. 8. Meta-analysis of Cadence (steps/min) in the physical activity and control groups.
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3.3.6. Meta-analysis of the walking speed Two hundred and twenty-three dementia patients were involved in three trials; they were enrolled in the meta-analysis on the Walking speed. 14, 20-21 Heterogeneity was checked in eligible studies [P<0.00001, I2 = 99%]. We chose a random-effect model to summarize the mean effect size. The pooled result revealed that physical activity cannot adequately improve the Walking speed [MD = 13.21, 95%CI (-8.01, 34.43), P=0.22] (Fig. 9).
Fig. 9. Meta-analysis of walking speed in the physical activity and control groups.
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3.3.7. Meta-analysis of the Barthel Index (BI) BI is a scale used to measure performance in the activities of daily living (ADL). Two of 14 trials, involving 356 patients, which were enrolled in the meta-analysis reported the Barthel Index (BI). 17, 18 We identified homogeneity in the three studies that were assessed [P = 0.78, I2 =0%]. Therefore, a fixed-effect model of analysis was chosen to pool the mean effect size. Pooled results revealed that physical activity cannot appropriately improve the Barthel Index [MD = 0.67, 95%CI (-0.01, 1.35), P=0.05] (Fig. 10).
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Fig. 10. Meta-analysis of the Barthel Index on the physical activity and control groups.
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3.3.8. Meta-analysis of the Berg Balance Scale (BBS) The berg balance scale is a scale for measuring balance among older people with balance function impairment. Two trials, including 356 patients, provided the Berg Balance Scale (BBS). 17, 18 Homogeneity was detected in the incorporated studies [P = 0.32, I2 = 0%]; then, a fixed-effect model of analysis was performed to calculate the mean effect size. Physical exercise can significantly enhance the Berg Balance Scale (BBS) scores [MD = 3.62, 95%CI (1.51, 5.73), P=0.0008] (Fig. 11).
Fig. 11. Meta-analysis of the Berg Balance Scale in the physical activity and control groups. 3.3.9. Meta-analysis of the step length (cm) One hundred and sixty-two dementia patients in two trials identified the step length (cm). 14, 21 There was heterogeneity between the two studies [P = 0.16, I2 = 50%]. Therefore, a random effects model of analysis was used. The pooled result showed physical exercise I cannot improve the step length (cm), [MD = 3.85, 95%CI (-0.14, 7.85), P=0.06] (Fig. 12).
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Fig. 12. Meta-analysis of the step length (cm) in the physical activity and control groups.
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3.3.10. Meta-analysis of Cornell depression in the dementia scale One hundred and sixty-two dementia patients from two trials had Cornell depression according to the dementia scale. 15, 18 There was homogeneity in the two studies [P = 0.25, I2 = 24%]. Therefore, a fixed-effect model of analysis was used. Pooled results showed physical exercise cannot improve the Cornell depression in the dementia scale [MD = -0.40, 95%CI (-1.34, 0.53), P=0.40] (Fig. 13).
Fig. 13. Meta-analysis of Cornell depression in the dementia scale for the physical activity and control groups.
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3.4. Qualitative analysis Outcomes reported in one RCT cannot be pooled for comparative analysis. These outcomes included executive function and language ability, the waist/hip ratio, symbol digit modalities test, and move. Although these outcomes cannot be pooled, further studies should explore the potential of these outcomes for dementia patients. 3.5. Publication bias The funnel plot cannot be performed because all outcomes have few included RCTs. 4. Discussion 4.1. Reporting quality The evaluation index included randomization sequence generation, allocation concealment, blinding of participants and study personnel, blinding of outcome assessors, incomplete outcome data, selective reporting and other biases. In terms of the domain of blinding of participants and personnel, 10 included studies were judged
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with an unclear risk of bias and one had high risk. In blinding of the outcome assessment, three studies evaluated an unclear risk of bias, which may result from an inappropriate design for blinding, lack of obvious information on blinding of the outcome assessment in these studies, and evaluation bias. For association concealment, 9 studies were considered to have an unclear risk of bias, and specific explanations for this domain were not found. Because all outcomes were objective, they cannot influence the outcomes related to implementation of blinding for personnel. Overrated intervention effects may result from insufficient allocation concealment. Hence, we should carefully evaluate the reliability of pooled results. To draw a more reliable conclusion, we hope that researchers will emphasize blinding, allocation concealment and complete outcome data in further studies. Among 14 studies included in this research, only two studies were assessed as Grade A, and one study was a low level RCT. Low-quality studies have greater bias in quality control and will affect the results of this study to some extent. 4.2. Necessities Dementia is a disease that gradually develops and an appropriate exercise program can improve the condition of dementia patients. Exercise may improve the patient quality of life and delay dementia progression. The approach for improving safe, effective exercise methods for dementia patients is an important target for health care workers. 23-26 This meta-analysis showed that physical activity can effectively improve the condition of Time up and go (seconds), NPI-caregiver total score, Function Reach (cm), Cadence, steps/min and Berg Balance Scale. The successful exploration of physical activity and its operation process reflect the limitations of traditional care for dementia patients. We hope that clinical staff members can improve and update their old care manners and then use the direction of evidence-based nursing theory. Published studies have suggested that physical activity programs affect dementia patients and have many other advantages. 4.3. Limitations 4.3.1. Limitations to this meta-analysis This study only searched the PubMed, Web of Science, EMbase, CNKI, WanFang and VIP databases without including SpringerLink, Sciencedirect, Chinese Biomedical Literature Database (CBM) and other databases. As a result, there is a risk of incomplete study retrieval. In addition, this study only included English and Chinese studies because of language limitations, which may result in selection bias and affect the credibility of the pooled results in this study. 4.3.2. Limitations for included literature Physical activity is beneficial for dementia patients, but there remain some questions for clinical promotion. The positive function of physical exercise has achieved consensus, but the application of the form and intensity of it does not yet include unified regulations. Physical activity for those patients should be more standardized and systematic. As a result, more studies need to explore a standard operational approach. We hope researchers will perform more studies to provide more standardized, scientific, rationalized approaches for clinical use.
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In conclusion, physical activity can effectively improve the condition of dementia patients in the Time up and go (seconds), NPI-caregiver total score, Function Reach (cm), Cadence, steps/min and Berg Balance Scale tasks, making physical activity worthwhile for broad use in hospitals. Conflicts of interest
All of the contributing authors declare that they have no conflicts of interest.
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