Multi-site rTMS with cognitive training improves apathy in the long term in Alzheimer’s disease: A 4-year chart review

Moreno, Alcira Suarez; Nǵuyen, Jean-Paul; Calmelet, Astrid; Saout, Estelle Le; Damier, Philippe; Decker, Laure de; Malineau, Catherine; Nizard, Julien; Canouï‐Poitrine, Florence; Lefaucheur, Jean‐Pascal

doi:10.1016/j.clinph.2022.02.017

Cited by 8 publications

(16 citation statements)

References 49 publications

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“…It was found that patients who received active stimulation had improved reaction times, whereas those who received sham stimulation showed no improvement ( Vanderhasselt et al, 2006 ). In other report ( Suarez-Moreno et al, 2022 ), long-term improvement in apathy and more general cognitive improvement only in patients who responded well to the initial 6-week NeuroAD™ treatment.…”

Section: Discussionmentioning

confidence: 81%

Randomized, sham-controlled, clinical trial of repetitive transcranial magnetic stimulation for patients with Alzheimer’s dementia in Japan

Saitoh

Hosomi

Mano

et al. 2022

Front. Aging Neurosci.

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BackgroundSeveral 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.MethodsForty-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)].ResultsIn 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.ConclusionThis 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.

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Section: Discussionmentioning

confidence: 81%

Randomized, sham-controlled, clinical trial of repetitive transcranial magnetic stimulation for patients with Alzheimer’s dementia in Japan

Saitoh

Hosomi

Mano

et al. 2022

Front. Aging Neurosci.

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“…It is worth noting that there was an overlap in the participants enrolled in the studies conducted by Cirillo in 2023 and Esposito in 2022. There were 4 studies each that focused on patients with Alzheimer’s (AD) ( n = 143) ( 38 , 41 , 46 , 47 ) and Parkinson’s disease (PD) ( 34 , 36 , 39 , 44 ) ( n = 187), 3 studies involving patients with MCI ( n = 56) ( 35 , 37 , 40 ); and 1 study each for patients with chronic stroke ( n = 13) ( 43 ), mild TBI ( n = 15) ( 45 ), and primary progressive aphasia (PPA) ( n = 20) ( 42 ). The majority of the studies were conducted in Europe (France ( 46 , 47 ), Italy ( 35 , 37 ), and Spain ( 42 )) and North America (Canada ( 34 , 45 ), United States ( 34 , 39–41 )), and 4 studies were performed in East Asia [China ( 36 , 38 ) and Japan ( 43 , 44 )].…”

Section: Resultsmentioning

confidence: 99%

“…Nearly all of the included studies employed high-frequency (HF) rTMS as an intervention ( 34–44 , 46 , 47 ), whereas 2 studies used low-frequency (LF) rTMS ( 44 , 45 ). Two studies used a combination of HF rTMS and cognitive training (“NeuroAD”) ( 46 , 47 ), while one study utilized a combination of HF rTMS and transcranial Direct Current Stimulation (tDCS) ( 38 ). The median intensity of stimulation was 100% of the resting motor threshold (RMT) (ranging from 80 to 120% RMT).…”

Section: Resultsmentioning

confidence: 99%

Repetitive transcranial magnetic stimulation for apathy in patients with neurodegenerative conditions, cognitive impairment, stroke, and traumatic brain injury: a systematic review

Espiritu,

Hara,

Tolledo

et al. 2023

Front. Psychiatry

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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.

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“…Moreover, increased motor excitability and cortical reorganization in AD may explain the frontomedial shift in motor areas, which is interpreted as a compensatory mechanism that preserves motor programming despite AD progression [21]. Most studies have shown that rTMS can effectively enhance the cognition [22,23], emotion [24], and language [25][26][27] in patients with AD. However, other studies have provided different perspectives.…”

Section: Introductionmentioning

confidence: 99%

“…For instance, some studies have suggested that high-frequency rTMS is more effective compared to low-frequency rTMS in enhancing the cognitive abilities of patients with AD [42,43]. The use of multiple targets can result in a more pronounced improvement than using a single target [24,44]. Low-frequency rTMS has also been suggested to improve memory function in patients with AD [45].…”

Section: Introductionmentioning

confidence: 99%

Unlocking the Potential of Repetitive Transcranial Magnetic Stimulation in Alzheimer’s Disease: A Meta-Analysis of Randomized Clinical Trials to Optimize Intervention Strategies

Li,

Lan,

Liu

et al. 2024

JAD

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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.

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Multi-site rTMS with cognitive training improves apathy in the long term in Alzheimer’s disease: A 4-year chart review

Cited by 8 publications

References 49 publications

Randomized, sham-controlled, clinical trial of repetitive transcranial magnetic stimulation for patients with Alzheimer’s dementia in Japan

Randomized, sham-controlled, clinical trial of repetitive transcranial magnetic stimulation for patients with Alzheimer’s dementia in Japan

Repetitive transcranial magnetic stimulation for apathy in patients with neurodegenerative conditions, cognitive impairment, stroke, and traumatic brain injury: a systematic review

Unlocking the Potential of Repetitive Transcranial Magnetic Stimulation in Alzheimer’s Disease: A Meta-Analysis of Randomized Clinical Trials to Optimize Intervention Strategies

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