Hypothalamic pituitary adrenocortical and sympathetic nervous system responses to the cold presser test in Alzheimer's disease

Background: Increased basal activity of the hypothalamic-pituitary-adrenoco rtical (HPA) axis has been repeatedly demonstrated in Alzheimer's disease ( AD), and some studies suggest increased basal activity of the sympathetic n ervous system (SNS) in this disorder; however, the effects of AD on HPA axi s or SNS responses to a standardized aversive stressor have not been examin ed. The neuroendocrine response to aversive stress may be relevant to the p athophysiology of AD. Methods. Plasma adrenocorticotropic hormone (ACTH), cortisol, norepinephrin e (NE), and epinephrine responses to a 1-min cold pressor test (CPT)were me asured in nine medically healthy AD outpatients (age 76 +/- 1 years) and ni ne age- and gender-matched medically healthy cognitively normal older subje cts (age 76 +/- 1 year). Results: The cortisol response to CPT was increased in the AD group but the ACTH response did not differ between groups. Basal NE responses to CPT did not differ between groups, the blood pressure response to CPT was higher i n the AD subjects. Conclusions: These results suggest increased HPA axis responsiveness to CPT at the level of the adrenal cortex in AD. The results also suggest increas ed basal sympathoneural activity and increased cardiovascular responsivenes s to sympathoneural stimulation in AD under the conditions of this experime ntal protocol. Increased SNS stimulatory modulation of the adrenal cortex i s a possible mechanism contributing to the observed enhanced cortisol respo nse to CPT in these AD subjects. Biol Psychiatry 2000;48:247-254 (C) 2000 S ociety of Biological Psychiatry.