The Effect of Repeated Transcranial Magnetic Stimulation on Off-line Resting Electroencephalographic Signal in Alzheimer's Disease

To Investigate the Effect of Application of Repeated Trans-cranial Magnetic Stimulation (rTMS) Applied on the Left Prefrontal Cortex on Electroencephalography Signal Recorded From Brain Regions Involved in Cognitive Function in Patients With Alzheimer's Disease (AD)

The purpose of this study is to examine whether the rTMS (repetitive Transcranial Magnetic Stimulation) could change cortical excitability measured by off-line EEG in Alzheimer's Disease (AD) patients.

Upon meeting the inclusion criteria and providing informed consent, each participant will complete a series of 21 sessions of rTMS over the course of four weeks.During the first visit, they will be asked to undergo 1 hour of EEG (Electroencephalograph) before they start the repetitive transcranial magnetic stimulation sessions (rTMS), 0.5-hour of memory testing using MoCA and Trail Making Test (Trial A and B), 1 hour of rTMS and 1 hour of EEG after rTMS. The second visit will start approximately 24-72 hours after the first visit. During visit 2 to visit 20, participants will receive about 1 hour of TMS session 5 days a week for 4 weeks. During the 21st visit, which will be approximately one day after the last TMS session, participants will be asked to repeat 1 hour of EEG before TMS; 0.5-hour of memory testing using MoCA and Trail Making Test (Trial A and B), 1 hour TMS and 1 hour of EEG after TMS. For this study, a questionnaire concerning any potential side effects will be administrated before and after each session.

Inclusion Criteria:

• Males and females,
• Age 55-85 years old,
• Able to consent and agrees to participate (if patient does not have capacity to give a consent then a caregiver will be asked )
• Fluent in English
• Diagnosed with probable AD (NINCDS-ADRDA criteria) mild stage as defined by a composite score of 1 or less on clinical dementia rating scale (CDR)

Exclusion Criteria:

• Other neurological illness that would interfere with cognitive function (significant stroke, seizure d/o, Parkinson, Huntington etc.).
• Psychiatric illness known to affect cognition such as schizophrenia/schizo-affective disorder, substance use disorder within 1 year of study, active depression or anxiety disorder or history of recurrent major mood disorder prior to cognitive change.
• Medications: benzodiazepines will be exclusionary. Other psychotropic medications including Acetyl Choline Esterase inhibitors will be allowed but the dose needs to be stable for at least one month prior to the start and during the study. Patients taking medications that might increase the risk of seizures should not participate in the study.
• Subjects with metal anywhere in the head, excluding the mouth, is generally a contraindication to TMS. This includes shrapnel, and screws and clips from surgical procedures unless the physical properties of the metal object are known and there is a strong reason for using TMS.
• Subjects with cardiac pacemakers and implanted medication pumps should not participate in most TMS studies.
• TMS also should not be performed in patients with electrodes inside the heart which might provide a low-resistance current path to electrically sensitive tissue.
• Persons with serious heart disease are at increased risk in the event of a seizure,
• Persons with increased intracranial pressure, as in acute large infarctions or trauma, are also at increased risk in the event of a seizure, and should not receive TMS.
• Pregnant women or women in child bearing age that might be pregnant.
• Patients who are already enrolled in another study.