The Wandering Nerve: Gateway to Boost Alzheimer's Disease Related Cognitive Performance

Inclusion Criteria:

• Fluent in English

• Willingness and ability to comply with scheduled visits, magnetic resonance imaging (MRI) scanning, laboratory tests, and other study procedures.

• Subjects with well-controlled vascular risk factors, such as treated hypertension,treated hyperlipidemia or well controlled Type II diabetes will be included.

• Stable medications for at least 30 days.

• Mini Mental State Exam adjusted for age and education of 25 to 30, inclusive or aTelephone Interview for Cognitive Status score of at least 32

• Perform within 1.5 S.D. of age and education matched norms on the Logical MemoryParagraph Delayed Recall

• Geriatric Depression Scale < 11

• Aged 60-85, inclusive

• Right-handed

• Reduced vision is allowed if it can be corrected with MRI-goggles

Exclusion Criteria:

• Prior known diagnosis of mild cognitive impairment (MCI) or dementia

• Use of investigational drugs or devices within 60 days prior to screening

• Subjects with contraindications to MRI cannot participate (i.e., implanted metalincluding pacemakers, cerebral spinal fluid shunts, aneurysm clips, artificial heartvalves, ear implants or metal/foreign objects in the eyes and those with a historyof claustrophobia)

• Pregnant.

• Major psychiatric disorders such as schizophrenia, schizoaffective disorder, majoraffective disorder in mid-life, or treatment with electroconvulsive therapy (ECT) (Mild depression that is well treated with stable dose of selective serotonergicreuptake inhibitor (SSRI) antidepressants will be allowed).

• Have a history of major head trauma defined as a loss of consciousness and/or traumarequiring hospitalization

• Substance abuse within the past 2 years

• Active hematological, renal, pulmonary, endocrine or hepatic disorders.

• Evidence of cortical infarcts or strategically placed lacunar infarct (e.g. dorsalmedial nucleus of thalamus). MRI evidence of mild white matter signal abnormalitieswill be allowed.

• Active cancer, metabolic encephalopathy, infection

• Active cardiovascular disease, stroke, congestive or severe heart failure

• Huntington's disease, hydrocephalus or seizure disorder

• Cataracts, glaucoma, detached retina's, eye surgery involving the muscles; droopyeyelids, penetrating eye wounds and use of anticholinergic eye drop use

• Weight equal to or greater than 300 lbs (weight limit of the MRI table).

• Recurrent vaso-vagal syncopal episodes

• Unilateral or bilateral vagotomy

• Severe valvular disorder (i.e. prosthetic valve or hemodynamically relevant valvulardiseases)

• Sick sinus syndrome

• Hypotension due to autonomic dysfunction