Brain glucose and ketone utilization in brain aging and neurodegenerative diseases.

To meet its high energy demands, the brain mostly utilizes glucose. However, the brain has evolved to exploit additional fuels, such as ketones, especially during prolonged fasting. With aging and neurodegenerative diseases (NDDs), the brain becomes inefficient at utilizing glucose due to changes in glia and neurons that involve glucose transport, glycolytic and Krebs cycle enzyme activities, and insulin signaling. Positron emission tomography and magnetic resonance spectroscopy studies have identified glucose metabolism abnormalities in aging, Alzheimer's disease (AD) and other NDDs in vivo. Despite glucose hypometabolism, brain cells can utilize ketones efficiently, thereby providing a rationale for the development of therapeutic ketogenic interventions in AD and other NDDs. This review compares available ketogenic interventions and discusses the potential of the potent oral Ketone Ester for future therapeutic use in AD and other NDDs characterized by inefficient glucose utilization.