Interventions for post-stroke apathy and their effects: A scoping review

Abstract

Objective

This scoping review aimed to comprehensively map interventions for post-stroke apathy and their effects.

Data sources

The literature search for this review was performed using PubMed, Cumulative Index to Nursing and Allied Health Literature, and Web of Science, targeting studies published until August 7, 2025.

Review methods

This scoping review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for scoping reviews. The population included patients with post-stroke apathy; the concept focused on post-stroke apathy assessment and interventions and their effects. The context covered both general and community healthcare settings. Controlled vocabulary (e.g., MeSH terms) such as “post-stroke apathy,” “intervention,” and “effect” was used to formulate the search strategy. The eligible studies were independently screened by three reviewers, and final inclusion was determined through discussion.

Results

Of the 565 studies identified, 13 met the inclusion criteria (n = 13). The mapping revealed that pharmacological interventions not only improved and prevented post-stroke apathy symptoms but also alleviated emotional blunting, reduced loss of motivation and interest, and enhanced social behavior and participation. Non-pharmacological interventions were associated with symptom relief and recovery over time. Furthermore, combined pharmacological and non-pharmacological approaches contributed to improvements not only in post-stroke apathy but also in depression, language function, and behavioral aspects.

Conclusion

The findings suggest that appropriate treatment for post-stroke apathy may lead to symptom relief, improvement, and prevention while enhancing language function, behavior, and social participation. Future research should focus on systematic reviews and meta-analyses to establish evidence-based recommendations for post-stroke apathy treatment strategies and their optimal combinations.

Keywords

Post-stroke apathy intervention scoping review

Introduction

Post-stroke apathy, characterized by reduced motivation and diminished emotional expression, is distinct from depression and affects 20%–30% of stroke survivors.^1,2 Its development is attributed to biological factors, such as lesion location and neurotransmitter imbalance,^3,4 and psychological factors, including daily activity limitations and social isolation.⁴ Post-stroke apathy is associated with general cognitive decline, including Mini-Mental State Examination score reduction and memory, attention, and reasoning impairments.^1,2,5,6 It also leads to decreased independence in activities of daily living, functional recovery delays, and increased caregiver burden.^5,7,8 Furthermore, apathy often coexists with depression, with potential bidirectional exacerbation.⁹ Given these challenges, timely assessment and appropriate intervention are essential for supporting affected patients’ rehabilitation and social reintegration.

Both pharmacological and non-pharmacological treatments have been explored for post-stroke apathy. Pharmacological agents, such as selective serotonin reuptake inhibitors and acetylcholinesterase inhibitors, have shown promise in alleviating symptoms and improving functional outcomes.^10,11 Non-pharmacological approaches, including problem-solving therapy and group-based interventions, have also demonstrated potential in reducing apathy and improving long-term engagement.^10,12

While apathy has been extensively studied in the context of neurodegenerative diseases, most systematic reviews have also focused on them.^13–15 In contrast, comprehensive evidence for post-stroke apathy interventions is limited. Previous narrative reviews may have introduced selection bias due to non-systematic study inclusion, and few studies have directly compared pharmacological and non-pharmacological approaches. Therefore, a scoping review is warranted to clarify the state of research and identify evidence gaps in this context.¹⁶ This scoping review was aimed at mapping assessment methods and treatment strategies and their effectiveness in managing post-stroke apathy to inform future research and clinical practice in stroke rehabilitation.

Methods

A scoping review was chosen to comprehensively map the assessment methods and treatment strategies and their effectiveness for post-stroke apathy. Given the condition's multifaceted nature—encompassing biological, psychological, and social factors—various pharmacological and non-pharmacological interventions have been explored. However, their comparative effectiveness remains unclear. Previous reviews have primarily focused on dementia-related apathy or lacked a systematic methodology, leading to a potential selection bias. A scoping review is well-suited for identifying knowledge gaps, summarizing a broad range of evidence, and establishing a framework for future systematic investigations in this emerging research area. This scoping review was performed according to the methodological framework proposed by Arksey and O'Malley and subsequently expanded.^17–19 The protocol adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) Extension for Scoping Reviews checklist.^19,20

Study eligibility and criteria

The patient population included individuals with post-stroke apathy. The Concept was focused on mapping assessments, interventions, and their effects on post-stroke apathy. The Context encompassed both general and community healthcare settings.

The inclusion criteria were as follows: studies with participants exhibiting symptoms of post-stroke apathy; studies explicitly describing the treatment or intervention aimed at alleviating post-stroke apathy, including details on intervention content, frequency, and outcome measures; studies whose design included interventional investigations, such as pre-post studies within a group, quasi-randomized controlled trials, and randomized controlled trials; studies reported as research articles; and studies published in English.

The exclusion criteria were as follows: Studies without participants exhibiting symptoms of post-stroke apathy; studies focused on apathy symptoms associated with dementia, Parkinsonian syndromes, and post-stroke depression; studies whose design included descriptive studies (e.g., theoretical studies and qualitative studies) or reviews (e.g., integrative reviews, systematic reviews, and scoping reviews); studies that were published as dissertations, protocol papers, conference proceedings, reviews, or letters; and studies published in languages other than English.

This scoping review prioritized studies that facilitated statistical comparison and the collection of comparable quantitative data. Qualitative studies, while valuable for understanding practical challenges and success factors in supporting patients with post-stroke apathy, were excluded because their outcome measures differ from those of quantitative studies, limiting the scope for statistical comparison. Furthermore, studies involving participants with co-occurring post-stroke depression were excluded, as it would be difficult to determine whether the observed effects were attributable to depression or apathy.

Search selection and data extraction

A literature search was conducted using PubMed, Cumulative Index to Nursing and Allied Health Literature (CINAHL), and Web of Science, targeting articles published up to August 7, 2025, to comprehensively examine interventions for post-stroke apathy and their effects. PubMed covers key studies in the fields of medicine and neuroscience, providing abundant information on the pathology of apathy and pharmacological interventions. CINAHL specializes in nursing and rehabilitation research, enabling effective searches for studies on non-pharmacological interventions. Web of Science allows cross-disciplinary searches and is an excellent resource for identifying high-impact studies and analyzing citation relationships. A preliminary search in PubMed was performed based on the Population, Concept, and Context framework, by using synonyms for terms such as “apathy,” “post-stroke,” and “intervention” to generate keywords. A search strategy incorporating both controlled vocabulary, including MeSH terms, and free-text terms was developed for PubMed and adapted for other databases (Supplemental material 1). Additionally, reference lists of relevant studies were manually screened to ensure a comprehensive review from medical, rehabilitation, and interdisciplinary perspectives.

All retrieved studies were imported into Rayyan software, and duplicates were removed. In the first screening phase, two independent reviewers (S.H. and K.I.) assessed the eligibility of the studies based on their titles and abstracts. A third reviewer (T.K.) resolved any discrepancies and made the final decision regarding inclusion or exclusion. In the second screening phase, the full texts of the selected studies were obtained and reviewed by two reviewers (S.H. and K.I.) according to the inclusion and exclusion criteria. Disagreements were resolved through team discussions or consultation with a third reviewer (T.K.). The selection process is presented in the PRISMA flow diagram (Figure 1).

Data were independently extracted by three reviewers (S.H., K.I., and T.K.) using a pre-designed tabular form, which was developed through team discussions based on the review questions. The extracted data included information about authors, study objectives, study design, participants, outcomes, and key findings. Since the main treatment effects for post-stroke apathy were diverse, data were extracted in a descriptive and deductive manner and mapped accordingly. Any discrepancies were resolved through discussion among the three reviewers (S.H., K.I., and T.K.).

Results

Study selection

The study selection process is illustrated in Figure 1. A database search identified 565 articles, of which 340 remained after the removal of duplicates. In the initial screening phase based on titles and abstracts, the inter-reviewer agreement (%) between S.H. and K.I. was 85.8%. Following evaluation by a third reviewer (T.K.), 23 articles proceeded to the secondary screening phase. After full-text review, the inter-reviewer agreement (%) between S.H. and K.I. was 87.0%. Subsequently, following evaluation by a third reviewer (T.K.), 13 studies met the eligibility criteria and were included in this scoping review.

The characteristics of the included studies

Table 1 and Supplemental Material 2 summarizes the characteristics of the included investigations in this scoping review, of which four were randomized controlled trials (nos. 1, 2, 3, and 4),^10,21–23 two were secondary analyses of randomized controlled trials (nos. 5 and 6),^4,24 two were quasi-experimental design study (no. 7 and 8),^25,26 one was a single-group pre-post comparison study (no. 9),²⁷ and four were case reports (nos. 10, 11, 12, and 13).^28–31 The sample sizes ranged from 13 to 154 for randomized controlled trials (nos. 1, 2, 3, and 4),^21–23,30 from 30 to 1369 for the secondary analyses of randomized controlled trials (nos. 5 and 6),^4,24 and from 13 to 55 for the quasi-experimental design study (no. 7, 8).^25,26 The single-group pre-post comparison study had a sample size of 10 (no. 9).²⁷

Table 1.

Characteristics of studies examining the impact of interventions for post-stroke apathy.

ID	Author	Research design	Sample size (n)	Intervention	Main outcome
1	Starkstein et al. (2016)²³	RCT	N = 20 (6 intervention, 7 placebo)	Nefiracetam (900 mg/day in divided doses)	Apathy scale
2	Chen et al. (2018)²¹	RCT	N = 132 (82 intervention, 50 control)	Motor Relearning Program	Apathy Evaluation Scale-Clinical
3	Mikami et al. (2013)¹⁰	RCT	N = 154 (51 intervention, 56 intervention, 47 placebo)	Escitalopram (10 mg/day for ≤ 65 years; 5 mg/day for > 65 years) Problem Solving Therapy	Apathy Scale (clinician version)
4	Robinson et al. (2009)²²	RCT	N = 70 (22 intervention, 26 intervention, 22 placebo)	Nefiracetam (600 mg/day or 900 mg/day, 150 mg capsules twice daily)	Apathy Scale (clinician version)
5	Tay et al. (2023)⁴	Secondary analysis of RCT	N = 1369 (68 intervention, 688 placebo)	Fluoxetine 20 mg once daily	Montgomery–Åsberg Depression Rating Scale
6	Skidmore et al. (2015)²⁴	Secondary analysis of RCT	N = 30 (15 intervention, 15 control)	Strategy training	Apathy Evaluation Scale
7	Sasaki et al. (2017)²⁶	Quasi-experimental designs	N = 13 (7 intervention, 6 sham)	rTMS was administered as five consecutive daily sessions in an outpatient setting	Apathy Scale Quick Inventory of Depressive Symptomatology
8	Maeda et al. (2025)²⁵	Quasi-experimental designs	N = 55 (18 with apathy, 37 without apathy)	Gait training	Apathy Scale
9	Berthier et al. (2022)²⁷	Pre-post comparison	N = 10	Donepezil (5 mg, escalated to 10 mg) and intensive language-action therapy (30 h).	Western Aphasia Battery-Aphasia Quotient Stroke Aphasia Depression Questionnaire-21
10	Autret et al. (2013)²⁸	Case report	N = 1	Zolpidem (a single dose of 10 mg)	Apathy Inventory
11	Kohno et al. (2010)²⁹	Case report	N = 1	Ropinirole (orally from 0.75 mg daily)	Neuropsychiatric Inventory
12	Watanabe et al. (1995)³¹	Case report	N = 1	Methylphenidate 5 mg bid	Behavioral observation Single-photon emission computed tomography Stroop task with positron emission tomography
13	Mitaki et al. (2016)³⁰	Case report	N = 1	A single TMS session involving 10 trains, each 10 s long at 5 Hz, with five trains applied to each hemisphere.	Japanese version of the Apathy Scale Resting state functional MRI

RCT: randomized controlled study; MRI: magnetic resonance imaging.

Treatment methods and outcomes

Among these investigations, seven and five reported pharmacological and non-pharmacological treatments, respectively. Regarding the pharmacological treatment, nefiracetam was administered at 900 mg/day (divided doses) or as 150 mg capsules twice daily for 12 weeks (nos. 1 and 4).^22,23 Escitalopram was administered in the morning at 10 and 5 mg/day, respectively, for individuals younger and older than 65 years. Additionally, problem-solving therapy was conducted six times in weeks 1, 2, 3, 4, 6, and 10 and again in months 4, 5, 6, 8, 10, and 12 (no. 3).³⁰ Fluoxetine was administered at a dose of 20 mg/day for 6 months (no. 5).⁴ Donepezil was administered at a dose of 5 mg/day for 4 weeks, followed by 10 mg/day for another 4 weeks, and intensive language action therapy was administered for 2 weeks (no. 9).²⁷ Zolpidem was administered as a single 10 mg dose on days 2, 4, and 5 during a 9-day study period (no. 10).²⁸ Ropinirole and methylphenidate were, respectively, administered at 0.75 mg/day and 5 mg twice daily (no. 11).²⁹

Regarding non-pharmacological treatments, the motor relearning program involved 40 min of physical therapy five times a week for 4 weeks (no. 2).²¹ Repetitive transcranial magnetic stimulation (rTMS) was applied in sessions of 10 stimuli for 10 s each at 5 Hz to both hemispheres, repeated five times over 2 weeks (no. 7).²⁶ Another rTMS protocol involved five consecutive sessions over five days with a sham stimulation group (no. 13).³⁰ Strategy training and reflective listening were performed for 45 min per day, five times a week, in addition to inpatient rehabilitation (no. 6).²⁴ Gait training was conducted for 6 weeks. Participants underwent a maximum of 1 h per day of physical therapy programs, with at least 20 min dedicated to gait training each day (no. 8).²⁵ Intensive language action therapy, a combination of pharmacological treatment and rehabilitation, was performed for 30 h in conjunction with donepezil administration (no. 9).²⁷

The primary outcomes assessed included scores on scales for apathy and depression as well as neuropsychological and neuroimaging indicators. Apathy was evaluated using the Apathy Scale,³² Apathy Evaluation Scale,³³ Clinical Version of the Apathy Scale,³³ Apathy Inventory,³⁴ and Neuropsychiatric Inventory and its Japanese version. Depression was assessed using the Montgomery-Åsberg Depression Rating Scale,³⁵ Quick Inventory of Depressive Symptomatology,³⁶ and Stroke Aphasia Depression Questionnaire-21.³⁷ Neuropsychological evaluations included the Western Aphasia Battery Aphasia Quotient³⁸ and Stroop test. Neuroimaging evaluations involved single-photon emission computed tomography, positron emission tomography, resting-state functional magnetic resonance imaging, and behavioral observations.

Main treatment effects

The interventions for post-stroke apathy and their main effects are shown in Table 2. Among the pharmacological treatments, escitalopram (10 mg/day) significantly improved apathy (Apathy Scale: 3.474; 95% CI: 1.793–6.729; p < 0.0001). Furthermore, a significant interaction was noted between time and the treatment group that received nefiracetam (900 mg/day) (F = 4.0, df = 3, 65, p < 0.01), suggesting a reduction in apathy. In contrast, nefiracetam 600 mg/day showed no significant improvement (F = 1.3, df = 3, 65, p = 0.29). Additionally, zolpidem (10 mg) significantly alleviated emotional blunting, decreased motivation, and loss of interest associated with apathy (H = 6.8, 7.0, and 7.7, respectively, all p < 0.05). Ropinirole (0.75 mg/day) contributed to the reduction of Neuropsychiatric Inventory scores (12→3), indicating alleviation of apathy (no p-value listed). Methylphenidate (5 mg) improved patient interest, social behavior, and participation in activities (no p-value listed).

Table 2.

Main treatment effects in post-stroke apathy.

Author, Year	Intervention	Effects								Changes main outcome
Author, Year	Intervention	Apathy	Depression	Cognition	Language	Behavior	Brain structural changes	Cerebral blood flow	Brain functional connections	Changes main outcome
Starkstein et al. (2016)²³	Nefiracetam (900 mg/day)	−	−	−						AS: 1.2 (95% CI: −14.8 to 17.2), p = 0.43
Mikami et al. (2013)¹⁰	Escitalopram (10 mg/day)	＋		−						AS: 3.474 (95% CI: 1.793 to 6.729), p < 0.0001
Robinson et al. (2009)²²	Nefiracetam (900 mg)	＋	−							AS: time-treatment group interaction: F = 4.0, df = 3, 65, p < 0.01
Robinson et al. (2009)²²	Nefiracetam (600 mg)	−	−							AS: time-treatment group interaction: F = 1.3, df = 3, 65, p = 0.29
Tay et al. (2023)⁴	Fluoxetine (20 mg)	−	＋							MADRS: fluoxetine baseline = 0.38 [0.84]; 6 months = 0.63 [1.08] p < 0.001).
Berthier et al. (2022)²⁷	Donepezil (10 mg)	−	−		＋		＋			SADQ-21: mean change: -2.0 ± 2.7, p = 0.125
Autret et al. (2013)²⁸	Zolpidem (10 mg)	＋				＋				Apathy Inventory: H corrected for ties = 6.8, 7.0, and 7.7 for emotional blunting, lack of initiative and lack of interest, respectively, all p < 0.05.
Kohno et al. (2010)²⁹	Ropinirole (0.75 mg)	＋						＋		NPI score changed from 12 to 3 (no p-value listed)
Watanabe et al. (1995)³¹	Methylphenidate (5 mg)			＋		＋		＋		Patient's interest, social behavior, personal hygiene, and activity participation were improved (no p-value listed)
Chen et al. (2018)²¹	Motor relearning program	＋								AES-C: Bobath therapy was associated with a 1.63-fold higher risk of post-stroke apathy compared to the motor relearning program (no p-value listed)
Mikami et al. (2013)¹⁰	Problem solving therapy	＋		−						AS: 1.84 (95% CI: 1.208 to 2.804), p < 0.0001
Skidmore et al. (2015)²⁴	Strategy training	＋								AES differed significantly over time (F [2, 28] = 3.56, p = 0.041) but showed only a marginal difference between treatment groups (F[1, 26] = 4.05, p = 0.054).
Maeda et al. (2025)²⁵	Gait training	＋	＋							There was a significant difference between the apathy and non-apathy groups (p < 0.01).
Sasaki et al. (2017)²⁶	rTMS	＋	＋							AS: 47.5 ± 31.9% vs. 1.7 ± 27.8%, respectively, p = 0.02
Mitaki et al. (2016)³⁰	rTMS	＋							＋	Japanese version of the AS score changed from 29 to 19 (no p-value listed)
Berthier et al. (2022)²⁷	Donepezil (10 mg) and ILAT	＋	＋		＋		＋			SADQ-21: mean change: −2.9 ± 2.2, p = 0.007

+: present; −: absent; blank: unknown.

Regarding non-pharmacological treatments, the motor-relearning program was more effective than Bobath therapy in reducing apathy (Clinical version of Apathy Evaluation Scale: Bobath therapy was associated with 1.629 times higher apathy risk than that associated with the motor-learning program). Problem-solving therapy significantly alleviated apathy (Apathy Scale: 1.84, 95% CI: 1.208–2.804; p < 0.0001). Strategy training showed a significant improvement over time (F(2,28) = 3.56, p = 0.041); however, the differences between the intervention groups were limited (F(1,26) = 4.05, p = 0.054). Gait training resulted in significant improvements over time in physical and psychiatric outcomes in patients with apathy (all p < 0.05); however, differences between apathy and non-apathy groups after the intervention were limited to Apathy Scale and CES-D scores (p < 0.01), with no significant differences in other functional measures. rTMS resulted in significant alleviation of apathy (Apathy scale: 47.5% ± 31.9% vs. 1.7% ± 27.8%, p = 0.02) and improvement in scores on the Japanese version of the AS (from 29 to 19, no p-value listed). Furthermore, the combination of donepezil (10 mg) and intensive language action therapy resulted in improvements in apathy, depression, language, and behavior (Stroke Aphasia Depression Questionnaire-21: mean change −2.9 ± 2.2, p = 0.007), contributing to a reduction in apathy.

Discussion

This scoping review comprehensively mapped pharmacological and non-pharmacological interventions for post-stroke apathy and examined their effects. Among pharmacological treatments, escitalopram and zolpidem significantly improved motivation-related symptoms, while ropinirole and methylphenidate contributed to apathy alleviation. However, nefiracetam's effectiveness varied by dosage. Non-pharmacological approaches, including motor relearning programs, problem-solving therapy, gait training, and rTMS, were effective in reducing apathy symptoms. Especially, strategy training and donepezil combined with intensive language-action therapy improved apathy, depression, behavior, and language function.

Pharmacological interventions for apathy in patients with Parkinson's disease and dementia have been effective,³⁹ and exercise and mindfulness reduced apathy symptoms in patients with Parkinson's disease.⁴⁰ However, this study focuses on post-stroke apathy and highlights unique features of its treatment. Compared to the limited impact of non-pharmacological therapies, such as exercise, occupational therapy, psychomotor therapy, and validation therapy, on apathy in dementia,⁴¹ this review suggests that non-pharmacological therapies may have a greater potential to affect behavioral aspects in post-stroke populations. These findings are significant from a rehabilitation perspective because behavioral engagement is essential for maximizing therapy effects and promoting independence in daily life.

The evaluation of post-stroke apathy interventions should include symptom improvement and broader domains, such as communication and social participation. Apathy can disrupt rehabilitation by reducing patient motivation and leading to disuse syndrome, which may cause secondary complications. Because many patients with cerebrovascular disease experience long-term disabilities,⁴² improving behavioral and communicative functions through targeted interventions is essential. From a clinical standpoint, these findings support the integration of apathy-focused strategies into comprehensive rehabilitation.

Moreover, this review suggests that non-pharmacological treatments may have benefits beyond the reduction of apathy symptoms, contributing to improvements in emotional regulation, communicative ability, and behavioral activation. While such interventions are common, standardization in terms of frequency, duration, and delivery is lacking. Previous studies have highlighted the limited quality of evidence supporting non-pharmacological approaches for apathy management in neurological conditions,^39,43 and similar concerns apply to post-stroke interventions. Thus, our results underscore the need for high-quality clinical trials to establish effective and standardized treatment protocols, guide the development of evidence-based guidelines, and contribute to consistency in clinical practice.

Although this review primarily analyzed non-pharmacological interventions led by rehabilitation professionals, it should be noted that clinical psychologists can also lead psychosocial and cognitive-behavioral interventions. Involving clinical psychologists could offer more tailored psychological approaches to enhance motivation, emotional regulation, and communicative function. Their participation may strengthen team-based, comprehensive rehabilitation strategies. Integrating pharmacological and non-pharmacological treatments may further improve post-stroke apathy outcomes. While pharmacological treatments remain under investigation and often require collaboration with specialists, such as psychiatrists and neurologists, non-pharmacological approaches can be led by rehabilitation professionals. The combined effects of these treatments should be evaluated for their impact on apathy symptoms, quality of life, functional recovery, and caregiver burden. Randomized controlled trials are especially needed to determine the optimal intervention combinations and validate their benefits.

This study has several limitations. The literature search was limited to English-language articles in PubMed, CINAHL, and Web of Science, potentially excluding relevant studies in other languages. Additionally, studies including patients with coexisting post-stroke depression were excluded, which may have led to an incomplete understanding of post-stroke apathy. The study also did not assess the methodological quality of the included articles, which limits the strength of its conclusions. Furthermore, qualitative studies were excluded, despite their potential to provide insight into patients’ lived experiences and contextual factors influencing treatment. Future systematic reviews and meta-analyses, incorporating both quantitative and qualitative studies, are needed to generate comprehensive evidence and support the development of tailored intervention strategies.

In summary, this review highlights the importance of addressing post-stroke apathy through both pharmacological and non-pharmacological treatments. The findings emphasize the value of rehabilitation-based strategies in managing post-stroke apathy and provide a foundation for developing comprehensive, evidence-based treatment guidelines. Further research is needed to refine these interventions and confirm their effectiveness in improving stroke-related apathy outcomes.

Clinical messages

Non-pharmacological strategies, especially motor relearning, problem-solving therapy, and rTMS, show potential and can be led by rehab professionals.

Combining pharmacologic and behavioral interventions may yield additive benefits in motivation, communication, and social participation.

Programs should be tailored to sustain long-term engagement, given apathy's impact on rehab adherence.

Supplemental Material

sj-docx-1-cre-10.1177_02692155251374911 - Supplemental material for Interventions for post-stroke apathy and their effects: A scoping review

Supplemental material, sj-docx-1-cre-10.1177_02692155251374911 for Interventions for post-stroke apathy and their effects: A scoping review by Someka Hijikuro, Takao Kaneko and Kohei Ikeda in Clinical Rehabilitation

Footnotes

ORCID iDs

Someka Hijikuro

Takao Kaneko

Kohei Ikeda

Author contributions

Someka Hijikuro and Kohei Ikeda contributed to the conceptualization of the study. The methodology was developed by Someka Hijikuro, Kohei Ikeda, and Takao Kaneko. Literature search and screening, as well as data extraction and analysis, were conducted by Someka Hijikuro, Kohei Ikeda, and Takao Kaneko. The original draft was written by Someka Hijikuro, while all authors, including Kohei Ikeda and Takao Kaneko, contributed to the review and editing of the manuscript. Kohei Ikeda supervised the study. This research was supported by SPS KAKENHI (Grant Number: JP20H03914). All authors have read and approved the final manuscript.

Funding

The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This work was supported by the Japan Society for the Promotion of Science (grant number JP20H03914).

Declaration of conflicting interests

The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Data availability statement

The data supporting the findings of this study are available within the article and its Supplemental materials. No additional data are available.

Supplemental material

Supplemental materials for this article are available online.

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