A Twin Study of Sex Differences in Genetic Risk for All Dementia, Alzheimer’s Disease (AD), and Non-AD Dementia

Article type: Research Article

Authors: Beam, Christopher R.^{a; b; *} | Kaneshiro, Cody^c | Jang, Jung Yun^a | Reynolds, Chandra A.^d | Pedersen, Nancy L.^{a; e} | Gatz, Margaret^{a; b; e; f}

Affiliations: [a] Department of Psychology, University of Southern California, Los Angeles, CA, USA | [b] Davis School of Gerontology, University of Southern California, Los Angeles, CA, USA | [c] Department of Psychology, University of Nevada, Las Vegas, Las Vegas, NV, USA | [d] Department of Psychology, University of California, Riverside, Riverside, CA, USA | [e] Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden | [f] Center for Economic and Social Research, University of Southern California, Los Angeles, CA, USA

Correspondence: [*] Correspondence to: Christopher R. Beam, PhD, Department of Psychology, Dornsife College of Letters, Arts and Sciences, Davis School of Gerontology, 3620 S. McClintock Ave, SGM 501, Los Angeles, CA 90089-1061, USA. Tel.: +1 (213) 740 0726; E-mail: [email protected].

Abstract: Background:While sex differences in incidence of Alzheimer’s disease (AD) and potential explanations have received considerable attention, less attention has been paid to possible sex differences in genetic risk for AD. Objective:We examined sex differences in genetic and environmental influences on disease risk and age at onset for All Dementia, AD Only, and Non-AD Dementia. Methods:Twin pairs were drawn from the Swedish Twin Registry. All Dementia analysis included 9,467 pairs; AD only, 8,696 pairs; and non-AD dementia, 8,195 pairs. APOE analyses included 1,740 individual twins with measured ɛ4 alleles. Dementia diagnoses were based on clinical workup and national health registry linkage. Results:Although within-pair correlations for All Dementia and AD Only were higher for women than for men, sex differences did not statistically differ for genetic or environmental etiology of All Dementia, AD Only, and Non-AD dementia. Similar results were observed when looking at specific genetic effects (APOE ɛ4). Co-twin control analyses indicated that among twin pairs discordant for dementia, female twins without dementia had approximately 40% greater risk of developing dementia, compared with their male counterparts, in the 2–5 years following the first twin’s diagnosis. Conclusion:For All Dementia, AD Only, and Non-AD Dementia, genetic influences could be equated across sex. Co-twin analyses, however, suggest greater risk to female than to male co-twins of dementia cases even though sex differences in either genetic or shared environmental influences on the risk of dementia could not be differentiated.

Keywords: Alzheimer’s disease, APOE ɛ4, sex differences, twin studies

DOI: 10.3233/JAD-191192

Journal: Journal of Alzheimer's Disease, vol. 76, no. 2, pp. 539-551, 2020