tDCS for Cognitive Impairment in Parkinson's Disease

(tDCS-PD-fMRI Trial)

Overseen By Ji Hyun Ko, PhD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: University of Manitoba

Must not be taking: Tricyclics, Neuroleptics, others

Disqualifiers: Dementia, Severe hypertension, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 6 weeks

36 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, if you are taking tricyclic antidepressants, neuroleptic medications, or other drugs that lower seizure threshold, you may not be eligible to participate.

What data supports the effectiveness of the treatment High-definition transcranial direct current stimulation (tDCS) for cognitive impairment in Parkinson's Disease?

Research shows that tDCS can improve certain cognitive functions in Parkinson's patients, like executive functions, which involve planning and decision-making. However, the effects on other cognitive areas like memory and attention are less clear, and more research is needed to confirm long-term benefits. ^{1 2 3 4 5}

Is transcranial direct current stimulation (tDCS) safe for humans?

Research shows that tDCS is generally safe for humans, with no reports of serious or lasting side effects when used at standard levels (up to 4 milliamperes for 40 minutes). This includes studies involving over 33,200 sessions and 1,000 subjects, even among potentially vulnerable groups like the elderly and those with mood disorders. ^{3 6 7 8 9}

How does high-definition transcranial direct current stimulation (tDCS) differ from other treatments for cognitive impairment in Parkinson's disease?

High-definition transcranial direct current stimulation (tDCS) is unique because it is a non-invasive brain stimulation technique that modulates brain activity to improve cognitive and motor functions in Parkinson's disease, unlike traditional drug therapies that primarily target symptoms through medication. It involves applying a mild electrical current to specific brain areas, which can enhance cognitive abilities and reduce movement-related symptoms without the side effects associated with medications. ^{1 2 3 4 5}

What is the purpose of this trial?

Parkinson's disease (PD) has been classically regarded as a "movement disorder", so earlier work has focused on treating motor symptoms only. As PD patients now have longer life expectancy, the relatively slowly progressing cognitive deficits (compared to their motor deficits) have become one of the major challenges. Approximately 80% of PD patients eventually become demented. Therefore cognitive dysfunction is one of the most significant factors affecting the quality of life of patients with PD. While dementia in Parkinson's disease is routinely treated by cholinesterase inhibitors (e.g., donepezil and rivastigmine), their efficacy on mild cognitive impairment found in non-demented PD is questionable. Alternative approaches have been proposed including transcranial direct current stimulation (tDCS) but no consensus has been reached. This can be attributed mainly to: (1) imprecise knowledge of the underlying functional circuitry mediating this disease manifestation and (2) inter-individual variability. Here, the investigators will utilize a novel personalized network analysis approach to elucidate on the underlying mechanisms of the effect of tDCS on cognitive dysfunction in non-demented PD patients. It has been well documented that the caudate nucleus plays an important role in cognitive dysfunction found in PD. In the investigators' preliminary resting-state functional magnetic resonance imaging (fMRI) study, they have shown that the connectivity of the right caudate nucleus is correlated to cognitive status of PD patients measured by the Montreal Cognitive Assessment (MoCA). The investigators hypothesize that tDCS on the left and/or right dorsolateral prefrontal cortex may restore the functional connectivity of the right caudate nucleus which may in turn improve patients' cognitive performance.

Eligibility Criteria

This trial is for English-speaking adults over 40 with Parkinson's Disease who can consent and have at least two classic symptoms without other known causes. They should not be demented, as determined by a specific cognitive test, and must not have severe movement issues that could affect scans.

Inclusion Criteria

My mental health will be checked by a specialist.

Fluent in English

I have been diagnosed with Parkinson's disease based on having at least two main symptoms.

Exclusion Criteria

I experience unusual movement or sensory symptoms not typical for Parkinson's disease.

I am not pregnant or breastfeeding.

You have other health conditions that can change the balance of minerals in your body or make you more likely to have seizures.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive transcranial direct current stimulation (tDCS) on the left and/or right dorsolateral prefrontal cortex to improve cognitive performance

6 weeks

Weekly visits for tDCS sessions

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• High-definition transcranial direct current stimulation

Trial Overview The study tests if high-definition transcranial direct current stimulation (tDCS) on the prefrontal cortex can improve cognitive function in non-demented Parkinson's patients by affecting brain connectivity.

Participant Groups

Group I: Real tDCS right Active Control 1 Intervention

Real anodal tDCS (right DLPFC)

Group II: Sham tDCS Placebo Group 1 Intervention

sham tDCS (30sec ramp-up and 3sec ramp-down)

Who Is Running the Clinical Trial?

University of Manitoba

Lead Sponsor

Trials

628

Recruited

209,000+

Parkinson Society Canada

Collaborator

Trials

4

Recruited

160+

Findings from Research

Transcranial direct current stimulation (tDCS) shows potential in improving executive functions in Parkinson's disease patients, with a strong effect size (g = 1.51) reported in a meta-analysis of 8 studies involving 168 participants.

However, the study found no significant effects on other cognitive areas like attention, memory, and language, and it could not establish a clear cause-effect relationship between tDCS and cognitive improvements, indicating the need for further research and methodological enhancements.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcranial Direct Current Stimulation to Enhance Cognitive Impairment in Parkinson's Disease: A Systematic Review and Meta-Analysis. Suarez-García, DMA., Grisales-Cárdenas, JS., Zimerman, M., et al.[2020]

Transcranial direct current stimulation (tDCS) has shown significant improvements in motor function for patients with Parkinson's disease (PD), based on a systematic review of 10 studies conducted over the last decade.

While tDCS appears to enhance neurophysiological mechanisms in the PD brain, the exact physiological processes behind its long-term effects on cortical excitability remain unclear, indicating a need for further research.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcranial direct current stimulation in Parkinson's disease: Neurophysiological mechanisms and behavioral effects. Broeder, S., Nackaerts, E., Heremans, E., et al.[2019]

In a study involving nine patients with Parkinson's disease, five consecutive days of anodal transcranial direct current stimulation (tDCS) over the motor cortex and cerebellum significantly improved levodopa-induced dyskinesias, as measured by the UPDRS IV scale (p < 0.001).

While the study showed promising results for reducing dyskinesias, other motor and cognitive symptoms did not show significant changes with either tDCS or sham treatment, indicating that tDCS may specifically target dyskinesias in Parkinson's patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cerebellar and Motor Cortical Transcranial Stimulation Decrease Levodopa-Induced Dyskinesias in Parkinson's Disease. Ferrucci, R., Cortese, F., Bianchi, M., et al.[2019]

Transcranial direct current stimulation (tDCS) may enhance global cognition and recognition memory in Alzheimer's disease (AD) patients, and improve certain executive functions in Parkinson's disease (PD) patients, based on a systematic review of 17 randomized controlled trials.

Despite these promising results, the review highlights the need for larger studies with standardized measures and long-term follow-ups to better understand the lasting effects of tDCS and to refine clinical guidelines for its application in neurodegenerative disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcranial Direct Current Stimulation (tDCS) as a Useful Rehabilitation Strategy to Improve Cognition in Patients With Alzheimer's Disease and Parkinson's Disease: An Updated Systematic Review of Randomized Controlled Trials. Cammisuli, DM., Cignoni, F., Ceravolo, R., et al.[2022]

In a study of 18 Parkinson's disease patients, anodal transcranial direct current stimulation (tDCS) at 2 mA on the left dorsolateral prefrontal cortex significantly improved working memory performance compared to sham stimulation.

The study suggests that the effectiveness of tDCS in enhancing cognitive function in Parkinson's patients is influenced by both the intensity of the stimulation and the specific brain area targeted, highlighting the potential for tailored noninvasive brain therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of transcranial direct current stimulation on working memory in patients with Parkinson's disease. Boggio, PS., Ferrucci, R., Rigonatti, SP., et al.[2022]

In a pilot study involving five healthy adults, repeated transcranial direct current stimulation (tDCS) significantly improved regional cerebral blood flow in the right superior frontal gyrus, suggesting potential cognitive enhancement.

The tDCS sessions were well-tolerated with no reported adverse events, indicating a safe application of this technique for enhancing brain function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Changes of regional cerebral blood flow after repeated transcranial direct current stimulation in healthy participants: a pilot study. Jeong, H., Song, IU., Chung, YA., et al.[2023]

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]

Transcranial direct current stimulation (tDCS) has been found to be safe for use in humans, with no severe complications reported in studies involving both adults and children when applied at intensities of 4 mA or less for up to 60 minutes.

Animal studies indicate that the electrical current used in tDCS is significantly lower than the threshold that could cause permanent changes to brain tissue, suggesting a strong safety profile for this neurorehabilitation method.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of Transcranial Direct Current Stimulation in Neurorehabilitation. Ko, MH.[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]

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

Transcranial Direct Current Stimulation to Enhance Cognitive Impairment in Parkinson's Disease: A Systematic Review and Meta-Analysis. [2020]

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

Transcranial direct current stimulation in Parkinson's disease: Neurophysiological mechanisms and behavioral effects. [2019]

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

Cerebellar and Motor Cortical Transcranial Stimulation Decrease Levodopa-Induced Dyskinesias in Parkinson's Disease. [2019]

4. Switzerland pubmed.ncbi.nlm.nih.gov

Transcranial Direct Current Stimulation (tDCS) as a Useful Rehabilitation Strategy to Improve Cognition in Patients With Alzheimer's Disease and Parkinson's Disease: An Updated Systematic Review of Randomized Controlled Trials. [2022]

5. Netherlands pubmed.ncbi.nlm.nih.gov

Effects of transcranial direct current stimulation on working memory in patients with Parkinson's disease. [2022]

6. England pubmed.ncbi.nlm.nih.gov

Changes of regional cerebral blood flow after repeated transcranial direct current stimulation in healthy participants: a pilot study. [2023]

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

Safety of Transcranial Direct Current Stimulation: Evidence Based Update 2016. [2022]

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

Safety of Transcranial Direct Current Stimulation in Neurorehabilitation. [2023]

9. 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]