Sex, amyloid, and APOE ε4 and risk of cognitive decline in preclinical Alzheimer's disease: Findings from three well-characterized cohorts

Rachel F. Buckley*, Elizabeth C. Mormino, Rebecca E. Amariglio, Michael J. Properzi, Jennifer S. Rabin, Yen Ying Lim, Kathryn V. Papp, Heidi I. L. Jacobs, Samantha Burnham, Bernard J. Hanseeuw, Vincent Dore, Annette Dobson, Colin L. Masters, Michael Waller, Christopher C. Rowe, Paul Maruff, Michael C. Donohue, Dorene M. Rentz, Dylan Kirn, Trey HeddenJasmeer Chhatwal, Aaron P. Schultz, Keith A. Johnson, Victor L. Villemagne, Reisa A. Sperling, Collaborators Alzheimer's Dis Neur; Australian Imaging Biomarker Lifes; Harvard Aging Brain Study

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

124 Citations (Web of Science)


Introduction: Our objective was to investigate the effect of sex on cognitive decline within the context of amyloid beta (A beta) burden and apolipoprotein E genotype. Methods: We analyzed sex-specific effects on A beta-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, A beta-positron emission tomography, and apolipoprotein epsilon 4 were examined with quadratic time effects over a median of 4 years of follow-up. Results: Apolipoprotein epsilon 4 prevalence and A beta burden did not differ by sex. Sex did not directly influence cognitive decline. Females with higher A beta exhibited faster decline than males. Post hoc contrasts suggested that females who were A beta and apolipoprotein epsilon 4 positive declined faster than their male counterparts. Discussion: Although A beta did not differ by sex, cognitive decline was greater in females with higher A beta. Our findings suggest that sex may play a modifying role on risk of Alzheimer's disease-related cognitive decline. (C) 2018 the Alzheimer's Association. Published by Elsevier Inc. All rights reserved.
Original languageEnglish
Pages (from-to)1193-1203
Number of pages11
JournalAlzheimer's & Dementia
Issue number9
Publication statusPublished - 1 Sept 2018


  • Preclinical Alzheimer's disease
  • Amyloid
  • APOE
  • Sex
  • Gender
  • Cognitive decline
  • AGE

Cite this