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

Wake Forest University (WFU)

Status: Completed

Conditions: Prehypertension; Prediabetic State; Mild Cognitive Impairment; Insulin Resistance; Middle Age

Treatments: Other: High Diet; Other: Low Diet

Study type: Interventional

Funder types: Other

Identifiers

NCT02463084

IRB 00022512

Details and patient eligibility

About

This study compares the effects of a one-month diet high in saturated fat (SF), glycemic index (GI), and salt (Na+) to a diet low in these nutritional parameters on memory and other cognitive functions, on MRI measures of brain structure, function, and perfusion, as well as on blood and cerebrospinal fluid levels of amyloid-beta (Aβ), insulin, lipids (total cholesterol, HDL, LDL, oxidized LDL, and triglycerides), cytokines, apolipoprotein E (ApoE), apolipoprotein J, cortisol, soluble low density lipoprotein receptor-related protein (sLRP), and glucose in middle-aged adults (45-65 years of age) with normal cognition or mild cognitive impairment.

Enrollment: 60 patients

Sex: All

Ages: 45 to 65 years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

1. 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).
2. 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

1. Diabetes not controlled by diet or exercise; current or previous use of diabetes medications

2. Average systolic blood pressure on three occasions <90 or >139 mm/Hg, diastolic blood pressure <60, or current use of anti-hypertensive medications;

3. Clinically significant elevations in liver function tests as follows: SGOT > 1.5 X ULN, SGPT > 1.5 X ULN, Alkaline Phosphate > 1.5 ULN.

4. Clinically significant elevations in lipid profile as follows: LDL>190, triglycerides>340, or total cholesterol>260 and LDL/HDL ratio >3.0.

5. 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;

6. Significant medical illness or organ failure, such as uncontrolled hypertension or cardiovascular disease, chronic obstructive pulmonary disease, liver disease, or kidney disease;

7. Current use of antipsychotic, anti-depressant, anti-convulsant, anticoagulant, anxiolytic, or sedative medications;

8. Current use of cognition-enhancing medications;

9. Current use of glucocorticoids;

10. Current use of cholesterol-lowering medications, including:

    1. HMG-CoA Reductase Inhibitors [Statins: Atorvastatin (Lipitor), Fluvastatin (Lescol or Lescol EX), Lovastatin, Pravastatin (Pravachol), Rosuvastatin (Crestor), Simvastatin (Zocor)]
    2. Bile Acid Resins [Cholestyramine (Questran), Colestipol, Colesevelam (Welchol)]
    3. Fibric Acids Derivatives [Fenofibrate (Tricor), Gemfibrozil]
    4. Combinations [Amlodipine/Atorvastatin, Niacin/Lovastatin (Advicor), Ezetimibe/Simvastatin (Vytorin)]
    5. Miscellaneous Categories [Ezetimibe (Zetia), Niacin aka Nicotinic acid (Niaspan)
    6. Over-the-counter [Red yeast rice, Niacinamide, Omega 3 fatty acids (fish or flax seed), Slo-Niacin]

11. 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.

12. BMI ≤ 18.5

13. Current weight <110 pounds

14. 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.

15. If female, menstruation in the past 12 months or hysterectomy and current hormone replacement therapy medication.

16. 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

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

---

60 participants in 2 patient groups

Low Diet

Experimental group

Description:

Diet intervention consisting of foods with low saturated fats, low glycemic index and low salt

Treatment:

Other: Low Diet

High Diet

Experimental group

Description:

Diet intervention consisting of foods with high saturated fats, high glycemic index and high salt

Treatment:

Other: High Diet