A subtle disturbance in the feedback regulation of the hypothalamic-pituitary-adrenal axis in the early phase of Alzheimer's disease.

In an attempt to find if a disturbance in the function of the feedback regulation of the hypothalamic-pituitary-adrenal axis is an early feature in Alzheimer's disease (AD), 35 outpatients (mean age 76.8 years) with a mild to moderate AD were compared to 20 controls (mean age 73.8 years) in their response to different doses of dexamethasone. After 0.5 mg dexamethasone, serum cortisol levels were significantly less suppressed in patients with early AD (p = .03) and these patients were significantly more often dexamethasone nonsuppressors (serum cortisol > or = 138 nmol/l) than controls (14/35 vs. 2/20; p = .03). Nonsuppression to 1 mg dexamethasone did not differ between groups (2/35 vs. 0/20). Plasma adrenocorticotropin levels were significantly lower in patients with Alzheimer's disease (n = 16) after 0.5 mg as well as after 1.0 mg dexamethasone (p = .01 and p < .001, respectively). The relationship between cortisol resistance to dexamethasone suppression and pathophysiology of AD is discussed.