ArticleThe journal of prevention of Alzheimer's disease
Ketone Ester Effects on Biomarkers of Brain Metabolism and Cognitive Performance in Cognitively Intact Adults ≥ 55 Years Old. A Study Protocol for a Double-Blinded Randomized Controlled Clinical Trial.
Article in The journal of prevention of Alzheimer's disease. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT07364162 (Exogenous Ketone Ester Supplementation in ICU Delirium), which is not on this map. Cited by 8 papers, 1 of them a synthesis that pooled it.
What it found
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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.
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.
Exogenous Ketone Ester Supplementation in ICU Delirium (KETONES ICU)
Who cites it
8 citing papers in PubMed, 1 synthesis or guideline pooled it, 11 citations in OpenAlex.
- Feasibility of Using Magnetic Resonance Spectroscopy Test Biomarkers to Diagnose Alzheimer's Disease: Systematic Evaluation and Meta-Analysis.Actas espanolas de psiquiatria · 2024Pooled it
- Review
- Clinical Trials and Translational Advances in Metabolic Targeting.Cancer treatment and research · 2026Review
- Regulatory Landscapes of Protein Acylations in Neuroinflammation: From Molecular Mechanisms to Therapeutic Targets.Neurochemical research · 2025Review
- Providing alternative fuel for the brain in anorexia nervosa: a review of the literature on ketones and their effects on metabolism and the brain.Translational psychiatry · 2025Review
- Potential therapeutic benefit of exogenous ketone ester administration in delirium: a narrative review.Critical care (London, England) · 2025Review
- β-hydroxybutyrate and ischemic stroke: roles and mechanisms.Molecular brain · 2024Review
- Ketogenic diet administration later in life improves memory by modifying the synaptic cortical proteome via the PKA signaling pathway in aging mice.Cell reports. Medicine · 2024Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundKetone bodies have been proposed as an "energy rescue" for the Alzheimer's disease (AD) brain, which underutilizes glucose. Prior research has shown that oral ketone monoester (KME) safely induces robust ketosis in humans and has demonstrated cognitive-enhancing and pathology-reducing properties in animal models of AD. However, human evidence that KME may enhance brain ketone metabolism, improve cognitive performance and engage AD pathogenic cascades is scarce.
objectivesTo investigate the effects of ketone monoester (KME) on brain metabolism, cognitive performance and AD pathogenic cascades in cognitively normal older adults with metabolic syndrome and therefore at higher risk for AD.
designDouble-blinded randomized placebo-controlled clinical trial.
settingClinical Unit of the National Institute on Aging, Baltimore, US.
participantsFifty cognitively intact adults ≥ 55 years old, with metabolic syndrome.
interventionDrinks containing 25 g of KME or isocaloric placebo consumed three times daily for 28 days. OUTCOMES: Primary: concentration of beta-hydroxybutyrate (BHB) in precuneus measured with Magnetic Resonance Spectroscopy (MRS). Exploratory: plasma and urine BHB, multiple brain and muscle metabolites detected with MRS, cognition assessed with the PACC and NIH toolbox, biomarkers of AD and metabolic mediators in plasma extracellular vesicles, and stool microbiome. DISCUSSION: This is the first study to investigate the AD-biomarker and cognitive effects of KME in humans. Ketone monoester is safe, tolerable, induces robust ketosis, and animal studies indicate that it can modify AD pathology. By conducting a study of KME in a population at risk for AD, we hope to bridge the existing gap between pre-clinical evidence and the potential for brain-metabolic, pro-cognitive, and anti-Alzheimer's effects in humans.
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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 OpenQuestion graph.