Association of Androgens and Gonadotropins with Amnestic Mild Cognitive Impairment and Probable Alzheimer’s Disease in Chinese Elderly Men

Article type: Research Article

Authors: Li, Yan^{a; b; c; d; 1} | Li, Sha^{a; b; c; 1} | Xu, Shunjiang^e | Yu, Hong^d | Tang, Longmei^f | Liu, Xiaoyun^{b; g} | Wang, Xuemei^d | Zhang, Yuanyuan^d | Zhang, Kaixia^e | Mi, Shixiong^{a; b; c} | Chen, Meiqin^{a; b; c} | Cui, Huixian^{a; b; c; *}

Affiliations: [a] Department of Human Anatomy, Hebei Medical University, Shijiazhuang, P. R. China | [b] Neuroscience Research Center, Hebei Medical University, Shijiazhuang, P. R. China | [c] Hebei Key Laboratory of Neurodegenerative Disease Mechanism, Shijiazhuang, P. R. China | [d] College of Nursing, Hebei Medical University, Shijiazhuang, P. R. China | [e] Central Laboratory, The First Hospital of Hebei Medical University, Shijiazhuang, P. R. China | [f] Department of Epidemiology and Statistics, School of Public Health, Hebei Medical University, Shijiazhuang, P. R. China | [g] Department of Neurology, The Second Hospital of Hebei Medical University, Shijiazhuang, P. R. China

Correspondence: [*] Correspondence to: Huixian Cui, PhD, Department of Human Anatomy, Hebei Medical University, 361 Zhongshan East Road, Shijiazhuang, Hebei, 050017, PR China. Tel./Fax: +86 311 86266615; E-mail: cuihxhebmu@126.com.

Note: [1] These authors contributed equally to this work.

Abstract: Background:Age-related hormone changes play important roles in cognitive decline in older men, and apolipoprotein E ɛ4 (APOE ɛ4) is a risk factor for Alzheimer’s disease (AD). Objective:This study aimed to investigate the interactive role of androgen decline and APOE ɛ4 genotype in the pathogenesis of amnestic mild cognitive impairment (aMCI) and AD. Methods:In total, 576 elderly men over 65 years old from communities in Shijiazhuang were enrolled in this study, including 243 with normal cognition (NC), 271 with aMCI, and 62 with probable AD. Cognitive function was evaluated with a battery of neuropsychological tests. The serum levels of androgen and gonadotropin were detected by ELISA and chemiluminescence immunoassay. Results:The levels of free testosterone (FT) and dihydrotestosterone (DHT) were lower in the aMCI group (p < 0.05), and even lower in the AD group (p < 0.001), but the levels of follicle stimulating hormone (FSH) and luteinizing hormone (LH)were higher in AD group (p < 0.01), comparing with that in NC or aMCI group. The interaction of lower FT or DHT levels with APOE ɛ4 had a risk role in global cognitive impairment (p < 0.05). The area under the curve (AUC) of the ROC curve for predicting aMCI by serum FT levels was 0.745. Conclusion:These results indicated that the interaction of androgen decline and APOE ɛ4 genotype play a role in aMCI and AD. Serum FT levels have a predictive value for aMCI and might be a potential biomarker for prodromal AD.

Keywords: Alzheimer’s disease, amnestic mild cognitive impairment, androgen, APOE, gonadotropin, testosterone

DOI: 10.3233/JAD-200233

Journal: Journal of Alzheimer's Disease, vol. 78, no. 1, pp. 277-290, 2020