Hypothalamic-pituitary-adrenal system function in patients with alzheimerʹs disease

The neuropathologic hallmarks of Alzheimerʹs disease (AD) are very prominent in the hippocampus, a brain site which is pivotal for the regulation of the hypothalamic-pituitary-adrenal (HPA) system. Thus, the combined dexamethasone-suppression/CRH-stimulation-test outcome in patients with AD was compared to that of healthy elderly controls to assess — with a more refined neuroendocrine challenge procedure—HPA function in AD. Cortisol secretion after dexamethasone (DEX) pretreatment and before CRH was increased in Alzheimerʹs patients and 21% of this group were DST-nonsuppressors. None of the healthy control subjects escaped DEX-induced suppression of cortisol. However, after additional CRH administration, AD patients released significantly less cortisol and ACTH than the control subjects. No correlations were found between any of the endocrine parameters and degree of severity of dementia. It is concluded that the DST part of the DEX/CRH test better reflects glucocorticoid feedback disturbances, probably at a suprapituitary level. The CRH part of the DEX/CRH-test outcome might indicate the loss of endogenous CRH-Arginine-Vasopressin (AVP) synergism of the HPA system of these patients.