Therapeutic Diets in Alzheimer's Disease

Study Overview
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Brief Summary
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By doing this study, researchers hope to learn how the ketogenic and Therapeutic Lifestyles Changes diets affect cognition in patients with Alzheimer's disease.

Official Title
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Therapeutic Diets in Alzheimer's Disease

Conditions
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Alzheimer Disease

Intervention / Treatment
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* Behavioral: Ketogenic Diet
* Behavioral: Therapeutic Lifestyles Changes Diet


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of AD by current McKhann et al. criteria CDR global score of 0.5 or 1 Agreed cooperation from an appropriate study partner Speaks English as primary language Age 50 to 90 No medication changes within the past 30 days Exclusion Criteria: Resides in a nursing home or dementia special care unit, or cannot control diet A potentially confounding serious medical risk including insulin-requiring diabetes, cancer requiring chemotherapy or radiation within the past 5 years, or a recent cardiac event (i.e. heart attack, angioplasty, etc.) Participating in another clinical trial or using an investigational drug or therapy within 30 days of the Screening Visit A history of renal stones

Ages Eligible for Study
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Minimum Age: 50 Years
Maximum Age: 90 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ketogenic Diet<br>Study partners will be instructed to assist participants in adherence to a 1:1 ketogenic diet (approximately 70% fat, <10% carbohydrate, and 20% protein as energy). The diet will encourage ≥4 servings of non-starchy vegetables and 1/2 cup of berries daily. Participants will be provided an emulsified medium chain triglyceride supplement with a target intake of 1-2 tablespoons per day and micronutrient supplements consisting of multivitamin, vitamin D, calcium, and phosphorus. After the 3-month ketogenic diet, participants will complete a 1-month washout period in which they halt adherence to the ketogenic diet and resume their normal diet. | Behavioral: Ketogenic Diet<br>* Three-month 1:1 ketogenic diet intervention (approximately 70% fat, <10% carbohydrate, and 20% protein).<br>|
| Active Comparator: Therapeutic Lifestyles Changes Diet<br>Study partners will be instructed to assist participants in adherence to the Therapeutic Lifestyles Changes diet. The diet consists of 20-35% fat, 50-60% carbohydrate, and  15% protein as energy. Fat intake will comprise <7% saturated fat, ≤20% monounsaturated fat, and ≤10% polyunsaturated fat as total energy. Cholesterol consumption will be ≤200mg per day. Participants are encouraged to eat ≥2 servings of fruit and ≥5 servings of vegetables per day. | Behavioral: Therapeutic Lifestyles Changes Diet<br>* Three-month diet intervention that is low in fat and cholesterol, high in fruits, vegetables, and whole grains, and moderate in protein.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in cognitive performance on the Alzheimer's Disease Assessment Scale Cognitive Subscale (ADASCog11) | Cognitive performance will be assessed by a psychometrician using the Alzheimer's Disease Assessment Scale Cognitive Subscale (ADASCog11). The ADAS-Cog is an Alzheimer's disease specific, multi-domain cognitive assessment scored from 0-70 points with higher scores indicating poorer cognitive performance. | Baseline, 12 Weeks | 
| Change in cognitive performance on the Mini-Mental State Exam (MMSE) | Global cognitive performance will be assessed by a psychometrician using the Mini-Mental State Exam (MMSE). The MMSE is a brief cognitive questionnaire with a maximum score of 30 points where higher scores indicate better cognitive performance. | Baseline, 12 Weeks | 
| Change in cognitive performance on the Logical Memory Test (LMT) | The Logical Memory, subtest of the WMS-R is a standardized assessment of narrative episodic memory. A short story is orally presented, and the examinee is asked to recall the story immediately. | Baseline, 12 Weeks | 
| Change in cognitive performance by Stroop test | Reaction time and accuracy will be assessed by a psychometrician using the Stroop test. | Baseline, 12 Weeks | 
| Change in Clinical Dementia Rating (CDR) | The Clinical Dementia Rating is a 5-point scale (CDR 0, 0.5, 1, 2, and 3) used to characterize six domains of cognitive and functional performance applicable to Alzheimer disease and related dementias. CDR 0 indicates no dementia and higher values indicate more severe dementia. The scores of all six domains are averaged to form a global CDR score. Change in score from baseline to 3 months will be assessed. | Baseline, 12 Weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in cerebral concentration of N-Acetylaspartate (NAA) | Concentration of cerebral N-Acetylaspartate is measured using magnetic resonance spectroscopy in a 3T clinical scanner. | Baseline, 12 Weeks | 
| Change in blood platelet mitochondrial function | Cytochrome c oxidase activity of blood platelets will be determined as a pseudo first order-rate constant (sec-1/mg protein) by measuring the oxidation of reduced cytochrome c at 550 nm. | Baseline, 6 Weeks, 12 Weeks | 
| Change in self-reported symptoms by study partner | Severity of symptoms will be measured via a self-reported symptoms questionnaire, answered by participant study partners. | Baseline, 6 Weeks, 12 Weeks |