Inclusion Criteria:

• MCI diagnosis: Participants will be diagnosed with MCI by consensus of a team of physicians and neuropsychologists experienced in the diagnosis of MCI, using the Petersen (Petersen, 1999, 2001) criteria for amnestic MCI or multiple domain MCI with amnestic features: a) the presence of subjective memory complaints, evaluated via detailed patient history and informant interview, b) objective verification of memory impairment as measured by neuropsychological tests, c) normal general cognitive function, d) intact or only mildly impaired activities of daily living, and e) absence of dementia per NINCDS/ADRDA and/or DSM-IV criteria

Exclusion Criteria:

The following exclusion criteria will be used, based on initial physical examination, medical history, lab work, and oral glucose tolerance test (OGTT) results:

• Diagnosis of diabetes or other relevant glucoregulatory disorders
• Use of any oral anti-diabetic compounds
• Clinically significant elevations in liver function
• Significant neurological disease that might affect cognition, other than MCI, including Alzheimer's disease, large-vessel stroke, Parkinson's disease, multiple sclerosis, recent severe head injury (loss of consciousness for more than 30 minutes in the past year), or remote head injury resulting in permanent cognitive or neurological sequelae
• History or current evidence of congestive heart failure (CHF)
• History of documented ischemic cardiac disease, i.e., angina, MI, angioplasty, stent, or CABG
• History of cardiac or vascular surgery, or significant arrhythmia within the last year; or planned major intervention such as cardiac surgery or stenting. A history of cardiac surgery for non-ischemic indications (i.e., valve repair or replacement) greater than one year prior to enrollment is not exclusionary if all other criteria are met
• Significant ECG abnormalities including heart rate less than 50 or greater than 100 beats per minute (dependent upon the individual's general health); any previously unrecognized arrhythmia requiring further intervention
• Significant peripheral edema at the time of screening
• Significant medical illness or organ failure, including but not limited to renal disease, hepatic disease, and unstable cardiac disease
• Regular current use of antipsychotic, anticonvulsive, anxiolytic, or sedative medications; antidepressant medications are not exclusionary, provided the individual does not have current major depression
• A current diagnosis of major depression or other significant psychiatric comorbidity
• Clinically significant anemia at the time of screening
• Fasting triglyceride level greater than 400
• Fasting glucose 125 or greater, or two-hour glucose value greater than 199 during the OGTT; participants will be notified if their fasting blood sugar (monitored every 3 months) exceeds 125, and they will be withdrawn from further participation if their fasting blood sugar exceeds 125 for two consecutive months
• For the MRI substudy, additional exclusion criteria include 1) previous exposure to work involving the cutting or grinding of metal, 2) the presence of a pacemaker, aneurysm clip, or other implanted metal device that would prohibit MRI procedures, and 3) significant history of claustrophobia