Increased glucocorticoid production and altered cortisol metabolism in women with mild to moderate Alzheimer's disease

Background: Abnormalities at several levels of the hypothalmic-pituitary-ad renal axis, which may promote glucocorticoid dependent neurodegeneration, h ave been reported in patients with Alzheimer's disease. In this study we ha ve explored the possibility that peripheral cortisol metabolism is enhanced and glucocorticoid production is increased compensatory in patients with m ild to moderate Alzheimer's disease. Methods: Urinary excretion of cortisol and its principal conjugated metabol ites was studied in ten women with mild to moderate Alzheimer's disease, se ven healthy elderly women and seven young women. Results: There was an age-related fall in glucocorticoid production (median , 2009 [range 1828-4201] vs. 9315 [range 3613-16,244] mug/24 hours in elder ly vs. young control subjects). A-ring metabolism (i.e,, the irreversible i nactivation of cortisol by 5 alpha- and 5 beta -reductases) was reduced in old age. However, patients with Alzheimer's disease showed persistence of c ortisol metabolite excretion. Glucocorticoid production was significantly i ncreased in patients with Alzheimer's disease versus healthy elderly contro l subjects (median, 7269 [range 6005-15,335] vs. 2009 [range 1828-4201] mug /24 hours), and patients with Alzheimer's disease had increased A-ring redu ction of cortisol. Conclusions: An increased glucocorticoid production is an early feature of Alzheimer's disease and may be secondary to enhanced metabolic clearance of cortisol by A-ring reduction. Biol Psychiatry 2001;49:547-552 (C) 2001 Soc iety of Biological Psychiatry.