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Dexamethasone effects on cortisol secretion in Alzheimer’s disease: Some clinical and hormonal features in suppressor and nonsuppressor patients

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Abstract

Alterations in the hypothalamic-pituitary-adrenal axis (HPAA) and failure of dexamethasone (DXT) to suppress cortisol secretion occur in Alzheimer’s disease (AD). This study was aimed to settle possible differences in some clinical (age, body weight, body mass index, dementia severity) and hormonal parameters in AD patients non-responders to overnight 1 mg-DXT suppression test compared with the responder subjects. ACTH, cortisol and dehydroepiandrosterone sulphate (DHEAS) day-time levels were assessed in 25 AD patients and in 12 age-matched healthy controls before DXT administration. In view of their neuroprotective effects, plasma levels of Insulin-like Growth Factor-I (IGF-I) and of IGF-Binding Proteins (IGFBPs) were also determined. After DXT, 8 AD subjects (32%) showed cortisol levels above the conventional cut-off of 140 nmol/L. No significant differences were found in clinical parameters in suppressor vs nonsuppressor patients. AD subjects showed higher cortisol, cortisol/DHEAS ratios, and lower DHEAS levels in comparison with controls. Both ACTH and cortisol levels were not different in suppressor and nonsuppressor patients, but DHEAS levels were significantly lower in nonsuppressor cases, who also exhibited ACTH and cortisol periodicities more altered than in suppressor and in control subjects. IGF-I and IGFBP-3 levels were lower and those of IGFBP-1 higher in nonsuppressor than in suppressor cases and in healthy controls. IGF-I/IGFBPs system data were correlated with cognitive impairment and adrenal steroid levels in AD patients.

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References

  1. Raskind M.A., Peskind E., Rivard M.-F., Veith R., Barnes R. The dexamethasone suppression test and cortisol circadian rhythm in primary degenerative dementia. Am. J. Psychiatry 1982, 139: 1468–1471.

    CAS  PubMed  Google Scholar 

  2. Skare S., Pew B., Dysken M. The dexamethasone suppression test in dementia: a review of the literature. J. Geriatr. Psychiatry Neurol. 1990, 3: 124–138.

    Article  CAS  PubMed  Google Scholar 

  3. Carroll B.J., Feinberg M., Greden J.F., Tarika J., Albala A.A., Haskett R.F., James N., Kronfold Z., Lohr N., Steinert M., deVigne J.P., Young E. A specific laboratory test for the diagnosis of melancholia. Standardization, validation and clinical utility. Arch. Gen. Psychiatry 1981, 38: 15–22.

    Article  CAS  PubMed  Google Scholar 

  4. Herbert J. Neurosteroids, brain damage, and mental illness. Exp. Gerontol. 1998, 33: 713–727.

    Article  CAS  PubMed  Google Scholar 

  5. Davous P., Roudier M., Piketty M.L., Abramowitz C., Lamour Y. Pharmacological modulation of cortisol secretion and dexamethasone suppression in Alzheimer’s disease. Biol. Psychiatry 1988, 23: 13–24.

    Article  CAS  PubMed  Google Scholar 

  6. Balldin J., Blennow K., Brane G., Gottfries C.G., Karlsson I., Regland B., Wallin A. Relationship between mental impairment and HPA axis activity in dementia disorders. Dementia 1994, 5: 252–256.

    CAS  PubMed  Google Scholar 

  7. Magri F., Locatelli M., Balza G., Molla G., Cuzzoni G., Fioravanti M., Solerte S.B., Ferrari E. Changes in endocrine circadian rhythms as markers of physiological and pathological brain aging. Chronobiol. Intern. 1997, 14: 385–396.

    Article  CAS  Google Scholar 

  8. Wilkinson C.W., Peskind E.R., Raskind M.A. Decreased hypothalamic-pituitary-adrenal axis sensitivity to cortisol feedback inhibition in human aging. Neuroendocrinology 1997, 65: 79–90.

    Article  CAS  PubMed  Google Scholar 

  9. Boscaro M., Paoletta A., Scarpa E., Barzon L., Fusaro P., Fallo F., Sonino N. Age-related changes in glucocorticoid fast feedback inhibition of adrenocorticotropin in man. J. Clin. Endocrinol. Metab. 1998, 83: 1380–1383.

    CAS  PubMed  Google Scholar 

  10. Huizenga N.A.T.M., Koper J.W., DeLange P., Pols H.A.P., Stolk R.P., Grobbee D.E., De Jong F.H., Lamberts S.W.J. Interperson variability but intraperson stability of baseline plasma cortisol concentrations, and its relation to feedback sensitivity of the hypothalamuspituitary-adrenal axis to a low dose of dexamethasone in elderly individuals. J. Clin. Endocrinol. Metab. 1998, 83: 47–54.

    CAS  PubMed  Google Scholar 

  11. De Kloet E.R., Van der Vies J., DeWied D. The site of suppressive action of dexamethasone on pituitary-adrenal activity. Endocrinology 1974, 94: 61–73.

    Article  PubMed  Google Scholar 

  12. De Kloet E.R., Vreugdenhil E., Oitzl M.S., Joëls M. Brain corticosteroids receptor balance in health and disease. Endocr. Rev. 1998, 19: 269–301.

    PubMed  Google Scholar 

  13. Mc Ewen B.S. Stress and aging hippocampus. Front. Neuroendocrinol. 1999, 20: 49–70.

    Article  Google Scholar 

  14. Svec F., Lopez A. Antiglucocorticoid actions of dehydroepiandrosterone and low concentration in Alzheimer’s disease. Lancet 1989, i: 1335–1336.

    Article  Google Scholar 

  15. Behl C. Effects of glucocorticoids on oxidative stress-induced hippocampal cell death: implication for the pathogenesis of Alzheimer’s disease. Exp. Gerontol. 1998, 33: 689–696.

    Article  CAS  PubMed  Google Scholar 

  16. Kalimi M., Shafagoj Y., Loria R., Padgett D., Regelson W. Antiglucocorticoid effects of dehydroepiandrosterone (DHEA). Mol. Cell. Biochem. 1994, 131: 99–104.

    Article  CAS  PubMed  Google Scholar 

  17. Baulieu E.E., Robel P. Dehydroepiandrosterone and dehydroepiandrosterone sulfate as neuroactive neurosteroids. J. Endocrinol. 1996, 150: S221–S239.

    CAS  PubMed  Google Scholar 

  18. Kimonides V.G., Khatibi N.H., Svendsen C.N., Sofroniew M.V., Herbert J. Dehydroepiandrosterone (DHEA) and DHEA-sulfate (DHEAS) protect hippocampal neurons against excitatory amino acid-induced neurotoxicity. Proc. Natl. Acad. Sci. USA 1998, 95: 1852–1857.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Guazzo E.P., Kirkpatrick P.J., Goodyer I.M., Shiers H.M., Herbert J. Cortisol, dehydroepiandrosterone (DHEA), and DHEA sulfate in the cerebrospinal fluid of man: relation to blood levels and the effects of age. J. Clin. Endocrinol. Metab. 1996, 81: 3951–3960.

    CAS  PubMed  Google Scholar 

  20. Sunderland T., Merril C.R., Harrington M.G., Lawlor B.A., Molchan S.E., Martinez R., Murphy D.R. Reduced plasma dehydroepiandrosterone concentrations in Alzheimer’s disease. Lancet 1989, ii: 570.

    Article  Google Scholar 

  21. Näsman B., Olsson T., Backstrom T., Eriksson S., Grankvist K., Viitanen M., Bucht G. Serum dehydroepiandrosterone sulfate in Alzheimer’s disease and multi-infarct dementia. Biol. Psychiatry 1991, 30: 684–690.

    Article  PubMed  Google Scholar 

  22. Murialdo G., Nobili F., Rollero A., Gianelli M.V., Copello F., Rodriguez G., Polleri A. Hippocampal perfusion and pituitary-adrenal axis in Alzheimer’s disease. iNeuropsychobiology (in press).

  23. Torres-Aleman I. Insulin-like Growth Factors as mediators of functional plasticity in the adult brain. Horm. Metab. Res. 1999, 31: 114–119.

    Article  CAS  PubMed  Google Scholar 

  24. Hoffman A.R., Lieberman S.A., Butterfield G., Thompson J., Hintz R.L., Ceda G.P., Marcus R. Functional consequences of somatopause and its treatment. Endocr. Rev. 1997, 7: 73–76.

    Article  CAS  Google Scholar 

  25. Connor B., Beilharz E.J., Williams C., Synk R., Gluckman P.D., Faull R.L.M., Dragunow M. Insulin-like growth Factor-I (IGF-I) immunoreactivity in the Alzheimer’s disease temporal cortex and hippocampus. Mol. Brain Res. 1997, 49: 283–290.

    Article  CAS  PubMed  Google Scholar 

  26. Morales A.J., Nolan J.J., Nelson J.C., Yen S.S.C. Effects of replacement dose of dehydroepiandrosterone in men and women of advancing age. J. Clin. Endocrinol. Metab. 1994, 78: 1360–1367.

    CAS  PubMed  Google Scholar 

  27. Pfeilschifter J., Scheidt-Nave C., Leidig-Bruckner G., Woitge H.W., Blum W.F., Wüster C., Haack D., Ziegler R. Relationship between circulating Insulin-like Growth Factor components and sex hormones in a population-based sample of 50- to 80-year-old men and women. J. Clin. Endocrinol. Metab. 1996, 81: 2534–2540.

    CAS  PubMed  Google Scholar 

  28. Casson P.R., Santoro N., Elkind-Hirsch K., Carson S.A., Hornsby P.J., Abraham G., Buster J.E. Postmenopausal dehydroepiandrosterone administration increases free insulin-like growth factor -I and decreases high-density lipoprotein: a six-month trial. Fertil. Steril. 1998, 70: 107–110.

    Article  CAS  PubMed  Google Scholar 

  29. Jones J., Clemmons D.R. Insulin-like growth factors and their binding proteins: biological actions. Endocr. Rev. 1995, 16: 3–34.

    CAS  PubMed  Google Scholar 

  30. McKhann G., Drachman D., Folstein M., Katzman R., Price D., Stadlan E.M. Clinical diagnosis of Alzheimer’s disease: report of the NINCDS/ADRDA Work Group under the auspices of Department of Health and Human Services Task Force on Alzheimer’s Disease. Neurology 1984, 34: 939–944.

    Article  CAS  PubMed  Google Scholar 

  31. Folstein M.F., Folstein S.E., McHughes P.R. Mini Mental State: a practical method for grading the cognitive state of patients for clinicians. J. Psychiatry Res. 1975, 12: 189–198.

    Article  CAS  Google Scholar 

  32. Reisberg B., Ferris S., De Leon M.J., Croock T. The global deterioration scale for assessment of primary degenerative dementia. Am. J. Psychiatry 1982, 139: 1136–1139.

    CAS  PubMed  Google Scholar 

  33. Tsagarakis S., Grossman A. The hypothalamus-pituitary-adrenal axis in senescence. Front. Neuroendocrinol. 1999, 20: 70–91.

    Google Scholar 

  34. Swanwick G.R.J., Kirby M., Bruce I., Buggy F., Coen R.F., Cakley D., Lawlor B.A. Hypothalamic-pituitary-adrenal axis dysfunction in Alzheimer’s disease: lack of association between longitudinal and cross-sectional findings. Am. J. Psychiatry 1998, 155: 286–289.

    CAS  PubMed  Google Scholar 

  35. Sapolsky R.M., Plotsky P.M. Hypercortisolism and its possible neural bases. Biol. Psychiatry 1990, 27: 973.

    Article  Google Scholar 

  36. O’Brien J.T., Schweitzer I., Ames D., Tuckwell V., Mastwyk M. Cortisol suppression by dexamethasone in the healthy elderly: effect of age, dexamethasone levels, and cognitive function. Biol. Psychiatry 1994, 36: 389–394.

    Article  PubMed  Google Scholar 

  37. Hatzinger M., Z’Brun A Hemmeter U., Seifritz E., Baumann F., Holsboer-Trachsler E., Heuser I. Hypothalamic-pituitary-adrenal system function in patients with Alzheimer’s disease. Neurobiol. Aging 1995, 16: 205–209.

    Article  CAS  PubMed  Google Scholar 

  38. Miller A.H., Sastri G., Speranza A.J. jr, Lawlor B.A., Mohs R.C., Ryan T.M., Gabriel S.M., Serby M., Schneider J., Davis K.L. Lack of association between cortisol hypersecretion and non suppression on the DST in patients with Alzheimer’s disease. Am. J. Psychiatry 1994, 151: 267–270.

    CAS  PubMed  Google Scholar 

  39. Martignoni E., Petraglia F., Costa A., Bono G., Genazzani A.R., Nappi G. Dementia of the Alzheimer type and hypothalamus-pituitary-adrenal axis: changes in cerebrospinal fluid corticotropin releasing factor and plasma cortisol levels. Acta Neurol. Scand. 1990, 81: 452–456.

    Article  CAS  PubMed  Google Scholar 

  40. Waltman C., Blackman M.R., Chrousos G.P., Riemann C., Harman S.M. Spontaneous and glucocorticoid-inhibited cortisol secretion in healthy young and old men. J. Clin. Endocrinol. Metab. 1991, 73: 495–502.

    Article  CAS  PubMed  Google Scholar 

  41. Bornstein S.R., Chrousos G.P. Adrenocorticotropin (ACTH)- and non-ACTH-mediated regulation of the adrenal cortex: neural and immune inputs. J. Clin. Endocrinol. Metab. 1999, 84: 1729–1736.

    Article  CAS  PubMed  Google Scholar 

  42. Rollero A., Murialdo G., Fonzi S., Garrone S., Gianelli M.V., Gazzerro E., Barreca A., Polleri A. Relationship between cognitive function, growth hormone and Insulin-like Growth Factor-I plasma levels in aged subjects. Neuropsychobiology 1998, 38: 73–79.

    Article  CAS  PubMed  Google Scholar 

  43. Guan J., Williams C., Gunning M., Mallard C., Gluckman P. The effects of IGF-I treatment after hypoxic-ischemic brain injury in adult rats. J. Cereb. Blood Flow Metab. 1993, 13: 609–616.

    Article  CAS  PubMed  Google Scholar 

  44. Doré S., Kar S., Quirion R. Insulin-like Growth Factor-I protects and rescues hippocampal neurons against?-amyloid- and human amylin-induced toxicity. Proc. Natl. Acad. Sci. USA 1997, 94: 4772–4777.

    Article  PubMed  PubMed Central  Google Scholar 

  45. Lee P.D.K., Giudice L.C., Conover C.A., Powell D.R. Insulin-like growth factor binding protein-1: recent findings and new directions. Proc. Soc. Exp. Biol. Med. 1997, 216: 319–357.

    Article  CAS  PubMed  Google Scholar 

  46. Conover C.A., Clarkson J.T., Bale L.K. Effect of glucocorticoids on Insulin-like Growth Factor regulation of IGF-binding protein expression in fibroblasts. Endocrinology 1995, 136: 1403–1410.

    CAS  PubMed  Google Scholar 

  47. Suwanichkul A., Allander S.V., Morris S.L., Powell D.R. Glucocorticoids and insulin regulate expression of the human gene for Insulin-like Growth Factor- Binding protein-1 through proximal promoter element. J. Biol. Chem. 1994, 269: 30835–30841.

    CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Endocrinological and Metabolic Sciences, University of Genova, Viale Benedetto XV 6, I-16132, Genova, Italy

    G. Murialdo, A. Barreca, A. Rollero, G. Timossi, M. V. Gianelli & A. Polleri

  2. Department of Internal Medicine, Clinical Neurophysiology Service, University of Genova, Italy

    F. Nobili & G. Rodriguez

  3. Institute of Occupational Medicine, Epidemiology Service, University of Genova, Italy

    F. Copello

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  1. G. Murialdo
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Murialdo, G., Barreca, A., Nobili, F. et al. Dexamethasone effects on cortisol secretion in Alzheimer’s disease: Some clinical and hormonal features in suppressor and nonsuppressor patients. J Endocrinol Invest 23, 178–186 (2000). https://doi.org/10.1007/BF03343703

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