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

被引：198

作者：

Buckley, Rachel F. ^{[1
,2
,3
,4
,5
]}

Mormino, Elizabeth C. ^{[6
]}

Amariglio, Rebecca E. ^{[3
,4
,5
]}

Properzi, Michael J. ^{[3
,4
]}

Rabin, Jennifer S. ^{[4
,7
]}

Lim, Yen Ying ^{[1
]}

Papp, Kathryn V. ^{[3
,4
,5
]}

Jacobs, Heidi I. L. ^{[8
,9
]}

Burnham, Samantha ^{[10
]}

Hanseeuw, Bernard J. ^{[3
,4
,5
,11
]}

Dore, Vincent ^{[12
]}

Dobson, Annette ^{[13
]}

Masters, Colin L. ^{[1
]}

Waller, Michael ^{[13
]}

Rowe, Christopher C. ^{[14
,15
,16
]}

Maruff, Paul ^{[17
]}

Donohue, Michael C. ^{[18
]}

Rentz, Dorene M. ^{[3
,4
,5
]}

Kirn, Dylan ^{[3
,4
,5
]}

Hedden, Trey ^{[8
]}

Chhatwal, Jasmeer ^{[3
,4
]}

Schultz, Aaron P. ^{[3
,4
,5
]}

Johnson, Keith A. ^{[8
]}

Villemagne, Victor L. ^{[14
,15
,16
]}

Sperling, Reisa A. ^{[3
,4
,5
]}

机构：

[1] Univ Melbourne, Florey Inst, Melbourne, Vic, Australia

[2] Univ Melbourne, Melbourne Sch Psychol Sci, Melbourne, Vic, Australia

[3] Massachusetts Gen Hosp, Dept Neurol, Harvard Aging Brain Study, Boston, MA 02114 USA

[4] Harvard Med Sch, Boston, MA 02115 USA

[5] Brigham & Womens Hosp, Ctr Alzheimer Res & Treatment, Dept Neurol, 75 Francis St, Boston, MA 02115 USA

[6] Stanford Univ, Dept Neurol, Stanford, CA 94305 USA

[7] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA

[8] Harvard Med Sch, Massachusetts Gen Hosp, Dept Radiol, Div Nucl Med & Mol Imaging, Boston, MA USA

[9] Maastricht Univ, Alzheimer Ctr Limburg, Sch Mental Hlth & Neurosci, Fac Hlth Med & Life Sci, Maastricht, Netherlands

[10] CSIRO Hlth Biosecur, Australian eHlth Res Ctr, Parkville, Vic, Australia

[11] Catholic Univ Louvain, Inst Neurosci, Clin Univ St Luc, Dept Neurol, Brussels, Belgium

[12] CSIRO Hlth Biosecur, Australian eHlth Res Ctr, Brisbane, Qld, Australia

[13] Univ Queensland, Sch Publ Hlth, Fac Med, Brisbane, Qld, Australia

[14] Austin Hlth, Dept Nucl Med, Heidelberg, Vic, Australia

[15] Austin Hlth, Ctr PET, Heidelberg, Vic, Australia

[16] Univ Melbourne, Austin Hlth, Dept Med, Melbourne, Vic, Australia

[17] Cogstate Ltd, Melbourne, Vic, Australia

[18] Univ Southern Calif, Dept Neurol, San Diego, CA USA

来源：

ALZHEIMERS & DEMENTIA | 2018年 / 14卷 / 09期

基金：

澳大利亚国家健康与医学研究理事会; 加拿大健康研究院; 美国国家卫生研究院;

关键词：

Preclinical Alzheimer's disease; Amyloid; APOE; Sex; Gender; Cognitive decline; HEALTHY OLDER-ADULTS; APOLIPOPROTEIN-E GENOTYPE; GENDER-DIFFERENCES; PRECURSOR PROTEIN; BETA-DEPOSITION; BRAIN STRUCTURE; SENILE PLAQUE; DEMENTIA; AGE; ASSOCIATION;

D O I：

10.1016/j.jalz.2018.04.010

中图分类号：

R74 [神经病学与精神病学];

学科分类号：

100204 [神经病学];

摘要：

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.

引用

页码：1193 / 1203

页数：11

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