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

• DOI: 10.1073/pnas.1913042117
• Publication Date: 2020-03-03T21:45:14Z
• Authors: Lilianne R. Mujic...; Anar Amgalan; Syed Fahad Sultan; Botond Antal; Xiaofei Sun; Steven Skiena; Andrew Lithen; Noor Adra; Eva-Maria Ratai; Corey Weistuch; Sindhuja Tirumala...; Helmut H. Strey; Ken A. Dill; Steven M. Stuffle...; Richard L. Veech; Kieran Clarke
• Keywords: Brain Aging; Aging brain

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