Enhancing Neuroplasticity and Frontal Lobe Function in Patients With Mild Alzheimer's Disease

NCT01847586 | Completed DMC

• 1 other identifier: 215/2012
• Study Type: interventional
• Target: 49
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to determine if a novel brain stimulation approach using magnetic stimulation (Transcranial Magnetic Stimulation \[TMS\]) can improve memory and thinking processes in individuals with mild Alzheimer's disease (AD).

Conditions

Alzheimer's Disease

Keywords

Alzheimer's Disease; Brain stimulation; transcranial magnetic stimulation

Outcome Measures

Primary Outcomes (1)

• Paired Associated Stimulation induced Long-term potentiation as a measure of neuroplasticity in the dorsolateral prefrontal cortex

  We are using a novel technique of TMS- EEG as developed by our group. Through this technique, not only motor evoked potential (MEP) but also cortical evoked activity (CEA) is recorded continuously while TMS is being delivered to the cortex. Thus, PAS-induced LTP could be indexed through the potentiation of not only MEP but also of CEA. TMS-EEG has been used by our group and others. Our group has used TMS-EEG in healthy individuals and patients with severe mental illness to study several neurophysiological phenomena in M1 and DLPFC such as cortical inhibition, gamma oscillations, and recently LTP. In summary, we propose to combine PAS with TMS-EEG to assess DLPFC neuroplasticity in patients with mild AD and then deliver a 2-week course of daily repetitive PAS (rPAS) to enhance DLPFC neuroplasticity and function as indexed by the N-back task. This will be measured to see if there are any changes after 1 day, 7 days and 14 days of the intervention procedure.

  14 days

Secondary Outcomes (1)

• N-back Task

  pre-intervention (baseline) and then 1, 7, 14 days after intervention

Study Arms (3)

Alzheimer's disease-rPAS

EXPERIMENTAL

The intervention procedure will done in this group is r-Paired Associative Stimulation. This involves the repetitive pairing of electrical stimulation of the median nerve with - 25 ms later - transcranial magnetic stimulation (TMS) of the contralateral DLPFC

Procedure: Paired Associative Stimulation

Alzheimer's disease-rPAS-C

PLACEBO COMPARATOR

The intervention procedure being done with this group is PAS-C. This is a control Paired Associative Stimulation paradigm in which TMS to the left DLPFC follows the electrical stimulation of the right median nerve by 100 ms, and, thus, does not result in contemporaneous occurrence of the two stimulations in the cortex and consequently no LTP.

Procedure: Paired Associative Stimulation-Control

Control

OTHER

Controls will have a one time Paired Associative Stimulation-Control (PAS-C) paradigm intervention in which TMS to the left DLPFC follows the electrical stimulation of the right median nerve by 100 ms, and, thus, does not result in contemporaneous occurrence of the two stimulations in the cortex and consequently no LTP.

Procedure: Paired Associative Stimulation-Control

Interventions

Paired Associative Stimulation PROCEDURE

PAS simulates in humans the induction of long-term potentiation (LTP), a prototype of synaptic neuroplasticity. PAS involves the repetitive pairing of electrical stimulation of the median nerve with - 25 ms later - transcranial magnetic stimulation (TMS) of the contralateral DLPFC. As such, these two stimulations arrive simultaneously in the DLPFC and result in potentiation of TMS induced cortical evoked potential, analogous to in vitro LTP.

Alzheimer's disease-rPAS

Paired Associative Stimulation-Control PROCEDURE

PAS-C is a control PAS paradigm in which TMS to the left DLPFC follows the electrical stimulation of the right median nerve by 100 ms, and, thus, does not result in contemporaneous occurrence of the two stimulations in the cortex and consequently no LTP.

Alzheimer's disease-rPAS-C; Control

Eligibility Criteria

• Age: 65 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Older Adult (65+)

You may qualify if:

• Age 65 or above
• Meet NINCDS-ADRDA and DSM-IV TR criteria for a current diagnosis of Alzheimer's Disease
• Stable does of acetylcholinesterase inhibitors for at least 3 months
• Willingness and ability to speak English
• Willingness and ability to provide informed consent
• Corrected visual ability that enables reading of newspaper headlines and corrected hearing capacity that is adequate to respond to a raised conversational voice.

You may not qualify if:

• Meets criteria for an Axis I diagnosis within the past 12 months other than Dementia of the Alzheimer type.
• Mini Mental Status Examination score of 16 or less as described above
• Meets diagnostic criteria for current alcohol or other drug dependence within 6 months of testing
• Electroconvulsive Therapy (ECT) within 6 months of testing.
• Left handedness.
• Incompetency to consent
• Any contraindication for TMS
• Age 65 or above
• Willingness and ability to speak English
• Willingness and ability to provide informed consent
• Corrected visual ability that enables reading of newspaper headlines and corrected hearing capacity that is adequate to respond to a raised conversational voice.
• Meets criteria for an Axis I diagnosis other than simple phobias or adjustment disorder.
• Other neurological disorder affecting central nervous system.
• Psychotropic medication except for sedative /hypnotics at a stable dose for at least 4 weeks.
• Left handedness

Sponsors & Collaborators

• Centre for Addiction and Mental Health: lead

Study Sites (1)

Centre for Addiction and Mental Health

Toronto, Ontario, M6J 1H4, Canada

Location

Related Publications (1)

• Kumar S, Zomorrodi R, Ghazala Z, Goodman MS, Blumberger DM, Daskalakis ZJ, Fischer CE, Mulsant BH, Pollock BG, Rajji TK. Effects of repetitive paired associative stimulation on brain plasticity and working memory in Alzheimer's disease: a pilot randomized double-blind-controlled trial. Int Psychogeriatr. 2023 Mar;35(3):143-155. doi: 10.1017/S1041610220003518. Epub 2020 Nov 16.

  PMID: 33190659 DERIVED

MeSH Terms

Conditions

Alzheimer Disease

Condition Hierarchy (Ancestors)

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

Study Officials

• Tarek Rajji, MD

  Centre 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
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Staff Psychiatrist and Clinician Researcher

Study Record Dates

• First Submitted: April 26, 2013
• First Posted: May 7, 2013
• Study Start: April 1, 2013
• Primary Completion: October 1, 2016
• Study Completion: October 1, 2017
• Last Updated: January 24, 2018

Record last verified: 2018-01

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)