Cognitive Enhancement of Repetitive Transcranial Magnetic Stimulation in Patients With Mild Cognitive Impairment and Early Alzheimer's Disease: A Systematic Review and Meta-Analysis.
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SUBMITTER: Xie Y
PROVIDER: S-EPMC8461243 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:IntroductionTranscranial magnetic stimulation (TMS) is a non-invasive intervention that holds promise for improving cognitive function in individuals with Alzheimer's disease (AD). However, the effectiveness of this therapy and the optimal TMS parameters has not reached a consensus. The purpose of the meta-analysis was to systematically discern the effectiveness of different components of TMS protocols on cognitive improvement in patients with mild cognitive impairment (MCI) and AD.MethodsThe meta-analysis was preregistered on Prospero (registration number: CRD42022345482). PubMed, Web of Science, Science Direct, and Cochrane Library databases were used to search, screen and identify eligible studies with the following keywords: Transcranial Magnetic Stimulation OR TMS OR theta burst stimulation AND Alzheimer OR Alzheimers OR Alzheimer's OR mild cognitive impairment OR MCI. Randomized controlled trials (RCTs) of participants with accepted standardized diagnostic criteria were searched by two authors independently. The risk of bias was assessed using an adapted Cochrane Risk of Bias tool. Standardized mean difference (SMD) and 95% confidence interval (CI) were calculated using the random-effects models. Subgroup analyses were performed to investigate the influential factors.ResultsA total of 21 studies and 25 trials were included in this meta-analysis. The findings revealed a significant overall cognition improvement of real stimulation compared with sham stimulation (short-term effects: SMD, 0.91; 95% CI 0.44-1.38; P < 0.01; long-lasting effects: SMD, 0.91; 95% CI 0.27-1.55; P < 0.01). Subgroup analysis demonstrated that stimulation of the left dorsolateral prefrontal cortex and bilateral cerebellums, as well as moderate frequency stimulation (5 Hz and 10 Hz) on mild and moderate cognitive impairment patients, were more effective than other TMS protocols. However, the additional application of cognitive training showed no significant improvement.ConclusionCognitive improvement effect of TMS was demonstrated in MCI and AD patients in both short-term assessment and long-lasting outcomes, and the efficiency of TMS is affected by the stimulation frequency, stimulation site, and participant characteristics. Further RCTs are needed to validate the findings of our subgroup analysis.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022345482, identifier: CRD42022345482.
| S-EPMC10389278 | biostudies-literature
Project description: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.
| S-EPMC7842279 | biostudies-literature
Project description:Apathy is a common and disabling behavioral concomitant of many neurodegenerative conditions. The presence of apathy with Mild Cognitive Impairment (MCI) is linked with heightened rates of conversion to Alzheimer's disease. Improving apathy may slow the neurodegenerative process. The objective was to establish the efficacy of repetitive transcranial magnetic stimulation (rTMS) in improving apathy in older adults with MCI. An 8-week, double-blind, randomized, sham-controlled cross-over study was conducted in nine subjects (66 ± 9 years) with apathy and MCI. Subjects were randomized to rTMS or sham treatment (5 days/week) for 2 weeks following which they underwent a 4-week treatment-free period. Subjects then crossed-over to receive the other treatment for 2 weeks. The primary (apathy (AES-C)) and secondary (cognition (3MS & MMSE), executive function (TMT-A & TMT-B), and clinical global impression (CGI)) outcomes were assessed at baseline, 2, 6, and 8 weeks. After adjusting for baseline, there was a significantly greater improvement in the AES-C with rTMS compared to sham treatment at 2 weeks. There was significantly greater improvement in 3MS, MMSE, TMT-A, and CGI-I with rTMS compared to the sham treatment. This study establishes that rTMS is efficacious in improving apathy in subjects with MCI.
| S-EPMC7334038 | biostudies-literature
Project description:BackgroundAmnestic mild cognitive impairment (aMCI) is considered to be the prodromal stage of Alzheimer's disease (AD). The precuneus (PCUN) may be an imaging marker for monitoring the progression of AD. Meanwhile, cognitive impairment in AD patients is closely related to functional connectivity (FC) changes in the salience network (SN). We hypothesize that there are specific neuroimaging biomarkers in the SN and that FC changes in aMCI patients after repetitive transcranial magnetic stimulation (rTMS) intervention are associated with cognitive function. The purpose of this study was to first investigate the pattern of functional changes in aMCI patients and healthy controls (HCs) and then compare the functional changes in aMCI patients before and after rTMS targeting to PCUN and its correlation with cognitive function.MethodsThirty-six HCs and 61 aMCIs were recruited for our study. Eleven people in the aMCI group received rTMS intervention 5 days a week for 4 weeks. Using the right anterior insula as the seed-of-interest, we first compared FC changes in HC and aMCI patients and then compared cognitive function in aMCI patients before and after rTMS. The above is the functional connection analysis of seed-to-voxel. Moreover, we investigated the FC changes in aMCI patients after rTMS intervention and its correlation with cognitive function.ResultsCompared with HC, the aMCI group showed altered FC in bilateral parahippocampal gyrus, bilateral inferior parietal lobule, left middle frontal gyrus, and left middle temporal gyrus. Moreover, rTMS at PCUN improved the cognitive function of aMCI patients, which was related to the altered FC in posterior cerebellar lobes (CPL).ConclusionsOur findings suggest that rTMS targeting PCUN is a promising, noninvasive approach to ameliorating cognitive dysfunction in aMCI patients, and that this cognitive improvement is accompanied by brain connectivity modulation.
| S-EPMC10498083 | biostudies-literature
Project description:Repetitive transcranial magnetic stimulation (rTMS) is a noninvasive technique that could improve cognitive function. It is being developed as a non-pharmacological intervention to alleviate symptoms of cognitive deterioration. We assessed the efficacy of rTMS in improving cognitive functioning among people with Mild Cognitive Impairment (MCI) in a partially-blinded, sham-controlled randomized trial. Out of 91 subjects screened, 31 participants with MCI (mean age 70.73; SD = 4.47), were randomly assigned to one of three groups: (A) Active rTMS; (B) Active rTMS with Computerized Cognitive Training RehaCom; and (C) Sham control. The study evaluated cognitive function using the DemTect, FAS, and CANTAB tests before and after the stimulation. The following treatment protocol was applied: 2000 pulses at 10 Hz, 5-s train duration, and 25-s intervals at 110% of resting MT delivered over the left Dorsolateral Prefrontal Cortex (DLPFC) five times a week for 2 weeks. After 10 sessions of high-frequency rTMS, there was an improvement in overall cognitive function and memory, assessed by the DemTect evaluation, with no serious adverse effects. Analysis of differences in time (after 10 sessions) between studied groups showed statistically significant improvement in DemTect total score (time by group interaction p = 0.026) in favor of rTMS+RehaCom. The linear regression of CANTAB Paired Associates Learning revealed significant differences in favor of rTMS+RehaCom in three subtests. Our study shows that 10 sessions of rTMS over the left DLPFC (alone as well as combined with Computerized Cognitive Training) can have a positive impact on cognitive function in people with MCI. Further research should investigate the underlying mechanism and determine the optimal parameters for rTMS, which will be important for its efficacy in clinical settings.
| S-EPMC10726746 | biostudies-literature
Project description:Transcranial magnetic stimulation (TMS) is a noninvasive brain stimulation technique with potential to improve memory. Mild cognitive impairment (MCI), which still lacks a specific therapy, is a clinical syndrome associated with increased risk of dementia. This study aims to assess the effects of high-frequency repetitive TMS (HF rTMS) on everyday memory of the elderly with MCI. We conducted a double-blinded randomized sham-controlled trial using rTMS over the left dorsolateral prefrontal cortex (DLPFC). Thirty-four elderly outpatients meeting Petersen's MCI criteria were randomly assigned to receive 10 sessions of either active TMS or sham, 10 Hz rTMS at 110% of motor threshold, 2,000 pulses per session. Neuropsychological assessment at baseline, after the last session (10th) and at one-month follow-up, was applied. ANOVA on the primary efficacy measure, the Rivermead Behavioural Memory Test, revealed a significant group-by-time interaction (p = 0.05), favoring the active group. The improvement was kept after one month. Other neuropsychological tests were heterogeneous. rTMS at 10 Hz enhanced everyday memory in elderly with MCI after 10 sessions. These findings suggest that rTMS might be effective as a therapy for MCI and probably a tool to delay deterioration.
| S-EPMC4487699 | biostudies-literature
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.
| S-EPMC8067941 | biostudies-literature
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.
| S-EPMC6912947 | biostudies-literature
Project description:ObjectivePost-stroke cognitive impairment (PSCI) is resistant to treatment. Recent studies have widely applied repetitive transcranial magnetic stimulation (rTMS) to treat various brain dysfunctions, such as post-stroke syndromes. Nonetheless, a protocol for PSCI has not been established. Therefore, this study is aimed to evaluate the therapeutic effect of our high-frequency rTMS protocol for PSCI during the chronic phase of stroke.MethodsIn this prospective study, ten patients with PSCI were enrolled and received high-frequency rTMS on the ipsilesional dorsolateral prefrontal cortex (DLPFC) for 10 sessions (5 days per week for 2 weeks). Cognitive and affective abilities were assessed at baseline and 2 and 14 weeks after rTMS initiation. To investigate the therapeutic mechanism of rTMS, the mRNA levels of pro-inflammatory cytokines (interleukin (IL)-6, IL-1β, transforming growth factor beta [TGF-β], and tumor necrosis factor alpha [TNF-α]) in peripheral blood samples were quantified using reverse transcription polymerase chain reaction, and cognitive functional magnetic resonance imaging (fMRI) was conducted at baseline and 14 weeks in two randomly selected patients after rTMS treatment.ResultsThe scores of several cognitive evaluations, i.e., the Intelligence Quotient (IQ) of Wechsler Adult Intelligence Scale, auditory verbal learning test (AVLT), and complex figure copy test (CFT), were increased after completion of the rTMS session. After 3 months, these improvements were sustained, and scores on the Mini-Mental Status Examination and Montreal Cognitive Assessment (MoCA) were also increased (p < 0.05). While the Geriatric Depression Scale (GeDS) did not show change among all patients, those with moderate-to-severe depression showed amelioration of the score, with marginal significance. Expression of pro-inflammatory cytokines was decreased immediately after the ten treatment sessions, among which, IL-1β remained at a lower level after 3 months. Furthermore, strong correlations between the decrease in IL-6 and increments in AVLT (r = 0.928) and CFT (r = 0.886) were found immediately after the rTMS treatment (p < 0.05). Follow-up fMRI revealed significant activation in several brain regions, such as the medial frontal lobe, hippocampus, and angular area.ConclusionsHigh-frequency rTMS on the ipsilesional DLPFC may exert immediate efficacy on cognition with the anti-inflammatory response and changes in brain network in PSCI, lasting at least 3 months.
| S-EPMC8980431 | biostudies-literature
Project description:BackgroundCognitive impairment is a prevalent consequence of stroke, seriously affecting recovery and quality of life while imposing substantial burdens on both patients' families and society. Repetitive transcranial magnetic stimulation (rTMS) has emerged as an effective intervention for post-stroke cognitive impairment (PSCI). However, the a lack of standardized and explicit guidelines regarding rTMS application parameters. Therefore, this study systematically evaluated the efficacy of various parameters of rTMS in treating PSCI and explored its potential mechanism.MethodsWe conducted a comprehensive search across seven scientific databases, namely China National Knowledge Infrastructure (CNKI), Wanfang Data Knowledge Service Platform (Wanfang), China Science and Technology Journal Database (VIP), Web of Science, PubMed, Embase, and Cochrane Library, to identify randomized controlled trials (RCTs) investigating the efficacy of rTMS for PSCI. The search encompassed the period from database creation until July 28, 2023. To evaluate the risk of bias in included studies, we employed the Cochrane recommended risk of bias assessment tool. Furthermore, we extracted relevant clinical application parameters associated with rTMS and performed comparative analyses to assess their therapeutic effects under different parameter settings.ResultsThe present study included 45 RCTs involving a total of 3,066 patients with PSCI. Both high-frequency repetitive transcranial magnetic stimulation (HF-rTMS) and low-frequency repetitive transcranial magnetic stimulation (LF-rTMS) demonstrated safety and efficacy, yet failed to exhibit significant differentiation in terms of cognitive improvement. Furthermore, intermittent theta burst stimulation (iTBS), although yielding positive results, did not surpass traditional rTMS in effectiveness. Combining HF-rTMS with LF-rTMS resulted in superior efficacy compared to single rTMS intervention. Moreover, the combination of rTMS with other cognitive therapies exhibited potential for enhanced benefits among patients.ConclusionrTMS can effectively and safely enhance cognitive function, improve quality of life, and enhance activities of daily living in patients with PSCI. Furthermore, the combination of rTMS with other conventional rehabilitation methods can yield additional positive effects. However, due to insufficient evidence, an optimal parameter protocol for rTMS can not be currently recommended. Future research should prioritize orthogonal experimental design methods that incorporate multiple parameters and levels to determine the optimal parameter protocol for rTMS in PSCI.
| S-EPMC10985147 | biostudies-literature