INTRODUCTION
Elderly people aged 65 years or more accounted for 18.4% of Korea’s population in 2023. It is expected to increase to 20.6% in 2025 in Korea to enter a super-aged society [1]. In the pre-dementia stage, the prevalence of mild cognitive impairment (MCI) has been reported to be 22.4%, with the rate of worsening to dementia being 12~15% per year [2-4]. In particular, the transition rate of Alzheimer’s disease (AD) in MCI has been reported to be 10~40% per year, with 64% of MCI converted to AD at 2 years after MCI [5,6].
MCI is a syndrome that includes various causative diseases and clinical manifestations. It is divided into amnestic MCI and non-amnestic MCI. Amnestic MCI has a high frequency. Clinical diagnosis of amnestic MCI is based on the following: 1) complaint of memory loss (subjective), 2) memory impairment compared to normal same age (objective), 3) memory is impaired, but other areas are normal, 4) activities of daily living (ADLs) are normal, 5) insufficiency in meeting criteria for the diagnosis of dementia. Non-amnestic MCI refers to functional disorders in areas such as directional/visual space, execution, and language other than memory [7-9]. MCI has memory deterioration, meaning that normal cognitive function and ADL are possible [10]. However, early detection and therapeutic intervention are important because MCI is a risk factor for dementia, especially AD.
Treatment of dementia-related diseases can be divided into pharmacological therapy and non-pharmacological therapy. Although pharmacological therapy using brain improvement agents is recommended, reports about their clear therapeutic effects are currently unavailable [11]. Effects of various non-pharmacological intervention methods have been reported [12-15]. Dementia of irreversible brain disease places a considerable burden on individuals and families. It is a national task in an aging society. Active treatment is required at the MCI stage. Thus, applying an effective intervention program of cognitive function is important.
In this context, this study examined and analyzed nonpharmacological intervention studies applied to domestic MCI subjects based on literature review to provide basic data for developing effective programs of therapeutic intervention for MCI and dementia.
METHODS
1. Study Design
This was a literature review study that analyzed characteristics and results of non-pharmacological intervention studies on MCI.
2. Subjects of Study
1) Literature search strategy
This systematic review was conducted following the by 2020 Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRIZMA) statement adopted by the Cochran Collaboration and NECA (National Evidence-Based Health Care Collaborating Agency) [16].
2) Key question
Literature was selected according to PICO (participants, intervention, comparisons, outcomes) form of systematic review.
• Participants: MCI diagnosis, senior aged 65 years or more
• Intervention: (non-pharmacological) programs for MCI
• Comparison: non-intervention, general intervention
• Outcomes: effects of cognitive function
3) Database and search terms
Search was conducted in May 2024 using major web-based domestic academic databases, including KISS (Korean Studies Information Service System), DND (Dementia and Neurocognitive Disorders), KJAN (Journal of Korean Academy of Nursing), and RCPHN (Research in Community and Public Health Nursing). Search year was limited to the last 10 years (2015~2024). Search words were 'mild cognitive impairment' and 'mild cognitive impairment program'.
4) Literature selection process
To increase reliability of the research, two researchers discussed criteria for searching, selecting and excluding papers, reviewed them independently or together, and repeatedly tested them several times.
First, papers were selected or excluded by looking at their titles and abstracts. Selection criterion were: an experimental study with intervention (program) and a diagnosis of MCI. There was no true experimental design. The most suitable, quasi- experiments and single experiment were included. Duplicate papers and papers on non-MCI or those with MCI and a dual diagnosis (dementia, stroke, etc.) were excluded first. Non-experimental studies, literature review (meta-analysis and systematic review), and non-intervention studies were excluded next. By reviewing the full text, papers without having cognitive function as the dependent variable and papers that were inappropriate such as age and protocol were then excluded. A total of 15 papers were finally included in this study. The process of inclusion and exclusion of study subjects is shown in Figure 1.
3. Data Analysis
To meet the research purpose for the 15 papers selected for this study, two researchers (assistant 1) revised and supplemented the mutual review, discussion, analysis, and records for each process. Research characteristics (publishing year, journal name, number of samples, experimental design, type of intervention, and measurement tool) and effect of intervention were analyzed and presented in figures and tables.
RESULTS
1. Selection and Results of This Study
Among domestic DBs, there were a total of 355 documents on ‘mild cognitive impairment’, including 224 documents in KISS, 116 in DND, and 15 in JKAN, JKPMHN, KJAN, or RCPHN. As a result of the search for the last 10 years (2015-2024), there were a total of 277 documents (167 in KISS, 97 in DND, and 13 in KJAN or RCPHN). As a result of searching for ‘mild cognitive impairment programs’ within the last 10 years, a total of 65 were found, including (61 in KISS, 2 in DND, 1 in KJAN, and 1 in RCPHN). The suitability of this study was repeatedly verified. Finally, 15 papers were selected. The procedure for selecting subjects for this study is shown in Figure 1.
2. General Characteristics of Selected Studies
General characteristics of this study are summarized in Table 1. As a result of analyzing general characteristics, the diagnosis was MCI in all 15 (100.0%) papers. As for research design, there was no true experiment. Nine (60.0%) papers had a non-equivalent control group design and six (40.0%) had a one group design. As for the distribution of publication years, there were 4 (26.7%) papers published in 2023, 3 (20.0%) in 2020, 2 (13.3%) each in 2021 and 2015, and 1 each in 2022, 2019, 2018, and 2017. Academic fields of published journals included medical science (n=5, 33.3%), occupational therapy (n=4, 26.8%), nursing (KJAN, RCPHN, n=2, 13.3%), sports science (n=2, 13.3%), and social science (n=2, 13.3%). Intervention program configuration included single program (n=8, 53.3%) and complex program (n=7, 46.7%).
3. Characteristics and Results of MCI Intervention Studies
Characteristics and results of intervention studies are shown in Table 2. As a result of analyzing types and contents of intervention programs, types of single programs included virtual reality (VR)-based immersion P (program) balanced exercise, eye movement exercise, tablet-based cognitive P, good posture walking, virtual reality cognitive rehabilitation P, dual-task virtual reality P, individual board game P, and individual cognitive P (traditional tales and games). Types of complex programs included dual task P (balance exercise and computer training), computer cognitive P and home workbook, cognition-exercise P using step cognitive stimulation P (physical activity and cognition activity), dementia prevention P (DPP), and dualtask P (exercise and cognitive).
Contents of the intervention programs included computer (virtual reality) utilization (n=5), exercise and cognitive combined (step, language and calculation) (n=4), exercise (balance, eye movement, and walking) (n=3), exercise-computer (n=1), board game (n=1), and traditional play (n=1).
After analyzing outcomes after an intervention program in the experimental group, cognitive function was found to be improved significantly in all 15 papers and memory was improved significantly in 5 papers. Among them, intervention programs that showed significant effects of memory were virtual reality-based immersion P, computer and workbook, independent board game P, dual-task VR P, and exercise-cognitive combined dual task P. Other dependent variables that showed significant effects after the intervention program were depression, balance ability, fall, and gait. Programs that showed significant effects were double tasks (balance exercise and computer) in depression, good posture in falls, and cognitive-step exercise in walking.
Tools used to measure cognitive functions included Mini-Mental State Examination (MMSE) (n=4), Montreal Cognitive Assessment-Korean (MoCA-K) (n=5), MMSE+MoCA-K (n=1), Loewenstein Occupational Cognitive Assessment Geriatric (LOTCA-G) (n=4), Short form of Literacy Independence Cognitive Assessment (S-LICA) (n=2), Large Allen Cognitive Level Screen (LACLS) (n=1), and Consortium to Establish a Registry for Alzheimer's Disease Assessment Packet-Korean (CERAD-K) (n=1). Brain measurements used Fullerton Advanced Balance Scale (FAB), Korean-Color Word Stroop Test (K-CWST), Functional Near-Infrared Spectroscopy (f-NIRs), and Electroncephalogram (EEG).
DISCUSSION
Based on results of this study, general characteristics and effects of MCI intervention studies are discussed and research limitations are suggested below.
First, general characteristics and results of MCI intervention studies are presented in Tables 1 and 2. Looking at general characteristics, the diagnosis was MCI in all (100.0%) studies because this study excluded complex diagnosis (those with dementia, stroke, DM, and so on). Thus, it is difficult to interpret whether it is a result of MCI when interventional treatment is performed on a complex diagnosis. For the study design, pure experimental RCT was recommended for systematic consideration. However, most studies performed quasi experiments 9 (60.0%) and included a single experimental group 6 (40.0%). Thus, caution is needed when performing interpretation.
Academic fields of published journals included Medical Science for 5 (33.3%) papers, occupational therapy for 4 (26.8%), nursing for 2 (13.3%), sports science for 2 (13.3%), and social science for 2 (13.3%). Among them, DND was classified as medical while KJAN and RCPHN were classified as Nursing. Since neurocognitive disorders corresponded to DSM (Diagnostic and Statistical Manual of Mental Disorders)-5, mild cognitive impairment has also become an important area in psychiatry. Nevertheless, MCI studies reported in the JKPMHN (Journal of Korean Academy of Psychiatric Mental Health Nursing) were insufficient.
By selecting intervention studies for the last 10 years, this study found trends of VR and computer programs in addition to exercise and cognition. In the past, MCI interventions showed a tendency to recall, and laughter therapy in addition to exercise and cognition [17].
In particular, it was appropriate to select a paper with cognitive function as the dependent variable to determine whether the intervention program had a cognitive function effect. However, it was insufficient to determine whether or not the dementia was transitional because most studies did not have ADL measurements. Several tools were used together to measure cognitive function, including MMSE, MoCA-K, MMSE+MoCA-K, LOTCA-G, S-LICA, LACLS, CERAD-K, FAB, K-CWST, f-NIRs, and EEG.
Intervention types were divided into single and complex programs. Detailed intervention included computer (virtual reality) in 5 studies, exercise and cognitive complex (step, language and calculation),exercise (balance, eye movement, and walking) in 3 studies, exercise-computer, board game, traditional play, etc.
Effects of cognitive function on dual tasks rather than single tasks have been reported [18,19], supporting results of this study. Complex programs of this study included dual task P (balance exercise and computer training), computer cognitive P and home workbook, cognition-exercise P using step cognitive stimulation P (physical activity and cognition activity), dementia prevention P (DPP), and dual-task P (exercise and cognitive). Nevertheless, single programs that showed cognitive improvement in this study were virtual reality-based immersion P, balanced exercise, eye movement exercise, tablet-based cognitive P, good posture walking, VR cognitive rehabilitation P, dual-task VR P, individual board game P, individual cognitive P. Contents of single programs were mainly exercise, computer, and VR programs.
As a result of analyzing effects of intervention programs on the experimental group, cognitive function showed statistically significant improvement in all 15 studies (15 intervention programs). Memory also showed statistically significant improvement in 5 intervention programs, followed by virtual reality-based immersion P, computer and workbook, independent board game P, dual-task VR P, and exercise-cognitive complex dual-task P. In other words, cognitive training and exercise using computers could lead to memory improvement.
Programs that showed significant effects on depression, balance, falls, and walking in MCI subjects included double tasks (balance exercise and computer) showing effects on depression, good posture on falls, and cognitive-step exercise on walking. In other words, exercise and cognitive training could positively affect cognitive function, emotion, and physical balance.
There are pharmacological and non-pharmacological therapies for treating dementia-related diseases. Effects of non-pharmacological therapies on cognitive function have been reported [20-22]. In particular, the intervention with an exercise-cognitive double task has been reported to be able to improve attention and memory, similar to results of an exercise-cognitive, music-dance program in preceding studies [23,24].
To summarize non-pharmacological interventions for MCI, recent research has added exercise, cognitive therapy, and VR and computer activities utilizing the flow of the 4th industry, individual use, and fun of games.
The present study (paper) has some limitations. First, only domestic studies were selected and RCT design or control experiments were insufficient. In addition, diagnosis of amnestic MCI and non-amnestic MCI was not distinguished when constructing the intervention program. Thus, the effectiveness of the program was considered insufficient. Moreover, the effectiveness of the intervention program was not verified through a meta-analysis. Selection and exclusion of papers were intended to consider all systematic review criteria. However, due to a large number of non-open-access papers on academic sites, they were limited to reliable academic sites.
In addition, although non-pharmacological interventions appeared to use a single task or single program, it was difficult to distinguish because contents were complexly mixed. Thus, it was unclear which contents were effective. In this context, the non-pharmacological program for MCI in the future requires detailed diagnosis and intervention development according to symptoms, which is considered a therapeutic evidence. In addition, MCI starts with memory decline. If cognitive decline gradually worsens, it can negatively affect emotions, body, daily life, and quality of life. and be diagnosed with irreversible dementia. Thus, integrated therapeutic intervention is necessary. Based on this, an evidence-based nursing intervention program for MCI and dementia needs to be developed to promote the health of the people.
CONCLUSION
Mild Cognitive Impairment (MCI) is one of the risk factors for transition to dementia. This study reviewed characteristics and results of MCI intervention (non-pharmacological) studies and used them as basic data for effective program development to further contribute to the prevention of MCI and dementia.
For the method, 15 papers were selected by referring to the PRIZMA guideline for systematic review manual (Cochran collaboration and NECA), and the characteristics and results of MCI intervention studies were analyzed. As a result, there were many complex programs and more computer and VR use than before The intervention program of this study (15 papers) had a significant difference in overall cognitive function, but memory verification was only 5 papers.
In the end, considering that the main symptom of MCI is memory loss, the development of memory improvement programs is a priority, and it is suggested to develop therapeutic effective interventions including overseas literature in the future. This study is considered to have contributed to establishing the direction of MCI interventions.
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