Metabolic Brain Disorders: Prodromes, Symptoms, and Syndromes

Life is a self-organizing and self-sustaining process that involves energy transformation, primarily regulated by the brain. The brain's main structure consists of terminally differentiated, postmitotic, non-replaceable cells, whose proper functioning and longevity depend solely on glucose-based energy metabolism. Glucose serves as the primary substrate for cellular respiration and anaerobic processes, which are essential for maintaining proper neuronal function, homeostasis, and cell repair. Research indicates that brain aging and neurodegenerative changes result from an age-related decline in glucose metabolism, largely due to a deficiency in nicotinamide adenine dinucleotide (NAD). This deficiency is particularly harmful to brain structures that contain neurons with the highest energy demands. The first signs of brain aging typically appear in the hypothalamus, as well as in the GABAergic and glutamatergic structures of the cerebral cortex and subcortical nuclei. Early symptoms of senile brain changes often manifest as systemic metabolic disorders like insulin resistance and type 2 diabetes. These are accompanied by alterations in brain energy metabolism, leading to neurological and psychiatric disorders that correspond to the affected brain regions. Over time, these changes gradually impact the brain's regions with the highest energy consumption. Current clinical studies suggest that early supplementation with NAD precursors may help slow the aging and neurodegeneration processes. However, this protective therapy appears to be less effective once the disease is fully developed.