Chrono-neuroendocrinological aspects of physiological aging and senile dementia

The circadian pattern of melatonin and cortisol secretion was evaluated in two groups of elderly subjects (aged 66-90 years), one with Alzheimer's type of multiinfarct dementia (n = 27) and the other without cognitive impairment (n = 16); 13 clinically healthy women aged 20 to 30 years were chosen as controls. All demented patients had severe mental impairment, corresponding to stage 6 of the Global Deterioration Scale. All subjects, either young or aged, were studied as in-patients and were well synchronized with respect to meal timing, diurnal activity and nocturnal rest. At the population mean cosinor analysis (Halberg, 1969) both melatonin and cortisol circadian rhythms reached statistical significance in the three groups of subjects. However, the melatonin circadian profile was clearly flattened in the two groups of elderly subjects by comparison with young controls, due to the selective impairment of melatonin nocturnal secretion. In both elderly groups, but particularly in demented patients, plasma cortisol levels were significantly higher by comparison to young controls, particularly at evening and night time. A significant direct relationship linked the subjects' age and the nadir values of plasma cortisol. Furthermore, the sensitivity of the hypothalamo-pituitary-adrenal axis to dexamethasone (DXM) suppression test (1 mg orally at 2300) was significantly reduced in both elderly groups, and especially in old demented patients, by comparison with young controls. Finally, plasma cortisol response to pulse i.v. injection of a small dose of synthetic corticotropin (Synacthen 2,500 ng) was significantly higher and more prolonged in old demented patients than in mentally healthy old subjects and in young controls.(ABSTRACT TRUNCATED AT 250 WORDS)