Normal aging of the brain is accompanied by a slight but permanent decrease in the formation of energy in the brain due to changes in the work of various systems involved in cerebral energy supply. There is a decrease in cerebral blood flow, damage to BBB, decreases glucose metabolism, and there are impaired mitochondria in the nerve and glial cells. Desensitization of neuronal insulin receptors plays an important role in the change in glucose metabolism , which is especially enhanced by stress under the influence of cortisol, followed by dysfunction of these receptors as a result of changes in the structure and function of membranes. Decreased aerobic glucose metabolism and the relative predominance of glycolysis cause intracellular neuronal acidosis. Acidification promotes the intensification of free radical oxidation, damaging the membrane, nucleus and other structures of neurons (J. Bralet et al., 1991; S. Rehncrona et al., 1989; cit. To E. Roberts, T. Sick, 1996). A significant decrease in pH triggers the mechanisms of apoptosis – programmed cell death (D. Di ng et al., 2000) .
Especially significant violations of energy metabolism in older people are observed under stress. At the same time, the energy metabolism storage paths associated with the use of ketone bodies as an energy substrate are activated, glycolysis is further enhanced, which leads to acidosis and increased free-radical processes. An increase in the release of the excitatory glutamate mediator during stress leads to the accumulation of intracellular calcium, under the influence of which Ca-dependent proteases, endonucleases, and phospholipases are activated, causing the degradation of the most important neuron structures. The chain of these processes leads to neurodegeneration and contributes to the development of AD.