Pioglitazone Or Exercise to Treat Mild Cognitive Impairment (MCI)

Inclusion Criteria: * Community-dwelling, over 55 years old, able to give full informed consent, willing to be randomized * Able to perform a telephone interview * Able to speak, read and understand English * Potential volunteers on a statin drug, angiotensin converting enzyme inhibitor (ACE-I), angiotensin II receptor blocker (ARB), non-steroidal anti-inflammatory drug (NSAID), or Vitamin E supplement, are eligible but must be on a stable dose for at least 2 months * Women must be post-menopausal, as defined by no menses for 12 months * Must meet 3 of the 5 requirements for Metabolic Syndrome: * Waist measurement: greater than 102 cm for men and 88 cm for women * Fasting hypertriglyceridemia: 150 mg/dl (1.7 mmol/L) or higher * Low HDL cholesterol: less than 40 mg/dl (1.0 mmol/L) for men and 50 mg/dl (1.3 mmol/L) for women * Hypertension: higher than 130 mmHg systolic or 85 mmHg diastolic (average of 2 seated measurements) or currently using an antihypertensive medication * Elevated (untreated) fasting glucose: 100 mg/dl (5.6 mmol/L) or higher * Meet the study's 4-step screening process for MCI (to rule out dementia) Exclusion Criteria: * Diagnosis of diabetes mellitus (DM), defined as: Fasting Blood Sugar 126 or higher, a history of known DM, or treatment with any glucose lowering medication * Current diagnosis of dementia (or MMSE less than 24) or a neurological co-morbidity other than MCI that might affect cognition including: large vessel stroke, brain tumor, severe brain injury, multiple sclerosis, or Parkinson's disease * Current diagnosis of depression assessed by a Centers for Epidemiologic Studies Depression Scale (CES-D) score of 36 or less * Major psychiatric conditions such as bipolar disorder, psychosis, schizophrenia, or alcoholism that could affect the ability to understand and/or cooperate fully with the protocol * Significant cerebral vascular disease * Modified Hachinski score greater than 4 * Pregnant, lactating or having child bearing potential * Concomitant medications with significant cholinergic or anticholinergic effects or adverse effects on cognition including: antipsychotics, tricyclic antidepressants, anticonvulsants, sedative/hypnotics, anxiolytics, glucocorticoids (chronic or frequent intermittent), gingko biloba, NMDA receptor antagonists, cholinesterase inhibitors, strongly lipid soluble beta blockers (e.g., propranolol) * Hormone replacement therapy (male or female) * Visual/hearing impairment that would significantly impact the ability to undergo psychometric testing * Significant medical illness or organ failure including hepatic or renal failure, unstable cardiac disease, or life expectancy less than 18 months * Exercise-limiting conditions including: neuromuscular, joint/bone, cardiovascular, peripheral vascular, cerebrovascular or pulmonary disease; recent MI, pulmonary embolus, significant aortic stenosis; or exercise limiting obesity * Untreated B12 deficiency or hypothyroidism (stable treatment for at least 3 months is allowable) * Uncontrolled hypertension: over 160 mmHg systolic or 100 mmHg diastolic (stable treatment is allowable) * Endurance exercise training more than twice a week for 20 minutes (at a level that produces sweating) consistently during the last 6 months * Unstable weight in the last 6 months * Increased risk for Pio toxicity including: a) baseline liver dysfunction (over 2.5xULN for AST, ALT); b) hematocrit less than 33% men or 30% women; c) problematic edema; or d) congestive heart failure NYHA class II or greater * Stage 5 renal impairment (GFR less than 15 or dialysis) * Already taking a TZD or other drug that would modify insulin resistance (e.g. metformin), or has taken a TZD in the past and experienced a significant adverse effect or allergy * Currently taking any of following medications that may interact with Pio metabolism: atorvastatin at 80mg/day (lower doses are allowed), and medications with major CYP 3A4 inhibiting effects, such as nefazodone or systemic antifungal agents * Participating in another clinical trial