Modelling the Effects of Medium-Chain Triglycerides on Cerebral Ketone Body Metabolism

Abstract

Alzheimer’s Disease (AD) is a neurodegenerative disorder that causes drastic structural brain atrophy and affects multiple brain functions. Cerebral glucose hypometabolism, associated with senile plaque density formation, is a pre-symptomatic feature of AD and significantly contributes to AD’s future development and progression. As cerebral glucose metabolism gradually slows down due to advanced aging, a healthy adult brain experiences an 8% decrease in cerebral glucose metabolic rate (CGMR) compared to a decline of 20%–40% CGMR in AD patients. To bridge the increasing brain energy gap caused by glucose hypometabolism, ketone bodies (KBs) are used as a supplementary source of energy as cerebral KB metabolism remains unaffected in AD patients. Ketogenic interventions such as Medium-Chain Triglyceride (MCT)-induced treatment can help augment the brain’s energy source availability and might delay further cognitive decline. With this, we constructed a mathematical model on cerebral glucose and KB metabolism to illustrate the drastic effects of glucose hypometabolism on healthy aging individuals, Mild Cognitive Impairment (MCI) subjects, and AD patients. Through the generated simulations, we have shown that KB concentration levels rise during prolonged starvation, and in consideration of glucose hypometabolism, MCT-induced intervention increases the concentration levels of acetyl-CoA (AC) in MCI/AD patients. Furthermore, MCT-induced supplement helps increase the AC concentration levels in healthy adults under normal conditions.