Neuroendocrine Correlates of the Aging Brain in Humans

Abstract

Physiological brain aging is characterized by important biochemical and structural changes and by the unbalance among the different neurotransmitters and neuromodulators. The study of the circadian organization of neuroendocrine functions may be considered a clinically reliable tool to investigate the changes of the CNS and particularly of the limbic-hypothalamic system occurring in aged people. The circadian rhythms of plasma melatonin, ACTH and cortisol and of oral temperature were studied in 16 clinically healthy women aged 66-90 years and in 14 young controls aged 20-30. In addition, the effect of dexamethasone on the plasma cortisol circadian rhythm and the cortisol response to Synacthen pulse intravenous injection were evaluated. All subjects were studied as inpatients, with the same synchronization to the hospital life schedule. When compared with young controls, elderly subjects exhibited a reduction of the mean level and of the amplitude of the circadian rhythm of oral temperature, an increase of the mean level of ACTH and cortisol rhythms and a selective impairment of melatonin nocturnal secretion. Furthermore, elderly subjects showed a reduced sensitivity to the dexamethasone suppression test, by comparison to young controls. These changes were age-related and they may depend either on CNS modification or on alterations of the hormonal metabolic clearance.

Age-related changes of the hypothalamic-pituitary-adrenal axis: pathophysiological correlates

“…1), allowed us to detect a high percentage of`non-responders' (serum cortisol levels above 5 mg/dl the morning following DXM (66), in healthy old subjects (about 30%) and in old demented patients (50%). Indeed, the mean cortisol values recorded after DXM were significantly higher in elderly subjects and especially in demented patients than in young controls; moreover, patients with senile dementia also exhibited a delay of the cortisol response to DXM (67).…”

Salivary cortisol is associated with diagnosis and severity of late-life generalized anxiety disorder

“…Many studies have found an age-associated increase in HPA activity (Van Cauter et al, 1996), resulting in elevated cortisol levels (Lupien et al, 1994;Ferrari et al, 1995;Deuschle et al, 1997) and attenuation, or a flattening, of cortisol diurnal rhythm (van Coevorden et al, 1991) suggesting age-dependent HPA axis dysregulation. Additionally, it has long been speculated that chronic elevations of stress-related hormones such as cortisol can weaken multiple physiological systems of older adults resulting in impaired cardiovascular and immune function, as well as contributing to dementia, and mood and anxiety disorders.…”

6‐Sulfatoxymelatonin excretion and self‐reported sleep in good sleeping controls and 55–80‐year‐old insomniacs

“…1996). Lowered melatonin levels are also associated with ageing (Iguchi et al 1982;Touitou et al 1984;Sack et al 1986; as potential subjects if they met the following criteria: mean sleep onset latency (SOL) < 30 min, WASO < 30 min, final Waldhauser et al 1988;Sharma et al 1989;van Coevorden et al 1991Ferrari et al 1995Hajak et al 1996). Ageing is wake-up time (FWUT) > 06.00 h, TST > 7.5 h and SE > 85%.…”

“…Most of these studies report peak melatonin Attenburrow, M. E. J., Dowling, B. A., Sharpley, A. L. and Cowen, concentration is reduced in the aged (Iguchi et al 1982; Touitou P. J. Case-study of evening melatonin concentration in primary et al 1984;van Coevorden et al 1991Ferrari et al 1995insomnia. Br.…”