During clinical practice, degenerative diseases in some patients appear after exposure to a severe psychological stress. Several studies have suggested that the duration of exposure to corticosteroids or stress, the dose of corticosteroids and the vulnerability of the hippocampus, amygdala and prefrontal cortex areas targeted by elevated stress hormones, mediate the damaging effects of elevated corticosteroids. Although understanding what triggers the transition from adaptive plasticity to the maladaptive effects of stress in the elderly is important, one of the great challenges is to determine individual differences in vulnerability to stress-induced events in both animal and human populations, and to devise strategies that may help protecting the brain from permanent damage. This review provides the basis for creating interventions and educational programs during midlife in order to prevent dementia or other neurodegenerative diseases or to halt the progress of neurodegeneration in the early stages.