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The effects of repetitive transcranial magnetic stimulation in older adults with mild cognitive impairment: a protocol for a randomized, controlled three-arm trial.

ABSTRACT: BACKGROUND:Mild 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/DESIGN:In 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. DISCUSSION:The 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 REGISTRATION:Clinical 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 VERSION:This report is based on version 1, approved by the DSMB on 30 November, 2017 and amended on 14 August, 2018 and 19 September, 2019.

SUBMITTER: Taylor JL

PROVIDER: S-EPMC6912947 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

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The effects of repetitive transcranial magnetic stimulation in older adults with mild cognitive impairment: a protocol for a randomized, controlled three-arm trial.

Taylor Joy L JL Hambro Benjamin C BC Strossman Nicole D ND Bhatt Priyanka P Hernandez Beatriz B Ashford J Wesson JW Cheng Jauhtai Joseph JJ Iv Michael M Adamson Maheen M MM Lazzeroni Laura C LC McNerney Margaret Windy MW

BMC neurology 20191216 1

<h4>Background</h4>Mild 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 designe ...[more]

PMID: 31842821

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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.

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:IntroductionTraumatic brain injury (TBI) is a major public health problem affecting millions worldwide. Despite significant advances in medical care, there are limited effective interventions for improving cognitive and functional outcomes in TBI patients.MethodsThis randomized controlled trial investigated the safety and efficacy of combining repetitive transcranial magnetic stimulation (rTMS) and Cerebrolysin in improving cognitive and functional outcomes in TBI patients. Ninety-three patients with TBI were randomized to receive either Cerebrolysin and rTMS (CRB + rTMS), Cerebrolysin and sham stimulation (CRB + SHM), or placebo and sham stimulation (PLC + SHM). The primary outcome measures were the composite cognitive outcome scores at 3 and 6 months after TBI. Safety and tolerability were also assessed.ResultsThe study results demonstrated that the combined intervention of rTMS and Cerebrolysin was safe and well-tolerated by patients with TBI. Although no statistically significant differences were observed in the primary outcome measures, the descriptive trends in the study support existing literature on the efficacy and safety of rTMS and Cerebrolysin.DiscussionThe findings of this study suggest that rTMS and Cerebrolysin may be effective interventions for improving cognitive and functional outcomes in TBI patients. However, limitations of the study, such as the small sample size and exclusion of specific patient populations, should be considered when interpreting the results. This study provides preliminary evidence for the safety and potential efficacy of combining rTMS and Cerebrolysin in improving cognitive and functional outcomes in TBI patients. The study highlights the importance of multidisciplinary approaches in TBI rehabilitation and the potential for combining neuropsychological measurements and interventions to optimize patient outcomes.ConclusionFurther research is needed to establish these findings' generalizability and identify the optimal dosages and treatment protocols for rTMS and Cerebrolysin.

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.

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The effects of repetitive transcranial magnetic stimulation in older adults with mild cognitive impairment: a protocol for a randomized, controlled three-arm trial.

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The effects of repetitive transcranial magnetic stimulation in older adults with mild cognitive impairment: a protocol for a randomized, controlled three-arm trial.

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