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Transcranial pulse stimulation improves MMSE and MoCA scores in patients with Alzheimer's diseaseDifferent brain stimulation methods show specific benefits for Alzheimer's

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Key Takeaway
Note that TPS and rTMS offer specific cognitive improvements, but no single neuromodulation technique is universally superior.

This network meta-analysis evaluated the efficacy of various neuromodulation techniques (NMTs), including rTMS, tACS, tDCS, PBM, TES, TUS, and TPS, in patients with Alzheimer's disease aged 18 years and older. The study synthesized data from 1,445 patients to compare these interventions against sham stimulation across cognitive, functional, and neuropsychiatric outcomes.

Key findings indicate that transcranial pulse stimulation (TPS) significantly improved MMSE (MD = 3.92; 95% CI: 1.57 to 6.35), MoCA (MD = 4.99; 95% CI: 2.26 to 7.72), and BNT (MD = 4.02; 95% CI: 1.81 to 6.23) scores compared to sham. Additionally, rTMS showed favorable effects on ADAS-Cog scores (MD = -11.10; 95% CI: -14.51 to -7.71). Other techniques showed specific strengths: TES ranked highest for ADCS-ADL (SUCRA = 71.00%), TPS ranked highest for NPI (SUCRA = 92.3%), and tACS performed best on GDS (SUCRA = 69.5%).

The authors note that the evidence is limited by small sample sizes, heterogeneous stimulation protocols, and a lack of long-term data. Clinical application is currently limited by the lack of a single superior intervention, as different neuromodulation techniques appear to provide domain-specific benefits for cognitive, functional, or neuropsychiatric symptoms.

How this fits prior evidence

This network meta-analysis extends the evidence regarding rTMS for Alzheimer's disease, which previously showed small to moderate MMSE improvements in mild to moderate cases. This study adds specific data on other neuromodulation techniques, such as transcranial pulse stimulation (TPS), which showed significant improvements in MMSE, MoCA, and BNT scores. It also provides evidence for the efficacy of TES and tACS in specific functional and neuropsychiatric domains.

Living with Alzheimer's disease brings many challenges, from memory loss to changes in mood and daily habits. Because no single treatment works for everyone, researchers looked at several types of neuromodulation. These are techniques that use electricity, magnets, or light to stimulate the brain. They looked at 1,445 patients to see which methods helped with specific symptoms.

The results show that different methods work better for different problems. For example, transcranial pulse stimulation (TPS) helped improve memory scores and naming abilities. Another method, transcutaneous electrical stimulation (TES), ranked highest for helping patients manage their daily activities. Meanwhile, transcranial alternating current stimulation (tACS) showed the best results for improving mood scores.

While these findings are encouraging, the evidence is still early. The study notes that the small sample sizes and different ways the treatments were given make it hard to say which one is best overall. Because of these limitations and the lack of long-term data, patients should talk to their doctors to see which specific approach might fit their unique needs.

What this means for you:
Different brain stimulation methods target specific symptoms like memory, daily tasks, or mood in Alzheimer's patients.

Common questions

What types of brain stimulation were studied?

The study looked at several neuromodulation techniques. These include transcranial pulse stimulation (TPS), transcranial magnetic stimulation (rTMS), transcranial alternating current stimulation (tACS), transcutaneous electrical stimulation (TES), and others like transcranial ultrasound and photobiomodulation.

Which treatment helped with memory and naming?

Transcranial pulse stimulation (TPS) showed significant improvements in memory tests (MMSE and MoCA) and naming tests (BNT) compared to a sham treatment. These tests help measure how well a person can remember information and perform daily tasks.

How do these treatments differ in their results?

No single method was best for everything. For example, TES was ranked highest for helping with daily activities, while tACS showed the best performance for improving mood scores on the Geriatric Depression Scale.

Study Details

Study typeMeta analysis
EvidenceLevel 1
PublishedSep 2026
View Original Abstract ↓
BackgroundNeuromodulation techniques (NMTs) have shown potential therapeutic value in Alzheimer’s disease (AD), but the comparative efficacy of different modalities remains unclear. This study aimed to systematically compare and rank available NMTs to identify their relative benefits across cognitive, functional, and neuropsychiatric outcomes.ObjectiveTo evaluate and rank the efficacy of NMTs in improving cognitive function, activities of daily living (ADLs), and neuropsychiatric symptoms in AD patients, thereby providing evidence-based guidance for clinical intervention strategies.MethodsEnglish-language literature was systematically searched in PubMed, Web of Science, Cochrane Library, and EMBASE from database inception to February 2026. Inclusion criteria were randomized controlled trials (RCTs) of AD patients aged ≥18 years. Interventions included repetitive transcranial magnetic stimulation (rTMS), transcranial alternating current stimulation (tACS), transcranial direct current stimulation (tDCS), photobiomodulation (PBM), transcutaneous electrical stimulation (TES), transcranial ultrasound stimulation (TUS), transcranial pulse stimulation (TPS), deep brain stimulation (DBS), and sham stimulation (Sham). Outcome measures included Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), Alzheimer’ s Disease Assessment Scale-Cognitive Subscale (ADAS-Cog), Alzheimer’ s Disease Cooperative Study-Activities of Daily Living (ADCS-ADL), Boston Naming Test (BNT), Neuropsychiatric Inventory (NPI), and Geriatric Depression Scale (GDS). Data extraction and risk-of-bias assessment followed Cochrane guidelines. Network meta-analysis (NMA) was conducted in Stata 17.0, with effect sizes ranked by the surface under the cumulative ranking curve (SUCRA).ResultsA total of 36 RCTs involving 1,445 patients were included in the analysis. Compared with Sham, TPS significantly improved MMSE (MD = 3.92, 95% CI: 1.57 to 6.35; SUCRA = 97.50%), MoCA (MD = 4.99, 95% CI: 2.26 to 7.72; SUCRA = 69.25%), and BNT scores (MD = 4.02, 95% CI: 1.81 to 6.23; SUCRA = 81.8%). rTMS also showed favorable effects on ADAS-Cog scores (MD = −11.10, 95% CI: −14.51 to −7.71; SUCRA = 91.00%). Regarding activities of daily living, TES ranked highest on the ADCS-ADL scale (SUCRA = 71.00%). In terms of neuropsychiatric symptoms, TPS achieved the highest ranking for improving NPI scores (SUCRA = 92.3%), whereas tACS showed the best performance on GDS scores (SUCRA = 69.5%).ConclusionNeuromodulation interventions demonstrated domain-specific benefits in AD, with no single approach showing universal superiority. TPS demonstrated the greatest potential for improving global cognitive outcomes, while rTMS showed advantages in ADAS-Cog performance. Nevertheless, limited sample sizes, heterogeneous stimulation protocols, and insufficient long-term evidence restrict the generalizability of current findings. Future multicenter RCTs with standardized protocols and prolonged follow-up are needed to confirm these results and guide clinical implementation.Systematic review registrationPROSPERO, CRD420261364193.
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