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Repetitive Transcranial Magnetic Stimulation for Improving Cognitive Function in Patients With Mild Cognitive Impairment: A Systematic Review.

ABSTRACT: Background: Mild cognitive impairment (MCI) is an early stage of Alzheimer's disease. Repetitive transcranial magnetic stimulation (rTMS) has been widely employed in MCI research. However, there is no reliable systematic evidence regarding the effects of rTMS on MCI. The aim of this review was to evaluate the efficacy and safety of rTMS in the treatment of MCI. Methods: A comprehensive literature search of nine electronic databases was performed to identify articles published in English or Chinese before June 20, 2019. The identified articles were screened, data were extracted, and the methodological quality of the included trials was assessed. The meta-analysis was performed using the RevMan 5.3 software. We used the GRADE approach to rate the quality of the evidence. Results: Nine studies comprising 369 patients were included. The meta-analysis showed that rTMS may significantly improve global cognitive function (standardized mean difference [SMD] 2.09, 95% confidence interval [CI] 0.94 to 3.24, p = 0.0004, seven studies, n = 296; low-quality evidence) and memory (SMD 0.44, 95% CI 0.16 to 0.72, p = 0.002, six studies, n = 204; moderate-quality evidence). However, there was no significant improvement in executive function and attention (p > 0.05). Subgroup analyses revealed the following: (1) rTMS targeting the left hemisphere significantly enhanced global cognitive function, while rTMS targeting the bilateral hemispheres significantly enhanced global cognitive function and memory; (2) high-frequency rTMS significantly enhanced global cognitive function and memory; and (3) a high number of treatments ?20 times could improve global cognitive function and memory. There was no significant difference in dropout rate (p > 0.05) between the rTMS and control groups. However, patients who received rTMS had a higher rate of mild adverse effects (risk ratio 2.03, 95% CI 1.16 to 3.52, p = 0.01, seven studies, n = 317; moderate-quality evidence). Conclusions: rTMS appears to improve global cognitive function and memory in patients with MCI and may have good acceptability and mild adverse effects. Nevertheless, these results should be interpreted cautiously due to the relatively small number of trials, particularly for low-frequency rTMS.

SUBMITTER: Jiang L

PROVIDER: S-EPMC7842279 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Repetitive Transcranial Magnetic Stimulation for Improving Cognitive Function in Patients With Mild Cognitive Impairment: A Systematic Review.

Jiang Lijuan L Cui Huiru H Zhang Caidi C Cao Xinyi X Gu Nannan N Zhu Yikang Y Wang Jijun J Yang Zhi Z Li Chunbo C

Frontiers in aging neuroscience 20210114

<b>Background:</b> Mild cognitive impairment (MCI) is an early stage of Alzheimer's disease. Repetitive transcranial magnetic stimulation (rTMS) has been widely employed in MCI research. However, there is no reliable systematic evidence regarding the effects of rTMS on MCI. The aim of this review was to evaluate the efficacy and safety of rTMS in the treatment of MCI. <b>Methods:</b> A comprehensive literature search of nine electronic databases was performed to identify articles published in En ...[more]

PMID: 33519418

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Project description:BackgroundIt had been assumed that suppressing the undamaged contralesional motor cortex by repetitive low-frequency transcranial magnetic stimulation (rTMS) or increasing the excitability of the damaged hemisphere cortex by high-frequency rTMS will promote function recovery after stroke.ObjectivesTo assess the efficacy and safety of rTMS for improving function in people with stroke.Search methodsWe searched the Cochrane Stroke Group Trials Register (April 2012), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2012, Issue 4), the Chinese Stroke Trials Register (April 2012), MEDLINE (1950 to May 2012), EMBASE (1980 to May 2012), Science Citation Index (1981 to April 2012), Conference Proceedings Citation Index-Science (1990 to April 2012), CINAHL (1982 to May 2012), AMED (1985 to May 2012), PEDro (April 2012), REHABDATA (April 2012) and CIRRIE Database of International Rehabilitation Research (April 2012). In addition, we searched five Chinese databases, ongoing trials registers and relevant reference lists.Selection criteriaWe included randomised controlled trials comparing rTMS therapy with sham therapy or no therapy. We excluded trials that reported only laboratory parameters.Data collection and analysisTwo review authors independently selected trials, assessed trial quality and extracted the data. We resolved disagreements by discussion.Main resultsWe included 19 trials involving a total of 588 participants in this review. Two heterogenous trials with a total of 183 participants showed that rTMS treatment was not associated with a significant increase in the Barthel Index score (mean difference (MD) 15.92, 95% CI -2.11 to 33.95). Four trials with a total of 73 participants were not found to have a statistically significant effect on motor function (standardised mean difference (SMD) 0.51, 95% CI -0.99 to 2.01). Subgroup analyses of different stimulation frequencies or duration of illness also showed no significant difference. Few mild adverse events were observed in the rTMS groups, with the most common events being transient or mild headaches (2.4%, 8/327) and local discomfort at the site of the stimulation.Authors' conclusionsCurrent evidence does not support the routine use of rTMS for the treatment of stroke. Further trials with larger sample sizes are needed to determine a suitable rTMS protocol and the long-term functional outcome.

Project description:A more effective and better-tolerated site for repetitive transcranial magnetic stimulation (rTMS) for treating cognitive dysfunction in patients with bipolar disorder (BD) is needed. The primary visual cortex (V1) may represent a suitable site. To investigate the use of the V1, which is functionally linked to the dorsolateral prefrontal cortex (DLPFC) and anterior cingulate cortex (ACC), as a potential site for improving cognitive function in BD. Seed-based functional connectivity (FC) analysis was used to locate targets in the V1 that had significant FC with the DLPFC and ACC. Subjects were randomly assigned to 4 groups, namely, the DLPFC active-sham rTMS (A1), DLPFC sham-active rTMS (A2), ACC active-sham rTMS (B1), and ACC sham-active rTMS groups (B2). The intervention included the rTMS treatment once daily, with five treatments a week for four weeks. The A1 and B1 groups received 10 days of active rTMS treatment followed by 10 days of sham rTMS treatment. The A2 and B2 groups received the opposite. The primary outcomes were changes in the scores of five tests in the THINC-integrated tool (THINC-it) at week 2 (W2) and week 4 (W4). The secondary outcomes were changes in the FC between the DLPFC/ACC and the whole brain at W2 and W4. Of the original 93 patients with BD recruited, 86 were finally included, and 73 finished the trial. Significant interactions between time and intervention type (Active/Sham) were observed in the scores of the accuracy of the Symbol Check in the THINC-it tests at baseline (W0) and W2 in groups B1 and B2 (F = 4.736, p = 0.037) using a repeated-measures analysis of covariance approach. Group B1 scored higher in the accuracy of Symbol Check at W2 compared with W0 (p < 0.001), while the scores of group B2 did not differ significantly between W0 and W2. No significant interactions between time and intervention mode were seen between groups A1 and A2, nor was any within-group significance of FC between DLPFC/ACC and the whole brain observed between baseline (W0) and W2/W4 in any group. One participant in group B1 experienced disease progression after 10 active and 2 sham rTMS sessions. The present study demonstrated that V1, functionally correlated with ACC, is a potentially effective rTMS stimulation target for improving neurocognitive function in BD patients. Further investigation using larger samples is required to confirm the clinical efficacy of TVCS.

Project description:Individuals with amnestic mild cognitive impairment (aMCI) have a high risk of developing Alzheimer's disease. Although repetitive transcranial magnetic stimulation (rTMS) is considered a potentially effective treatment for cognitive impairment in patients with aMCI, the neuroimaging mechanisms are poorly understood. Therefore, we performed a double-blind randomized sham-controlled trial in which rTMS was applied to the left dorsolateral prefrontal cortex of aMCI patients recruited from a community near the Third Hospital Affiliated to Sun Yat-sen University, China. Twenty-four patients with aMCI were randomly assigned to receive true rTMS (treatment group, n = 12, 6 men and 6 women; age 65.08 ± 4.89 years) or sham stimulation (sham group, n = 12, 5 men and 7 women; age 64.67 ± 4.77 years). rTMS parameters included a stimulation frequency of 10 Hz, stimulation duration of 2 seconds, stimulation interval of 8 seconds, 20 repetitions at 80% of the motor threshold, and 400 pulses per session. rTMS/sham stimulation was performed five times per week over a period of 4 consecutive weeks. Our results showed that compared with baseline, Montreal Cognitive Assessment scores were significantly increased and the value of the amplitude of low-frequency fluctuation (ALFF) was significantly increased at the end of treatment and 1 month after treatment. Compared with the sham group, the ALFF values in the right inferior frontal gyrus, triangular part of the inferior frontal gyrus, right precuneus, left angular gyrus, and right supramarginal gyrus were significantly increased, and the ALFF values in the right superior frontal gyrus were significantly decreased in the treatment group. These findings suggest that high-frequency rTMS can effectively improve cognitive function in aMCI patients and alter spontaneous brain activity in cognitive-related brain areas. This study was approved by the Ethics Committee of Shenzhen Baoan Hospital of Southern Medical University, China (approval No. BYL20190901) on September 3, 2019, and registered in the Chinese Clinical Trials Registry (registration No. ChiCTR1900028180) on December 14, 2019.

Project description:BackgroundMild Cognitive Impairment (MCI) carries a high risk of progression to Alzheimer's disease (AD) dementia. Previous clinical trials testing whether cholinesterase inhibitors can slow the rate of progression from MCI to AD dementia have yielded disappointing results. However, recent studies of the effects of repetitive transcranial magnetic stimulation (rTMS) in AD have demonstrated improvements in cognitive function. Because few rTMS trials have been conducted in MCI, we designed a trial to test the short-term efficacy of rTMS in MCI. Yet, in both MCI and AD, we know little about what site of stimulation would be ideal for improving cognitive function. Therefore, two cortical sites will be investigated in this trial: (1) the dorsolateral prefrontal cortex (DLPFC), which has been well studied for treatment of major depressive disorder; and (2) the lateral parietal cortex (LPC), a novel site with connectivity to AD-relevant limbic regions.Methods/designIn this single-site trial, we plan to enroll 99 participants with single or multi-domain amnestic MCI. We will randomize participants to one of three groups: (1) Active DLPFC rTMS; (2) Active LPC rTMS; and (3) Sham rTMS (evenly split between DLPFC and LPC locations). After completing 20 bilateral rTMS treatment sessions, participants will be followed for 6 months to test short-term efficacy and track durability of effects. The primary efficacy measure is the California Verbal Learning Test-II (CVLT-II), assessed 1 week after intervention. Secondary analyses will examine effects of rTMS on other cognitive measures, symptoms of depression, and brain function with respect to the site of stimulation. Finally, selected biomarkers will be analyzed to explore predictors of response and mechanisms of action.DiscussionThe primary aim of this trial is to test the short-term efficacy of rTMS in MCI. Additionally, the project will provide information on the durability of cognitive effects and potentially distinct effects of stimulating DLPFC versus LPC regions. Future efforts would be directed toward better understanding therapeutic mechanisms and optimizing rTMS for treatment of MCI. Ultimately, if rTMS can be utilized to slow the rate of progression to AD dementia, this will be a significant advancement in the field.Trial registrationClinical Trials NCT03331796. Registered 6 November 2017, https://clinicaltrials.gov/ct2/show/NCT03331796. All items from the World Health Organization Trial Registration Data Set are listed in Appendix A.Protocol versionThis report is based on version 1, approved by the DSMB on 30 November, 2017 and amended on 14 August, 2018 and 19 September, 2019.

Project description:BackgroundWe aimed to determine the effects and tolerability of repetitive transcranial magnetic stimulation (rTMS) on apathy in patients with neurodegenerative conditions, mild cognitive impairment (MCI), stroke, and traumatic brain injury (TBI) via systematic review.MethodsWe conducted a systematic search in major electronic health databases, including PubMed, Scopus, and PsycINFO, covering the period from inception to June 2023. Comparative clinical trials and cohort studies, and studies with before-after designs were considered for inclusion. We used the Cochrane Risk of Bias and the National Institutes of Health (NIH) tools to assess methodological quality.ResultsOut of 258 records identified, 14 studies met our eligibility criteria (11 randomized controlled trials (RCT) and 3 studies utilized before-and-after designs) with a total of 418 patients (overall female-to-male ratio 1:1.17) included in the review. The overall methodological quality of the included studies was assessed to be fair to good. The stimulation parameters used varied considerably across the studies. The summary findings of our review indicate the following observations on the effects of rTMS on apathy: (1) the results of all included studies in Alzheimer's disease investigating the effects of rTMS on apathy have consistently shown a positive impact on apathy; (2) the majority of studies conducted in Parkinson's disease have not found statistically significant results; (3) a single study (RCT) on patients with primary progressive aphasia demonstrated significant beneficial effects of rTMS on apathy; (4) the trials conducted on individuals with MCI yielded varying conclusions; (5) one study (RCT) in chronic stroke suggested that rTMS might have the potential to improve apathy; (6) one study conducted on individuals with mild TBI did not find a significant favorable association on apathy; and (7) the use of different rTMS protocols on the populations described is generally safe.ConclusionThe feasibility of utilizing rTMS as a treatment for apathy has been suggested in this review. Overall, limited evidence suggests that rTMS intervention may have the potential to modify apathy among patients with AD, PPA, MCI and chronic stroke, but less so in PD and mild TBI. These findings require confirmation by larger, well-designed clinical trials.

Project description:BackgroundThe development of diagnostic tools capable of accurately identifying the pathophysiology of mild cognitive impairment (MCI) has become a crucial target considering the claim that disease-modifying treatments should be administered as early as possible in the disease course. Transcranial magnetic stimulation (TMS) protocols have demonstrated analytical validity in discriminating different forms of dementia; however, its value in daily clinical practice in MCI subjects is still unknown.ObjectiveTo evaluate the clinical value of TMS compared to amyloid markers on diagnostic confidence and accuracy in MCI subjects, considering clinicians' expertise.MethodsOne hundred seven MCI subjects were included and classified as MCI-Alzheimer disease (MCI-AD), MCI-frontotemporal dementia (MCI-FTD), MCI-dementia with Lewy bodies (MCI-DLB), or MCI-other in a three-step process based on (i) demographic, clinical, and neuropsychological evaluation (clinical work-up); (ii) clinical work-up PLUS amyloidosis markers or clinical work-up PLUS TMS measures; and (iii) clinical work-up PLUS both markers. Two blinded neurologists with different clinical expertise were asked to express a diagnostic confidence for each MCI subgroup, and ROC curve analyses were performed at each step.ResultsThe addition of TMS markers to clinical work-up significantly increased the diagnostic confidence for MCI-AD (p?=?0.003), MCI-FTD (p?=?0.044), and MCI-DLB (p?=?0.033) compared to clinical work-up alone, but not for MCI-other (p?>?0.05). No significant differences between the add-on effect of TMS and the add-on effect of amyloid markers to clinical work-up were observed (p?>?0.732), while the diagnostic confidence further increased when both markers were available. The greater the clinical expertise, the greater the flexibility in considering alternative diagnosis, and the greater the ability to modify diagnostic confidence with TMS and amyloid markers.ConclusionsTMS in addition to routine clinical assessment in MCI subjects has a significant effect on diagnostic accuracy and confidence, comparable to well-established biomarkers of amyloidosis.

Dataset Information

Repetitive Transcranial Magnetic Stimulation for Improving Cognitive Function in Patients With Mild Cognitive Impairment: A Systematic Review.

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Repetitive Transcranial Magnetic Stimulation for Improving Cognitive Function in Patients With Mild Cognitive Impairment: A Systematic Review.

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