Sex, amyloid, and <i>APOE</i> ε4 and risk of cognitive decline in preclinical Alzheimer's disease: Findings from three well‐characterized cohorts

Rachel F. Buckley(Brigham and Women's Hospital), Elizabeth C. Mormino(Equilibrium Research), Rebecca E. Amariglio(Brigham and Women's Hospital), Michael J Properzi(Harvard University), Jennifer S. Rabin(Harvard University), Yen Ying Lim(The University of Melbourne), Kathryn V. Papp(Brigham and Women's Hospital), Heidi I.L. Jacobs(Harvard University), Samantha C. Burnham(Australian e-Health Research Centre), Bernard Hanseeuw(Brigham and Women's Hospital), Vincent Doré(Australian e-Health Research Centre), Annette J. Dobson(The University of Queensland), Colin L. Masters(The University of Melbourne), Michael Waller(The University of Queensland), Christopher C. Rowe(The University of Melbourne), Paul Maruff(Prostate Cancer Foundation of Australia), Michael Donohue(University of Southern California), Dorene M. Rentz(Brigham and Women's Hospital), Dylan Kirn(Brigham and Women's Hospital), Trey Hedden(Harvard University), Jasmeer P. Chhatwal(Harvard University), Aaron P. Schultz(Brigham and Women's Hospital), Keith A. Johnson(Harvard University), Victor L. Villemagne(The University of Melbourne), Reisa A. Sperling(Brigham and Women's Hospital), on behalf of collaborators in the Alzheimer's Disease Neuroimaging Initiative(Alzheimer’s Disease Neuroimaging Initiative), the Australian Imaging, Biomarker and Lifestyle study of ageing(Alzheimer’s Disease Neuroimaging Initiative), the Harvard Aging Brain Study(The University of Melbourne)
Alzheimer s & Dementia
May 24, 2018
10.1016/j.jalz.2018.04.010
Cited by 283Open Access
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Abstract

INTRODUCTION: Our objective was to investigate the effect of sex on cognitive decline within the context of amyloid β (Aβ) burden and apolipoprotein E genotype. METHODS: We analyzed sex-specific effects on Aβ-positron emission tomography, apolipoprotein, and rates of change on the Preclinical Alzheimer Cognitive Composite-5 across three cohorts, such as the Alzheimer's Disease Neuroimaging Initiative, Australian Imaging, Biomarker and Lifestyle, and Harvard Aging Brain Study (n = 755; clinical dementia rating = 0; age (standard deviation) = 73.6 (6.5); female = 55%). Mixed-effects models of cognitive change by sex, Aβ-positron emission tomography, and apolipoprotein ε4 were examined with quadratic time effects over a median of 4 years of follow-up. RESULTS: Apolipoprotein ε4 prevalence and Aβ burden did not differ by sex. Sex did not directly influence cognitive decline. Females with higher Aβ exhibited faster decline than males. Post hoc contrasts suggested that females who were Aβ and apolipoprotein ε4 positive declined faster than their male counterparts. DISCUSSION: Although Aβ did not differ by sex, cognitive decline was greater in females with higher Aβ. Our findings suggest that sex may play a modifying role on risk of Alzheimer's disease-related cognitive decline.

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