Chapter 3.8 Stress and dementia

Dementia is a relatively well-defined condition characterized by a progressive decline of cognitive and performances, as a consequence of degenerative and/or vascular brain changes. Although the definition of stress remains still problematic, it is now well known that a chronic exposure to stressors is usually able to disrupt the physiological balance both at the cellular or the organism level, and to play a role in the onset and progression of some pathological conditions. Within this context, at systemic level stress includes all the neurohormonal and metabolic responses of the organism to external stressors; at cellular level, stress, mostly oxidative stress, may instead be a correlate of the aging process itself. The link between stress and cognitive impairment is probably to be found in the hippocampal changes, a crucial as well as vulnerable brain area involved in mood, cognitive and behavioural control, and in the mean time, a site with a very high density of glucocorticoid (GR) and mineralocorticoid (MR) receptors. Therefore, the hippocampal neuronal impairment is responsible for a continuous stress-induced activation of the hypothalamic-pituitary-adrenal (HPA) axis and an increased hypothalamic expression of corticotropin releasing factor (CRF) and vasopressin. Furthermore, the age-related changes of the adrenocortical secretory pattern could play a role in the pathophysiology of brain aging, fostering the brain exposure to a neurotoxic hormonal pattern. In this chapter, we examine particularly the evidence for a link between dementia and HPA activity on the basis of the data in the literature as well as of our personal findings.