Diet modulates brain network stability, a biomarker for brain aging, in young adults.

Abstract

Epidemiological studies suggest that insulin resistance accelerates progression of age-based cognitive impairment, which neuroimaging has linked to brain glucose hypometabolism. As cellular inputs, ketones increase Gibbs free energy change for ATP by 27% compared to glucose. Here we test whether dietary changes are capable of modulating sustained functional communication between brain regions (network stability) by changing their predominant dietary fuel from glucose to ketones. We first established network stability as a biomarker for brain aging using two large-scale (n = 292, ages 20 to 85 y; n = 636, ages 18 to 88 y) 3 T functional MRI (fMRI) datasets. To determine whether diet can influence brain network stability, we additionally scanned 42 adults, age < 50 y, using ultrahigh-field (7 T) ultrafast (802 ms) fMRI optimized for single-participant-level detection sensitivity. One cohort was scanned under standard diet, overnight fasting, and ketogenic diet conditions. To isolate the impact of fuel type, an independent overnight fasted cohort was scanned before and after administration of a calorie-matched glucose and exogenous ketone ester (d-β-hydroxybutyrate) bolus. Across the life span, brain network destabilization correlated with decreased brain activity and cognitive acuity. Effects emerged at 47 y, with the most rapid degeneration occurring at 60 y. Networks were destabilized by glucose and stabilized by ketones, irrespective of whether ketosis was achieved with a ketogenic diet or exogenous ketone ester. Together, our results suggest that brain network destabilization may reflect early signs of hypometabolism, associated with dementia. Dietary interventions resulting in ketone utilization increase available energy and thus may show potential in protecting the aging brain.

• Authors: Lilianne R Mujica-Parodi, Anar Amgalan, Syed Fahad Sultan, Botond Antal, Xiaofei Sun, Steven Skiena, Andrew Lithen, Noor Adra, Eva-Maria Ratai, Corey Weistuch, Sindhuja Tirumalai Govindarajan, Helmut H Strey, Ken A Dill, Steven M Stufflebeam, Richard L Veech, Kieran Clarke
• Journal: Proceedings of the National Academy of Sciences of the United States of America (Proc Natl Acad Sci U S A) Vol. 117 Issue 11 Pg. 6170-6177 (03 17 2020) ISSN: 1091-6490 [Electronic] United States
• PMID: 32127481 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)
• Copyright: Copyright © 2020 the Author(s). Published by PNAS.

Chemical References

• Insulin
• Ketones
• Glucose

Topics

• Adaptation, Physiological
• Adolescent
• Adult
• Aged
• Aged, 80 and over
• Aging (physiology)
• Brain (diagnostic imaging, physiology)
• Cognition (physiology)
• Datasets as Topic
• Dementia (diet therapy, physiopathology, prevention & control)
• Diet, Ketogenic
• Energy Metabolism (physiology)
• Feeding Behavior (physiology)
• Female
• Glucose (administration & dosage, metabolism)
• Humans
• Insulin (metabolism)
• Insulin Resistance (physiology)
• Ketones (administration & dosage, metabolism)
• Magnetic Resonance Imaging
• Male
• Middle Aged
• Nerve Net (physiology)
• Neuroimaging (methods)
• Young Adult