Metabolic Brain Disorders: Prodromes, Symptoms, and Syndromes

Life is a self-organizing and self-sustaining process that involves the transformation of energy, primarily regulated by the brain. The brain is made up of terminally differentiated postmitotic cells, and their proper functioning and longevity depend entirely on energy and glucose-fueled metabolism. Glucose metabolism is essential for maintaining normal neuronal function, homeostasis, and repair processes. Neurodegenerative changes begin to develop when glucose metabolism is insufficient. Brain involution often progresses in neuronal structures that have the highest levels of energy metabolism and activity. The primary age-related changes occur in the hypothalamus and in the GABA/glutamatergic systems of the cerebral cortex. These changes are closely linked to the age-related decline of nicotinamide adenine dinucleotide (NAD), which is a key mechanism that impairs glucose metabolism and leads to programmed neuronal death. Early warning signs typically include a combination of dysfunctions related to the affected areas. Research so far suggests that early supplementation with NAD precursors may slow the processes of aging and neurodegeneration.