Evidence map›Paper›PMID 41673697›Full record

ArticleTrials2026

The effect of exogenous ketone monoester supplementation on cerebral blood flow and functional brain characteristics in adults with subjective cognitive decline: study protocol for a randomized crossover trial.

Ethan Danielli, Aedan J Rourke, Geoff B Coombs, Michael D Noseworthy, Lawrence Mbuagbaw, Baraa K Al-Khazraji, Alexandra Papaioannou, Sabine Krumm, Jeremy J Walsh

Registry-linked trialAbstract readClinical Trial Protocol
In one paragraph

Article in Trials, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT06588946 (The Effect of Exogenous Β-OHB Supplementation on Cerebral Blood Flow and Functional Brain Characteristics in Adults with Subjective Cognitive Decline), which is not on this map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT06588946 phase2not yet recruitingnot on this map

The Effect of Exogenous Β-OHB Supplementation on Cerebral Blood Flow and Functional Brain Characteristics in Adults with Subjective Cognitive Decline

TypeinterventionalSponsorMcMaster UniversityRan2025 to 2027Enrolled48ConditionsSubjective Cognitive DeclineArmsKetone monoester (KME) supplement, Placebo supplement
3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors.

Ethan DanielliDepartment of Kinesiology, McMaster University, Hamilton, Canada.
Aedan J RourkeDepartment of Kinesiology, McMaster University, Hamilton, Canada.
Geoff B CoombsSchool of Psychology & Sport Science, Bangor University, Bangor, Wales.
Michael D NoseworthyDepartment of Electrical and Computer Engineering, McMaster University, Hamilton, Canada.
Lawrence MbuagbawDepartment of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, Canada.
Baraa K Al-KhazrajiDepartment of Kinesiology, McMaster University, Hamilton, Canada.
Alexandra PapaioannouGERAS Centre for Aging Research, McMaster University, Hamilton, Canada.
Sabine KrummMemory Clinic, Felix Platter Hospital, Basel, Switzerland.
Jeremy J WalshDepartment of Kinesiology, McMaster University, Hamilton, Canada. walshj18@mcmaster.ca.

Funding

Heart and Stroke Foundation of Canada G-24-0036504McMaster Institute for Research on Aging, McMaster University #20026262
6 · The paper itself

Abstract

backgroundThere is an urgent need for interventions which reduce dementia risk in aging adults. People with subjective cognitive decline (SCD) have a greater risk of developing dementia compared to age-matched cognitively normal individuals. Impaired cerebral blood flow (CBF) and cerebral glucose hypometabolism are leading mechanisms underlying dementia that could be ideal interventional targets for this population. Recent research, including our own work, has shown that oral consumption of ketone monoesters (KME) can improve CBF and cerebral metabolism, which in turn can improve cognition. The purpose of this study is to investigate the hypothesis that a 14-day KME supplementation intervention in middle-to-older adults with SCD will increase CBF, brain functional connectivity, and cognitive performance in comparison to placebo.

methodsA total of 34 middle-to-older adults (50% female, aged 55-75) with SCD will be recruited for this randomized placebo-controlled crossover double-blind trial. Participants will complete study visits immediately before and after 14 days of thrice-daily supplementation with a KME or a placebo. Following a minimum 14-day washout period, participants will repeat the protocol to complete study visits immediately before and after 14 days of thrice-daily supplementation with the other intervention (KME or placebo). The outcome measures are as follows: (1) CBF, functional brain connectivity, and cerebrovascular function as measured by brain magnetic resonance imaging (MRI) scans, (2) cognitive function assessed via a battery of validated psychometric tests, and (3) blood-borne neurotrophic factors via venous blood sample collection. DISCUSSION: This novel study aims to advance our understanding of how KME could be an effective intervention to combat dementia risk factors and improve aspects of brain health in middle-to-older adults with SCD.

trial registrationClinicalTrials.gov NCT06588946. Registered on 05 September 2024.

Indexed as

BrainCerebrovascular CirculationCognitionCognitive DysfunctionDietary SupplementsKetonesAgedCognitive EnhancementCross-Over StudiesDouble-Blind MethodFemaleHumansMagnetic Resonance ImagingMaleMiddle AgedRandomized Controlled Trials as TopicKetonesBrain functional connectivityCerebral blood flowCerebrovascular reactivityCognitive performanceKetone monoesterSubjective cognitive decline

Identifiers

PMID41673697
PMCPMC12998059

What Socratic holds

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LicenceCC BY-NC-ND
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Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.