Dementia of the Alzheimer type and hypothalamus‐pituitary‐adrenocortical axis: changes in cerebrospinal fluid corticotropin releasing factor and plasma cortisol levels

The activity of the hypothalamus‐pituitary‐adrenocortical (HPA) axis was explored in 10 patients with dementia of the Alzheimer type (DAT) and in 11 age‐matched controls, by measuring 1) corticotropin‐releasing factor (CRF) levels in cerebrospinal fluid (CSF), 2) the circadian changes of plasma cortisol, 3) and 4) the plasma cortisol response to dexamethasone suppression test (DST) and to CRF stimulation test. CSF CRF levels in DAT were significantly higher than in controls and inversely related to the Mini Mental State (MMS) score. The patients also displayed increased morning (0800 h) plasma cortisol values, with higher mesor and amplitude in the circadian pattern. Dexamethasone resistance was shown by 6 of the 10 DAT subjects. Plasma cortisol response to CRF administration was similar in the two groups, except for the peak values, which in DAT patients were reached earlier than in controls. The present data suggest an overactivity of HPA axis in DAT; its possible role in the evolution of the disease is discussed.

[1]  M. Franceschi,et al.  Neuroendocrinological function in Alzheimer's disease. , 1988, Neuroendocrinology.

[2]  B. McEwen,et al.  ABNORMAL CORTISOL RESPONSE IN ALZHEIMER'S DISEASE LINKED TO HIPPOCAMPAL ATROPHY , 1988, The Lancet.

[3]  Y. Lamour,et al.  Pharmacological modulation of cortisol secretion and dexamethasone suppression in alzheimer's disease , 1988, Biological Psychiatry.

[4]  E. Sinforiani,et al.  Acetyl-L-carnitine normalizes pituitary-adrenocortical hyperactivity in pathological ageing brain , 1988 .

[5]  D. Price,et al.  Immunohistochemical study of neurons containing corticotropin‐releasing factor in Alzheimer's disease , 1987, Synapse.

[6]  T. O'donohue,et al.  Spinal fluid CRF reduction in Alzheimer's disease , 1986, Neuropeptides.

[7]  Joseph B. Martin,et al.  Neuropeptide Y immunoreactivity is reduced in cerebral cortex in Alzheimer's disease , 1986, Annals of neurology.

[8]  B. McEwen,et al.  The neuroendocrinology of stress and aging: the glucocorticoid cascade hypothesis. , 1986, Endocrine reviews.

[9]  K. Davis,et al.  Cortisol and Alzheimer's disease, II: Dexamethasone suppression, dementia severity, and affective symptoms. , 1986, The American journal of psychiatry.

[10]  B. Reisberg,et al.  Dexamethasone suppression in dementia, depression, and normal aging. , 1986, The American journal of psychiatry.

[11]  K. Davis,et al.  Cortisol and Alzheimer's disease, I: Basal studies. , 1986, The American journal of psychiatry.

[12]  D. Price,et al.  Reciprocal changes in corticotropin-releasing factor (CRF)-like immunoreactivity and CRF receptors in cerebral cortex of Alzheimer's disease , 1986, Nature.

[13]  L. Iversen,et al.  Non-cholinergic neurotransmitter abnormalities in Alzheimer's disease. , 1986, British medical bulletin.

[14]  J. Nurnberger,et al.  Neuropeptides in human cerebrospinal fluid. , 1985, Life sciences.

[15]  D. F. Swaab,et al.  The suprachiasmatic nucleus of the human brain in relation to sex, age and senile dementia , 1985, Brain Research.

[16]  H. Dick,et al.  Neuroendocrine Studies in Alzheimer’s Disease , 1985 .

[17]  C. Kilts,et al.  Elevated concentrations of CSF corticotropin-releasing factor-like immunoreactivity in depressed patients. , 1984, Science.

[18]  G. Chrousos,et al.  The corticotropin-releasing factor stimulation test. An aid in the evaluation of patients with Cushing's syndrome. , 1984, The New England journal of medicine.

[19]  A. Elias,et al.  Corticotropin-releasing factor stimulation test. , 1984, The New England journal of medicine.

[20]  W. Vale,et al.  Influence of the frequency of ovine corticotropin-releasing factor administration on adrenocorticotropin and corticosterone secretion in the rat. , 1983, Endocrinology.

[21]  G. Långström,et al.  Dexamethasone Suppression Test and Serum Prolactin in Dementia Disorders , 1983, British Journal of Psychiatry.

[22]  A. Hoffman,et al.  Desensitization of corticotropin-releasing factor receptors. , 1983, Biochemical and biophysical research communications.

[23]  D L Price,et al.  Alzheimer's disease: a disorder of cortical cholinergic innervation. , 1983, Science.

[24]  J. Vaughan,et al.  Assay of corticotropin releasing factor. , 1983, Methods in enzymology.

[25]  F. Bloom,et al.  Chemical and biological characterization of corticotropin releasing factor. , 1983, Recent progress in hormone research.

[26]  C. P. Hughes,et al.  A New Clinical Scale for the Staging of Dementia , 1982, British Journal of Psychiatry.

[27]  W. Vale,et al.  Characterization of a 41-residue ovine hypothalamic peptide that stimulates secretion of corticotropin and beta-endorphin. , 1982, Science.

[28]  W. Vale,et al.  Characterization of a 41-residue ovine hypothalamic peptide that stimulates secretion of corticotropin and beta-endorphin , 1981 .

[29]  J. Simpson,et al.  NORADRENALINE IN ALZHEIMER-TYPE DEMENTIA AND DOWN SYNDROME , 1981, The Lancet.

[30]  P. Millard,et al.  Investigation of cerebrospinal fluid neuropeptides in idiopathic senile dementia. , 1981, Gerontology.

[31]  R. Katzman.,et al.  Reduced somatostatin-like immunoreactivity in cerebral cortex from cases of Alzheimer disease and Alzheimer senile dementa , 1980, Nature.

[32]  L. Squire,et al.  Preserved learning and retention of pattern-analyzing skill in amnesia: dissociation of knowing how and knowing that. , 1980, Science.

[33]  S. Folstein,et al.  "Mini-mental state". A practical method for grading the cognitive state of patients for the clinician. , 1975, Journal of psychiatric research.

[34]  M. Hamilton.  A RATING SCALE FOR DEPRESSION , 1960, Journal of neurology, neurosurgery, and psychiatry.