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

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

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).

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).

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