Overview

In this research study we want to learn more about the effects of non-invasive brain stimulation on memory and brain-network function in cognitively unimpaired older adults and in patients with amnestic mild cognitive impairment (aMCI).

This study will use a form of non-invasive brain stimulation called repetitive Transcranial Magnetic Stimulation (rTMS). rTMS will slightly alter activity in an area of your brain that controls memory. Changes resulting from this stimulation will be measured with behavioral tests of memory and general cognition, as well as by taking images of your brain with Magnetic Resonance Imaging (MRI).

Participants will come in for one baseline visit followed by 10 days of daily rTMS study visits (Monday through Friday) and an evaluation visit. Then, there will be a 2-week break. After this break, they will return for another baseline visit, an additional 10 days of rTMS, and a final evaluation visit.

Eligibility

Inclusion Criteria:

1. Between the ages of 40-99
2. Native English speakers
3. Willing and able to consent to the protocol and undergo imaging and neuropsychological testing at the specified time points
4. Patients with PPA will be asked to bring a study partner to all visits
5. Patients with very mild or mild PPA, patients with amnestic mild cognitive impairment and cognitively unimpaired participants with preclinical AD will be included.

Exclusion Criteria:

1. History of head trauma involving loss of consciousness or alteration in consciousness
2. Another major neurologic or psychiatric condition
3. Known presence of a structural brain lesion (e.g. tumor, cortical infarct)
4. Any contraindication to MRI, such as presence of pacemakers, aneurysm clips, artificial heart valves, ear implants, metal fragments, or foreign objects in the eyes, skin, or body
5. Longstanding premorbid history (i.e. longer than 10 years) of alcohol or substance abuse with continuous abuse up to and including the time that the symptoms leading to clinical presentation developed
6. Any significant systemic illness or unstable medical condition which could lead to difficulty complying with the study protocol.
7. Unwilling to return for follow-up, undergo neuropsychological testing, TMS, and MR imaging
8. History of unprovoked seizures (i.e., seizures that occur in the absence of a clear provocation such as hyponatremia, hypoglycemia, etc.).
9. Subjects who have a first degree relative (e.g., father, mother or sibling) with a seizure disorder.
10. Subjects currently taking, or plan to take, medications which are highly epileptogenic. These include: clozapine, high doses of bupropion (i.e., greater than 400mg daily), diphenhydramine, cyclosporine, isoniazid, imipenem, chloroquine, tramadol and theophylline.
11. Subjects actively on anti-amyloid treatments. This is because they are at risk for bleeding due to amyloid-related imaging abnormalities (ARIA) that could provoke seizures.