ABSTRACT
Several lines of evidence show that decreased metabolic rate precedes cognitive impairment in Alzheimer s disease (AD). Decreased neuronal metabolism contributes to neuronal atrophy and functional impairment and is thus an early occurring hallmark of AD. Factors that may contribute to a diminishment in neuronal metabolism are age, sex, APOE-ε 4 and decreased levels of sex hormones or melatonin. Several observations in postmortem brain indicate that activated neurons are better able to withstand aging and AD, a phenomenon we paraphrased as use it or lose it. Moreover, a number of pharmacological and non-pharmacological studies support the concept that activation of the brain has beneficial effects and may to a certain degree restore several aspects of cognition and other central functions. For instance, the circadian system of Alzheimer patients may be restimulated by exposing them to more light or transcutaneous nerve stimulation. A procedure allowing testing of the efficacy of putative stimulatory compounds such as neurotrophins and precursor cells has been developed in order to be able to culture human postmortem brain tissue.