Β-OHB Supplementation and Brain Health in Older Adults

The goal of this randomized placebo controlled crossover trial is investigate the effects of short-term ketone monoester (KME) supplementation to brain function in older adults with subjective cognitive decline. We will test the hypothesis that KME supplementation will increase cerebral blood flow and improve resting-state functional connectivity in the brain compared to placebo supplementation in older adults with subjective cognitive decline.

Participants will be randomly assigned to either placebo of KME supplementation for 14 days. Following a washout period, participants will complete the alternate condition for 14 days. Outcome measures will be assessed before and after each intervention period.

In this randomized placebo-controlled crossover double-blind designed clinical trial, 48 adults with SCD (50% female; aged 55 to 75 years old) will be allocated to a ketone monoester (KME) or placebo condition in random order (e.g., A-B or B-A), stratified by sex. Participants will be recruited from the local community through McMaster University, the local Alzheimer Society, and community outreach.

In total, participants will be asked to complete 5 visits. Data will be collected at a single site in Hamilton, Ontario associated with McMaster University. All interested individuals will complete an eligibility screening study visit (Visit 1) to establish inclusion/exclusion. Written, informed consent will be obtained before data collection. Demographic information and medical history will be collected at the beginning of Visit 1 to obtain information regarding medication use, medical history, age, years of education, and sex and gender-based variables. This information will be collected using a participant history questionnaire and the GENESIS-PRAXY questionnaire. Participants will also be introduced to the lab and the different tests that we will run during the experimental visits. Data will be collected at two time points for each condition: 1) Pre-intervention (Visits 2 \& 4: baseline); and post-intervention (Visits 3 \& 5: following 14-day intervention). In a randomized crossover design, participants will be randomly allocated to a condition (placebo or KME) for a 14-day intervention. Participants will then undergo a washout period, afterwhich participants will be complete the alternate condition including baseline data collection (Visit 4) and post-intervention visit (Visit 5) after the second 14-day intervention period.

Eligibility Criteria:
Inclusion Criteria:

* Being objectively cognitively normal as determined by a Montreal Cognitive Assessment (MoCA) score ≥26 with independent living and ambulating
* SCD will be determined using the Prospective-Retrospective Memory Questionnaire (PRMQ) following the SCD Initiative Working Group framework

Exclusion Criteria:

* A diagnosis of mild cognitive impairment, dementia, or psychiatric and/or mood disorders (e.g., major depression)
* MoCA score \<26
* Diagnosis of cardiometabolic disease (e.g., hypertension, type 2 diabetes)
* Obesity (BMI \>30 kg/m2)
* History of heart attack or stroke
* History of smoking
* Currently following a ketogenic diet or taking ketogenic supplements
* Having MRI contraindications
* Participants with literacy, visual, hearing, and/or speech issues, as well as individuals who are not proficient in English will not be eligible for this trial