Mild dementia is associated with increased adrenal secretion of cortisol and precursor sex steroids in women.

Context: Sex steroid levels decrease with increasing age, but little is known whether this is of importance for the age-related decline in cognitive function. Design and Patients: A cross-sectional study of 50 (26 men) consecutive patients under primary evaluation of cognitive impairment (D group) and 18 (9 men) matched healthy controls (C group). Measurements: Sex steroid and precursor levels were determined in serum and when measurable, in cerebrospinal fluid (CSF) using gas chromatography/mass spectroscopy (GC-MS) or liquid chromatography/mass spectroscopy (LC-MS). Sex hormone binding globulin (SHBG) and cortisol concentrations were measured using conventional assays. Results: Patients in the D group had higher 24-h urine cortisol level and increased serum levels of dehydroepiandrosterone (DHEA) and its sulfate ester DHEAS, androsterone (ADT), and estrone (E1) and its sulfate ester E1S, compared to the controls. When men and women were analyzed separately, increased serum concentrations of E1 and E1S were observed in both D men and D women whereas increased levels of other sex steroids and cortisol were seen only in D women. Conclusions: In both D men and women, serum E1 and E1S levels were increased whereas other changes were gender-specific and only seen in D women. Further studies are needed to determine whether these changes are a cause of, or merely a consequence of, cognitive impairment in elderly subjects.