Clinical trial NCT01847586: Enhancing Neuroplasticity and Frontal Lobe Function in Patients With Mild Alzheimer's Disease
Official title: Enhancing Neuroplasticity and Frontal Lobe Function in Patients With Mild Alzheimer's Disease
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Alzheimer's Disease
Keywords: Alzheimer's Disease
Brain stimulation
transcranial magnetic stimulation
Lead sponsor: Centre for Addiction and Mental Health
Sponsor class: OTHER
First posted: 2013-05-07
Enrollment: 49
Sex: ALL
Minimum age (years): 65
Standard ages: OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).

Detailed 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).

Eligibility 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

Primary outcomes:
measure: Paired Associated Stimulation induced Long-term potentiation as a measure of neuroplasticity in the dorsolateral prefrontal cortex
timeFrame: 14 days
Secondary outcomes:
measure: N-back Task
timeFrame: pre-intervention (baseline) and then 1, 7, 14 days after intervention
Other outcomes:
Locations:
city: Toronto
country: Canada
facility: Centre for Addiction and Mental Health
state: Ontario
Study officials:
affiliation: Centre for Addiction and Mental Health
name: Tarek Rajji, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.