Macronutrient Effects on Alzheimer's Disease (MEAL-2)

Inclusion criteria

• Subjects will be middle-aged (45 to 65 years of age) and will fall on the continuum from healthy (no pre-hypertension or insulin resistance) to pre-hypertensive and insulin resistant (pHAIR).
• Subjects will not be recruited based on memory status but will have normal memory or memory impairment with a diagnosis of mild cognitive impairment (MCI). Those subjects with MCI will have been assessed by physician and neuropsychologist experts and diagnosed with MCI according to Petersen criteria.

Exclusion criteria

• Diabetes not controlled by diet or exercise; current or previous use of diabetes medications
• Average systolic blood pressure on three occasions <90 or >139 mm/Hg, diastolic blood pressure <60, or current use of anti-hypertensive medications;
• Clinically significant elevations in liver function tests as follows: SGOT > 1.5 X ULN, SGPT > 1.5 X ULN, Alkaline Phosphate > 1.5 ULN.
• Clinically significant elevations in lipid profile as follows: LDL>190, triglycerides>340, or total cholesterol>260 and LDL/HDL ratio >3.0.
• Significant neurologic disease that might affect cognition, including AD (MCI will be allowed), stroke, Parkinson's disease, multiple sclerosis, or severe head injury with loss of consciousness > 30 minutes or with permanent neurologic sequelae;
• Significant medical illness or organ failure, such as uncontrolled hypertension or cardiovascular disease, chronic obstructive pulmonary disease, liver disease, or kidney disease;
• Current use of antipsychotic, anti-depressant, anti-convulsant, anticoagulant, anxiolytic, or sedative medications;
• Current use of cognition-enhancing medications;
• Current use of glucocorticoids;
• Current use of cholesterol-lowering medications, including:

• HMG-CoA Reductase Inhibitors [Statins: Atorvastatin (Lipitor), Fluvastatin (Lescol or Lescol EX), Lovastatin, Pravastatin (Pravachol), Rosuvastatin (Crestor), Simvastatin (Zocor)]
• Bile Acid Resins [Cholestyramine (Questran), Colestipol, Colesevelam (Welchol)]
• Fibric Acids Derivatives [Fenofibrate (Tricor), Gemfibrozil]
• Combinations [Amlodipine/Atorvastatin, Niacin/Lovastatin (Advicor), Ezetimibe/Simvastatin (Vytorin)]
• Miscellaneous Categories [Ezetimibe (Zetia), Niacin aka Nicotinic acid (Niaspan)
• Over-the-counter [Red yeast rice, Niacinamide, Omega 3 fatty acids (fish or flax seed), Slo-Niacin]
• Common allergies/sensitivities to the following food products: dairy, wheat, gluten, tree nuts or peanuts, eggs, corn, seafood and soy. Other food sensitivities will be assessed on a case-by-case basis.
• BMI ≤ 18.5
• Current weight <110 pounds
• Clinically significant iron deficiency: Hemoglobin <13.5 for white males, <12.2 for white females, <12.5 for black males, and <11.5 for black females.
• If female, menstruation in the past 12 months or hysterectomy and current hormone replacement therapy medication.
• Major digestive disorders, absorption issues, or surgeries, including bowel resection, inflammatory bowel diseases (Ulcerative colitis or Crohn's disease), or irritable bowel syndrome (IBS) with a tendency toward diarrhea