Biodistribution of [11C]Acetoacetate/[18F]Fluorodeoxyglucose in Subjects With Risk Factors for Alzheimer's Disease

Study Overview
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Brief Summary
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This is a single center imaging study that will recruit 60 participants who are enrolled in the Effect of a Ketogenic Diet on Alzheimer's Disease Biomarkers and Symptoms: Brain Energy for Amyloid Transformation in AD (BEAT-AD) Study protocol. This cohort of patients will receive a maximum of 3 [11C]Acetoacetate (AcAc)/[18F]Fluorodeoxyglucose (FDG) PET scans over 18 weeks as part of this supplemental trial.

Detailed Description
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The main objective of this study is to examine the brain biodistribution of [11C]AcAc/[18F]FDG, a proxy for acetoacetate (ketone body)/glucose metabolism in 3 study groups; 1) those without identifiable risk of Alzheimer's disease, 2) asymptomatic individuals with increased risk of Alzheimer's disease (such as pre diabetes),and 3) those with early Alzheimer's disease or MCI. Secondary objectives include determining the association between adipose tissue distribution/function and biomarkers of AD pathology.

Official Title
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Biodistribution of [11C]Acetoacetate/[18F]Fluorodeoxyglucose in Subjects With Varying Risk Factors for Alzheimer's Disease and Subjects on a Diet Intervention

Conditions
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Mild Cognitive Impairment

Intervention / Treatment
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* Other: [11C]Acetoacetate[18F]Fluorodeoxyglucose positron emission tomography scan


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Mild cognitive impairment or subjective memory complaints Stable medical condition and medications Ability to complete baseline assessments Exclusion Criteria: History of a clinically significant stroke Sensory impairment (visual, auditory) Diabetes requiring medication Current use of cholesterol/lipid lowering medications, anticonvulsants, drugs with potential interfering CNS effects (other than cholinesterase inhibitors or memantine), medications with significant anticholinergic activity, anti-parkinsonian medications or regular use of narcotic analgesics Untreated hypothyroidism or B12 deficiency

Ages Eligible for Study
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Minimum Age: 50 Years
Maximum Age: 85 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: Basic Science
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: No risk of disease<br>Subjects with no identifiable risk of Alzheimer's Disease | Other: [11C]Acetoacetate[18F]Fluorodeoxyglucose positron emission tomography scan<br>* A PET scan to measure uptake of acetoacetate and glucose in the brain will be administered to all participants enrolled in the study<br>|
| Experimental: Asymptomatic<br>Asymptomatic subjects with increased risk of Alzheimer's disease | Other: [11C]Acetoacetate[18F]Fluorodeoxyglucose positron emission tomography scan<br>* A PET scan to measure uptake of acetoacetate and glucose in the brain will be administered to all participants enrolled in the study<br>|
| Experimental: Early Alzheimer's or Mild Cognitive Impairment<br>Subjects with early Alzheimer's Disease or Mild Cognitive Impairment (MCI) | Other: [11C]Acetoacetate[18F]Fluorodeoxyglucose positron emission tomography scan<br>* A PET scan to measure uptake of acetoacetate and glucose in the brain will be administered to all participants enrolled in the study<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Brain biodistribution of [11C]AcAc | To assess brain metabolism of ketones (cerebral metabolic rate of acetoacetate/micromilliliters/100 g/min) | Baseline | 
| Brain biodistribution of [11C]AcAc | To assess change in brain metabolism of ketones (cerebral metabolic rate of acetoacetate/micromilliliters/100 g/min) | Change between baseline and four months | 
| Brain biodistribution of [18F]FDG - | To assess brain uptake of glucose (cerebral metabolic rate of glucose /micromilliliters/100 g/min) | Baseline | 
| Brain biodistribution of [18F]FDG - | To assess change in brain uptake of glucose (cerebral metabolic rate of glucose /micromilliliters/100 g/min) | Change between baseline and 4 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Memory, Cognitive