Search

Alzheimer's disease (AD) continues to lack definitive curative therapies, necessitating an urgent exploration of innovative approaches. This review provides a comprehensive analysis of recent clinical trials focusing on invasive and non-invasive brain stimulation techniques as potential interventions for AD. Deep brain stimulation (DBS), repetitive transcranial magnetic stimulation (rTMS), transcranial direct current stimulation (tDCS), and transcranial alternating current stimulation (tACS) are evaluated for their therapeutic efficacy, safety, and applicability. DBS, though invasive, has shown promising results in mitigating cognitive decline, but concerns over surgical risks and long-term effects persist. On the other hand, non-invasive methods like rTMS, tDCS, and tACS have demonstrated potential in enhancing cognitive performance and delaying disease progression, with minimal side effects, but with varied consistency. The evidence hints towards an individualized, patient-centric approach to brain stimulation, considering factors such as disease stage, genetic traits, and stimulation parameters. The review also highlights emerging technologies and potential future directions, emphasizing the need for larger, multi-center trials to confirm preliminary findings and establish robust clinical guidelines. In conclusion, while brain stimulation techniques present a promising avenue in AD therapy, further research is imperative for more comprehensive understanding and successful clinical implementation. Through this review, we aim to catalyze the scientific discourse and stimulate further investigation into these novel interventions for AD. [ABSTRACT FROM AUTHOR]

Background: Repetitive transcranial magnetic stimulation (rTMS) is an advanced and noninvasive technology that uses pulse stimulation to treat cognitive impairment. However, its specific effects have always been mixed with those of cognitive training, and the optimal parameter for Alzheimer's disease (AD) intervention is still ambiguous. Objective: This study aimed to summarize the therapeutic effects of pure rTMS on AD, excluding the influence of cognitive training, and to develop a preliminary rTMS treatment plan. Methods: Between 1 January 2010 and 28 February 2023, we screened randomized controlled clinical trials from five databases (PubMed, Web of Science, Embase, Cochrane, and ClinicalTrials. gov). We conducted a meta-analysis and systematic review of treatment outcomes and rTMS treatment parameters. Result: A total of 4,606 articles were retrieved. After applying the inclusion and exclusion criteria, 16 articles, comprising 655 participants (308 males and 337 females), were included in the final analysis. The findings revealed that rTMS significantly enhances both global cognitive ability (p = 0.0002, SMD = 0.43, 95% CI = 0.20–0.66) and memory (p = 0.009, SMD = 0.37, 95% CI = 0.09–0.65). Based on follow-up periods of at least 6 weeks, the following stimulation protocols have demonstrated efficacy for AD: stimulation sites (single or multiple targets), frequency (20 Hz), stimulation time (1–2 s), interval (20–30 s), single pulses (≤2500), total pulses (>20000), duration (≥3 weeks), and sessions (≥20). Conclusions: This study suggests that rTMS may be an effective treatment option for patients with AD, and its potential therapeutic capabilities should be further developed in the future. [ABSTRACT FROM AUTHOR]

Background: Several medications have been applied to Alzheimer's dementia patients (AD) but their efficacies have been insufficient. The efficacy and safety of 4 weeks of repetitive transcranial magnetic stimulation (rTMS) in Japanese AD were evaluated in this exploratory clinical trial. Methods: Forty-two patients, aged 60-93 years (average, 76.4 years), who were taking medication (> 6 months) and had Mini-Mental State Examination (MMSE) scores ≤ 25 and Clinical Dementia Rating Scale scores (CDR-J) of 1 or 2, were enrolled in this single-center, prospective, randomized, three-arm study [i.e., 120% resting motor threshold (120% RMT), 90% RMT for the bilateral dorsolateral prefrontal cortex, and Sham]. Alzheimer's Disease Assessment Scale-Japanese Cognitive (ADAS-J cog), Montreal Cognitive Assessment (MoCA-J), Clinical Global Impression of Change (CGIC), Neuropsychiatric inventory (NPI), and EuroQOL 5 Dimensions 5-Level (EQ-5D-5L) were administered. The primary endpoint was the mean change from baseline in the MMSE score (week 4). An active rTMS session involved applying 15 trains bilaterally (40 pulses/train at 10 Hz; intertrain interval, 26 s). Participants received ≥ 8 interventions within the first 2 weeks and at least one intervention weekly in the 3rd and 4th weeks. Full Analysis set (FAS) included 40 patients [120% RMT (n = 15), 90% RMT (n = 13), and Sham (n = 12)]. Results: In the FAS, MMSE, ADAS-J cog, MoCA-J, CDR-J, CGIC, NPI, and EQ-5D-5L scores between the three groups were not significantly different. Two patients were erroneously switched between the 120% RMT and 90% RMT groups, therefore, "as treated" patients were mainly analyzed. Post hoc analysis revealed significant treatment efficacy in participants with MMSE scores ≥ 15, favoring the 120% RMT group over the Sham group. Responder analysis revealed 41.7% of the 120% RMT group had a ≥ 3-point improvement in the ADAS-J cog versus 0% in the Sham group (Fisher's exact test, p = 0.045). The MoCA-J showed the same tendency but was not significant. Efficacy disappeared in week 20, based on the ADAS-cog and MoCA-J. No intervention-related serious adverse events occurred. Conclusion: This paper is the first report of using rTMS in Japanese AD patients. The treatment seems safe and moderate-mild stage AD should be target population of pivotal clinical trial with 120% RMT rTMS. [ABSTRACT FROM AUTHOR]

Background: Mild cognitive impairment (MCI) is an intermediary state between normal aging and dementia. It has a high risk of progression in patients with Alzheimer's disease (AD). Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive brain stimulation technique used to improve cognitive deficits in patients with MCI and AD. Although previous meta-analyses included studies carried on patients with MCI and AD, few studies have analyzed patients with MCI independently. This meta-analysis aimed to evaluate the effects and safety of rTMS on cognition function in patients with MCI and factors that may influence such effects. Methods: Data used in this study were searched and screened from different databases, including PubMed, Web of Science, Embase, the Cochrane Library, Chinese National Knowledge Infrastructure (CNKI), Chinese Technical Periodicals (VIP), Wanfang Database, and China BioMedical Literature Database (SinoMed). The retrieved studies were carefully reviewed, data were extracted, and the quality of data was assessed. Results: A total of 12 studies involving 329 patients with MCI were included in the present meta-analysis. The analyses results revealed that rTMS improved cognitive function [standardized mean difference (SMD) = 0.83, 95% confidence interval (CI) = 0.44–1.22, p = 0.0009] and memory function (SMD = 0.73, 95% CI = 0.48–0.97, p < 0.00001) in the MCI + rTMS active group when compared to the sham stimulation group. The showed that: (1) cognitive improvement was more pronounced under high-frequency rTMS stimulation of multiple sites, such as the bilateral dorsolateral prefrontal cortex and (2) more than 10 rTMS stimulation sessions produced higher improvement on cognition function in patients with MCI. Conclusions: This study shows that rTMS can improve cognitive function in patients with MCI, especially when applied at high frequency, multi-site, and for a prolonged period. However, further studies are required to validate these findings and explore more effective stimulation protocols and targets. Systematic Review Registration: [http://www.crd.york.ac.uk/PROSPERO/], identifier: CRD 42021238708. [ABSTRACT FROM AUTHOR]

A growing number of studies is using fMRI-based connectivity to guide transcranial magnetic stimulation (TMS) target identification in both normal and clinical populations. TMS has gained increasing attention as a potential therapeutic strategy also in Alzheimer's disease (AD), but an endorsed target localization strategy in this population is still lacking. In this proof of concept study, we prove the feasibility of a tailored TMS targeting approach for AD, which stems from a network-based perspective. Based on functional imaging, the procedure allows to extract individual optimal targets meanwhile accounting for functional variability. Single-subject resting-state fMRI was used to extract individual target coordinates of two networks primarily affected in AD, the default mode and the fronto-parietal network. The localization of these targets was compared to that of traditional group-level approaches and tested against varying degrees of TMS focality. The distance between individual fMRI-derived coordinates and traditionally defined targets was significant for a supposed TMS focality of 12 mm and in some cases up to 20 mm. Comparison with anatomical labels confirmed a lack of 1:1 correspondence between anatomical and functional targets. The proposed network-based fMRI-guided TMS approach, while accounting for inter-individual functional variability, allows to target core AD networks, and might thus represent a step toward tailored TMS interventions for AD. [ABSTRACT FROM AUTHOR]