Triangulating evidence from observational and Mendelian randomization studies of ketone bodies for cognitive performance.

Humans 3-Hydroxybutyric Acid Alzheimer Disease / genetics Cognition Ketone Bodies Ketones Mendelian Randomization Analysis Middle Aged
Alzheimer’s disease Cognitive performance Ketone bodies Mendelian randomization

Journal

BMC medicine
ISSN: 1741-7015
Titre abrégé: BMC Med
Pays: England
ID NLM: 101190723

Informations de publication

Date de publication:
04 09 2023
Historique:
received: 25 04 2023
accepted: 24 08 2023
medline: 6 9 2023
pubmed: 5 9 2023
entrez: 4 9 2023
Statut: epublish

Résumé

Ketone bodies (KBs) are an alternative energy supply for brain functions when glucose is limited. The most abundant ketone metabolite, 3-β-hydroxybutyrate (BOHBUT), has been suggested to prevent or delay cognitive impairment, but the evidence remains unclear. We triangulated observational and Mendelian randomization (MR) studies to investigate the association and causation between KBs and cognitive function. In observational analyses of 5506 participants aged ≥ 45 years from the Whitehall II study, we used multiple linear regression to investigate the associations between categorized KBs and cognitive function scores. Two-sample MR was carried out using summary statistics from an in-house KBs meta-analysis between the University College London-London School of Hygiene and Tropical Medicine-Edinburgh-Bristol (UCLEB) Consortium and Kettunen et al. (N = 45,031), and publicly available summary statistics of cognitive performance and Alzheimer's disease (AD) from the Social Science Genetic Association Consortium (N = 257,841), and the International Genomics of Alzheimer's Project (N = 54,162), respectively. Both strong (P < 5 × 10 BOHBUT was positively associated with general cognitive function (β = 0.26, P = 9.74 × 10 Triangulation of evidence suggests that BOHBUT has a beneficial effect on cognitive performance. Our findings raise the hypothesis that increased BOHBUT may improve general cognitive functions, delaying cognitive impairment and reducing the risk of AD.

Sections du résumé

BACKGROUND
Ketone bodies (KBs) are an alternative energy supply for brain functions when glucose is limited. The most abundant ketone metabolite, 3-β-hydroxybutyrate (BOHBUT), has been suggested to prevent or delay cognitive impairment, but the evidence remains unclear. We triangulated observational and Mendelian randomization (MR) studies to investigate the association and causation between KBs and cognitive function.
METHODS
In observational analyses of 5506 participants aged ≥ 45 years from the Whitehall II study, we used multiple linear regression to investigate the associations between categorized KBs and cognitive function scores. Two-sample MR was carried out using summary statistics from an in-house KBs meta-analysis between the University College London-London School of Hygiene and Tropical Medicine-Edinburgh-Bristol (UCLEB) Consortium and Kettunen et al. (N = 45,031), and publicly available summary statistics of cognitive performance and Alzheimer's disease (AD) from the Social Science Genetic Association Consortium (N = 257,841), and the International Genomics of Alzheimer's Project (N = 54,162), respectively. Both strong (P < 5 × 10
RESULTS
BOHBUT was positively associated with general cognitive function (β = 0.26, P = 9.74 × 10
CONCLUSIONS
Triangulation of evidence suggests that BOHBUT has a beneficial effect on cognitive performance. Our findings raise the hypothesis that increased BOHBUT may improve general cognitive functions, delaying cognitive impairment and reducing the risk of AD.

Identifiants

DOI: 10.1186/s12916-023-03047-7 PMID: 37667256 PMC: PMC10478491
pubmed: 37667256
doi: 10.1186/s12916-023-03047-7
pii: 10.1186/s12916-023-03047-7
pmc: PMC10478491
doi:

Substances chimiques

3-Hydroxybutyric Acid TZP1275679
Ketone Bodies 0
Ketones 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't Research Support, N.I.H., Extramural

Langues

eng

Sous-ensembles de citation

IM

Pagination

340

Subventions

Organisme : Medical Research Council
ID : MR/R024227/1
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 221854/Z/20/Z
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_UU_00011/4
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/S011676/1
Pays : United Kingdom
Organisme : Wellcome Trust
Pays : United Kingdom
Organisme : NIA NIH HHS
ID : R01 AG056477
Pays : United States

Informations de copyright

© 2023. BioMed Central Ltd., part of Springer Nature.

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Auteurs

Wichanon Sae-Jie (W)

Department of Mathematics, Faculty of Science, Mahidol University, Bangkok, 10400, Thailand.

Suangsuda Supasai (S)

Department of Molecular Tropical Medicine and Genetics, Faculty of Tropical Medicine, Mahidol University, Bangkok, 10400, Thailand.

Mika Kivimaki (M)

UCL Brain Sciences, University College London, 149 Tottenham Court Road, London, W1T 7NF, UK.

Jackie F Price (JF)

Usher Institute, University of Edinburgh, Edinburgh, EH8 9AG, UK.

Andrew Wong (A)

MRC Unit Lifelong Health and Ageing at UCL, London, UK.

Meena Kumari (M)

Institute of Cardiovascular Science, Faculty of Population Health, University College London, London, WC1E 6BT, UK.
Institute for Social and Economic Research, University of Essex, Colchester, UK.

Jorgen Engmann (J)

Institute of Cardiovascular Science, Faculty of Population Health, University College London, London, WC1E 6BT, UK.

Tina Shah (T)

Institute of Cardiovascular Science, Faculty of Population Health, University College London, London, WC1E 6BT, UK.

Amand F Schmidt (AF)

Institute of Cardiovascular Science, Faculty of Population Health, University College London, London, WC1E 6BT, UK.
UCL British Heart Foundation Research Accelerator, Department of Cardiology, Division Heart and Lungs, University College London, London, UK.

Tom R Gaunt (TR)

MRC Integrative Epidemiology Unit, Bristol Medical School, University of Bristol, Bristol, BS8 2BN, UK.
NIHR Bristol Biomedical Research Centre, University Hospitals Bristol National Health Service Foundation Trust and University of Bristol, Bristol, UK.

Aroon Hingorani (A)

Institute of Cardiovascular Science, Faculty of Population Health, University College London, London, WC1E 6BT, UK.

Pimphen Charoen (P)

Institute of Cardiovascular Science, Faculty of Population Health, University College London, London, WC1E 6BT, UK. pimphen.cha@mahidol.edu.
Department of Tropical Hygiene, Faculty of Tropical Medicine, Mahidol University, Ratchawithi Road, Ratchathewi, Bangkok, 10400, Thailand. pimphen.cha@mahidol.edu.
Integrative Computational Bioscience (ICBS) Center, Mahidol University, Bangkok, Thailand. pimphen.cha@mahidol.edu.

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Classifications MeSH

questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Triangulating evidence from observational and...
questionsmedicales.fr › Lipides › Acides gras › Acides gras volatils › Butyrates › Hydroxy-butyrates › Acide 3-hydroxy-butyrique › Triangulating evidence from observational and...
questionsmedicales.fr › Troubles mentaux › Troubles neurocognitifs › Démence › Maladie d'Alzheimer › Triangulating evidence from observational and...
questionsmedicales.fr › Phénomènes psychologiques › Processus mentaux › Cognition › Triangulating evidence from observational and...
questionsmedicales.fr › Composés chimiques organiques › Cétones › Corps cétoniques › Triangulating evidence from observational and...
questionsmedicales.fr › Composés chimiques organiques › Cétones › Triangulating evidence from observational and...
questionsmedicales.fr › Techniques d'investigation › Analyse de randomisation mendélienne › Triangulating evidence from observational and...
questionsmedicales.fr › Personnes › Tranches d'âge › Adulte › Adulte d'âge moyen › Triangulating evidence from observational and...