Neuromodulation for Depression and Memory Loss in Older Adults
Recruiting in Palo Alto (17 mi)
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Academic
Recruiting
Sponsor: Hebrew SeniorLife
Must not be taking: Neuroactive drugs
Disqualifiers: Seizures, Implanted devices, Eczema, others
No Placebo Group
Trial Summary
What is the purpose of this trial?This project aims to explore the feasibility and effects of a symptom-specific, brain-circuit-based, home-based neuromodulation therapy for addressing mood and memory symptoms in older adults with major depressive disorder (MDD) in the context of dementia.
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 data supports the effectiveness of the treatment for depression and memory loss in older adults?
Research shows that transcranial direct current stimulation (tDCS) can help improve depression symptoms and memory in older adults. One study found that tDCS improved memory performance in healthy older adults, while another study showed that tDCS could enhance memory in Alzheimer's patients. Additionally, transcranial alternating current stimulation (tACS) has been shown to improve working memory in healthy individuals, suggesting potential benefits for cognitive functions.
12345Is transcranial direct current stimulation (tDCS) and transcranial alternating current stimulation (tACS) safe for humans?
Both tDCS and tACS are generally considered safe for humans, with most side effects being mild and temporary. However, tDCS has been associated with rare cases of skin irritation and mood changes, and there is one report of a seizure in a child, though the link to tDCS is unclear. tACS has fewer safety reports, but no persistent adverse effects have been noted.
678910How does the treatment of tACS and tDCS for depression and memory loss in older adults differ from other treatments?
tACS and tDCS are unique because they are non-invasive brain stimulation techniques that use electrical currents to modulate brain activity, potentially improving memory and reducing depression symptoms without the need for medication. Unlike traditional treatments, these methods can be administered at home and have shown promise in enhancing specific types of memory in older adults.
15111213Eligibility Criteria
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.
+6 more
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.
+5 more
Trial Timeline
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
Participant Groups
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.
1Treatment groups
Experimental Treatment
Group I: tDCS prefrontal cortex + tASC angular gyrus in MDD in the context of ADExperimental Treatment1 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.
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Hinda and Arthur Marcus Institute for Aging ResearchBoston, MA
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Who Is Running the Clinical Trial?
Hebrew SeniorLifeLead Sponsor
Brain & Behavior Research FoundationCollaborator
References
Transcranial Direct Current Stimulation Enhances Episodic Memory in Healthy Older Adults by Modulating Retrieval-Specific Activation. [2021]Memory decline has become an issue of major importance in the aging society. Anodal transcranial direct current stimulation (atDCS) is a viable tool to counteract age-associated episodic memory deterioration. However, the underlying neural mechanisms are unclear. In this single-blind, sham-controlled study, we combined atDCS and functional magnetic resonance imaging to assess the behavioral and neural consequences of multiple-session atDCS in older adults. Forty-nine healthy older adults received either 10 sessions of anodal or sham stimulation over the left dorsolateral prefrontal cortex. Before and after stimulation, participants performed a source memory task in the MRI scanner. Compared to sham stimulation, atDCS significantly improved item memory performance. Additionally, atDCS significantly increased regional brain activity around the stimulation area in the prefrontal cortex and extended to the bilateral anterior cingulate cortex. Neural changes in the prefrontal cortex correlated with memory gains. Our findings therefore indicate that multiple-session offline atDCS may improve memory in older adults by inducing neural alterations.
The effect of γ-tACS on working memory performance in healthy controls. [2018]Transcranial Direct Current Stimulation (tDCS) has been widely investigated for its potential to enhance cognition, and in particular working memory, however to date standard approaches to stimulation have shown only modest effects. Alternative, more specialised, forms of current delivery may be better suited to cognitive enhancement. One such method is transcranial Alternating Current Stimulation (tACS) which delivers stimulation at a specific frequency and has been shown to entrain endogenous cortical oscillations which underlie cognitive functioning. To date there has been no comparison of the effects of tACS to those of tDCS on cognitive enhancement. In a randomised repeated-measures study design we assessed the effect of gamma (γ)-tACS, tDCS and sham tDCS on working memory in 18 healthy participants who attended three sessions held at least 72h apart. Pre- and post-stimulation working memory performance was assessed using the 2 and 3-back. Our findings indicated the presence of a selective improvement in performance on the 3-back task following γ-tACS compared with tDCS and sham stimulation. The current findings provide support for further and more detailed investigation of the role of γ-tACS as a more specialised approach to neuromodulation.
Prolonged visual memory enhancement after direct current stimulation in Alzheimer's disease. [2022]Immediately after patients with Alzheimer's disease (AD) receive a single anodal transcranial direct current stimulation (tDCS) session their memory performance improves. Whether multiple tDCS sessions improve memory performance in the longer term remains unclear.
Exposure to gamma tACS in Alzheimer's disease: A randomized, double-blind, sham-controlled, crossover, pilot study. [2021]To assess whether exposure to non-invasive brain stimulation with transcranial alternating current stimulation at γ frequency (γ-tACS) applied over Pz (an area overlying the medial parietal cortex and the precuneus) can improve memory and modulate cholinergic transmission in mild cognitive impairment due to Alzheimer's disease (MCI-AD).
A Clinical Case Series of Acute and Maintenance Home Administered Transcranial Direct Current Stimulation in Treatment-Resistant Depression. [2023]Transcranial direct current stimulation (tDCS) is a noninvasive neurostimulation technique being translated clinically for the treatment of depression. There is limited research documenting the longer-term effectiveness and safety of tDCS treatment. This case series is the first report of remotely supervised, home-administered tDCS (HA-tDCS) for depression in a clinical setting.
Adverse events of tDCS and tACS: A review. [2020]Transcranial direct current stimulation (tDCS) and transcranial alternating current stimulation (tACS) have been applied to many research issues because these stimulation techniques can modulate neural activity in the human brain painlessly and non-invasively with weak electrical currents. However, there are no formal safety guidelines for the selection of stimulus parameters in either tDCS or tACS. As a means of gathering the information that is needed to produce safety guidelines, in this article, we summarize the adverse events of tDCS and tACS. In both stimulation techniques, most adverse effects are mild and disappear soon after stimulation. Nevertheless, several papers have reported that, in tDCS, some adverse events persist even after stimulation. The persistent events consist of skin lesions similar to burns, which can arise even in healthy subjects, and mania or hypomania in patients with depression. Recently, one paper reported a pediatric patient presenting with seizure after tDCS, although the causal relationship between stimulation and seizure is not clear. As this seizure is the only serious adverse events yet reported in connection with tDCS, tDCS is considered safe. In tACS, meanwhile, no persistent adverse events have been reported, but considerably fewer reports are available on the safety of tACS than on the safety of tDCS. Therefore, to establish the safety of tDCS and tACS, we need to scan the literature continuously for information on the adverse events of both stimulation techniques. Further safety investigations are also required.
Tolerability and blinding of 4x1 high-definition transcranial direct current stimulation (HD-tDCS) at two and three milliamps. [2020]Transcranial direct current stimulation (tDCS) is an in-demand form of neuromodulation generally regarded as safe and well tolerated. However, few studies have examined the safety, tolerability, or blinding of High Definition (HD-) tDCS, especially in older adults and at stimulation intensities of 2 milliamps (mA) or greater.
Safety of Transcranial Direct Current Stimulation: Evidence Based Update 2016. [2022]This review updates and consolidates evidence on the safety of transcranial Direct Current Stimulation (tDCS). Safety is here operationally defined by, and limited to, the absence of evidence for a Serious Adverse Effect, the criteria for which are rigorously defined. This review adopts an evidence-based approach, based on an aggregation of experience from human trials, taking care not to confuse speculation on potential hazards or lack of data to refute such speculation with evidence for risk. Safety data from animal tests for tissue damage are reviewed with systematic consideration of translation to humans. Arbitrary safety considerations are avoided. Computational models are used to relate dose to brain exposure in humans and animals. We review relevant dose-response curves and dose metrics (e.g. current, duration, current density, charge, charge density) for meaningful safety standards. Special consideration is given to theoretically vulnerable populations including children and the elderly, subjects with mood disorders, epilepsy, stroke, implants, and home users. Evidence from relevant animal models indicates that brain injury by Direct Current Stimulation (DCS) occurs at predicted brain current densities (6.3-13 A/m(2)) that are over an order of magnitude above those produced by conventional tDCS. To date, the use of conventional tDCS protocols in human trials (≤40 min, ≤4 milliamperes, ≤7.2 Coulombs) has not produced any reports of a Serious Adverse Effect or irreversible injury across over 33,200 sessions and 1000 subjects with repeated sessions. This includes a wide variety of subjects, including persons from potentially vulnerable populations.
Safety of repeated sessions of transcranial direct current stimulation: A systematic review. [2019]Repeated sessions of transcranial direct current stimulation (tDCS) are increasingly used for therapeutic applications. However, adverse events (AEs) associated with repeated sessions have not been comprehensively evaluated.
A Systematic Review on the Acceptability and Tolerability of Transcranial Direct Current Stimulation Treatment in Neuropsychiatry Trials. [2018]Transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation investigated as a treatment for several neuropsychiatric disorders. Notwithstanding tDCS-induced adverse events (AEs) are considered to be low and transient, systematic review analyses on safety and tolerability of tDCS derive mostly from single-session studies.
Using multisession tDCS stimulation as an early intervention on memory bias processing in subthreshold depression. [2022]Transcranial direct current stimulation (tDCS) as an intervention tool has gained promising results in major depression disorder. However, studies related to subthreshold depression's (SD) cognitive deficits and neuromodulation approaches for the treatment of SD are still rare. We adopted Beck's cognitive model of depression and tested the tDCS stimulation effects on attentional and memory deficits on SD. First, this was a single-blinded, randomized, sham-controlled clinical trial to determine a 13-day tDCS modulation effect on 49 SD (27: Stimulation; 22: Sham) and 17 healthy controls. Second, the intervention effects of the consecutive and single-session tDCS were compared. Furthermore, the attentional and memory biases were explored in SD. Anodal tDCS was administrated over left dorsolateral prefrontal cortex for 13 consecutive days. Attentional and memory bias were assessed through a modified Sternberg task and a dot-probe task on the 1st, 2nd, and 15th day while their EEG was being recorded. After the 13-day tDCS stimulation (not after single-session stimulation), we found reduced memory bias (Stimulation vs. Sham, p = .02, r2  = .09) and decreased mid-frontal alpha power (p < .01, r2  = .13). In contrast, tDCS did not affect any attentional related behavioral or neural indexes (all ps > .15). Finally, reduced depressive symptoms (e.g., BDI score) were found for both groups. The criteria of SD varied across studies; the efficacy of this protocol should be tested in elderly patients. Our study suggests memory bias of SD can be modulated by the multisession tDCS and alpha power could serve as a neural index for intervention.
Long-lasting, dissociable improvements in working memory and long-term memory in older adults with repetitive neuromodulation. [2023]The development of technologies to protect or enhance memory in older people is an enduring goal of translational medicine. Here we describe repetitive (4-day) transcranial alternating current stimulation (tACS) protocols for the selective, sustainable enhancement of auditory-verbal working memory and long-term memory in 65-88-year-old people. Modulation of synchronous low-frequency, but not high-frequency, activity in parietal cortex preferentially improved working memory on day 3 and day 4 and 1 month after intervention, whereas modulation of synchronous high-frequency, but not low-frequency, activity in prefrontal cortex preferentially improved long-term memory on days 2-4 and 1 month after intervention. The rate of memory improvements over 4 days predicted the size of memory benefits 1 month later. Individuals with lower baseline cognitive function experienced larger, more enduring memory improvements. Our findings demonstrate that the plasticity of the aging brain can be selectively and sustainably exploited using repetitive and highly focalized neuromodulation grounded in spatiospectral parameters of memory-specific cortical circuitry.
Theta tACS impairs episodic memory more than tDCS. [2023]Episodic memory deficits are a common consequence of aging and are associated with a number of neurodegenerative disorders (e.g., Alzheimer's disease). Given the importance of episodic memory, a great deal of research has investigated how we can improve memory performance. Transcranial electrical stimulation (TES) represents a promising tool for memory enhancement but the optimal stimulation parameters that reliably boost memory are yet to be determined. In our double-blind, randomised, sham-controlled study, 42 healthy adults (36 females; 23.3 ± 7.7 years of age) received anodal transcranial direct current stimulation (tDCS), theta transcranial alternating current stimulation (tACS) and sham stimulation during a list-learning task, over three separate sessions. Stimulation was applied over the left temporal lobe, as encoding and recall of information is typically associated with mesial temporal lobe structures (e.g., the hippocampus and entorhinal cortex). We measured word recall within each stimulation session, as well as the average number of intrusion and repetition errors. In terms of word recall, participants recalled fewer words during tDCS and tACS, compared to sham stimulation, and significantly fewer words recalled during tACS compared with tDCS. Significantly more memory errors were also made during tACS compared with sham stimulation. Overall, our findings suggest that TES has a deleterious effect on memory processes when applied to the left temporal lobe.