Cerebrovascular Function, Cognition
Conditions
Keywords
Beta-hydroxybutyrate (β-OHB), cerebral blood flow, cognition, brain connectivity
Brief summary
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.
Interventions
OTHERPlacebo
Ingestion of a taste-matched calorie-free placebo drink followed by 90 minutes of rest.
DIETARY_SUPPLEMENTβ-OHB
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.
Sponsors
Alzheimer's Society of Brant, Haldimand Norfolk, Hamilton Halton
McMaster University
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Intervention 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.
Eligibility
Sex/Gender
ALL
Age
55 Years to 75 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Brain network connectivity | 90 minutes | 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. |
| Cerebral blood flow | 90 minutes | Sum of blood flow in the internal carotid and vertebral arteries via phase contrast MRI in ml/min. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Attention and working memory | 90 minutes | Computer battery to assess working memory (digit symbol substitution task) based on the number of correct responses in 120 seconds. |
| Executive function | 90 minutes | Computer battery to assess executive function (Stroop test) based on Stroop Cost (reaction times to incongruent stimuli minus congruent stimuli). |
| Working memory | 90 minutes | Computer battery to assess working memory (n-back test) based on N2 reaction time |
Other
| Measure | Time frame | Description |
|---|---|---|
| Mean arterial pressure | 90 minutes | Automated blood pressure cuff measurement of brachial artery pressure in mmHg. |
| Plasma beta-hydroxybutyrate | 90 minutes | Measured via finger capillary samples in mM |
Countries
Canada
Contacts
Primary ContactJeremy Walsh, PhD
Outcome results
None listed