Sex Differences in in vivo Alzheimer’s Disease Neuropathology in Late Middle-Aged Hispanics

Article type: Research Article

Authors: Luchsinger, José A.^{a; b; *} | Palta, Priya^{a; b} | Rippon, Brady^a | Soto, Luisa^a | Ceballos, Fernando^a | Pardo, Michelle^a | Laing, Krystal^c | Igwe, Kay^c | Johnson, Aubrey^c | Tomljanovic, Zeljko^c | He, Hengda^c | Reitz, Christiane^{c; d; e} | Kreisl, William^{c; d; e} | Razlighi, Qolamreza^{c; d; e; f} | Teresi, Jeanne^g | Moreno, Herman^g | Brickman, Adam M.^{c; d; e}

Affiliations: [a] Department of Medicine, College of Physicians and Surgeons, Columbia University Irving Medical Center, New York, NY, USA | [b] Department of Epidemiology, Joseph P. Mailman School of Public Health, Columbia University Irving Medical Center, New York, NY, USA | [c] Department of Neurology, College of Physicians and Surgeons, Columbia University Irving Medical Center, New York, NY, USA | [d] Taub Institute for Research on Alzheimer’s Disease and the Aging Brain, Columbia University Irving Medical Center, New York, NY, USA | [e] Gertrude H. Sergievsky Center, Columbia University Irving Medical Center, New York, NY, USA | [f] Department of Biomedical Engineering, Columbia University, New York, NY, USA | [g] Research Division, Hebrew Home in Riverdale, Bronx, NY, USA | [h] Department of Neurology, SUNY Downstate Medical Center, Brooklyn, NY, USA

Correspondence: [*] Correspondence to: José A. Luchsinger, MD MPH, Columbia University Irving Medical Center, 622 West 168th Street, PH9 Center room 210, New York, NY 10032, USA. Tel.: +1 212 305 4730; Fax: +1 212 305 9349; E-mail: [email protected].

Abstract: Background:Females may have a higher risk of dementia than males. It is not clear if sex differences in Alzheimer’s disease (AD) neuropathology explain the higher risk of dementia in females. Sex differences in AD neuropathology might begin in middle age, decades before the sex differences in dementia are apparent. Objective:To examine sex differences in in vivo AD neuropathology in late middle age. Methods:We conducted a cross-sectional comparison of AD biomarkers among 266 Hispanic males and females (mean age: 64.0; 71.8% females) without dementia. Amyloid burden was measured as global standardized uptake value ratio (SUVR) with18F-Florbetaben positron emission tomography (PET). Neurodegeneration was ascertained as cortical thickness in AD signature areas using brain magnetic resonance imaging. Tau burden was measured as tau SUVR in the middle/inferior temporal gyri and medial temporal cortex with 18F-MK-6240 in 75 of the 266 participants. Results:Females had higher amyloid SUVR and tau SUVR in the middle/inferior temporal gyri than males. However, females had higher cortical thickness than males and performed better in a test of verbal memory despite having higher AD neuropathology burden. Conclusion:Higher amyloid and tau in females compared to males in late middle-age may explain the reported higher dementia risk in elderly females compared to males. Longitudinal follow-up is necessary to examine whether higher amyloid and tau burden in late middle age is followed by increased neurodegeneration and cognitive decline in females as compared with males.

Keywords: Amyloid, cognition, Hispanics, neurodegeneration, sex differences, tau

DOI: 10.3233/JAD-191183

Journal: Journal of Alzheimer's Disease, vol. 74, no. 4, pp. 1243-1252, 2020