Oestrogen replacement therapy may improve memory functioning in the absence of APOE ε4

Article type: Research Article

Authors: Burkhardt, M.S.^{a; b} | Foster, J.K.^{a; c} | Laws, S.M.^a | Baker, L.D.^d | Craft, S.^d | Gandy, S.E.^e | Stuckey, B.G.A.^f | Clarnette, R.^a | Nolan, D.^g | Hewson-Bower, B.^b | Martins, R.N.^{a; e; *}

Affiliations: [a] Sir James McCusker Alzheimer's Disease Research Unit, School of Psychiatry and Clinical Neurosciences, University of Western Australia, Hollywood Private Hospital, Perth, Western Australia, Australia | [b] School of Psychology, Murdoch University, Perth, Western Australia, Australia | [c] Neurosciences Unit, Health Department of Western Australia, Australia | [d] Geriatric Research Education and Clinical Center, Veteran Affairs Puget Sound Health Care System, Seattle, WA, USA | [e] Farber Institute for Neurosciences of Thomas Jefferson University, 900 Walnut Street, Suite 467, Philadelphia, USA | [f] Keogh Institute for Medical Research, Department of Endocrinology and Diabetes, Sir Charles Gairdner Hospital, Nedlands, Western Australia, Australia | [g] Centre for Clinical Immunology and Biomedical Statistics, Royal Perth Hospital and Murdoch University, Perth, Western Australia, Australia

Correspondence: [*] Corresponding author: A/Prof Ralph Martins, The Sir James McCusker Alzheimer's Disease Research Unit, School of Psychiatry and Clinical Neurosciences, The University of Western Australia, c/o Hollywood Private Hospital, 115 Monash Avenue, Nedlands, Perth Western Australia 6009, Australia. Tel.: +61 8 9346 6703; Fax: +61 8 9346 6666; E-mail: [email protected].

Abstract: There is currently intense controversy regarding the use of hormone replacement therapy (HRT) in postmenopausal women, in relation to its therapeutic efficacy in Alzheimer's disease (AD). It has been suggested that the benefits of HRT may be modified by apolipoprotein E (APOE) genotype (the major genetic risk factor for AD). Here we report the findings of the first study designed to systematically explore the interaction of (a) oestrogen replacement therapy (ERT) and (b) possession of an ε4 allele of APOE on specific elements of episodic learning and memory that are commonly used indices of age-related cognitive decline. This data represents a cross-sectional analysis of the interaction of ERT and APOE genotype on learning and memory in a cohort of 181 healthy postmenopausal women [ERT users (n = 101, mean age 65.40 ± 6.34); ERT non-users (n = 80, mean age 67.03 ± 6.80)] residing in Perth, Western Australia. The highest level of learning (trials 2–5; P < 0.05) and memory (e.g. total number of items recalled; P < 0.05) performance was observed in women taking ERT who were not carriers of the APOE ε4 allele. APOEε4 carriers receiving ERT performed no better on episodic memory testing than APOE ε4 carriers who were not receiving ERT. These cognitive differences related to genetic profile, were noted on both recall and recognition (P = 0.005) tests of memory. The findings have significance for evaluating whether and when ERT may be clinically indicated. Specifically, ERT may benefit the cognitive functioning of women not carrying the APOE ε4 allele.

Keywords: oestrogen supplementation, post-menopausal women, cognition, apolipoprotein E genotype, Alzheimer's disease

DOI: 10.3233/JAD-2004-6302

Journal: Journal of Alzheimer's Disease, vol. 6, no. 3, pp. 221-228, 2004