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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: ancelin@montp.inserm.fr.
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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

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