Hostname: page-component-586b7cd67f-r5fsc Total loading time: 0 Render date: 2024-11-24T07:43:28.829Z Has data issue: false hasContentIssue false
  • English
  • Français

Hormonal treatment, mild cognitive impairment and Alzheimer's disease

Published online by Cambridge University Press:  01 February 2008

Joanne Ryan ,
Jaqueline Scali ,
Isabelle Carriere ,
Karen Ritchie  and
Marie-Laure Ancelin
Joanne Ryan
Affiliation:
Inserm, U888, Montpellier, F-34093 France; Univ Montpellier 1, Montpellier, F-34000 France.
Jaqueline Scali
Affiliation:
Inserm, U888, Montpellier, F-34093 France; Univ Montpellier 1, Montpellier, F-34000 France.
Isabelle Carriere
Affiliation:
Inserm, U888, Montpellier, F-34093 France; Univ Montpellier 1, Montpellier, F-34000 France.
Karen Ritchie
Affiliation:
Inserm, U888, Montpellier, F-34093 France; Univ Montpellier 1, Montpellier, F-34000 France.
Marie-Laure Ancelin*
Affiliation:
Inserm, U888, Montpellier, F-34093 France; Univ Montpellier 1, Montpellier, F-34000 France.
*
*Correspondence should be addressed to: M. L. Ancelin, Inserm U888, Epidemiology and Clinical Research in Nervous System Pathologies, Hôpital La Colombière, 39 av Ch. Flahault, BP 34493, 34093 Montpellier Cedex 5, France. Phone: +33 4 99 61 45 62; Fax: +33 4 99 61 45 79; Email: [email protected].
Get access Rights & Permissions [Opens in a new window]

Abstract

A plethora of in vitro and in vivo studies have supported the neuroprotective role of estrogens and their impact on the neurotransmitter systems implicated in cognition. Recent hormonal replacement therapy (HRT) trials in non-demented postmenopausal women suggest a temporary positive effect (notably on verbal memory), and four meta-analyses converge to suggest a possible protective effect in relation to Alzheimer's disease (reducing risk by 29 to 44%). However, data from the only large randomized controlled trial published to date, the Women's Health Initiative Memory Study, did not confirm these observations and have even suggested an increase in dementia risk for women using HRT compared to controls. Apart from methodological differences, one key shortcoming of this trial has probably been the focus on late-onset (postmenopausal) hormonal changes, i.e. at a time when the neurodegenerative process has already begun and without taking into account individual lifetime exposure to hormone variability. Multifactorial models based on an exhaustive view of all hormonal events throughout the reproductive life (rather than on a specific exposure to a given steroid) together with other risk factors (notably genetic risk factors related to estrogen receptor polymorphisms) should be explored to clarify the role of hormonal risk factors, or protective factors for cognitive dysfunction and dementia.

Keywords

cognitionequine estrogenstransdermal estradiolestrogen receptorlifetime hormonal statusobservation studyrandomized controlled trial
Type
MCI CONFERENCE PAPER
Information
International Psychogeriatrics , Volume 20 , Issue 1 , February 2008 , pp. 47 - 56
Copyright
Copyright © International Psychogeriatric Association 2007

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Ancelin, M. L. and Ritchie, K. 2005. Lifelong endocrine fluctuations and related cognitive disorders. Current Pharmaceutical Design, 11, 4229–4252.CrossRefGoogle ScholarPubMed
Anderson, G. L. et al. . 2004. Effects of conjugated equine estrogen in postmenopausal women with hysterectomy: the Women's Health Initiative randomized controlled trial. JAMA, 291, 1701–1712.Google ScholarPubMed
Behl, C. 2002. Oestrogen as a neuroprotective hormone. Nature Reviews Neuroscience, 3, 433–442.CrossRefGoogle ScholarPubMed
Brandi, M. L. et al. . 1999. Association of the estrogen receptor alpha gene polymorphisms with sporadic Alzheimer's disease. Biochemical Biophysical Research Communications, 265, 335–338.CrossRefGoogle ScholarPubMed
den Heijer, T. et al. . 2004. Variations in estrogen receptor alpha gene and risk of dementia, and brain volumes on MRI. Molecular Psychiatry, 9, 1129–1135.CrossRefGoogle ScholarPubMed
Dunkin, J. et al. . 2005. Reproductive events modify the effects of estrogen replacement therapy on cognition in healthy postmenopausal women. Psychoneuroendocrinology, 30, 284–296.CrossRefGoogle ScholarPubMed
Edland, S. D.Rocca, W. A.Petersen, R. C.Cha, R. H. and Kokmen, E. 2002. Dementia and Alzheimer disease incidence rates do not vary by sex in Rochester, Minn. Archives of Neurology, 59, 1589–1593.CrossRefGoogle Scholar
Espeland, M. A. et al. . 2004. Conjugated equine estrogens and global cognitive function in postmenopausal women: Women's Health Initiative Memory Study. JAMA, 291, 2959–2968.CrossRefGoogle ScholarPubMed
Ettinger, B.Barrett-Connor, E.Hoq, L. A.Vader, J. P. and Dubois, R. W. 2006. When is it appropriate to prescribe postmenopausal hormone therapy? Menopause, 13, 404–410.CrossRefGoogle ScholarPubMed
Farquhar, C. M.Marjoribanks, J.Lethaby, A.Lamberts, Q. and Suckling, J. A. 2005. Long term hormone therapy for perimenopausal and postmenopausal women. Cochrane Database of Systematic Reviews, CD004143.Google Scholar
Forsell, C. et al. . 2001. Investigations of a CA repeat in the oestrogen receptor beta gene in patients with Alzheimer's disease. European Journal of Human Genetics, 9, 802–804.CrossRefGoogle Scholar
Harman, S. M. et al. . 2005. KEEPS: The Kronos Early Estrogen Prevention Study. Climacteric, 8, 3–12.CrossRefGoogle ScholarPubMed
Hogervorst, E.Williams, J.Budge, M.Riedel, W. and Jolles, J. 2000. The nature of the effect of female gonadal hormone replacement therapy on cognitive function in post-menopausal women: a meta-analysis. Neuroscience, 101, 485–512.CrossRefGoogle ScholarPubMed
Hogervorst, E.Yaffe, K.Richards, M. and Huppert, F. 2002. Hormone replacement therapy to maintain cognitive function in women with dementia (Cochrane Review). Cochrane Database of Systematic Reviews, CD0037.Google Scholar
Isoe-Wada, K. et al. . 1999. Positive association between an estrogen receptor gene polymorphism and Parkinson's disease with dementia. European Journal of Neurology, 6, 431–435.CrossRefGoogle ScholarPubMed
Ji, Y.Urakami, K.Wada-Isoe, K.Adachi, Y. and Nakashima, K. 2000. Estrogen receptor gene polymorphisms in patients with Alzheimer's disease, vascular dementia and alcohol-associated dementia. Dementia and Geriatric Cognitive Disorders, 11, 119–122.CrossRefGoogle ScholarPubMed
Kok, H. S. et al. . 2006. Cognitive function across the life course and the menopausal transition in a British birth cohort. Menopause, 13, 19–27.CrossRefGoogle Scholar
Kravitz, H. M.Meyer, P. M.Seeman, T. E.Greendale, G. A. and Sowers, M. R. 2006. Cognitive functioning and sex steroid hormone gene polymorphisms in women at midlife. American Journal of Medicine, 119, S94–S102.CrossRefGoogle ScholarPubMed
Lambert, J. C. et al. . 2001. Are the estrogen receptors involved in Alzheimer's disease? Neuroscience Letters, 306, 193–197.CrossRefGoogle ScholarPubMed
Leblanc, E. S.Janowsky, J.Chan, B. K. and Nelson, H. D. 2001. Hormone replacement therapy and cognition: systematic review and meta-analysis. JAMA, 285, 1489–1499.CrossRefGoogle ScholarPubMed
MacLennan, A. H. et al. . 2006. Hormone therapy, timing of initiation, and cognition in women aged older than 60 years: the REMEMBER pilot study. Menopause, 13, 28–36.CrossRefGoogle ScholarPubMed
Maki, P. and Hogervorst, E. 2003. The menopause and HRT. HRT and cognitive decline. Best Practice & Research Clinical Endocrinology & Metabolism, 17, 105–122.CrossRefGoogle ScholarPubMed
Marx, J. 1996. Searching for drugs that combat Alzheimer's. Science, 273, 50–53.CrossRefGoogle ScholarPubMed
Olsen, L. et al. . 2006. Estrogen receptor alpha and risk for cognitive impairment in postmenopausal women. Psychiatric Genetics, 16, 85–88.CrossRefGoogle ScholarPubMed
Pirskanen, M. et al. . 2005. Estrogen receptor beta gene variants are associated with increased risk of Alzheimer's disease in women. European Journal of Human Genetics, 13, 1000–1006.CrossRefGoogle ScholarPubMed
Rapp, S. R. et al. . 2003. Effect of estrogen plus progestin on global cognitive function in postmenopausal women: the Women's Health Initiative Memory Study: a randomized controlled trial. JAMA, 289, 2663–2672.CrossRefGoogle ScholarPubMed
Rasgon, N. L. et al. . 2005. Endogenous and exogenous hormone exposure and risk of cognitive impairment in Swedish twins: a preliminary study. Psychoneuroendocrinology, 30, 558–567.CrossRefGoogle ScholarPubMed
Resnick, S. M. et al. . 2006. Effects of combination estrogen plus progestin hormone treatment on cognition and affect. Journal of Clinical Endocrinology and Metabolism, 91, 1802–1810.CrossRefGoogle ScholarPubMed
Rigaud, A. S.Andre, G.Vellas, B.Touchon, J. and Pere, J. J. 2003. No additional benefit of HRT on response to rivastigmine in menopausal women with AD. Neurology, 60, 148–149.CrossRefGoogle ScholarPubMed
Ritchie, K. et al. . 2004. Prevalence of DSM-IV psychiatric disorder in the French elderly population. British Journal of Psychiatry, 184, 147–152.CrossRefGoogle ScholarPubMed
Rymer, J.Wilson, R. and Ballard, K. 2003. Making decisions about hormone replacement therapy. BMJ, 326, 322–326.CrossRefGoogle ScholarPubMed
Schneider, L. S.Farlow, M. R.Henderson, V. W. and Pogoda, J. M. 1996. Effects of estrogen replacement therapy on response to tacrine in patients with Alzheimer's disease. Neurology, 46, 1580–1584.CrossRefGoogle ScholarPubMed
Shumaker, S. A. et al. . 2003. 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. JAMA, 289, 2651–2662.CrossRefGoogle ScholarPubMed
Shumaker, S. A. et al. . 2004. Conjugated equine estrogens and incidence of probable dementia and mild cognitive impairment in postmenopausal women: Women's Health Initiative Memory Study. JAMA, 291, 2947–2958.CrossRefGoogle ScholarPubMed
Skouby, S. O. et al. . 2005. Climacteric medicine: European Menopause and Andropause Society (EMAS) 2004/2005 position statements on peri- and postmenopausal hormone replacement therapy. Maturitas, 51, 8–14.CrossRefGoogle ScholarPubMed
Urakami, K. et al. . 2001. Causative genes in Alzheimer's disease [in Japanese]. Nippon Ronen Igakkai Zasshi, 38, 117–120.CrossRefGoogle ScholarPubMed
Usui, C. et al. . 2006. No genetic association between the myeloperoxidase gene -463 polymorphism and estrogen receptor-alpha gene polymorphisms and Japanese sporadic Alzheimer's disease. Dementia and Geriatric Cognitive Disorders, 21, 296–299.CrossRefGoogle ScholarPubMed
Wimo, A.Winblad, B.Aguero-Torres, H. and von Strauss, E. 2003. The magnitude of dementia occurrence in the world. Alzheimer Diseases and Associated Disorders, 17, 63–67.CrossRefGoogle ScholarPubMed
Writing Group for the Women's Health Initiative Investigators 2002. Risks and benefits of estrogen plus progestin in healthy postmenopausal women. JAMA, 288, 321–333.CrossRefGoogle Scholar
Yaffe, K.Sawaya, G.Lieberburg, I. and Grady, D. 1998. Estrogen therapy in postmenopausal women: effects on cognitive function and dementia. JAMA, 279, 688–695.CrossRefGoogle ScholarPubMed
Yaffe, K.Lui, L. Y.Grady, D.Stone, K. and Morin, P. 2002. Estrogen receptor 1 polymorphisms and risk of cognitive impairment in older women. Biological Psychiatry, 51, 677–682.CrossRefGoogle ScholarPubMed
Zandi, P. P. et al. . 2002. Hormone replacement therapy and incidence of Alzheimer disease in older women: the Cache County Study. JAMA, 288, 2123–2129.CrossRefGoogle ScholarPubMed