Non-invasive Brain Stimulation for Dementia

(ACDCStim Trial)

Overseen By HomeStim Study

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Hebrew SeniorLife

Must not be taking: Neuroactive drugs

Disqualifiers: Major psychiatric disorders, Seizures, others

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

Compensation: Varies

Number of Visits: 20

Duration: 4 weeks

144 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a non-invasive brain stimulation method to assist older adults with mild memory issues or mild dementia. The goal is to determine if this treatment can enhance memory, mobility, and thinking skills. Participants will try different combinations of the treatment at home, guided by a caregiver. Individuals with mild cognitive challenges who can follow instructions and have a supportive caregiver might find this trial suitable. As an unphased trial, it provides a unique opportunity to explore innovative treatments in a flexible research setting.

Will I have to stop taking my current medications?

The trial excludes participants using neuroactive drugs, so you may need to stop taking such medications to participate. However, the protocol does not specify a washout period.

What prior data suggests that this non-invasive brain stimulation is safe for older adults with mild cognitive impairment or mild dementia?

Research shows that tACS (transcranial alternating current stimulation) is generally easy for people to handle. In studies with patients who have mild Alzheimer's disease, no serious side effects appeared. Some individuals might experience mild and temporary side effects, but these are not serious.

Similarly, tDCS (transcranial direct current stimulation) is considered safe and non-invasive. Studies indicate it provides a painless way to stimulate the brain. Participants with Alzheimer's disease did not report any significant negative effects.

When combined, tACS and tDCS are safe and well-tolerated, with no severe side effects reported. This combination has been tested in people with mild to moderate Alzheimer's disease.

Overall, current evidence suggests these brain stimulation methods are safe, with only mild and short-lived side effects, if any. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about non-invasive brain stimulation for dementia because it offers a unique approach to managing this condition without drugs. Unlike traditional treatments that often involve medications like cholinesterase inhibitors or memantine, this method uses electrical currents to stimulate specific brain regions, potentially enhancing cognitive function. The study explores different combinations of transcranial alternating current stimulation (tACS) and transcranial direct current stimulation (tDCS), which are applied over the left angular gyrus and prefrontal cortex. This approach could lead to new ways of improving memory and thinking skills with fewer side effects, making it an exciting potential option for those with dementia.

What evidence suggests that this trial's treatments could be effective for dementia?

This trial will evaluate the effects of non-invasive brain stimulation treatments, including transcranial alternating current stimulation (tACS) and transcranial direct current stimulation (tDCS), on improving thinking and memory in people with mild memory problems or dementia. Participants will be assigned to different treatment arms, including combinations of active and sham interventions. Research has indicated that tACS can boost memory and thinking skills, with some studies noting improvements in specific memory tests. Similarly, tDCS has shown significant improvements in overall brain function scores, such as MoCA and MMSE, which measure general brain health. When used together, tACS and tDCS treatments have demonstrated notable improvements in thinking abilities, attention, and mental flexibility. These findings suggest that these brain stimulation methods could effectively address memory and thinking issues in dementia. ^{1 2 3 6 7}

Who Is on the Research Team?

Alvaro Pascual-Leone, MD; PhD

Principal Investigator

Hebrew SeniorLife

Brad Manor, PhD

Principal Investigator

Hebrew SeniorLife

Are You a Good Fit for This Trial?

This trial is for older adults with mild cognitive impairment or mild dementia who can read, write, and communicate in English. They must have a caregiver willing to learn and administer brain stimulation treatments. Participants should not have severe psychiatric disorders, major vision impairments, skin conditions on the scalp, or score below 18 on the MoCA test.

Inclusion Criteria

I am willing and able to consent to participate in the study.

Caregiver/Administrators must have self-reported computer proficiency and willingness to learn how to use tES as defined by 'yes' answers to specific questions

My caregiver is available on weekdays to help with my treatment.

Exclusion Criteria

Participants must not have contraindications to tES, as recorded on a standardized screening questionnaire

I do not have any disabilities that stop me from performing tasks.

Caregiver/Administrators must not have mild cognitive impairment defined by a MoCA score ≤26 during the in-person screen

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Pre-intervention assessments

Participants undergo a set of assessments before the intervention begins

1 week

Treatment

Participants receive daily home-based brain stimulation intervention for 4 weeks

4 weeks

20 sessions (home-based)

Post-intervention assessments

Participants undergo assessments immediately following the brain stimulation intervention

1 week

Follow-up

Participants are monitored for safety and effectiveness at 3 and 6 months post-intervention

6 months

What Are the Treatments Tested in This Trial?

Interventions

• Non-invasive Brain Stimulation

Trial Overview

The study tests if remote brain stimulation by caregivers can improve memory, mobility, and executive function in dementia patients. It involves active/sham transcranial direct current (tDCS) and alternating current (tACS) stimulations to see which combination is effective.

How Is the Trial Designed?

Group I: tACS(AG) + tDCS(PFC) combo active Experimental Treatment 1 Intervention

Participants (Ps) will undergo 20min of daily home-based tACS active + tDCS active intervention over the left angular gyrus and prefrontal cortex for 4 weeks by their trained caregiver/administrators (As).

Group II: tACS(AG) active + tDCS(PFC) sham Active Control 1 Intervention

Participants (Ps) will undergo 20min of daily home-based tACS active + tDCS sham intervention over the left angular gyrus and prefrontal cortex for 4 weeks by their trained caregiver/administrators (As).

Group III: tACS(AG) sham + tDCS(PFC) active Active Control 1 Intervention

Participants (Ps) will undergo 20min of daily home-based tACS sham + tDCS active intervention over the left angular gyrus and prefrontal cortex for 4 weeks by their trained caregiver/administrators (As).

Group IV: tACS(AG) sham + tDCS(PFC) sham Placebo Group 1 Intervention

Participants (Ps) will undergo 20min of daily home-based tACS sham + tDCS sham intervention over the left angular gyrus and prefrontal cortex for 4 weeks by their trained caregiver/administrators (As).

Who Is Running the Clinical Trial?

Hebrew SeniorLife

Lead Sponsor

Trials

52

Recruited

273,000+

BrightFocus Foundation

Collaborator

Trials

5

Recruited

430+

National Institute on Aging (NIA)

Collaborator

Trials

1,841

Recruited

28,150,000+

Published Research Related to This Trial

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]

Transcranial Direct Current Stimulation (tDCS) is generally considered safe, but there are concerns that it could lead to significant negative effects in healthy individuals.

The scientific community needs to be alerted about the potential risks of tDCS, emphasizing the importance of protecting healthy volunteers from possible harm.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of transcranial direct current stimulation in healthy participants. Boccard-Binet, S., Sen, A.[2021]

Noninvasive brain stimulation (NIBS) techniques, particularly repetitive transcranial magnetic stimulation (rTMS), significantly improved behavioral and psychological symptoms of dementia (BPSD) immediately after treatment, with a moderate effect size based on a meta-analysis of 10 studies involving 324 patients.

While rTMS showed lasting benefits at follow-up visits, transcranial direct current stimulation (tDCS) did not demonstrate significant improvements, indicating that rTMS may be a more effective option for managing BPSD in dementia patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The role of noninvasive brain stimulation for behavioral and psychological symptoms of dementia: a systematic review and meta-analysis. Wang, X., Mao, Z., Yu, X.[2021]

A meta-analysis of 4 studies found that transcranial direct current stimulation (tDCS) alone did not significantly improve the naming ability of patients with dementia.

However, when tDCS was combined with language or cognitive training, it resulted in a large effect size (SMD=0.72), indicating a significant improvement in naming ability for dementia patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combined Effects of tDCS and Language/Cognitive Intervention on the Naming of Dementia Patients: A Systematic Review and Meta-Analysis. Byeon, H.[2022]

In a pilot study involving 30 older adults with depression and/or anxiety, transcranial direct current stimulation (tDCS) significantly improved executive functioning, particularly inhibitory processing and cognitive flexibility, as evidenced by better performance on the Stroop test and Trail Making Test-Part B.

The study suggests that tDCS may be a promising non-invasive treatment to enhance cognitive processing in geriatric patients, although it did not show significant effects on attention or working memory.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

tDCS over the left prefrontal Cortex improves mental flexibility and inhibition in geriatric inpatients with symptoms of depression or anxiety: A pilot randomized controlled trial. Figeys, M., Villarey, S., Leung, AWS., et al.[2022]

In a study involving 34 patients with mild cognitive impairment (MCI), those receiving 20 days of anodal transcranial direct current stimulation (tDCS) showed significant improvements in cognitive functions, including episodic verbal memory and overall cognitive function, compared to a sham group.

The results suggest that anodal tDCS may enhance cognitive symptoms in MCI patients, indicating its potential as a therapeutic tool, although further research is needed to clarify the underlying mechanisms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects on cognition of 20-day anodal transcranial direct current stimulation over the left dorsolateral prefrontal cortex in patients affected by mild cognitive impairment: a case-control study. Fileccia, E., Di Stasi, V., Poda, R., et al.[2020]

Transcranial direct current stimulation (tDCS) shows potential as a non-invasive treatment for improving memory in elderly individuals with mild cognitive impairment or Alzheimer's disease, but only five out of 13 studies reviewed demonstrated positive effects.

The study highlighted significant variability in tDCS protocols and noted methodological weaknesses, indicating a need for more rigorous research to better understand the effectiveness and long-term benefits of tDCS on memory.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of Transcranial Direct Current Stimulation on Memory of Elderly People with Mild Cognitive Impairment or Alzheimer's Disease: A Systematic Review. da Silva, ER., Rodrigues Menezes, IR., Brys, I.[2022]

Transcranial direct current stimulation (tDCS) was found to be safe and well-tolerated in a study involving 20 patients with mild or major neurocognitive disorders, with an attrition rate of 0% and no serious adverse events reported.

However, the study did not find any statistically significant improvements in cognitive functioning when comparing the active tDCS group to the sham group, indicating that tDCS may not enhance cognitive performance in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and Feasibility of Transcranial Direct Current Stimulation for Cognitive Rehabilitation in Patients With Mild or Major Neurocognitive Disorders: A Randomized Sham-Controlled Pilot Study. Inagawa, T., Yokoi, Y., Narita, Z., et al.[2022]

Multisession anodal tDCS showed no significant improvement in global cognition or specific cognitive domains in patients with Alzheimer's disease and mild cognitive impairment, with mean differences of -0.13 points and -0.53 points respectively, indicating limited efficacy.

The review included eight studies, highlighting a need for more extensive research with larger sample sizes and standardized outcome measures to better assess the effectiveness of tDCS in cognitive impairment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Meta-Analysis of the Effect of Multisession Transcranial Direct Current Stimulation on Cognition in Dementia and Mild Cognitive Impairment. Inagawa, T., Narita, Z., Sugawara, N., et al.[2022]

Transcranial direct current stimulation (tDCS) has shown promise in enhancing cognitive functions, particularly declarative and working memory, in elderly individuals experiencing cognitive decline, based on a review of 16 studies.

Standardized tDCS protocols, specifically applying 2 mA for 30 minutes over the left dorso-lateral prefrontal cortex, appear to be effective in slowing cognitive deterioration, although individual differences necessitate personalized adjustments for optimal results.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New Methods, Old Brains-A Systematic Review on the Effects of tDCS on the Cognition of Elderly People. Siegert, A., Diedrich, L., Antal, A.[2021]

Low intensity transcranial electrical stimulation (TES) is considered safe, with no serious adverse events reported in over 18,000 sessions across various populations, including healthy individuals and patients with neurological or psychiatric conditions.

While moderate adverse events like skin burns from tDCS are rare, mild adverse events such as headaches and fatigue are more common, and the safety profile is consistent across different age groups and vulnerable populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Low intensity transcranial electric stimulation: Safety, ethical, legal regulatory and application guidelines. Antal, A., Alekseichuk, I., Bikson, M., et al.[2023]

Transcranial direct current stimulation (tDCS) is a low-cost and portable technique that can modulate brain function, making it a promising tool for treating psychiatric disorders.

While tDCS has been widely used in research to study brain processes, its specific effects on psychiatric patients are not well understood, highlighting the need for further investigation into its mechanisms of action and optimal use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The application of tDCS in psychiatric disorders: a brain imaging view. Baeken, C., Brunelin, J., Duprat, R., et al.[2020]

Citations

1.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC7158579/

TRanscranial AlterNating current Stimulation FOR patients ...

In our preliminary experiments, 30 sessions of tACS intervention resulted in improvement in ADAS‐Cog scores (mean ± SD: 3.12 ± 2.35 vs 0.67 ± 2.13). According ...

2.

researchprotocols.org

researchprotocols.org/2022/4/e37282/

The Effect of Transcranial Alternating Current Stimulation ...

The primary outcomes are changes in Wechsler Memory Scale Older Adult Battery and Alzheimer Disease Assessment Scale scores. Secondary outcomes ...

3.

sciencedirect.com

sciencedirect.com/science/article/pii/S1935861X23017412

The impact of gamma transcranial alternating current ...

The application of gamma tACS has shown promising results in the improvement of cognitive and memory processes that are impacted in patients with MCI/AD. These ...

4.

alzres.biomedcentral.com

alzres.biomedcentral.com/articles/10.1186/s13195-024-01570-0

TRanscranial AlterNating current stimulation FOR patients ...

This study aimed to clarify beneficial effects of gamma tACS on cognitive functioning in AD and to elucidate effects on hippocampal gamma oscillation activity.

5.

frontiersin.org

frontiersin.org/journals/aging/articles/10.3389/fragi.2021.632545/full

A Novel Program to Improve Cognitive Function in ...

The results show significant cognitive improvement at post-intervention in both groups, while the Exr + tACS protocol lead to superior cognitive ...

6.

alzres.biomedcentral.com

alzres.biomedcentral.com/articles/10.1186/s13195-023-01297-4

Home-based transcranial alternating current stimulation (tACS ...

Results. We expect that this intervention is safe and feasible and results in the improvement of cognition, entrainment of gamma oscillations, ...

7.

frontiersin.org

frontiersin.org/journals/neurology/articles/10.3389/fneur.2022.962684/full

Transcranial alternating current stimulation combined with ...

In addition, tACS is a safe form of stimulation and may have mild and transient side effects without serious adverse events (9). Therefore, tACS ...