Efficacy of repetitive transcranial magnetic stimulation in post-stroke cognitive impairment: an overview of systematic reviews

Objective The reliability of clinical evidence depends on high-quality meta-analyses/ systematic reviews (MAs/SRs). However, there has been no assessment of the quality of MAs/SRs for repetitive transcranial magnetic stimulation (rTMS) in post-stroke cognitive impairment (PSCI), both nationally and internationally. This article seeks to use radar plotting to visually present the quality of MAs/SRs on rTMS for improving cognitive function in PSCI, aiming to offer an intuitive foundation for clinical research. Methods Eight Chinese or English databases were systematically searched to collect comprehensive literature, and the retrieval time ranged from inception to 26 March 2024. Literature ranking was calculated using six dimensions: publication year, design type, AMSTAR-2 score, PRISMA score, publication bias, and homogeneity. Finally, radar plots were drafted to present a multivariate literature evaluation. The GRADE tool assessed the strength of evidence for the outcome indicators included in the MAs/SRs. Results The 17 articles included had average scores of 12.29, 17, 9.88, 9.71, 12.88, and 12.76 for each dimension. The radar plot showed that an article published in 2023 had the highest rank and a large radar plot area, while an article published in 2021 had the lowest rank and a small radar plot area. The GRADE tool evaluation revealed that 51 pieces of evidence were of very low quality, 67 were of low quality, 12 were of moderate quality, and only one was of high quality. Conclusion The average rank score of literature ranged from 8.50 to 17, with higher rankings indicating greater significance in literature reference. Variations in literature quality were attributed to inadequate study planning, irregular literature search and screening, insufficient description of inclusion criteria for studies, and inadequate consideration of bias risk in the included studies. Most MAs/SRs indicated that rTMS was more effective than the control group in enhancing the global cognitive function and activities of daily living in PSCI patients. However, the overall quality of the literature was generally low and needs validation from future high-quality evidence. Systematic review registration:https://www.crd.york.ac.uk/prospero/, identifier CRD42023491280.


Introduction
Post-stroke cognitive impairment (PSCI) refers to the clinical symptoms where cognitive function is affected to varying degrees after a stroke and lasts up to 6 months (1,2).According to a survey, it was found that between 17 and 92% of stroke patients experience cognitive dysfunction 3 months after the onset of the condition, which has a significant negative impact on the life quality and activities of daily living (ADL) of patients (3).Patients with PSCI exhibit complex clinical symptoms due to the etiology of the disease, the location and size of the lesion, and potential complications.Typical symptoms include attention deficits, memory impairment, and learning difficulties (4).PSCI has an impact on the communication and daily life abilities of patients.It also decreases their compliance and motivation for rehabilitation and can progress into dementia as the disease worsens.This significantly hinders the rehabilitation process and prevents patients from rejoining their families and society (5).
Comprehensive strategies to address PSCI involve managing established risk factors, utilizing pharmacotherapy, and participating in rehabilitation (6).The primary approaches to prevent PSCI consist of reducing the risk factors for stroke, averting the onset of stroke, and implementing secondary stroke prevention measures (7).Hypertension, hyperglycemia, and hyperlipidemia are common risk factors for cognitive impairment, actively controlling which can effectively reduce the risk of cognitive decline (8).There is still a lack of consistent guidelines internationally regarding drug treatment for PSCI, and the currently commonly used drugs often cause various adverse reactions, such as gastrointestinal disorders (9).Traditional Chinese rehabilitation methods, such as herbal and acupuncture treatments, have not shown significant success in treating cognitive impairment (10).Additionally, cognitive function training, including general cognitive training and enriched rehabilitation training, is time-consuming, tedious, and often leads to poor patient compliance, posing challenges in achieving the desired outcomes (11).Contemporary rehabilitation treatments frequently include neuromodulation and artificial intelligence technologies.While studies have shown that artificial intelligence technologies such as computerized training, virtual reality, and rehabilitation robots can effectively improve the cognitive function of patients with PSCI, they are not widely used in clinical practice due to the high equipment costs (12,13).Neuromodulation techniques like transcranial direct current stimulation (tDCS) and repetitive transcranial magnetic stimulation (rTMS) are frequently employed to improve cognitive function in both clinical and experimental settings nowadays (14,15).rTMS is a non-invasive neuromodulation technique with the advantages of high safety, few side effects, and simple operation (16).rTMS generates induced currents by pulsed magnetic fields acting on the cerebral cortex, altering the membrane potential of nerve cells, thereby affecting the metabolism of substances in the brain and triggering a series of physiological and biochemical responses (17).Based on the varying frequencies of stimulation, it is categorized into low-frequency rTMS (≤1 Hz) and high-frequency rTMS (>1 Hz).Low-frequency rTMS reduces the excitability of the cerebral cortex and functions in an inhibitory capacity.In contrast, high-frequency rTMS raises the excitability of the cerebral cortex and serves an excitatory function.Repeated superimposed pulsed stimulation leads to a cumulative effect, which can impact both localized and distal regions, resulting in long-term inhibitory and excitatory effects (18).
The stimulation pulse can be classified into single-pulse, double-pulse, and repetitive transcranial magnetic stimulation.Additionally, rTMS comprises two distinct stimulation modes: intermittent theta burst stimulation (iTBS) and continuous theta burst stimulation (cTBS).In recent years, there has been much focus on the effectiveness of rTMS in PSCI.Many studies have confirmed its clinical effectiveness, showing improvements in global cognitive function, executive function, and activities of daily living (ADL) (14,19).Currently, Numerous articles have been published on meta-analyses/systematic reviews discussing the effectiveness of rTMS for post-stroke cognitive impairment.However, the consistency of intervention methods, outcome indicators, and conclusions in these articles was low, and the quality varied.Low-quality MAs/SRs may mislead and hinder research development to a certain extent, and evaluating published MAs/SRs is vital to promote the development of rTMS in the field of PSCI.Currently, relevant studies have yet to be published in this area.
The overview of systematic review is a method for a comprehensive study of evidence from multiple relevant MAs/SRs.Compared to MAs/SRs, it can provide higher quality evidence (20).The article utilizes radar plots to present data in six dimensions: qualitative evaluation of publication year, design type, homogeneity, publication bias, and quantitative assessment using the AMSTAR-2 methodological quality score, PRISMA report quality score (21,22).Additionally, the article utilized the GRADE tool to assess the strength of evidence in MAs/SRs outcome indicators, aiming to analyze the quality of the literature qualitatively and quantitatively with the assistance of a radar plot and the GRADE tool.This approach provides a visual foundation for decision-making in clinical settings.

Study enrollment and reporting
Our study (CRD42023491280) has been officially registered in the International Prospective Register of Systematic Reviews, PROSPERO.Although the reporting guideline for overviews is currently in progress, we have presented our findings using the Preferred Reporting Items for Meta-Analyses and Systematic Reviews (PRISMA) 2020 (23, 24).

Inclusion criteria 2.2.1 Study design
Chinese and English meta-analyses/systematic reviews based on randomized controlled trials (RCTs) investigating the effectiveness of rTMS for PSCI were incorporated into the study.

Subjects
The study subjects were patients with PSCI (there is no clear diagnostic gold standard, but for reference, a definite stroke event and cognitive impairment within 6 months of the stroke event) of any age and gender.

Interventions
In the experimental group, rTMS was administered alone or in combination with other treatments such as routine treatment,

Outcome indicators
The primary outcome indicators include (

Exclusion criteria
Six categories of literature were not considered in the study: (1) no definitive diagnosis of PSCI; (2) other types of literature were excluded, such as meta-analyses and systematic reviews on rTMS treatment for PSCI, which included animal experiments, cohort studies, case-control studies, and cross-sectional studies; (3) repeatedly published literature; (4) dissertations or conference articles; (5) MAs/SRs with less than five studies included; and (6) literature that compares two rTMS approaches.

Literature screening and data extraction
Two authors (LZ and SG) independently searched the literature following the established search strategy.They performed quality assessment and initial screening based on title, abstract, and other relevant information.Subsequently, data extraction and verification were carried out to finalize the inclusion.In the event of disagreements, the third author (CW) reviewed the extracted information, and any inconsistencies were discussed among the three parties to reach a consensus.If the source material is incomplete, attempt to contact the author for additional information to enhance it.An evaluation information collection form was created using Excel 2016 software, encompassing publication year, design type, homogeneity, publication bias, AMSTAR-2 methodological quality score, and PRISMA report quality score.

Methodological quality assessment
The AMSTAR-2 scale ( 25) is a revised version of the AMSTAR scale with 16 entries, 7 of which are vital entries (2, 4, 7, 9, 11, 13, and 15).Each entry is answered as "yes, " "partially yes, " or "no" based on the fulfillment of evaluation criteria.The AMSTAR-2 scale categorizes the methodological quality of MAs/SRs into four levels: "high" if ≤1 non-vital entry is defective; "moderate" if >1 non-vital entry is defective; "low" if one vital entry is defective with or without non-vital entries; and "very low" if >1 vital entry is defective with or without non-vital entries.Individual entries with a reporting rate ≤ 50% were considered to have missing reporting information, reporting rate = [(number of studies with full reporting of entries + number of studies with partial reporting)/total number of included studies] × 100%.Two authors (LZ and SG) independently evaluated the methodological quality of the included literature.

Report quality assessment
The PRISMA Statement Inventory (26) assesses the quality of a study report based on the completeness of 27 entries.Each entry is scored as 1 for complete report, 0.5 for partial report, and 0 for failure to report, totaling 27 points.A score below 15 indicates a significant lack of information, 15 to 21 suggests some deficiencies, and > 21 to 27 indicates a relatively complete study.Two authors (LZ and SG) independently assessed the reporting quality of the literature included.

Evidence quality assessment
The GRADE tool (27)  included MAs/SRs.Any differences in their assessments were resolved through discussion with a third author (CW) to achieve a consensus.

Radar plot evaluation entries included in the study
According to the method of Panesar et al. (28), a multidimensional analysis evaluation of the included MAs/SRs is conducted from six dimensions: qualitative evaluation of publication year, design type, homogeneity, and publication bias, as well as quantitative evaluation using the AMSTAR-2 methodological score and the PRISMA report quality score.In the AMSTRA-2 scale, a score of 1 is given for a "yes" evaluation, 0.5 for a "partially yes" evaluation, and 0 for a "no" evaluation (29).The PRISMA scale follows a scoring principle where 1 point is given for standardized and correct use of each entry, 0.5 points for inadequate use, and 0 points for incorrect use or failure to use, with a total of 27 points available (25).The more recent the publication year, the higher the evidence level of the literature.MAs/SRs were designated as high quality when the type of study included was an randomized controlled trial.When more than half of the included MAs/SRs have outcome indicators of p ≥ 0.01, I 2 ≤ 50%, they will be judged as high homogeneity and assigned the highest rank, and if less than half, the literature will be judged as low homogeneity and assigned the lowest rank.When the literature uses a funnel plot or other methods for publication bias assessment, it will be judged as having low publication bias and assigned the highest rank; if not mentioned, it will be judged as having high publication bias and assigned the lowest rank.The ranking conversion of other projects is conducted according to the methods of medical statistics.The principle of ranking conversion is based on the methods of medical statistics.The highest ranking level is the total amount of literature, and the highest score for other indicators is assigned based on the total amount of literature.Finally, the evaluation rankings are included in the radar chart coordinates, and the average score of all rankings is taken as the ranking means.

Radar plot drawing
The score sheet includes the basic information of the first author, publication year, design type, degree of homogeneity, and risk of publication bias evaluation scale.Also, it also records the scores of each methodological quality assessment of the AMSTAR-2 and the quality assessment of the PRISMA report.This information was imported into a table to draw and optimize a radar plot (30).

Literature retrieval result
A total of 199 documents were collected, and 156 documents remained after the removal of 43 duplicates by EndNote.Initially, 129 articles were excluded after reviewing their titles and abstracts.After conducting a more thorough analysis of the complete text, 10 articles were eliminated for different reasons.These reasons encompassed non-MAs/SRs, lack of complete texts, control groups incorporating rTMS, research involving patients with other neurological conditions, non-RCTs, MAs/SRs with less than five studies, and replicated published research.Finally, 17 studies met the criteria and were used for overviews (31)(32)(33)(34)(35)(36)(37)(38)(39)(40)(41)(42)(43)(44)(45)(46)(47).The specifics of the literature screening process are illustrated in Figure 1.

Basic features of the included literature
Seventeen articles (31)(32)(33)(34)(35)(36)(37)(38)(39)(40)(41)(42)(43)(44)(45)(46)(47) were included in the study, with 7 (31-35, 44, 45) in Chinese and 10 (36-43, 46, 47) in English, all published between 2021 and 2023.The MAs/SRs comprised only randomized controlled trials, with the studies varying from 5 to 61 and sample sizes ranging from 192 to 4,021 cases.All but one of the studies described the quality assessment tools used and meta-analyses of the results of the included studies.The risk of bias assessment tools used in most studies was the Cochrane and PEDro scales; one (41) study used the Modified Jadad scale scoring system and one (44) did not perform a risk of bias assessment.MMSE, MoCA, BI, MBI, RBMT, and LOTCA were among the primary outcome indicators used.Thirteen (31-41, 43, 47) articles reported financial support.Most studies concluded that rTMS has advantages in treating PSCI but emphasized the need for more, higher-quality studies to validate the results.For detailed information, refer to Table 1.

Comparison of the publication year
The significance of each research study on clinical guidance is related to the publication year, scope, and duration.Newer studies and those covering longer time spans contribute to more vital guidance for clinical practices.This study included 17 MAs/SRs.Therefore, the literature rankings published in 2023 were positioned as 17.The earliest publication date is 2021, containing five (31,33,34,42,46) studies; the latest is 2023, containing 10 (32, 36-40, 43-45, 47).Meanwhile, there were two (35,41) studies in 2022.

Comparison of study design
The most compelling form of clinical evidence for assessing the efficacy of a treatment is an randomized controlled trial.

Results of the quality assessment of literature reports
Every PRISMA statement entry with a reporting completeness of less than 50% was deemed to be considerably underreported.Entry 7 (retrieval; 35%), entry 10 (information; 50%), entry 14 (study bias; 47%), entry 15 (outcome evidence quality; 41%), entry 22 (presentation of the quality of outcome evidence; 41%), entry 24 (other information; 21%), and entry 27 (shared information; 18%) were the entries with the most significant information deficiencies.

Radar plot for multi-dimensional evaluation items
Refer to Table 2 for details.

Results of radar plot evaluation
The radar plot demonstrates that all six evaluation dimensions of Xie et al. (38) are higher than the rank average score, with a larger radar plot area and the highest significance in literature references.Three studies (33, 41, 46) had four evaluation dimensions below the rank average score, with smaller radar plot areas and lesser literature reference significance.Three studies (31,42,44) had five evaluation   (Continued)

Results of the GRADE evidence quality rating evaluation
The quality of evidence was evaluated for eight outcome indicators and 131 pieces of evidence related to global cognitive functioning, executive functioning, working memory, memory, attention, ADL, depression, and cognitive deterioration in the 17 articles included in the study.The GRADE approach was utilized to evaluate and analyze the strength of evidence for these outcome indicators.Evidence-based RCT was initially classified as high quality, but this classification could change due to publication bias, risk of bias, inconsistency, imprecision, and indirectness (48).Ultimately, the GRADE quality assessment revealed that 51 evidence were of very low quality, 67 were of low quality, one was of high quality, and 12 were of moderate quality (Supplementary Table S5).

Adverse events
Thirteen studies included in the analysis (31-34, 36, 38-41, 43, 45-47) mentioned the occurrence of adverse effects following rTMS therapy.The frequently mentioned adverse effects were mild headache, dizziness, nausea, and vomiting, as well as other effects, including loss of appetite, anxiety, and fatigue.However, these symptoms reportedly lessened after a brief period of rest.This suggests that rTMS is a safe and effective therapeutic method for managing post-stroke cognitive impairment in patients.

Summary of evidence
This study included 17 (31)(32)(33)(34)(35)(36)(37)(38)(39)(40)(41)(42)(43)(44)(45)(46)(47) MAs/SRs based on RCTs published between 2021 and 2023.Seven were in Chinese (31-35, 45, 46), and 10 were in English (36-43, 46, 47).The average rank score of the 17 included articles ranged from 8.50 to 17.00, with an overall average rank score of 12.42.Xie et al. (38) had the highest quality articles with an average rank score of 17.00, while Liu et al. (42) had the lowest quality articles with an average rank score of 8.50.Only two articles (33, 44) did not apply a forest plot to the stated results.Seventeen articles had AMSTRA-2 scale scores of 5-11 and PRISMA scale scores of 12-25.5.Eight articles (31,32,34,36,(38)(39)(40)47) have addressed and discussed the heterogeneity and documented the high levels of heterogeneity.The low scores were primarily caused by low methodological quality and report quality.Those that need to be strengthened in terms of methodological quality are: (1) the search must be thorough and methodical, considering the language of publication and conducting a thorough search of gray literature to   (3) the risk of bias in included studies should be assessed using appropriate evaluation tools, emphasizing the rational use of funnel plots or other tools to report publication bias; and (4) research funding sources and related support descriptions.Those that need to be strengthened in terms of quality of reporting are: (1) the introduction should describe the research on clinical issues according to the PICOS principle; (2) in order to ensure transparency in research, studies need to be registered in advance in an international preregistration database, outlining the research plan; (3) the researcher should rationally explain and discuss the heterogeneity of the results in the report of the findings; and (4) in the discussion section, in addition to explaining the research findings of the article, it is also necessary to extensively discuss the limitations of its inclusion in the article.The above illustrates the low quality of MAs/SRs regarding rTMS treatment of PSCI patients, and there is still much room for improvement.

Pathogenesis of post-stroke cognitive impairment
Post-stroke cognitive impairment, a common complication following a stroke, is characterized by attention deficit and memory impairment.These symptoms significantly affect the capacity of rehabilitation and adapt to society.On one hand, post-stroke motor and cognitive deficits impact the implementation of rehabilitation programs by stroke patients.On the other hand, PSCI reduces patients' motivation and initiative for rehabilitation therapy, affecting its efficacy and slowing down the rehabilitation process, which in turn has a significant influence on the family and society.There is an urgent need to create safer, more effective, and more acceptable rehabilitation treatments because the biomedical-medical-psychological paradigm has changed, and traditional rehabilitation treatments are highly limited in enhancing the patient's level of functioning.The process of PSCI pathologizing is still not fully understood.After stroke, ischemia leads to the emergence of an "ischemic penumbra" at the site of the lesion and in the surrounding area, and the expression of apoptosis-related proteins increases with the duration and degree of ischemia, resulting in cell death and neurological damage (49).As early as 1970, Tomlinson et al. (50) suggested that the development of cognitive dysfunction is linked to the volume of cerebral infarction.If the volume exceeds 100 mL, it may result in vascular dementia.Additionally, Zekry et al. (51) discovered that infarctions in specific brain regions, such as the frontal lobe and white matter, have a more pronounced impact on cognitive deficits, highlighting the crucial role of infarct location in the mechanism of cognitive impairments.They also concluded that the volume of cerebral infarcts only accounted for some of the cognitive decline in stroke patients and that the number of foci of infarcts was significantly correlated with the severity of cognitive deficits.PSCI was previously thought to be connected to damage in specific brain regions like the internal olfactory cortex and the hippocampus, which are associated with Alzheimer's disease (AD) (52).Individuals with AD and PSCI experience similar neuropathological processes, and research has revealed that individuals with PSCI exhibit AD-specific abnormalities, such as elevated amyloid beta-protein deposition (53).Furthermore, research has shown that cognitive impairment after a stroke is linked not only to the localization of the lesion but also to the distal areas of the lesion and the broader neural networks.For instance, there is a correlation with decreased functional connectivity within the default mode networks of the medial temporal lobe, posterior cingulate gyrus, and medial prefrontal cortex (54).Moreover, the pathological processes leading to PSCI may involve reduced blood flow in the brain, an inflammatory response, damage from oxygen radicals, and neurodegeneration of the brain (55-57).However, engaging in activities of daily living requires good motor skills and cognitive resource participation, which may involve analyzing, understanding, and learning daily activities.Enhancing and restoring cognitive function is as important as recovering motor function for patients to reintegrate fully into their families and society.

Possible mechanisms of repetitive transcranial magnetic stimulation for cognitive impairment
Cognitive function plays a critical role in predicting the progression of a stroke and is an essential determinant of the patient's post-stroke quality of life.Addressing cognitive impairment through effective treatment is of utmost importance.Here are several potential mechanisms through which rTMS, a widely used non-invasive treatment for enhancing cognitive function, operates: (1) rTMS is a significant tool for reconstructing part or all of the functional neural network.It not only brings about changes in the local cortical areas but also alters the function of the connected remote subcortical areas.Additionally, the improvement in function persists even after the stimulation is ceased (58).The neuroprotective effects of rTMS against cerebral ischemia may be achieved through enhancing blood oxygenation and local cerebral blood flow velocity, stimulating the expression of brain-derived neurotrophic factor (BDNF) in the brain tissue surrounding the infarct, and reducing ischemic injury-induced neuronal apoptosis in the peri-ischemic brain area.Moreover, BDNF enhances learning and memory by promoting synaptic transmission and neuronal plasticity in the central nervous system (59).Research has demonstrated that neurological disorders are linked to abnormal levels of brain metabolites, and it has been demonstrated that rTMS can normalize these levels and improve cognitive function (60).Resting-state functional magnetic resonance imaging (RS-fMRI) is an effective method for investigating structural and functional changes in the brain.In recent years, much RS-fMRI research has focused on neuroplasticity and treatment response related to rTMS.Maintaining optimal interactions between brain networks to enhance cognitive performance is crucial, and rTMS plays a role in enhancing functional connections within these networks to improve cognitive function (61).( 2) Research suggests that the mechanism by which rTMS enhances cognitive function may be through the modulation of antioxidant enzymes (62).rTMS can regulate neurotransmitters, including dopamine and gamma-aminobutyric acid (GABA).For example, rTMS on the dorsolateral prefrontal cortex (DLPFC) increases extracellular dopamine levels and regulates dopamine release in the anterior cingulate cortex and orbitofrontal cortex, where dopamine plays a vital role in cognitive processes.(3) rTMS not only affects the stimulated area but also induces changes in cortical and subcortical functional connectivity.The prefrontalstriatal neural circuit is an important cognitive control center that plays a dominant role in behavioral inhibition, impulse control, and decision-making, and increasing its connectivity improves cognitive function (63).The study found that after TMS was applied to the DLPFC of healthy subjects, it was found to induce neuronal activity in several connected brain regions by functional magnetic resonance imaging (fMRI).Furthermore, it was found that this area and other prefrontal cortex regions are involved in attention and memory processes (64).The hippocampus is a part of the brain mainly involved in learning and memory.The granule cells of the hippocampal dentate gyrus are involved in spatial navigation processes based on location strategies, participating in the temporary storage of spatial information, and are closely related to anxiety control and contextual learning.Research on rats has shown that rTMS enhances the excitability of hippocampal dentate gyrus granule cell neurons, playing a positive role in promoting cognitive function recovery (65).When cognitive impairments occur, various resting-state networks of patients (such as attention and sensory-motor networks) all undergo abnormalities.These networks interact with each other and collectively control attention and other cognitive domains.After receiving rTMS treatment, it was discovered through fMRI that rTMS promotes normalizing abnormal resting-state network structures (66).( 4) rTMS can alter the structure of dendritic spines and the expression of synaptic proteins, neurotransmitters, and cognition-related metabolites.rTMS can also modulate synaptic transmission, resulting in long-term potentiation or inhibition associated with learning and memory (67).( 5 endothelial growth factor (VEGF) has been identified as a neurotrophic factor in the peripheral nervous system, which can improve cell survival and promote cell proliferation and axon growth.VEGF in the hippocampus area can enhance learning and memory.Insulin-like growth factor is an influential growth factor in the central nervous system, which can significantly reduce brain damage caused by hypoxia and improve long-term memory and cognitive abilities in rats.Erythropoietin is expressed in the cortex and hippocampal neurons and is associated with high synaptic plasticity and cognitive function (68).rTMS-induced increase in amyloid precursor protein levels may mediate neuroprotective effects, preventing oxidative death of nerve cells and thereby improving cognitive function (69).

Current status of research on repetitive transcranial magnetic stimulation for the treatment of post-stroke cognitive impairment
This study summarizes the features of current clinical rTMS applications for treating PSCI patients.(1) These include a standard stimulation frequency of 1 Hz for low-frequency stimulation and 10 Hz for high-frequency stimulation.Three studies (38,41,43) comparing the effectiveness of high and low-frequency stimulation concluded that the two had no significant difference in improving cognitive function.(2) The DLPFC, including the left, right, contralateral, and affected DLPFC, is a commonly targeted site for stimulation.Among these, the left DLPFC is the most frequently stimulated.It is important to note that the stimulation frequency varies across studies for the same stimulation site.High-frequency stimulation of the DLPFC is a common approach, but its actual effects still need to be determined.(3) No specific guidelines recommend stimulation intensity, but 80% to 120% is typically utilized in clinical treatment.(4) The intervention time and period varied across the studies.The most common session duration was 20 min, with the most extended period lasting 12 weeks and the shortest lasting 1 week.The majority of studies had an intervention period of 4 weeks.Forty sessions of low-frequency stimulation were more effective than 20 or 10 sessions, and 15 sessions of highfrequency stimulation were more productive than 20 or 10 sessions.(5) The effect of stimulation during the acute or subacute phase of stroke is more significant than during the chronic phase, according to the post-stroke duration study (40).(6) The details of the rTMS treatment regimen, such as the number of sessions, the time between sessions, and the number of pulses in each session, are not well-documented.(7) The predominant adverse effects reported in the MAs/SRs examined in this research were headache and dizziness.These symptoms were alleviated by rest, suggesting that rTMS could have broad utility in real-world scenarios.
There are several limitations to using rTMS in treating PSCI clinical trials.(1) The effectiveness of rTMS for PSCI and the degree of its effectiveness remain uncertain, as most of the RCT experimental groups were administered rTMS alongside other treatments.(2) The excitation thresholds of different areas in the cortex vary.Most recent studies have focused on measuring the motor thresholds of the patient's motor cortex to gauge the stimulus intensity.However, it remains unclear whether the stimulus intensity derived from motor cortex stimulation can be extrapolated to the stimulation of cognitive functional areas.(3) Much of the research has emphasized the activation of the DLPFC, but other functional regions, including the primary motor cortex, temporal lobe, and frontal lobe, have also been explored.The findings indicate that rTMS may enhance cognitive function in PSCI patients.However, it remains unclear whether stimulating multiple sites yields more pronounced effects than stimulating a single site.(4) Repetitive transcranial magnetic stimulation is a rather complex non-pharmacological intervention method.In clinical applications, it is often used as an adjuvant therapy.Determining relevant stimulation parameters, such as stimulation site, frequency, intensity, and duration, mainly relies on the therapist's experience or references to previous studies without considering individual differences.Future clinical research should consider the individual characteristics of PSCI patients to improve the reliability, accuracy, and replicability of trials.
The research has a few limitations: (1) Only Chinese and English articles were included, and paper or gray articles were not searched, so there may have been omissions.(2) The study only included 17 pieces of literature, with an average quality rank score of 12.42.The GRADE quality of evidence score was mainly low-quality, and the limited number and low quality of the literature may impact the scientific validity and accuracy of the study results.(3) Despite crossassessment by our study members, the results of this study are inevitably somewhat subjective.Therefore, clinical staff should consider the actual situation when using this data for clinical decision-making.

Conclusion
In conclusion, this study demonstrates the need to further improve the quality of the literature on MAs/SRs of transcranial magnetic stimulation for treating patients with post-stroke cognitive impairment.To ensure higher-quality evidence for clinical use, researchers conducting MAs/SRs should rigorously adhere to the AMSTAR-2 and PRISMA standards, enhancing the quality of analytical approaches and reports.Although current evidence suggests that rTMS enhances global cognitive function and activities of daily living in PSCI patients, this should be corroborated in future studies, considering issues such as low-quality and limited articles.

FIGURE 1 Flow
FIGURE 1Flow chart of the literature search and study selection process.
avoid query bias; (2) when documenting the included studies, it is essential to provide comprehensive details on the subjects, interventions, outcome indicators, study design, and study location;

FIGURE 2
FIGURE 2Radar plot for inclusion literature.
The control group received sham-rTMS, other treatments, or sham-rTMS combined with other therapies.There were no restrictions on the parameters of the stimulation site, stimulation frequency, and stimulation time of rTMS.
CPT) or Visual-CPT; (b) executive function measured by Word of Color Word Test, Color of Color Word Test, Tower of London test, Victoria Stroop Test-time (VST-time), Victoria Stroop Test-error words (VST-error words), Loewenstein Occupational Therapy of Cognitive Assessment (LOTCA), Stroop Color and Word Test-C section (SCWT-Cs), or Stroop Color and Word Test-Consuming (SCWT-C); (c) working memory measured by Digit Symbol Test (DST), Digital Span Test (DS), Digital Span Forward Test (DSF), Digital Span Backward Test (DSB), Trail Making Test-A (TMT-A), Trail Making Test-A times (TMT-A times), Trail Making Test-A errors (TMT-A errors), or Repeatable Battery for the Assessment of Neuropsychological Status (RBANS); (d) memory measured by the Rivermead Behavior Memory Test (RMBT), Verbal learning test, Visual Learning Test, Forward Visual Span, or Backward Visual Span; (e) cognitive deterioration was measured by P300 latency or P300 amplitude.The secondary outcome indicators include (1) activities of daily living measured through the only six 10.3389/fneur.2024.1378731

TABLE 1
Characteristics of included meta-analyses/systematic reviews.

TABLE 2
Multivariate evaluation of the six dimensions and rank of the included literature.
) Studies have shown that rTMS can regulate the levels of growth factors.Vascular