Noninvasive Brain Stimulation for Alzheimer's Disease

Overseen By Robert M. G. Reinhart, PhD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Boston University Charles River Campus

Must be taking: Cholinesterase inhibitors

Disqualifiers: Stroke, Traumatic brain injury, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 1 year

204 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial allows participants to continue taking certain medications, including antidepressants, Alzheimer's medications, and various heart and blood pressure medications. However, if you are on medications not listed, it's best to check with the trial coordinators.

What data supports the effectiveness of the treatment for Alzheimer's disease?

Research suggests that transcranial direct current stimulation (tDCS), a noninvasive method of brain stimulation, may help improve cognitive function and slow cognitive decline in people with Alzheimer's disease. Studies have shown improvements in memory and cognitive stability, indicating potential benefits of this treatment. ^{1 2 3 4 5}

Is noninvasive brain stimulation safe for humans?

Transcranial direct current stimulation (tDCS), including its high-definition version (HD-tDCS), is generally considered safe and well-tolerated for various neurological and psychiatric conditions, with any adverse effects being low and temporary. ^{1 2 6 7 8}

How does noninvasive brain stimulation differ from other treatments for Alzheimer's disease?

Noninvasive brain stimulation, specifically transcranial direct current stimulation (tDCS), is unique because it uses a mild electrical current to stimulate the brain without the need for medication. This method is non-pharmacological, meaning it doesn't involve drugs, and it aims to improve cognitive function and delay cognitive decline in Alzheimer's patients. ^{1 2 9 10 11}

What is the purpose of this trial?

The investigators will evaluate the theory that Alzheimer's disease-related memory impairment derives from the inefficient orchestration of rhythmic activity at the level of large-scale cortical networks. The results as expected to elucidate AD-related pathophysiology and set groundwork for the development of drug-free interventions for improving memory in AD and related dementias.

Eligibility Criteria

This trial is for people aged 50-100 with Alzheimer's or mild cognitive impairment due to Alzheimer's, having certain memory performance scores. Healthy individuals can join if they meet specific cognitive norms. Participants must not have severe mental health issues, significant past brain conditions, or be on excluded medications.

Inclusion Criteria

Do you have a diagnosis of Mild Cognitive Impairment or Alzheimer's disease?

Exclusion Criteria

Have you ever had a diagnosis of epilepsy, or do you have current or past history of seizures?

Do you have a history of neurological problems such as stroke or head injury such as traumatic brain injury?

Do you have any skin sensitivity on your face or scalp (the study involves placing a fabric cap, several electrodes and some water-soluble gel at these sites)?

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive low-intensity, high-definition, transcranial electrical current stimulation while performing computer-based tasks

1 year

Follow-up

Participants are monitored for memory performance and cognitive function after treatment

4 weeks

Treatment Details

Interventions

• High definition transcranial electrical current stimulation

Trial Overview The study tests whether noninvasive brain stimulation using high definition transcranial electrical current can improve memory in those with Alzheimer's by affecting rhythmic activity in the brain. It aims to pave the way for drug-free treatments.

Participant Groups

Group I: active stimulation Experimental Treatment 1 Intervention

Memory performance data is collected during active brain stimulation and reported 1 year later

Group II: sham stimulation Placebo Group 1 Intervention

Memory performance data is collected during sham brain stimulation and reported 1 year later

Who Is Running the Clinical Trial?

Boston University Charles River Campus

Lead Sponsor

Trials

125

Recruited

14,100+

Findings from Research

Transcranial direct current stimulation (tDCS) is a safe and noninvasive method that shows promise in treating cognitive decline associated with Alzheimer's disease and mild cognitive impairment.

The review highlights the need for further large-scale clinical trials to better understand the mechanisms of tDCS and improve its application in clinical settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Potential of Transcranial Direct Current Stimulation in Alzheimer's Disease: Optimizing Trials Toward Clinical Use. Pilloni, G., Charvet, LE., Bikson, M., et al.[2022]

Transcranial direct current stimulation (tDCS) significantly improved cognitive function in patients with mild to moderate Alzheimer's disease, based on a meta-analysis of seven studies involving 146 patients, with a standardized mean difference of 0.37.

Single sessions of tDCS were effective, particularly when stimulating the temporal cortex, while repeated sessions and lower current densities did not show significant benefits, highlighting the need for careful consideration of treatment parameters.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcranial Direct Current Stimulation Improves Cognitive Function in Mild to Moderate Alzheimer Disease: A Meta-Analysis. Cai, M., Guo, Z., Xing, G., et al.[2020]

In a study involving 34 Alzheimer's disease patients, both anodal and cathodal transcranial direct current stimulation (tDCS) significantly improved cognitive function as measured by the mini-mental state examination (MMSE) compared to sham stimulation.

tDCS also reduced the P300 latency, a measure associated with cognitive processing, indicating potential benefits in neurorehabilitation for Alzheimer's patients, although it did not affect motor cortex excitability.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A double-blind randomized clinical trial on the efficacy of cortical direct current stimulation for the treatment of Alzheimer's disease. Khedr, EM., Gamal, NF., El-Fetoh, NA., et al.[2022]

In a study involving 10 patients with Alzheimer's disease, anodal transcranial direct current stimulation (AtDCS) significantly improved recognition memory performance, while cathodal tDCS (CtDCS) led to a decline in performance.

tDCS is shown to be a safe and inexpensive method that could enhance cognitive function in Alzheimer's patients, suggesting potential for further research on its use alongside other treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcranial direct current stimulation improves recognition memory in Alzheimer disease. Ferrucci, R., Mameli, F., Guidi, I., et al.[2022]

A patient with early-onset Alzheimer's disease showed significant improvements in immediate recall (39%) and delayed recall (23%) after daily transcranial direct current stimulation (tDCS) for 8 months, indicating potential cognitive benefits.

The results suggest that tDCS may help stabilize cognitive functions and possibly slow cognitive decline in Alzheimer's disease, warranting further investigation in clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Can 8 months of daily tDCS application slow the cognitive decline in Alzheimer's disease? A case study. Bystad, M., Rasmussen, ID., Grønli, O., et al.[2018]

High-Definition transcranial Direct Current Stimulation (HD-tDCS) at amplitudes up to 4 mA was well tolerated by 292 older adults, with no safety-related adverse events reported and mostly mild sensations experienced during sessions.

The study demonstrated effective blinding for both participants and researchers, indicating that the sham stimulation was convincing, which supports the use of higher amplitudes for potentially greater therapeutic effects in older adults.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tolerability and blinding of high-definition transcranial direct current stimulation among older adults at intensities of up to 4 mA per electrode. El Jamal, C., Harrie, A., Rahman-Filipiak, A., et al.[2023]

A systematic review of 64 studies involving 2262 participants found that transcranial direct current stimulation (tDCS) has a low dropout rate (6% for active and 7.2% for sham), indicating good acceptability among participants.

Despite the low dropout rates, many studies inadequately reported adverse events (AEs), highlighting a need for improved guidelines to standardize AE reporting in tDCS research.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Systematic Review on the Acceptability and Tolerability of Transcranial Direct Current Stimulation Treatment in Neuropsychiatry Trials. Aparício, LVM., Guarienti, F., Razza, LB., et al.[2018]

High Definition transcranial direct current stimulation (HD-tDCS) is safe and well-tolerated in older adults, with no serious adverse events reported during a study involving 101 participants at stimulation intensities of 2 mA and 3 mA.

The study demonstrated effective blinding, as participants could not accurately distinguish between active and sham stimulation, indicating that HD-tDCS can be reliably used in clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tolerability and blinding of 4x1 high-definition transcranial direct current stimulation (HD-tDCS) at two and three milliamps. Reckow, J., Rahman-Filipiak, A., Garcia, S., et al.[2020]

Transcranial electrical stimulation (tES) methods, including tDCS, tACS, tRNS, and tPCS, were effective in reversing cognitive impairments caused by beta-amyloid in a rat model of Alzheimer's disease, indicating potential therapeutic benefits.

Among the different stimulation paradigms, tRNS showed the most significant improvement in memory performance, suggesting that various tES techniques could be viable options for treating cognitive deficits in Alzheimer's patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ameliorative Effects of Different Transcranial Electrical Stimulation Paradigms on the Novel Object Recognition Task in a Rat Model of Alzheimer Disease. Zarifkar, AH., Zarifkar, A., Nami, M., et al.[2022]

A novel treatment combining rTMS and tDCS (rTMS-tDCS) significantly improved neuropsychiatric symptoms in Alzheimer's disease patients compared to single-tDCS and sham treatments, with benefits observed at both 4 and 12 weeks after treatment.

The rTMS-tDCS technique also enhanced cognitive function and sleep quality, demonstrating its efficacy and safety, as adverse events were minimal and short-lived.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of simultaneous rTMS-tDCS over bilateral angular gyrus on neuropsychiatric symptoms in patients with moderate Alzheimer's disease: A prospective, randomized, sham-controlled pilot study. Hu, Y., Jia, Y., Sun, Y., et al.[2023]

This study involves 100 older adults with mild-to-moderate Alzheimer's disease and investigates the effects of 6 months of at-home transcranial direct current stimulation (tDCS) on cognitive performance and other outcomes.

The trial aims to provide robust evidence on the safety and efficacy of tDCS as a treatment for Alzheimer's symptoms, addressing limitations of previous studies that had smaller sample sizes and shorter stimulation durations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neurostimulation for cognitive enhancement in Alzheimer's disease (the NICE-AD study): a randomized clinical trial. Gulley, E., Verghese, J., Blumen, HM., et al.[2022]

References

1. Korea (South) pubmed.ncbi.nlm.nih.gov

Potential of Transcranial Direct Current Stimulation in Alzheimer's Disease: Optimizing Trials Toward Clinical Use. [2022]

2. United States pubmed.ncbi.nlm.nih.gov

Transcranial Direct Current Stimulation Improves Cognitive Function in Mild to Moderate Alzheimer Disease: A Meta-Analysis. [2020]

3. Switzerland pubmed.ncbi.nlm.nih.gov

A double-blind randomized clinical trial on the efficacy of cortical direct current stimulation for the treatment of Alzheimer's disease. [2022]

4. United States pubmed.ncbi.nlm.nih.gov

Transcranial direct current stimulation improves recognition memory in Alzheimer disease. [2022]

5. England pubmed.ncbi.nlm.nih.gov

Can 8 months of daily tDCS application slow the cognitive decline in Alzheimer's disease? A case study. [2018]

6. United States pubmed.ncbi.nlm.nih.gov

Tolerability and blinding of high-definition transcranial direct current stimulation among older adults at intensities of up to 4 mA per electrode. [2023]

7. United States pubmed.ncbi.nlm.nih.gov

A Systematic Review on the Acceptability and Tolerability of Transcranial Direct Current Stimulation Treatment in Neuropsychiatry Trials. [2018]

8. United States pubmed.ncbi.nlm.nih.gov

Tolerability and blinding of 4x1 high-definition transcranial direct current stimulation (HD-tDCS) at two and three milliamps. [2020]

9. Iran pubmed.ncbi.nlm.nih.gov

Ameliorative Effects of Different Transcranial Electrical Stimulation Paradigms on the Novel Object Recognition Task in a Rat Model of Alzheimer Disease. [2022]

10. United States pubmed.ncbi.nlm.nih.gov

Efficacy and safety of simultaneous rTMS-tDCS over bilateral angular gyrus on neuropsychiatric symptoms in patients with moderate Alzheimer's disease: A prospective, randomized, sham-controlled pilot study. [2023]

11. England pubmed.ncbi.nlm.nih.gov

Neurostimulation for cognitive enhancement in Alzheimer's disease (the NICE-AD study): a randomized clinical trial. [2022]