Enhanced hypothalamic-pituitary-adrenocortical axis responses to physostigmine in normal aging

BACKGROUND The purpose of this study was to determine the effects of normal human aging on the hypothalamic-pituitary-adrenocortical (HPA) axis response to the centrally active cholinesterase inhibitor physostigmine. This drug stimulates the HPA axis at a suprapituitary level by increasing central nervous system (CNS) cholinergic activity. METHODS Plasma ACTH, beta-endorphin (beta E) and cortisol responses to a 10-minute infusion of physostigmine (.0125 mg/kg) were compared between groups of 10 normal older subjects (71 +/- 2 years [mean +/- SEM]) and 9 normal young subjects (27 +/- 2 years). Plasma physostigmine concentrations were measured to assess the comparability of the pharmacologic stimulus between groups. RESULTS Endocrine responses were substantially greater in older subjects than young subjects for ACTH (p < .01), beta E (p < .01) and cortisol (p < .01). Plasma physostigmine concentrations did not differ between older and young subjects. CONCLUSION This study demonstrated increased HPA axis responsivity to a CNS cholinergic stimulus in normal human aging.