ENHANCED ADRENAL SENSITIVITY TO ADRENOCORTICOTROPIC HORMONE (ACTH) ISEVIDENCE OF HPA AXIS HYPERACTIVITY IN ALZHEIMERS-DISEASE

Adrenal sensitivity was assessed in 16 non-depressed patients with NIN CDS/ADRDA Alzheimer's disease (AD) and 18 control subjects by measurin g cortisol response to low dose (0.05 mu g/kg i.v.) exogenous adrenoco rticotrophic hormone (ACTH). Controlling for sex and medication, both peak cortisol level (peak-baseline) and area under cortisol response c urve (AUC above baseline) were significantly greater in AD subjects. T his shows that HPA axis hyperactivity as demonstrated by enhanced adre nal sensitivity to ACTH, occurs in AD. Similar findings have been repo rted to occur in depression. Among AD subjects, AUC cortisol response correlated with current age (r = 0.70, P = 0.001) and age at onset of dementia (r = 0.73, P = 0.001) and an inverse correlation was seen bet ween cortisol AUC and cognitive test (CAMCOG) score (r = -0.51, P = 0. 044). Our findings suggest that HPA axis hyperactivity in AD is associ ated with advancing age and cognitive dysfunction. Such changes may be cause, or consequence, of neuronal loss.