Relationships between cortisol, dehydroepiandrosterone sulphate and insulin-like growth factor-I system in dementia

Changes in the hypothalamus-pituitary-adrenal axis (HPAA) function, entaili ng elevated cortisol circulating titres, occur in aging and in some neurolo gical conditions, such as Alzheimer's disease IAD). Excess cortisol has neu rotoxic effects which affect hippocampal neurones. Dehydroepiandrosterone s ulphate (DHEAS) has an antiglucocorticoid activity and neuroprotective effe cts, but its levels decrease with aging. Glucocorticoids influence the prod uction of insulin-like growth factor-I (IGF-I) and modify its systemic and neurotrophic biological activity by inducing changes in IGF-binding protein s (IGFBPs). We looked for relationships between cortisol, DHEAS levels, and IGF-I - IGFBPs system in AD. Cortisol, DHEAS and GH levels at 02:00, 08:00 , 14:00, 20:00 h, basal IGF-I, IGFBP-1 and IGFBP-3 levels were determined b y RIAs or IRMA in 25 AD patients, aged 58-89 yr, and in 12 age-matched heal thy controls. AD subjects had higher cortisol, lower DHEAS levels and incre ased cortisol/DHEAS ratio (C/Dr) than controls. In AD cases, total IGF-I, I GFBP-3, and IGF-I/]GFBP ratios were significantly lowered, while IGFBP-1 le vels were significantly higher than in controls. We found a significant inv erse correlation between IGF-I and IGFBP-3 levels vs C/Dr, and between both IGF-I/IGFBPs ratios vs mean cortisol levels. IGFBP-3 correlated directly w ith DHEAS. Cortisol was directly and IGF-I inversely correlated with cognit ive impairment. In AD patients we found that alterations in HPAA function a nd elevated C/Dr are related to lowered total and free IGF-I levels. These findings and their relationship to cognitive impairment suggest that change s in hormonal set-up might influence the clinical presentation of the disea se.