Oral Ketone Monoester Supplementation and Resting-state Brain Connectivity

Study Overview
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Brief Summary
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People who report subjective memory complaints have a greater risk of developing dementia. Memory issues may be an early warning sign of dysfunctional cerebral glucose metabolism and cerebral blood flow. Interventions that can restore cerebral metabolism and enhance cerebral blood flow may protect against conversion to dementia. Exogenous ketone supplements have been shown rapidly improves brain network function in young adults. Further, infusion studies demonstrate that ketone bodies enhance cerebral blood flow in cognitively normal adults. Whether acute ketone monoester supplementation can improve brain function in adults with subjective memory complaints is currently unknown. This study will investigate the effects of a single ketone monoester dose on resting-state functional connectivity in the default mode network and resting cerebral blood flow in adults with subjective memory complaints.

Official Title
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The Impact of Acute Oral Ketone Monoester Supplementation on Resting-state Brain Connectivity in Adults With Memory Complaints

Conditions
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Cerebrovascular Function, Cognition

Intervention / Treatment
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* Other: Placebo
* Dietary Supplement: β-OHB


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: between the ages of 55 and 70 presence of subjective memory complaints as determined by the Prospective- Retrospective Memory Questionnaire cognitively normal, e.g. score ≥26 on the Montreal Cognitive Assessment Exclusion Criteria: Presence of obesity (body mass index > 30 kg/m^2) Presence of known cardiovascular disease Presence of type 2 diabetes History of cardiovascular events requiring hospitalization in the past 3 years (e.g., heart attack, stroke) History of concussion(s) with persistent symptoms Currently following a ketogenic diet and/or taking ketone body supplements Diagnosis of any form of Alzheimer's disease or dementia

Ages Eligible for Study
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Minimum Age: 55 Years
Maximum Age: 75 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: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: A randomized double-blind placebo-controlled crossover design will be used to test two conditions. Participants will consume 60 mL of: 1) a drink containing a ketone monoester supplement ([R]-3-hydroxybutyl [R]-3-hydroxybutyrate; 0.3 g β-OHB/kg body weight); and 2) a taste-matched calorie-free inert placebo drink.
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Single dose of a taste-matched calorie-free placebo | Other: Placebo<br>* Ingestion of a taste-matched calorie-free placebo drink followed by 90 minutes of rest.<br>|
| Experimental: β-OHB<br>Single dose of a ketone monoester ([R]-3-hydroxybutyl [R]-3-hydroxybutyrate; 0.6 g β-OHB/kg body weight) | Dietary Supplement: β-OHB<br>* Ingestion of a high dose [R]-3-hydroxybutyl [R]-3-hydroxybutyrate (0.6 g β-OHB/kg body weight) followed by 90 minutes of rest.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Brain network connectivity | Functional connectivity of the default mode network (DMN) is measured via functional MRI. Changes in BOLD signal in each region are determined by independent component analysis and then functional connectivity is measured as a Pearson correlation (r) between the neural regions comprising the DMN and transformed into a z score. | 90 minutes | 
| Cerebral blood flow | Sum of blood flow in the internal carotid and vertebral arteries via phase contrast MRI in ml/min. | 90 minutes | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Working memory | Computer battery to assess working memory (n-back test) based on N2 reaction time | 90 minutes | 
| Executive function | Computer battery to assess executive function (Stroop test) based on Stroop Cost (reaction times to incongruent stimuli minus congruent stimuli). | 90 minutes | 
| Attention and working memory | Computer battery to assess working memory (digit symbol substitution task) based on the number of correct responses in 120 seconds. | 90 minutes | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Beta-hydroxybutyrate (β-OHB), cerebral blood flow, cognition, brain connectivity