Enhancing Working Memory in Patients With Early Alzheimer's Disease Through the Use of rTMS

NCT02537496 | Completed DMC

• 1 other identifier: 005/2015
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 1

Brief Summary

In this study the investigators aim at assessing and then enhancing neuroplasticity in the dorsolateral prefrontal cortex (DLPFC) and working memory - a key function of DLPFC - in patients with mild Alzheimer's disease (AD). The investigators will use Paired Associative Stimulation (PAS) paradigm to measure neuroplasticity and then a 4-week course of high-frequency repetitive Transcranial Magnetic Stimulation (rTMS) to the DLPFC to enhance cognitive function. Clinical and cognitive assessments will be done at baseline, one week, one month and 6 months after the rTMS course. Healthy controls will also be enrolled to carry out baseline cognitive assessments and a baseline measurement of neuroplasticity.

Conditions

Alzheimer's Disease

Keywords

Alzheimer's Disease; Brain stimulation; Transcranial Magnetic Stimulation; Neuroplasticity; cognitive enhancement; TMS-EEG; rTMS; PAS

Outcome Measures

Primary Outcomes (1)

• Change in N-back Task Performance

  The N-Back is a working memory task where the subject is presented with a sequence of stimuli (letters). The task consists of indicating when the current stimulus matches the one from N steps earlier in the sequence. By measuring the accuracy on the N-back task, the investigators will assess the working memory at baseline and compare the change at 7days, 4 weeks and 6 months post-intervention. The investigators' pilot data suggests that this test is most discriminatory between AD participants and healthy controls. The N-back task will be administered while recording EEG online to assess theta-gamma coupling.

  pre-intervention (baseline) and then 7 days, 4 weeks and 6 months after intervention

Secondary Outcomes (4)

• Changes in Theta Phase-Gamma Amplitude Coupling

  Change from baseline at 7 days, 4 weeks and 6 months after intervention.

• Changes in DLPFC Neuroplasticity

  Change from baseline at 7 days, 4 weeks and 6 months after intervention.

• Changes in Cognitive Function Measures Scores

  Change from baseline at 7 days, 4 weeks and 6 months after intervention.

• Validating a new scale for insight in Alzheimer's disease.

  Change from baseline at 7 days and 6 months after intervention.

Study Arms (3)

Alzheimer's disease rTMS

EXPERIMENTAL

The intervention procedure done in this group is repetitive Transcranial Magnetic Stimulation.

Procedure: Repetitive Transcranial Magnetic Stimulation

Alzheimer's disease rTMS Sham

SHAM COMPARATOR

The intervention procedure done in this group is Repetitive Transcranial Magnetic Stimulation - Sham

Procedure: Repetitive Transcranial Magnetic Stimulation - Sham

Healthy Control

NO INTERVENTION

Healthy control group will only participate in baseline assessments which include baseline neuropsychological testing and baseline measurement of neuroplasticity. This will be used to standardize neuropsychological test scores and to compare the baseline neuroplasticity between healthy participants and Alzheimer's disease (AD) participants. Healthy control group will not get rTMS intervention.

Interventions

Repetitive Transcranial Magnetic Stimulation PROCEDURE

Active treatment will be delivered at 90% resting motor threshold intensity. Stimulation will be administered at 20 Hz with 25 stimulation trains of 30 stimuli each with an inter-train interval of 30 sec. Treatment will be applied in sequential order bilaterally to the left and right DLPFC.

Also known as: rTMS

Alzheimer's disease rTMS

Repetitive Transcranial Magnetic Stimulation - Sham PROCEDURE

Same stimulation parameters and site as active condition will be used, but with placebo coil which will have minimal direct brain effects

Also known as: rTMS - Sham

Alzheimer's disease rTMS Sham

Eligibility Criteria

• Age: 55 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 55 years or above.
• Ability to understand and speak English.
• Confirmed Diagnosis of Probable AD by NIA-AA criteria.
• Either not taking Cognitive enhancers or taking them at a stable dose for the last 3 months.
• Willingness and ability to provide informed consent or an ability to assent and availability of a substitute decision maker willing to provide consent on participant's behalf.
• Corrected visual acuity enough to read newspaper headlines.
• Ability to hear a raised conversational voice, with hearing aids if needed.
• Age 55 or above.
• Willingness and ability to speak English.
• Willingness and ability to provide informed consent.
• Corrected visual acuity enough to read newspaper headlines.
• Ability to hear a raised conversational voice, with hearing aids if needed.

You may not qualify if:

• MOCA score \< 10.
• DSM IV - TR diagnosis of a current episode of mood disorder in the last 3 months.
• DSM IV - TR diagnosis of a current anxiety disorder in the last 3 months.
• DSM IV - TR diagnosis of a current substance use disorder in the last 3 months.
• DSM IV - TR diagnosis of a current or lifetime primary psychotic disorder.
• Diagnosis of intellectual disability or a neurodevelopmental disorder.
• Electroconvulsive Therapy treatment in the last 6 months.
• History of a seizure other than a febrile seizure in infancy.
• Currently taking Anticonvulsants or Benzodiazepines.
• Any contraindication for TMS or any other medical condition/circumstances that would make the study participation difficult for the participant.
• Meets criteria for a DSM IV - TR diagnosis other than simple phobias or Adjustment disorder.
• Any other neurological disorder affecting central nervous system.
• Psychotropic medication except for sedative /hypnotics at a stable dose for at least 4 weeks.
• History of seizure other than a febrile seizure in infancy
• Currently taking Anticonvulsants or Benzodiazepines.

Sponsors & Collaborators

• Centre for Addiction and Mental Health: lead
• Brain & Behavior Research Foundation: collaborator
• University of Toronto: collaborator

Study Sites (1)

Center for Addiction and Mental Health

Toronto, Ontario, M6J 1H1, Canada

Location

Related Links

• Description: The Centre for Addiction and Mental Health (CAMH) is the leading mental health and addictions research facility in Canada, and one of the largest in the world.

MeSH Terms

Conditions

Alzheimer Disease

Interventions

Transcranial Magnetic Stimulation

Condition Hierarchy (Ancestors)

Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Magnetic Field Therapy; Therapeutics

Study Officials

• Sanjeev Kumar, MD, FRCPC

  Center for Addiction and Mental Health

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Active placebo coil will be used as a Sham condition. This coil effectively mimics the real stimulation producing somatic sensation and sound (contraction of scalp muscles) with minimal direct brain effects. Same stimulation parameters and site as active condition will be used.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Sanjeev Kumar, MD, FRCPC

Model Details: Participants will be assigned randomly to a 4-week repetitive course of either rTMS or control intervention (Sham rTMS) that is similar to rTMS but does not produce the same amount of brain stimulation.

Study Record Dates

• First Submitted: July 30, 2015
• First Posted: September 1, 2015
• Study Start: January 14, 2016
• Primary Completion: October 10, 2018
• Study Completion: October 10, 2018
• Last Updated: February 28, 2019

Record last verified: 2019-02

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)