Journal of Alzheimer’s Disease 13 (2008) 267–274 267 IOS Press Gonadotropins and Cognition in Older Women Mark A. Rodrigues a , Giuseppe Verdile a , Jonathan K. Foster a , Eva Hogervorst f , Karen Joesbury a , Satvinder Dhaliwal c , Elizabeth H. Corder h , Simon M. Laws a , Eugene Hone a , Richard Prince e , Amanda Devine b , Pankaj Mehta g , John Beilby i , Craig S. Atwood d and Ralph N. Martins a,∗ a Centre of Excellence for Alzheimer’s Disease Research and Care; The Sir James McCurker Alzheimer’s Disease Research Unit, Hollywood Private Hospital; Centre for Ageing and Alzheimer’s Disease, School of Exercise, Biomedical and Health Sciences, Edith Cowan University, Joondalup; School of Psychiatry and Clinical Neurosciences, University of Western Australia, WA, Australia b School of Exercise, Biomedical and Health Sciences, Edith Cowan University, Joondalup, WA, Australia c School of Public Health, Curtin University of Technology, WA, Australia d Department of Medicine, University of Wisconsin and Geriatrics Research, Education and Clinical Center, VA Hospital, Madison, Wisconsin 53705, USA and Centre for Aging and Alzheimer’s Disease and School of Biomedical & Sports Science, Edith Cowan University, Joondalup, WA 6027, Australia e School of Medicine and Pharmacology, SCGH Unit, University of Western Australia; Department of Endocrinology and Diabetes, Sir Charles Gairdner Hospital, Western Australian Institute for Medical Research, WA 6009, Australia f Loughborough University, Department of Human Sciences, UK g Institute For Basic Research In Developmental Disabilities, 1050 Forest Hill Road, Staten Island, NY 10314, Australia h Center for Demographic Studies, 346 Trent Hall, Duke University, Box 90409, Durham, NC 27708-0409, USA i PathCentre, Western Australian Centre for Pathology and Medical Research (Clinical Biochemistry), Nedlands, WA, Australia Abstract. Recent research studies associate elevated gonadotropin levels with dementia. Specifically, an age associated increase in levels of luteinizing hormone has been linked to an increased risk of Alzheimer’s disease. The objective of this study was to investigate the association between gonadotropin levels and cognition in older, healthy postmenopausal women. Cognitive func- tioning was compared with plasma levels of estradiol, luteinizing hormone, follicle stimulating hormone, Aβ40 and APOE genetic status in 649 community-dwelling, non-demented older women residing in Western Australia. High endogenous luteinizing hormone levels were associated with a lower cognitive score, especially in older women and in those women that were depressed. Unexpectedly, disproportionately well preserved cognitive functioning was found for the oldest women who had high endogenous levels of follicle stimulating hormone. The findings indicate that gonadotropins can impact upon cognitive functioning in older postmenopausal women, and that luteinizing hormone and follicle stimulating hormone may exert contrasting effects. Taken together, the findings have important implications for the development of possible preventive strategies for dementia. Keywords: Amyloid-β 40, APOE, Cambridge Cognitive Examination, estradiol, follicle stimulating hormone, gonadotropin releasing hormone, luteinizing hormone * Corresponding author: Ralph N. Martins, Centre for Aging and Alzheimer’s Disease, School of Exercise, Biomedical and Health Sciences, Edith Cowan University, Joondalup 6027, Australia. Tel.: +618 9347 4200/ 6304 5456; Fax: +618 9347 4212/ 6304 5851; E-mail: r.martins@ecu.edu.au. INTRODUCTION Alzheimer’s disease (AD) is a neurodegenerative dis- order characterised by amyloid-β (Aβ) deposition in and around cerebral neurons, neuronal death and at- rophy of the brain causing loss of cognitive functions ISSN 1387-2877/08/$17.00  2008 – IOS Press and the authors. All rights reserved