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Endokrinologische Aspekte bei Demenzerkrankungen im fortgeschrittenen Lebensalter

Hirn, Mann und Testosteron. Endokrinologische Aspekte bei Demenzerkrankungen im fortgeschrittenen Lebensalter. Christian Bancher Abteilung für Neurologie Landesklinikum Waldviertel Horn - Allentsteig. Gesellschaft der Ärzte 23. April 2008. Hirn, Mann und Testosteron.

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Endokrinologische Aspekte bei Demenzerkrankungen im fortgeschrittenen Lebensalter

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  1. Hirn, Mann und Testosteron Endokrinologische Aspekte bei Demenzerkrankungen im fortgeschrittenen Lebensalter Christian Bancher Abteilung für Neurologie Landesklinikum Waldviertel Horn - Allentsteig Gesellschaft der Ärzte 23. April 2008

  2. Hirn, Mann und Testosteron Geschlechtsspezifische Prävalenz

  3. Hirn, Mann und Testosteron Geschlechtsspezifische Inzidenz

  4. Östrogen ³1.25 mg/d Dosis * £0.625 mg/d Nie Östrogen ³15 Jahre Dauer † 4-14 Jahre £3 Jahre Nie 0.8 1 0 0.2 0.4 0.6 Risikoschätzung ‡ Hirn, Mann und Testosteron 1996: Protektiver Effekt postmenopausaler Hormon- substitutionstherapie für Demenz v. Alzheimer-Typ *P<0.01; †P<0.001. ‡Alzheimer Krankheit, senile Demenz, Demenz, und Senilität kombiniert. Paganini-Hill A et al. Arch Intern Med 1996;156:2213-2217.

  5. Hirn, Mann und Testosteron Östrogen bei Demenz v. Alzheimer-Typ • Reguliert acetylcholinerge Neurotransmission hoch • Fördert axonales sprouting in CA1 Neuronen • Reduziert Aß-Toxizität • Vermindert Aß-Produktion in Neuronen • Schützt vor oxydativem Stress „Estrogen therapy has been one of the most compelling potentialstrategies for prevention of dementia, primarily AD. Strongbiological evidence supports the beneficial effects of estrogenon the brain including neurotrophic effects, reductions in -amyloidaccumulation, enhanced neurotransmitter release and action,and protection against oxidative damage.“

  6. Hirn, Mann und Testosteron 2003: Erhöhtes Risiko für Demenz durch Östrogen und Gestagen Estrogen Plus Progestin and the Incidence of Dementia and Mild Cognitive Impairment in Postmenopausal Women The Women's Health Initiative Memory Study: A Randomized Controlled Trial Sally A. Shumaker, PhD; Claudine Legault, PhD; Stephen R. Rapp, PhD; Leon Thal, MD; Robert B. Wallace, MD; Judith K. Ockene, PhD, MEd; Susan L. Hendrix, DO; Beverly N. Jones III, MD; Annlouise R. Assaf, PhD; Rebecca D. Jackson, MD; Jane Morley Kotchen, MD, MPH; Sylvia Wassertheil-Smoller, PhD; Jean Wactawski-Wende, PhD; for the WHIMS Investigators JAMA. 2003;289:2651-2662.

  7. Hirn, Mann und Testosteron 2004: Erhöhtes Risiko für Demenz durch Östrogen Conjugated Equine Estrogens and Incidence of Probable Dementia and Mild Cognitive Impairment in Postmenopausal Women Women's Health Initiative Memory Study Sally A. Shumaker, PhD; Claudine Legault, PhD; Lewis Kuller, MD, DrPH; Stephen R. Rapp, PhD; Leon Thal, MD; Dorothy S. Lane, MD, MPH; Howard Fillit, MD; Marcia L. Stefanick, PhD; Susan L. Hendrix, DO; Cora E. Lewis, MD; Kamal Masaki, MD; Laura H. Coker, PhD; for the Women's Health Initiative Memory Study JAMA. 2004;291:2947-2958.

  8. Hirn, Mann und Testosteron Die Diskussion nach WHI….. • J Neurosci. 2007 Nov 28;27(48):13357-65 • Progesterone and estrogen regulate Alzheimer-like neuropathology in female 3xTg-AD mice. • Carroll JC, Rosario ER, Chang L, Stanczyk FZ, Oddo S, LaFerla FM, Pike CJ. • Neuroscience Graduate Program, Davis School of Gerontology, University of Southern California, Los Angeles, California 90089, USA. • Front Biosci. 2008 Jan 1;13:1083-9 • Estrogens and progesterone as neuroprotectants: what animal models teach us. • Singh M, Sumien N, Kyser C, Simpkins JW. • Department of Pharmacology and Neuroscience, University of North Texas Health Science Center, Fort Worth, TX 76107, USA. msingh@hsc.unt.edu • Biochem Biophys Res Commun. 2007 Aug 3;359(3):697-702 • Estrogen has anti-amyloidogenic effects on Alzheimer's beta-amyloid fibrils in vitro. • Morinaga A, Hirohata M, Ono K, Yamada M. • Department of Neurology and Neurobiology of Aging, Kanazawa University Graduate School of Medical Science, Kanazawa 920-8640, Japan.

  9. Hirn, Mann und Testosteron …sind Gonadotropine die Schuldigen ? • Clin Med Res. 2007 Oct;5(3):177-83 • The contribution of luteinizing hormone to Alzheimer disease pathogenesis. • Webber KM, Perry G, Smith MA, Casadesus G. • Department of Pathology, Case Western Reserve University, Cleveland, Ohio 44106, USA. • Endocr Metab Immune Disord Drug Targets. 2007 Dec;7(4):300-3 • Evidence for the role of luteinizing hormone in Alzheimer disease. • Webber KM, Casadesus G, Bowen RL, Perry G, Smith MA. • Department of Pathology, Case Western Reserve University, 2103 Cornell Road, Cleveland, Ohio 44106, USA. • LH höher bei Frauen • LH höher bei Individuen mit DAT • Höchste LH-Rezeptor Dichte im Hippocampus • Transgene Mäuse mit LH-Überexpression weisen kognitive Störung auf • Transgene APP-Mäuse, die mit dem anti-Gonatropin Leuprolide • behandelt wurden, wiesen bessere kognitive Leistung und • weniger Amyloidablagerungen auf

  10. Hirn, Mann und Testosteron Androgen, tau und Aß42 1997 - 2000: Proc Natl Acad Sci U S A. 1997 Jun 24;94(13):6612-7 The heat shock-induced hyperphosphorylation of tau is estrogen-independent and prevented by androgens: implications for Alzheimer disease. Papasozomenos SC. Department of Pathology and Laboratory Medicine, The University of Texas-Houston Medical School, Houston, TX 77030, USA. Proc Natl Acad Sci U S A. 2000 Feb 1;97(3):1202-5 Testosterone reduces neuronal secretion of Alzheimer's beta-amyloid peptides. Gouras GK, Xu H, Gross RS, Greenfield JP, Hai B, Wang R, Greengard P Laboratory of Molecular and Cellular Neuroscience and Fisher Center for Research o Alzheimer's Disease, The Rockefeller University, 1230 York Avenue, New York, NY 10021, USA. Neuroprotektiv ?

  11. Hirn, Mann und Testosteron . Testosteron niedriger bei DAT: Henne oder Ei ? Neuro Endocrinol Lett. 2001 Jun;22(3):163-8 Serum total testosterone is lower in men with Alzheimer's disease. Hogervorst E, Williams J, Budge M, Barnetson L, Combrinck M, Smith AD. Oxford Project To Investigate Memory and Ageing, University Department of Pharmacology and the Radcliffe Infirmary Trust, Oxford, United Kingdom Neuro Endocrinol Lett. 2003 Jun-Aug;24(3-4):203-8 Testosterone and gonadotropin levels in men with dementia. Hogervorst E, Combrinck M, Smith AD. Oxford Project To Investigate Memory and Ageing, Department of Pharmacology, University of Oxford, Oxford, UK. Exp Gerontol. 2004 Nov-Dec;39(11-12):1633-9 Low free testosterone is an independent risk factor for Alzheimer's disease. Hogervorst E, Bandelow S, Combrinck M, Smith AD. Oxford Project to Investigate Memory and Ageing, Department of Pharmacology, University of Oxford, Radcliffe Infirmary, Woodstock Rd, Oxford, OX2 6HE, UK. Neurology. 2004 Jan 27;62(2):188-93 Free testosterone and risk for Alzheimer disease in older men. Moffat SD, Zonderman AB, Metter EJ, Kawas C, Blackman MR, Harman SM, Resnick SM. Laboratory of Personality and Cognition, National Institute on Aging, Intramural Research Program, Baltimore, MD 21224, USA.

  12. Hirn, Mann und Testosteron Testosteron bei Männern mit DAT und MCI 63-85a, 15 AD, 17 MCI, 19 100mg TT i.m. /Wo, 13 Plac. …Testosterone supplementation may benefit selective cognitive functions in men with Alzheimer disease and mild cognitive impairment. Testosterone improves spatial memory in men with Alzheimer disease and mild cognitive impairment M. M. Cherrier, PhD, A. M. Matsumoto, MD, J. K. Amory, MD, S. Asthana, W. Bremner, MD, E. R. Peskind, MD, M. A. Raskind, MD and S. Craft, PhD NEUROLOGY 2005;64:2063-2068

  13. Hirn, Mann und Testosteron Pilotstudie Testosteron Aging Male. 2003 Mar;6(1):13-7 A pilot study on the effects of testosterone in hypogonadal aging male patients with Alzheimer's disease. Tan RS, Pu SJ. Geriatric Medicine and Gerontology Programs, Department of Family and Community Medicine, University of Texas, Houston, USA. • 36 Männer mit DAT, MMSE 17-22 • 10 hypogonadal (<240ng/dl) 5 TT: 5 Placebo • 12 Monate • MMSE 19,4 23,2, „placebo group deteriorated gradually“ Mechanismus: Androgen-Rezeptor vermittelt ? Neuroprotektiv ?

  14. Hirn, Mann und Testosteron Androgen oder Anti-Androgen ???? J Clin Psychiatry. 2007 Mar;68(3):439-44 Antiaggressive effect of cyproterone versus haloperidol in Alzheimer's disease: a randomized double-blind pilot study Huertas D, López-Ibor Aliño JJ, Molina JD, Chamorro L, Balanza J, Jiménez MP, Hornillos M. University of Alcalá, Madrid.

  15. Hirn, Mann und Testosteron Take home: Geschlechtshormone und Demenz im Alter • Östrogen: dzt. KI. Renaissance ? • Testosteron: wenig Daten,Hoffnung • LH, FSH: schuldig ? • Effekte: bestenfalls modest. Nebenwirkung ? • Entwicklung: Gonadotropin Modulatoren • Androgen-Rezeptor Modulatoren • cave: Hypothalamus-Hypophyse-Gonaden • Ausblick: nicht die primäre Hoffnung…..

  16. Hirn, Mann und Testosteron

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