EXPRESS: Brain energy metabolism and metabolic water in ageing, Alzheimer's, and other neurological diseases.

BACKGROUND/HYPOTHESIS: Glucose oxidation is the brain's main way of producing the energy needed for neuronal signaling and essential maintenance tasks. When the brain cannot produce or use energy efficiently, neurons become less functional and more vulnerable. Although ageing is thought to affect brain metabolism, precise measurements of oxidative glucose use are still limited. METHODS/RESULTS: This review brings together current evidence on how brain energy metabolism changes during healthy ageing, dementia, and major neurological disorders, using absolute measurements of oxygen consumption. Overall, the data show that oxidative glucose metabolism stays stable in healthy brain ageing. In contrast, it drops by up to ~40% in Alzheimer's disease, more with greater disease severity, and by ~ 25% in multiple sclerosis and hydrocephalus. These declines reduce the amount of ATP available for both signaling and basic cellular functions, which are essential for perception and cognition. Metabolic water production is proportionately reduced when CMRO2 decreases in diseased brain, and its secretion into interstitial fluid is diminished. CONCLUSION/INTERPRETATION: In disease, lower oxidative metabolic activity reduces metabolic water production, which may in turn affect brain fluid dynamics, including processes involved in neuroprotection and waste clearance.