Stress and dementia: the role of the hypothalamic-pituitary-adrenal axis

Abstract

Hippocampus plays a crucial role in learning and memory and, in spite of its remarkable plasticity, it is also particularly sensitive to stress hormones due to its high concentration of corticosteroid receptors. Indeed, adrenal steroids modulate hippocampal plasticity, acting on excitability and long term potentiation or depression. By a chronobiological approach, we studied the cortisol and DHEAS secretion in clinically healthy old subjects and in age-matched demented patients, including both the degenerative and the vascular type. When compared to young controls, both clinically healthy elderly subjects and demented patients, particularly those with AD, had significantly higher cortisol levels at night time, i.e. at the moment of the maximal sensitivity of HPA axis to stimulatory or inhibitory inputs. At the same time, a clear age- and disease-dependent reduction of DHEAS secretion was found. Thus the cortisol to DHEAS molar ratio was significantly higher in healthy old subjects, and even more in demented patients, when compared to young controls, and significantly linked to both age and cognitive impairment. Finally, the quantitative and qualitative changes of the adrenal secretory pattern were significantly correlated with the decline of hippocampal volumes, measured by MRI. In conclusion, several lines of evidence deal with a pathogenetic role of stress hormones in the occurrence and progression of cognitive disorders in elderly subjects. The consequent hippocampal neuronal impairment may in turn be responsible for the continuous activation of HPA axis and the increased hypothalamic expression of vasopressin and corticotropin releasing hormone.

Lifecourse Social Conditions and Racial and Ethnic Patterns of Cognitive Aging

“…It has also been shown that chronic life stress among healthy women prospectively predicts reductions in gray matter volume in the hippocampus (Gianaros et al 2007) and cortisol levels correlate with hippocampal volume (Lupien et al 1998). Chronic stress has thus been hypothesized to play a crucial role in development of dementia (Magri et al 2006). Gallo and Matthews hypothesize that SEP effects on health are partially mediated by the influence of negative emotions such as hostility, hopelessness, depression or anxiety (Gallo and Matthews 2003).…”

Activity Dependency and Aging in the Regulation of Adult Neurogenesis

“…This leads to a down-regulation of precursor cell proliferation in the adult dentate gyrus (Gould et al 1997;. The stress-induced effects of glucocorticoids have been linked to age-related cognitive problems in humans (Heffelfinger and Newcomer 2001;Magri et al 2006). In animal models, the effects of chronic stress and chronically high levels of corticosterone on adult neurogenesis have been rather difficult to assess, and the data do not yet provide a clear picture.…”

Effects of Glucocorticoids on Age-Related Impairments of Hippocampal Structure and Function in Mice

“…It also plays a key role in the endocrine functions of the hypothalamic-pituitary-adrenal axis (Miller and O¢Callaghan 2005;Magri et al 2006). As it is a principal neural target tissue for GCs, it is, therefore, reasonable to assume that such action may lead to specific cognitive deficits.…”