Neuromodulation for Depression and Memory Loss in Older Adults

Overseen By Davide Balos Cappon, MS; PhD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Hebrew SeniorLife

Must not be taking: Neuroactive drugs

Disqualifiers: Seizures, Implanted devices, Eczema, others

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

Compensation: Varies

Number of Visits: 20

Duration: 4 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests two types of brain stimulation treatments to determine their effectiveness for depression and memory problems in older adults with major depressive disorder and dementia. The treatments, transcranial alternating current stimulation (tACS) and transcranial direct current stimulation (tDCS), use gentle electrical currents applied to specific brain areas. Participants will try these treatments at home with a trained caregiver's assistance. Individuals experiencing depression symptoms and memory loss, particularly in the context of dementia, may be well-suited for this study. As an unphased trial, this study provides a unique opportunity to explore innovative treatments that could enhance quality of life.

Will I have to stop taking my current medications?

The trial excludes participants who use 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 neuromodulation therapy is safe for older adults with depression and memory loss?

Research has shown that two types of brain stimulation, tDCS and tACS, have been studied for their safety and effectiveness in treating major depressive disorder (MDD).

One study found that using tDCS at home for MDD was very safe, with participants handling it well over a 10-week period, indicating its general safety for home use. For tACS, some studies did not find it effective for MDD, but others reported good results without serious side effects.

Overall, both treatments appear safe and well-tolerated, with a low risk of side effects. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about using transcranial alternating current stimulation (tACS) and transcranial direct current stimulation (tDCS) for treating depression and memory loss in older adults because these techniques offer a non-invasive way to modulate brain activity. Unlike traditional treatments like medications and psychotherapy, which can take weeks to show effects, tACS and tDCS can potentially deliver quicker results by directly stimulating specific brain regions. This targeted approach might improve cognitive and mood symptoms with fewer side effects, offering a new hope for patients who haven't responded to other treatments. Additionally, the use of home-based sessions makes these treatments more accessible and convenient for older adults, who might face challenges with frequent clinic visits.

What evidence suggests that this trial's treatments could be effective for mood and memory symptoms in older adults with major depressive disorder?

Research has shown that transcranial direct current stimulation (tDCS) can help treat depression. One study found that tDCS significantly improved symptoms of depression. Another study showed that using tDCS at home reduced depressive symptoms over 10 weeks. Regarding transcranial alternating current stimulation (tACS), research indicates it can lessen depression symptoms and enhance thinking skills. One study found that tACS quickly improved depression, especially in women. In this trial, participants will receive both tDCS and tACS, which appear promising for treating mood and memory problems in older adults with major depressive disorder. ^{3 6 7 8 9}

Are You a Good Fit for This Trial?

This trial is for older adults with major depressive disorder and dementia who can follow the study's rules, communicate in English, and have a caregiver over 21 years old to help. Participants must be able to see well enough and not have severe arthritis or skin conditions on the scalp that could interfere with treatment.

Inclusion Criteria

My caregiver is at least 21 years old.

Caregiver/Administrators with self-reported computer proficiency and willingness to learn how to use tES as defined by specific criteria

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

Exclusion Criteria

I don't have conditions or take medications that would make tES unsafe for me.

You scored 18 or lower on the Montreal Cognitive Assessment (MoCA) during the in-person screening.

You have slight problems with memory and thinking, as measured by a test called MoCA with a score of 26 or lower during a face-to-face evaluation.

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 series of assessments before the intervention begins

1 week

Treatment

Participants receive home-based brain stimulation intervention with tDCS and tACS for 20 sessions over 4 weeks

4 weeks

20 sessions (home-based)

Post-intervention Assessments

Participants undergo assessments immediately after the intervention

1 week

Follow-up

Participants are monitored for safety and effectiveness after treatment, with assessments at 3 months post-intervention

3 months

What Are the Treatments Tested in This Trial?

Interventions

• Transcranial alternating current stimulation (tACS)
• Transcranial direct current stimulation (tDCS)

Trial Overview The trial tests home-based brain stimulation therapies—transcranial direct current stimulation (tDCS) and transcranial alternating current stimulation (tACS)—to improve mood and memory symptoms in older adults suffering from depression within the context of dementia.

How Is the Trial Designed?

Group I: tDCS prefrontal cortex + tASC angular gyrus in MDD in the context of AD Experimental Treatment 1 Intervention

Participants will undergo 20 sessions of home-based tDCS over the prefrontal cortex and tACS over the left angular gyrus.These sessions will take place five times a week for four weeks, with one daily stimulation session of no more than 20 minutes. The participant's home will be the setting for the completion of the brain stimulation intervention, which will be delivered by trained caregivers/study companions/administrators.

Who Is Running the Clinical Trial?

Hebrew SeniorLife

Lead Sponsor

Trials

52

Recruited

273,000+

Brain & Behavior Research Foundation

Collaborator

Trials

63

Recruited

2,900+

Published Research Related to This Trial

Transcranial Direct Current Stimulation (tDCS) has been shown to be safe, with no reports of Serious Adverse Effects or irreversible injuries across over 33,200 sessions involving more than 1,000 subjects, including vulnerable populations.

Safety assessments indicate that the current densities used in conventional tDCS (≤4 milliamperes) are significantly lower than those that could potentially cause brain injury, suggesting that tDCS protocols are well within safe limits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of Transcranial Direct Current Stimulation: Evidence Based Update 2016. Bikson, M., Grossman, P., Thomas, C., et al.[2022]

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]

In a study involving 49 healthy older adults, multiple sessions of anodal transcranial direct current stimulation (atDCS) significantly improved item memory performance compared to sham stimulation.

The improvement in memory was associated with increased brain activity in the prefrontal cortex and anterior cingulate cortex, suggesting that atDCS may enhance memory by inducing beneficial neural changes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcranial Direct Current Stimulation Enhances Episodic Memory in Healthy Older Adults by Modulating Retrieval-Specific Activation. Huo, L., Zheng, Z., Huang, J., et al.[2021]

In a case series of 16 treatment-resistant depression patients, home-administered transcranial direct current stimulation (HA-tDCS) showed clinical benefits, with 5 out of 12 patients responding within 6 weeks and 9 maintaining improvements after 12 weeks of treatment.

HA-tDCS was found to be safe and well-tolerated, with no significant cognitive impairments reported over up to 2 years of treatment, although two patients experienced mild side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Clinical Case Series of Acute and Maintenance Home Administered Transcranial Direct Current Stimulation in Treatment-Resistant Depression. Le, B., Alonzo, A., Bull, M., et al.[2023]

A systematic review of 158 studies involving 4130 participants found that repeated sessions of transcranial direct current stimulation (tDCS) do not significantly increase the risk of adverse events compared to sham treatments.

The study indicated that adverse event rates were consistent across different diagnostic groups, suggesting that tDCS is generally safe for various populations, although the potential for rare adverse events cannot be completely excluded.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of repeated sessions of transcranial direct current stimulation: A systematic review. Nikolin, S., Huggins, C., Martin, D., et al.[2019]

In a randomized, sham-controlled trial involving 49 participants with subthreshold depression, 13 days of transcranial direct current stimulation (tDCS) significantly reduced memory bias, indicating potential efficacy in addressing cognitive deficits associated with depression.

The study found that while tDCS did not impact attentional biases, it did lead to decreased mid-frontal alpha power, suggesting this neural measure could be a useful indicator of treatment effects in subthreshold depression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Using multisession tDCS stimulation as an early intervention on memory bias processing in subthreshold depression. Liu, C., Xie, Y., Hao, Y., et al.[2022]

Transcranial direct current stimulation (tDCS) is generally considered safe, with most adverse effects being mild and temporary; however, some cases of persistent skin lesions and rare instances of mania or hypomania have been reported, particularly in patients with depression.

Transcranial alternating current stimulation (tACS) has fewer reported adverse events, and no persistent effects have been documented, but more research is needed to fully establish its safety compared to tDCS.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse events of tDCS and tACS: A review. Matsumoto, H., Ugawa, Y.[2020]

In a study involving 20 participants with mild cognitive impairment due to Alzheimer's disease, γ-tACS significantly improved memory performance, as shown by increased scores on the Rey auditory verbal learning test and face-name associations, compared to sham stimulation.

The γ-tACS also enhanced cholinergic transmission, indicated by increased short latency afferent inhibition measured with TMS, suggesting a potential mechanism for its memory-enhancing effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Exposure to gamma tACS in Alzheimer's disease: A randomized, double-blind, sham-controlled, crossover, pilot study. Benussi, A., Cantoni, V., Cotelli, MS., et al.[2021]

In a study involving 42 healthy adults, both anodal transcranial direct current stimulation (tDCS) and theta transcranial alternating current stimulation (tACS) negatively impacted word recall compared to sham stimulation, indicating potential risks of using these methods for memory enhancement.

Participants experienced significantly more memory errors during tACS than during sham stimulation, suggesting that certain types of transcranial electrical stimulation may hinder rather than help memory processes in the left temporal lobe.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Theta tACS impairs episodic memory more than tDCS. Murray, NWG., Graham, PL., Sowman, PF., et al.[2023]

Repetitive transcranial alternating current stimulation (tACS) can enhance auditory-verbal working memory and long-term memory in older adults (ages 65-88) through targeted modulation of brain activity, showing significant improvements even one month after the intervention.

The study found that individuals with lower baseline cognitive function experienced greater and more lasting memory enhancements, indicating that this neuromodulation technique can effectively leverage the brain's plasticity in aging populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-lasting, dissociable improvements in working memory and long-term memory in older adults with repetitive neuromodulation. Grover, S., Wen, W., Viswanathan, V., et al.[2023]

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]

In a study involving 18 healthy participants, gamma (γ)-tACS showed a selective improvement in working memory performance on a 3-back task compared to tDCS and sham stimulation, suggesting its potential for cognitive enhancement.

The results indicate that γ-tACS may be a more effective method for neuromodulation than traditional tDCS, warranting further investigation into its applications for improving cognitive functions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effect of γ-tACS on working memory performance in healthy controls. Hoy, KE., Bailey, N., Arnold, S., et al.[2018]

In a study involving 15 Alzheimer's disease patients, five consecutive sessions of anodal transcranial direct current stimulation (tDCS) significantly improved visual recognition memory by 8.99% compared to a 2.62% decline with sham stimulation.

The memory improvement persisted for at least 4 weeks after the treatment, suggesting that anodal tDCS could be a promising adjuvant therapy for enhancing memory in Alzheimer's patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prolonged visual memory enhancement after direct current stimulation in Alzheimer's disease. Boggio, PS., Ferrucci, R., Mameli, F., et al.[2022]

Citations

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Transcranial alternating current stimulation and its effects on ... TACS has shown promise in ameliorating symptoms of both schizophrenia and depression in patients. TACS also improves cognition in both patients and healthy ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12177679/

Transcranial Electrical Stimulation in Treatment of Depression This systematic review and meta-analysis evaluates outcomes of various transcranial electrical stimulation treatments in patients with major depressive disorder

3. sciencedirect.com sciencedirect.com/science/article/pii/S1935861X24001025

Effect of add-on transcranial alternating current stimulation ... A study examining tACS's role in treating MDD revealed that tACS with 15 mA and 77.5 Hz was effective in alleviating depressive symptoms in MDD [8]. However, ...

4. psychiatrist.com psychiatrist.com/jcp/remote-trial-transcranial-alternating-current-stimulation-for-depression/

A Fully Remote Randomized Trial of Transcranial ... Conclusions: Rapid, clinically significant improvement in depression in adults with MDD was associated with tACS, particularly for women.

5. frontiersin.org frontiersin.org/journals/psychiatry/articles/10.3389/fpsyt.2024.1419243/full

a systematic review of treatment parameters and outcomes Across studies that published results on tACS outcome measures, tACS resulted in enhanced symptoms and/or improvements in overall psychopathology for ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10507344/

Transcranial alternating current stimulation for the treatment of ... Transcranial alternating current stimulation (tACS) is a non-invasive brain stimulation method that manipulates neural oscillations.

7. nature.com nature.com/articles/s41591-024-03305-y

Home-based transcranial direct current stimulation ... A 10-week home-based tDCS treatment with remote supervision in MDD showed high efficacy, acceptability and safety.

8. jamanetwork.com jamanetwork.com/journals/jamanetworkopen/fullarticle/2835422

Transcranial Electrical Stimulation in Treatment of ... Transcranial direct current stimulation and transcranial alternating current stimulation was associated with positive outcomes among patients with MDD and DPC ...

9. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5977072/

Transcranial Direct Current Stimulation (tDCS) Conclusions: tDCS constitutes a promising therapeutic alternative for patients with MDD, but its place in the therapeutic armamentarium remains ...