The study is designed as a systematic review on nonpharmacological interventions for patients with moderate to severe dementia. This review will be conducted in accordance with the Cochrane Handbook for Systematic Reviews of Interventions. The following databases will be searched: Cochrane CENTRAL, MEDLINE, EMBASE, CINAHL, PsycINFO, KoreaMED, KMbase, and KISS. The primary outcome will include the effect of the interventions on activities of daily living and behavioral and psychological symptoms of dementia. The literature search will be conducted based on search strategies designed for each database. The reviewers will independently assess the identified studies and extract the data. The risk of bias will be assessed and a meta-analysis will be conducted in accordance with the methodology for meta-analysis described in the Cochrane handbook. This systematic review will provide clinicians and policy makers with reliable evidence for developing and implementing nonpharmacological interventions for moderate to severe patients with dementia.
Dementia is a common neuropsychiatric syndrome that is usually chronic or progressive and causes deterioration of various mental functions, including cognitive, emotional, and mental [
Unfortunately, a cure for dementia has not been found. Although pharmacological agents, such as acetylcholinesterase inhibitors and N-methyl-D-aspartate receptor antagonists, are effective for temporary control of the symptoms of cognitive decline and improvement of the activities of daily living (ADL) of patients with Alzheimer’s disease (AD), they cannot restore premorbid levels of function or maintain adequate levels of function in patients in later stages of dementia [
Recent systematic reviews have shown that several NPIVs may improve the cognition, communication, interactions, BPSD, ADL, and/or QoL of PWD [
The principal strength of a systematic review is the capacity to identify salient and critical studies through the unmanageable numbers of existing medical literature using critical exploration, valuation, and synthesis [
This systematic review, which will include a meta-analysis, aims to identify and evaluate the efficacy of NPIVs on the ADL and BPSD of PWMSD. Thus, the proposed systematic review will attempt to answer the following research questions:
1) Which NPIVs improve the ADL and BPSD of PWMSD?
2) What are the effects of NPIVs on the ADL and BPSD of PWMSD?
This systematic review will be conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) Statement [
The systematic review will include studies involving people diagnosed with any type of dementia according to the criteria in the Diagnostic and Statistical Manual of Mental Disorders, Third Edition (DSM-III); Fourth Edition, Text Revision (DSMIV-TR); or Fifth Edition (DSM-5); International Classification of Diseases, Tenth Revision (ICD-10); or other accepted diagnostic criteria.
This systematic review will include PWD in the moderate to severe stages who met one of the following criteria: Clinical Dementia Rating score of 2 or more, Global Deterioration Scale score of 5 or more, Functional Assessment Staging score of 5 or more, Mini-Mental State Examination (MMSE) score of 20 or less, or Revised Hasegawa’s Dementia Scale score of 20 or less.
This systematic review will include studies involving any type of NPIV that were conducted in community settings or institutional settings. NPIVs can be categorized in four broad groups following the practice guideline [
This systematic review will employ ADL and BPSD as the primary outcomes and cognitive function and QoL as the secondary outcomes.
This systematic review will include randomized control trials (RCTs), quasi RCTs, non RCTs, cross-sectional studies, interrupted time series, and before-after studies that used the Study Design Algorithm for Medical Literature on Intervention [
This systematic review will search the following databases and reference lists of the included studies: Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE®, EMBASE®, CINAHL, PsycINFO, KoreaMED, KMbase, and KISS. This systematic review will not limit the geography or time of the study, but only publications written in English or Korean will be included.
One reviewer (R Na) will search the information sources. The search strategy will include the study population and intervention terms suggested by Medical Subject Headings (MeSH®) and Emtree®. The search terms will be adapted for use in other bibliographic databases with database-specific filters when available. Some syntax, including truncation, or Boolean operators, will be amended to the specific databases. A draft EMBASE search strategy is shown in
This systematic review will export the search results to End-Note™ X8.0.1 [Clarivate Analytics (formerly Thomson Reuters), Philadelphia, PA, USA] in which all reference records will be managed.
Two reviewers (R Na and YJ Kim) will independently select studies in the three phases listed below. If any discrepancies occur between the two reviewers, two additional reviewers (KW Kim and K Kim) will amend the decision. This systematic review will create a PRISMA flow diagram of the included and excluded studies.
1) Initial screening: potential papers will be identified for abstract retrieval, and any obviously irrelevant studies will be eliminated by screening their titles.
2) Secondary screening: potential papers will be identified for full text retrieval by screening their abstracts.
3) Tertiary screening: papers that should be included in the current systematic review will be identified by reading the full text, and the reasons for exclusion will be documented.
Two reviewers (R Na and YJ Kim) will collect the data. Eligible data will be independently extracted with a standardized form. Any discrepancies will be resolved by deliberation between R Na and YJ Kim or, if needed, with two other reviewers (KW Kim and K Kim).
Two reviewers (R Na and YJ Kim) will extract the data from the publications with a standardized data extraction form. The extracted data will be summarized as shown in
The primary outcomes of this systematic review will be ADL and BPSD of PWMSD. ADL, which will include Basic and Instrumental ADL [
The other primary outcome, BPSD, represents a heterogeneous group of noncognitive symptoms and behaviors [
The secondary outcomes will include the cognitive function and QoL of PWD. Cognitive function will be measured with standardized assessment tools, such as the Mini-Mental State Examination (MMSE), Severe Impairment Battery, Kingston Dementia Rating Scale, AD Assessment Scale-Cognitive Subscale, Brief Cognitive Screening Battery, Consortium to Establish a Registry for AD Assessment Tool (Korean version), Modified MMSE, and Montreal Cognitive Assessment [
Two reviewers (R Na and YJ Kim) will independently assess the risk of bias (RoB) in each study. All reviewers will discuss the quality of a study if the two reviewers disagree. The RoB of RCTs will be assessed with the RoB scale [
Two reviewers (YJ Kim and R Na) will conduct a meta-analysis of the outcomes with Review Manager if a sufficient number of studies are included. They will employ risk and odds ratios with 95% confidence intervals (CIs) for dichotomous outcomes and weighted mean differences (with 95% CIs) or standardized mean differences (with 95% CIs) for continuous outcomes. For missing data, we will attempt to contact the authors of the study to obtain the relevant information. Intention-to-treat data, if available, will be preferred.
This systematic review will consider the various characteristics of the participants and the study designs when evaluating the heterogeneity of the studies. Heterogeneity will be statistically tested with the chi-squared and I-squared tests [
This systematic review will conduct subgroup analyses of the participants (e.g., dementia subtype, dementia severity, or participant characteristics), interventions (types, providers, or settings), study designs, and follow-up periods if sufficient data are available.
This systematic review will assess publication bias with funnel plots of potential reporting bias if the number of studies in the meta-analysis is over 10.
This systematic review will assess the quality of the evidence for all outcomes with the Grading of Recommendations Assessment, Development and Evaluation (GRADE) [
This systematic review will examine the clinical efficacy of NPIVs on the ADL, BPSD, cognitive function, and QoL of PWMSD. Although the efficacy of NPIVs on PWD may differ according to the severity of dementia, recent reviews on NPIVs for PWD have not separately evaluated NPIVs efficacy on PWMSD or conducted relevant meta-analyses. To maximize the power of systematic reviews, restriction of publication language is not recommended. However, this systematic review will include studies written in English or Korean only for practical reasons, which will be a limitation of this study.
Nonetheless, this systematic review will provide clinicians and policy makers with reliable evidence for developing and implementing NPIVs for PWMSD.
This systematic review is supported by a grant from the National Institute of Dementia of Korea (Grant Number: NIDR-1703-0018), Republic of Korea.
Example of an advanced search strategy-EMBASE
1 | ‘dementia’/exp |
2 | ‘alzheimer disease’/exp |
3 | ‘frontotemporal dementia’/exp |
4 | ‘lewy body’/exp |
5 | ‘multiinfarct dementia’/exp |
6 | ‘normotensive hydrocephalus’/exp |
7 | ‘huntington chorea’/exp |
8 | parkinson AND disease AND dementia |
9 | vascular AND dementia |
10 | alcohol AND related AND dementia |
11 | #1 OR #2 OR #3 OR #4 OR #5 OR #6 OR #7 OR #8 OR #9 OR #10 |
12 | moderate:ab,ti |
13 | severe:ab,ti |
14 | moderate AND to AND severe:ab,ti |
15 | advanced:ab,ti |
16 | profound:ab,ti |
17 | #12 OR #13 OR #14 OR #15 OR #16 |
18 | #11 AND #17 |
19 | ‘therapy’/exp |
20 | ‘cognitive therapy’/exp |
21 | ‘art therapy’/exp |
22 | ‘aromatherapy’/exp |
23 | ‘massage’/exp |
24 | ‘touch’/exp |
25 | ‘animal assisted therapy’/exp |
26 | ‘exercise’/exp |
27 | ‘horticultural therapy’/exp |
28 | ‘virtual reality’/exp |
29 | ‘telerehabilitation’/exp |
30 | (nonpharmacological AND treatment$) OR |
31 | (nondrug AND treatment$) OR (nondrug AND therap$) |
32 | emotion AND oriented AND intervention$:ab,ti |
33 | cognitive AND oriented AND intervention$:ab,ti |
34 | psychotherapy$:ab,ti |
35 | recreation AND therapy$:ab,ti |
36 | validation AND therapy$:ab,ti |
37 | reminiscence AND therapy$:ab,ti |
38 | sensory AND stimulation AND intervention$:ab,ti |
39 | light AND therapy$:ab,ti |
40 | music AND therapy$:ab,ti |
41 | (snoezelen:ab,ti) OR (snoezelen AND multisensory AND stimulation:ab,ti) |
42 | doll AND therapy$:ab,ti |
43 | robot AND therapy$:ab,ti |
44 | multimodal AND therapy$:ab,ti |
45 | occupational AND therapy$:ab,ti |
46 | behavi?r AND therapy$:ab,ti |
47 | computer AND assisted AND therapy$:ab,ti |
48 | reality AND orientation$:ab,ti |
49 | cognitive AND training$:ab,ti |
50 | #19 OR #20 OR #21 OR #22 OR #23 OR #24 OR #25 OR |
51 | #18 AND #50 |
52 | ‘randomized controlled trial’/exp |
53 | ‘multicenter study’/exp |
54 | ‘clinical trial’/exp |
55 | ‘randomization’/exp |
56 | ‘single blind procedure’/exp |
57 | ‘crossover procedure’/exp |
58 | ‘placebo’/exp |
59 | ‘prospective study’/exp |
60 | double AND blind AND procedure |
61 | randomi?ed AND controlled AND trial$ |
62 | rct:ab,ti |
63 | random AND allocation |
64 | randomly AND allocated |
65 | allocated AND randomly |
66 | single AND blind$:ab,ti |
67 | double AND blind$:ab,ti |
68 | cross AND sectional AND study |
69 | before AND after AND study |
70 | #52 OR #53 OR #54 OR #55 OR #56 OR #57 OR #58 OR |
71 | ‘retrospective study’/exp |
72 | ‘cohort’/exp |
73 | ‘letter’/exp |
74 | case AND report |
75 | case AND study |
76 | abstract AND report |
77 | #71 OR #72 OR #73 OR #74 OR #75 OR #76 |
78 | #70 NOT #77 |
79 | #51 AND #78 |
80 | animal |
81 | human |
82 | #80 NOT (#80 AND #81) |
83 | #79 NOT #82 |
Data extraction variables
Content | Data items |
---|---|
Prospective study information | Author(s), Year of publication, Country |
Study design | Trial design |
Number of participants | Number of participants invited, number of participants screened, number of participants eligible, number of participants randomized, reasons for non-eligibility, reasons for drop-out |
Population | Severity of dementia, Type of dementia (e.g. Alzheimer’s disease, vascular dementia, dementia with Lewy bodies, frontotemporal dementia, etc.) Average age, Gender, ethnicity, Diagnostic criteria for dementia (e.g. DSM-III, DSM-IV, DSM-5, ICD-10, etc.), Diagnostic tool for severity of dementia (e.g. CDR, GDS, FAST, MMSE, etc.), Physical health comorbidity, Usage of antidementia drug |
Intervention | Name of treatment group, Type of non-pharmacological intervention, Frequency and duration of intervention, Intervention provider, length of intervention session, Mode of delivery (e.g. individual, group, combination) |
Comparison | Name and type of control group, Frequency and duration of intervention, Intervention provider, length of intervention session, Mode of delivery (e.g. individual, group, combination) |
Outcome | Detail of outcome measure |
Outcome measure | Baseline, Follow-up assessment, Losses to follow-up, Result |
Follow-up | Duration of follow-up, Drop-out rate |
Setting | Community, Institution |
DSM-III: Diagnostic and Statistical Manual of Mental Disorders, Third Edition, DSM-IV-TR: Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision, DSM-5: Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, ICD-10: International Classification of Diseases, Tenth Revision, CDR: Clinical Dementia Rating, GDS: Global Deterioration Scale, FAST: Functional Assessment Staging, MMSE: Mini-Mental State Examination