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 Hedden; Jasmeer 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

doi:10.1016/j.jalz.2018.04.010

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 journal › Article › Academic › peer-review

Abstract

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 language	English
Pages (from-to)	1193-1203
Number of pages	11
Journal	Alzheimer's & Dementia
Volume	14
Issue number	9
DOIs	https://doi.org/10.1016/j.jalz.2018.04.010
Publication status	Published - 1 Sept 2018

Keywords

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

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10.1016/j.jalz.2018.04.010

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Buckley, R. F., Mormino, E. C., Amariglio, R. E., Properzi, M. J., Rabin, J. S., Lim, Y. Y., Papp, K. V., Jacobs, H. I. L., Burnham, S., Hanseeuw, B. J., Dore, V., Dobson, A., Masters, C. L., Waller, M., Rowe, C. C., Maruff, P., Donohue, M. C., Rentz, D. M., Kirn, D., ... Collaborators Alzheimer's Dis Neur; Australian Imaging Biomarker Lifes; Harvard Aging Brain Study (2018). Sex, amyloid, and APOE ε4 and risk of cognitive decline in preclinical Alzheimer's disease: Findings from three well-characterized cohorts. Alzheimer's & Dementia, 14(9), 1193-1203. https://doi.org/10.1016/j.jalz.2018.04.010

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

abstract = "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.",

keywords = "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",

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

year = "2018",

month = sep,

day = "1",

doi = "10.1016/j.jalz.2018.04.010",

language = "English",

volume = "14",

pages = "1193--1203",

journal = "Alzheimer's & Dementia",

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Buckley, RF, Mormino, EC, Amariglio, RE, Properzi, MJ, Rabin, JS, Lim, YY, Papp, KV, Jacobs, HIL, Burnham, S, Hanseeuw, BJ, Dore, V, Dobson, A, Masters, CL, Waller, M, Rowe, CC, Maruff, P, Donohue, MC, Rentz, DM, Kirn, D, Hedden, T, Chhatwal, J, Schultz, AP, Johnson, KA, Villemagne, VL, Sperling, RA & Collaborators Alzheimer's Dis Neur; Australian Imaging Biomarker Lifes; Harvard Aging Brain Study 2018, 'Sex, amyloid, and APOE ε4 and risk of cognitive decline in preclinical Alzheimer's disease: Findings from three well-characterized cohorts', Alzheimer's & Dementia, vol. 14, no. 9, pp. 1193-1203. https://doi.org/10.1016/j.jalz.2018.04.010

TY - JOUR

T1 - Sex, amyloid, and APOE ε4 and risk of cognitive decline in preclinical Alzheimer's disease

T2 - Findings from three well-characterized cohorts

AU - Buckley, Rachel F.

AU - Mormino, Elizabeth C.

AU - Amariglio, Rebecca E.

AU - Properzi, Michael J.

AU - Rabin, Jennifer S.

AU - Lim, Yen Ying

AU - Papp, Kathryn V.

AU - Jacobs, Heidi I. L.

AU - Burnham, Samantha

AU - Hanseeuw, Bernard J.

AU - Dore, Vincent

AU - Dobson, Annette

AU - Masters, Colin L.

AU - Waller, Michael

AU - Rowe, Christopher C.

AU - Maruff, Paul

AU - Donohue, Michael C.

AU - Rentz, Dorene M.

AU - Kirn, Dylan

AU - Hedden, Trey

AU - Chhatwal, Jasmeer

AU - Schultz, Aaron P.

AU - Johnson, Keith A.

AU - Villemagne, Victor L.

AU - Sperling, Reisa A.

AU - Collaborators Alzheimer's Dis Neur; Australian Imaging Biomarker Lifes; Harvard Aging Brain Study

PY - 2018/9/1

Y1 - 2018/9/1

N2 - 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.

AB - 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.

KW - Preclinical Alzheimer's disease

KW - Amyloid

KW - APOE

KW - Sex

KW - Gender

KW - Cognitive decline

KW - HEALTHY OLDER-ADULTS

KW - APOLIPOPROTEIN-E GENOTYPE

KW - GENDER-DIFFERENCES

KW - PRECURSOR PROTEIN

KW - BETA-DEPOSITION

KW - BRAIN STRUCTURE

KW - SENILE PLAQUE

KW - DEMENTIA

KW - AGE

KW - ASSOCIATION

U2 - 10.1016/j.jalz.2018.04.010

DO - 10.1016/j.jalz.2018.04.010

M3 - Article

C2 - 29803541

SN - 1552-5260

VL - 14

SP - 1193

EP - 1203

JO - Alzheimer's & Dementia

JF - Alzheimer's & Dementia

IS - 9

ER -