Nutrition Interventions for Cognitive Enhancement

Study Overview
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Brief Summary
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By doing this study, researchers hope to learn how the Mediterranean and low-fat eating patterns affect memory, brain volume, brain antioxidant status and cardio-metabolic biomarkers, such as blood pressure and blood glucose, in cognitively normal older adults. Researchers also plan to examine underlying processes relating the patterns to brain health.

Detailed Description
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Participants will be randomized to either a Mediterranean or low-fat eating pattern. Participation in the study will last about 13 months. Each person will be prescribed one of two eating patterns for 12 months. During the study, participants will be asked to track the food they eat and will be monitored by a registered dietitian. Participants will engage in monthly food demonstrations and cooking classes. Participants will pick up a bag of food items belonging to the prescribed eating pattern, on a weekly basis for 6 months, from a local grocery store chain. Participants have the option to continue in the study for up to 2 years for additional measurements. Potential participants need to be located within the Kansas City metro area.

Official Title
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Enhanced Mediterranean Diet for Alzheimer's Disease Prevention

Conditions
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Alzheimer Disease

Intervention / Treatment
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* Behavioral: Mediterranean Diet
* Dietary Supplement: Study Supplement
* Behavioral: Low-fat Diet


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Cognitively normal older adults over the age of 65 (MMSE score > 25; AD8 score of 2 or less; no prior diagnosis of MCI, AD or dementia; and not medically treated for cognitive impairment or dementia) Speak English as a primary language Live in the Kansas City, Metropolitan area Body Mass Index (BMI) range between 20 - 40 kg/m2 Exclusion Criteria: Serious medical risk, such as type 1 diabetes mellitus, cancer, recent cardiac event (e.g. heart attach, angioplasty) Taking the prescription drug Warfarin Nut allergy, fish allergy (does not include shellfish) Adherence to specialized diet regimen (e.g., vegan, etc.) Evidence of severe major depression (GDS-SF > 5) or presence of a major psychiatric disorder that in the investigator's opinion, could interfere with adherence to research assessments or procedures Alcohol (over 3 drinks per day or total of 18 per week) or drug abuse Unwilling to be randomized to one of two diet interventions Do not have access to or independence over grocery shopping and meal preparation (i.e. those in military, retirement community with reliance on dining facilities for meals) Already consume a Mediterranean diet Already consume a low-fat diet

Ages Eligible for Study
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Minimum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Participants will be randomized to a dietary intervention; Mediterranean or Low-Fat, and will follow this eating pattern for 12 months.
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Mediterranean Diet<br>Follow a Mediterranean eating pattern and take a study supplement for one year. Dietary education will be provided by a Registered Dietitian. | Behavioral: Mediterranean Diet<br>* Diet consisting of fruits, vegetables, whole grains, low-fat dairy, olive oil, seafood, nuts and beans. It is low in red and processed meats, solid fats and added sugars.<br>Dietary Supplement: Study Supplement<br>* Randomized to take a daily dose of either 2 grams of Omega 3 fatty acids or 2 grams of a Placebo.<br>|
| Active Comparator: Low-fat Diet<br>Follow a low-fat eating pattern and take a study supplement for one year. Dietary education will be provided by a Registered Dietitian. | Dietary Supplement: Study Supplement<br>* Randomized to take a daily dose of either 2 grams of Omega 3 fatty acids or 2 grams of a Placebo.<br>Behavioral: Low-fat Diet<br>* Diet consisting of fruits, vegetables, whole grains, low-fat dairy, and low-fat protein, with fat contributing no more than 25% of calories.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in a composite global cognition score | Alzheimer's Disease Cooperative Study-Preclinical Alzheimer Cognitive Composite (ADCS-PACC) and NIH Toolbox (NIH-TB) Cognition Battery and will be used to assess changes in a composite global cognition score at baseline, 6, and 12 months. | Baseline, 6 months and 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Verbal Memory Factor | Change in Verbal Memory Factor (derived from confirmatory factor analyses (CFA) of the following scales: Logical Memory I, Logical Memory II, and Selective Reminding Task) at baseline, 6 months and 12 months. CFA aggregates scores from across multiple subtests. | Baseline, 6 months and 12 months | 
| Change in Visuospatial Processing Factor | Change in Visuospatial Processing Factor (derived from confirmatory factor analyses (CFA) of the following scales: Stroop Color Naming, Digit Symbol, Block Design, and Trailmaking A) at baseline, 6 months and 12 months. CFA aggregates scores from across multiple subtests. | Baseline, 6 months and 12 months | 
| Change in Attention Factor | Change in Attention Factor (derived from confirmatory factor analyses (CFA) of the following scales: Digits Forward, Digits Backward, and Letter-Number Sequencing) at baseline, 6 months and 12 months. CFA aggregates scores from across multiple subtests. | Baseline, 6 months and 12 months | 
| Change in Executive Function Factor | Change in Executive Function Factor (derived from confirmatory factor analyses (CFA) of the following scales: NIH-TB Dimensional Change Card Sort Test, NIH-TB Flanker Inhibitory Control and Attention Test, Trailmaking B, and Category Fluency) at baseline, 6 months and 12 months. CFA aggregates scores from across multiple subtests. | Baseline, 6 months and 12 months | 
| Change in Speed of Processing Factor | Change in Speed of Processing Factor (derived from confirmatory factor analyses (CFA) of the following scales: of Crossing Off and NIH-TB Pattern Comparison Processing Speed Test) at baseline, 6 months and 12 months. CFA aggregates scores from across multiple subtests. | Baseline, 6 months and 12 months | 
| Change in brain volume | Change in whole brain and hippocampal volume as assessed via magnetic resonance imaging (MRI) at baseline and 12 months. | Baseline and 12 months | 
| Change in cerebral antioxidant levels | Antioxidant levels are measured in frontal and parietal regions of the brain using magnetic resonance spectroscopy in a 3 T clinical scanner. | Baseline and 12 months | 
| Change in blood pressure | Measure of both systolic blood pressure and diastolic blood pressure at baseline, 6 months, and 12 months. | Baseline, 6 months and 12 months | 
| Change in percentage of total fatty acids by weight | Measure of red blood cell (RBC)-phospholipids at baseline and 12 months. | Baseline and 12 months | 
| Change in total cholesterol | Measure of total cholesterol at baseline and 12 months | Baseline and 12 months | 
| Change in HDL cholesterol | Measure of HDL cholesterol at baseline and 12 months | Baseline and 12 months | 
| Change in total/HDL cholesterol ratio | Measure of total/HDL cholesterol ratio at baseline and 12 months | Baseline and 12 months | 
| Change in LDL cholesterol | Measure of LDL cholesterol at baseline and 12 months | Baseline and 12 months | 
| Change in triglycerides | Measure of triglycerides at baseline and 12 months | Baseline and 12 months | 
| Change in apolipoprotein B | Measure of apolipoprotein B, a measure of cardiovascular disease risk, at baseline and 12 months | Baseline and 12 months | 
| Change in lipoprotein(a) (Lp(a)) | Measure of Lp(a), a measure of cardiovascular disease risk, at baseline and 12 months | Baseline and 12 months | 
| Change in high sensitivity C-Reactive Protein (hs-CRP) | Measure of hs-CRP, a measure of inflammation, at baseline and 12 months | Baseline and 12 months | 
| Change in lipoprotein-associated phospholipase A2 (Lp-PLA2) | Measure of Lp-PLA2 activity, a measure of cardiovascular disease risk, at baseline and 12 months | Baseline and 12 months | 
| Change in insulin resistance score | Measure of intact insulin and c-peptide to determine an insulin resistance score at baseline and 12 months | Baseline and 12 months | 
| Change in fasting glucose | Measure of glucose at baseline and 12 months | Baseline and 12 months | 
| Change in Hemoglobin A1c (HbA1c) | Measure of HbA1c at baseline and 12 months | Baseline and 12 months | 
| Change in Trimethylamine N-oxide (TMAO) | Measure of TMAO, a measure of cardiovascular disease risk, at baseline and 12 months | Baseline and 12 months | 
| Change in a composite global cognition score post intervention | Alzheimer's Disease Cooperative Study-Preclinical Alzheimer Cognitive Composite (ADCS-PACC) and NIH Toolbox (NIH-TB) Cognition Battery and will be used to assess changes in a composite global cognition score at 24 and 36 months. | 24 and 36 months | 
| Change in Verbal Memory Factor post intervention | Change in Verbal Memory Factor (derived from confirmatory factor analyses (CFA) of the following scales: Logical Memory I, Logical Memory II, and Selective Reminding Task) at 24 and 36 months. CFA aggregates scores from across multiple subtests. | 24 and 36 months | 
| Change in Visuospatial Processing Factor post intervention | Change in Visuospatial Processing Factor (derived from confirmatory factor analyses (CFA) of the following scales: Stroop Color Naming, Digit Symbol, Block Design, and Trailmaking A) at 24 and 36 months. CFA aggregates scores from across multiple subtests. | 24 and 36 months | 
| Change in Attention Factor post intervention | Change in Attention Factor (derived from confirmatory factor analyses (CFA) of the following scales: Digits Forward, Digits Backward, and Letter-Number Sequencing) at 24 and 36 months. CFA aggregates scores from across multiple subtests. | 24 and 36 months | 
| Change in Executive Function Factor post intervention | Change in Executive Function Factor (derived from confirmatory factor analyses (CFA) of the following scales: NIH-TB Dimensional Change Card Sort Test, NIH-TB Flanker Inhibitory Control and Attention Test, Trailmaking B, and Category Fluency) at 24 and 36 months. CFA aggregates scores from across multiple subtests. | 24 and 36 months | 
| Change in Speed of Processing Factor post intervention | Change in Speed of Processing Factor (derived from confirmatory factor analyses (CFA) of the following scales: of Crossing Off and NIH-TB Pattern Comparison Processing Speed Test) at 24 and 36 months. CFA aggregates scores from across multiple subtests. | 24 and 36 months | 
| Measure of dietary adherence post intervention | Measure of dietary adherence through 3 day food records at 24 and 36 months | 24 and 36 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cognitive Impairment, Dementia, Alzheimer Disease, Mediterranean Diet, Low Fat Diet