pituitrin and Dementia--Vascular

Hippocampus plays a crucial role in learning and memory and, in spite of its remarkable plasticity, it is also particularly sensitive to stress hormones due to its high concentration of corticosteroid receptors. Indeed, adrenal steroids modulate hippocampal plasticity, acting on excitability and long term potentiation or depression. By a chronobiological approach, we studied the cortisol and DHEAS secretion in clinically healthy old subjects and in age-matched demented patients, including both the degenerative and the vascular type. When compared to young controls, both clinically healthy elderly subjects and demented patients, particularly those with AD, had significantly higher cortisol levels at night time, i.e. at the moment of the maximal sensitivity of HPA axis to stimulatory or inhibitory inputs. At the same time, a clear age- and disease-dependent reduction of DHEAS secretion was found. Thus the cortisol to DHEAS molar ratio was significantly higher in healthy old subjects, and even more in demented patients, when compared to young controls, and significantly linked to both age and cognitive impairment. Finally, the quantitative and qualitative changes of the adrenal secretory pattern were significantly correlated with the decline of hippocampal volumes, measured by MRI. In conclusion, several lines of evidence deal with a pathogenetic role of stress hormones in the occurrence and progression of cognitive disorders in elderly subjects. The consequent hippocampal neuronal impairment may in turn be responsible for the continuous activation of HPA axis and the increased hypothalamic expression of vasopressin and corticotropin releasing hormone.

Topics: Adult; Aged; Aging; Alzheimer Disease; Case-Control Studies; Circadian Rhythm; Cognition Disorders; Corticotropin-Releasing Hormone; Dehydroepiandrosterone; Dementia; Dementia, Vascular; Hippocampus; Humans; Hydrocortisone; Hypothalamo-Hypophyseal System; Middle Aged; Neuronal Plasticity; Pituitary-Adrenal System; Receptors, Steroid; Stress, Physiological; Vasopressins

Previously, alterations in neuronal metabolism were found in a number of brain areas of Alzheimer disease (AD) patients. In the present study we aimed at determining for the first time whether metabolic changes would also occur in vascular dementia (VD) patients in the supraoptic (SON), infundibular (INF), tuberomamillary (TMN), medial mamillary nuclei, vertical limb of the diagonal band of Broca (VDB), and nucleus basalis of Meynert. The Golgi complex (GC) size, cell size, and vasopressin mRNA levels (in the SON) were used as measures of neuronal metabolic activity in postmortem material. The GC immunoreactivity was clearly diminished in the SON, INF and TMN and was increased in the VDB of VD cases. Interestingly, in the SON and TMN, a decrease in the GC size was more pronounced in male than in female VD patients in accordance with the higher prevalence of VD in men. In 7 of 11 VD cases, vasopressin mRNA levels were significantly reduced which may contribute to urinary incontinence, one of the most common clinical symptoms in VD, and to the lower blood pressure values that are often registered at the later stages of the VD. Since the human TMN is the sole source of cerebral histamine, our data suggest deficient histaminergic transmission in the brain in VD. Diminished neuronal metabolism in the SON and INF was not observed in AD in this and previous studies, whereas the changes in the VDB and TMN are similar in VD and AD. In the present study we thus found decreased metabolic activity in several hypothalamic nuclei in VD indicating diminished production of certain hormones and neurotransmitters.

Topics: Aged; Aged, 80 and over; Cadaver; Cell Size; Dementia, Vascular; Female; Golgi Apparatus; Humans; Hypothalamus; In Situ Hybridization; Male; Middle Aged; Prosencephalon; RNA, Messenger; Tissue Distribution; Vasopressins