Enhancing Neuroplasticity and Frontal Lobe Function in Patients With Mild Alzheimer's Disease (TMS-AD)

Center for Addiction and Mental Health (CAMH)

Status: Completed

Conditions: Alzheimer's Disease

Treatments: Procedure: Paired Associative Stimulation; Procedure: Paired Associative Stimulation-Control

Study type: Interventional

Funder types: Other

Identifiers

NCT01847586

215/2012

Details and patient eligibility

About

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).

Full description

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 AD. The investigators will use a novel non-invasive brain stimulation approach, Paired Associative Stimulation (PAS). 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.

Specific Aim 1: To compare LTP in the DLPFC among patients with mild AD and healthy subjects.

Specific Aim 2: To assess the effect of a 2-week course of PAS (rPAS) as applied to the left DLPFC on LTP and performance on working memory in patients with mild AD in comparison with a 2-week course of PAS control condition (PAS-C, described below) (rPAS-C).

Enrollment: 49 patients

Sex: All

Ages: 65+ years old

Volunteers: Accepts Healthy Volunteers

Inclusion and exclusion criteria

Inclusion Criteria for patients:

• 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.

Exclusion Criteria for patients:

• 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

Inclusion Criteria for healthy controls:

• 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.

Exclusion Criteria for healthy controls:

• 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
• Any contraindication for TMS

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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49 participants in 3 patient groups, including a placebo group

Alzheimer's disease-rPAS

Experimental group

Description:

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

Treatment:

Procedure: Paired Associative Stimulation

Alzheimer's disease-rPAS-C

Placebo Comparator group

Description:

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.

Treatment:

Procedure: Paired Associative Stimulation-Control

Control

Other group

Description:

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.

Treatment:

Procedure: Paired Associative Stimulation-Control