Non-invasive Brain Stimulation Using Transcranial Direct Current Stimulation for Neuropsychiatric Symptoms of Dementia

Non Invasive Brain Stimulation for Treatment of Neuropsychiatric Symptoms of Dementia: An Open Label Pilot Study Using Transcranial Direct Current Stimulation

Agitation and aggression impose a tremendous burden on the individuals living with dementia, their families, caregivers, and healthcare systems. Neuropsychiatric symptoms of dementia (NPS) affect up to 80% of patients with Alzheimer's dementia. These symptoms impair patient and care giver's quality of life, increase the chances of hospitalization and also result in faster progression of the illness. The efficacy of current treatments is limited and the antipsychotic medications commonly used to treat these symptoms are associated with serious side effects. Transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation technique that uses a very low intensity electric current to modulate cortical excitability and brain plasticity. tDCS can be safely administered to awake persons and is very well tolerated. In this study the investigators will use tDCS to treat agitation related to NPSD.

Study Overview

• Status: Completed
• Conditions: Dementia; Alzheimer, Mixed Type (Etiology)
• Intervention / Treatment: Device: Transcranial Direct Current Stimulation

Detailed Description

Agitation and aggression impose a tremendous burden on the individuals living with dementia, their families, caregivers, and healthcare systems. Neuropsychiatric symptoms of dementia (NPS) affect up to 80% of patients with Alzheimer's dementia. These symptoms include aggression and agitation, anxiety, depression, hallucinations, and delusions. These symptoms impair patient and care giver's quality of life, increase the chances of hospitalization and also result in faster progression of the illness. The efficacy of current treatments is limited and the antipsychotic medications commonly used to treat these symptoms are associated with serious side effects including cerebrovascular events, falls and increased risk of death. Electroconvulsive Therapy may be effective as well, however it requires anaesthesia and adversely affects cognition. Non-pharmacological or behavioral interventions are universally recognized as the first line treatment for agitation and NPSD. They are most effective when individualized and delivered in a person centered approach. Transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation technique that uses a very low intensity electric current to modulate cortical excitability and brain plasticity. tDCS can be safely administered to awake persons and is very well tolerated. Studies in healthy individuals and patients with Alzheimer's disease have shown that tDCS applied to frontal brain regions can enhance cognitive function. Further, tDCS applied to frontal brain regions can improve depressive symptoms. The effects of tDCS on NPSD are not known. In this study the investigators will use tDCS to treat agitation related to NPSD.The objective of this proposal is to conduct an open label pilot study of tDCS for treatment of agitation.

• Study Type: Interventional
• Enrollment (Actual): 13
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M6J 1H4
      • Centre for Addiction and Mental Health

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 60 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. A clinical diagnosis of Dementia of Alzheimer's, or Mixed type.
2. Presence of agitation and/or aggression related to NPS as defined by: Agitation in cognitive disorders; International Psychogeriatric Association Provisional Consensus Clinical and Research Definition at the time of enrolment into the study.
3. Patient or Substitute Decision Maker (SDM) able and willing to provide consent for enrolment in the study.
4. Age 60 or above

Exclusion Criteria:

1. Having dementia other than Alzheimer's or Vascular or Mixed type.
2. DSM-5 Axis I diagnoses other than dementia that is thought to be significantly impacting the presentation such as bipolar disorder, major depressive disorder, or schizophrenia
3. Imminent safety risk that would interfere with safe conduct of the study.
4. Any contraindication to tDCS such as metal implants in cranium.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Transcranial Direct Current Stimulation; Transcranial Direct Current Stimulation (tDCS):All enrolled study participants will receive 10 sessions (5 per week X 2 weeks) of tDCS in an open label study. Inhibitory stimulation will be delivered to the frontal lobes.	Device: Transcranial Direct Current Stimulation; tDCS is a non-invasive brain stimulation that does not require general anaesthesia or surgical implantation of a device. It uses two AA size batteries to deliver direct current via rubber electrodes enclosed in saline soaked sponges.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The rate of successful completion of the 2 week tDCS treatment course and rates of treatment associated adverse effects of tDCS in agitation due to NPSD	This will be assessed by the successful completion of the intervention in at least 80% of participants without any treatment associated serious adverse effects	2 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Effects of a 2 week course of tDCS on agitation as assessed by Cohen Mansfield Agitation Inventory (CMAI).	Patients who undergo tDCS course will have reduced neuropsychiatric symptoms assessed using the Cohen Mansfield Agitation Inventory (CMAI). tDCS will result in a significant reduction in agitation as assessed by CMAI -frequency total score between baseline and post treatment follow up two weeks later. CMAI-frequency score ranges between 29 to 203 and CMAI-disruptiveness ranges from 29 to 145 for each category. Higher scores indicate worsening of symptoms.	2 weeks, 4 weeks
Effects of a 2 week course of tDCS on agitation as assessed by Neuropsychiatric Inventory (NPI).	Patients who undergo tDCS course will have reduced neuropsychiatric symptoms assessed using the Neuropsychiatric Inventory (NPI). tDCS will result in reduced burden of neuropsychiatric symptoms as assessed by Neuropsychiatric Inventory after the 2 week intervention. Each NPI domain is scored based on the interview conducted by the clinician. Frequency of symptoms are rated on a scale of 0 - 4 (Higher scores indicate symptoms occur more frequently). Severity / intensity of symptoms are rated on a scale of 0 to 3 (Higher scores indicate greater severity of symptoms). Caregiver distress is rated on a scale of 0 to 5 (Higher scores indicate increased caregiver distress).	2 weeks, 4 weeks
Effects of a 2 week course of tDCS on agitation and other neuropsychiatric symptoms related to dementia as assessed by Clinical Global Impression (CGI).	Patients who undergo tDCS course will have reduced neuropsychiatric symptoms as assessed using Clinical Global Impression -Improvement Scale CGI-I. tDCS will result in a significant improvement in clinical symptoms as assessed by CGI-I scale after the two week intervention. CGI-I scores range from 0-7, higher scores indicating worsening compared to at baseline.	2 weeks, 4 weeks
Effect of tDCS on caregiver burden in agitation due to NPSD as assessed by Zarit Burden Interview (ZBI)	tDCS will result in significant reduction in caregiver burden as assessed by Zarit Burden Interview (ZBI). Scores on the ZBI range from 0 to 88, score of 0-21 indicating little or no burden; 21-40 indicating mild to moderate burden; 41-60 indicating moderate to severe burden; and 61-88 indicating severe burden.	2 weeks

Collaborators and Investigators

• Sponsor: Centre for Addiction and Mental Health
• Investigators: Principal Investigator: Sanjeev Kumar, MD, FRCPC, CAMH

Study record dates

Study Major Dates

• Study Start (Actual): July 5, 2018
• Primary Completion (Actual): February 20, 2020
• Study Completion (Actual): February 20, 2020

Study Registration Dates

• First Submitted: July 13, 2018
• First Submitted That Met QC Criteria: August 17, 2018
• First Posted (Actual): August 20, 2018

Study Record Updates

• Last Update Posted (Actual): July 7, 2020
• Last Update Submitted That Met QC Criteria: July 2, 2020
• Last Verified: July 1, 2020

More Information

Terms related to this study

• Keywords: tDCS; neuropsychiatric symptoms; Dementia; Alzheimer Disease; Transcranial direct current stimulation; non-invasive brain stimulation; Mixed Dementia; agitation in dementia
• Additional Relevant MeSH Terms: Mental Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurocognitive Disorders; Dementia
• Other Study ID Numbers: 099/2017

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No