[Age as a risk factor for the development of dementias? Consideration of changes in cerebral glucose metabolism with...

Based on changes in glucose and related brain metabolism in aging, it is discussed whether or not age is a risk factor for dementia. Normal brain function is tightly coupled with the availability of sufficient amounts of ATP which is normally formed from the oxidation of glucose only. The glycolytic and oxidative cerebral glucose metabolism is controlled by various mechanisms. Glucose breakdown also contributes to the formation of the neurotransmitters acetylcholine, glutamate, aspartate, and GABA. ATP yields the basis for the maintenance of neuronal homeostasis via ion homeostasis, integrity of cellular components, and intracellular transportation processes. It is also necessary for the formation of several neurotransmitters and neurohormones. Normal cerebral aging is associated with an incipient perturbation in cerebral glucose and related metabolism causing an energy deficit and thus an imbalance of cell homeostasis beyond the seventh or eighth decade of life, pointing to a threshold phenomenon. Such processes may begin insidiously, but may be assumed to progress exponentially in a self-propagating manner. These events markedly reduce the biological plasticity of the brain which may become abnormal after cerebral stress situations such as ischemia, etc. Thus, the increasing damage of neuronal homeostasis may give rise to the assumption that age, or several age-related metabolic abnormalities at the cellular level, may be regarded as risk factors for dementia.