Sex differences in associations between APOE ε2 and longitudinal cognitive decline

Madeline E. Wood; Lisa Y. Xiong; Yuen Yan Wong; Rachel F. Buckley; Walter Swardfager; Mario Masellis; Andrew S.P. Lim; Emma Nichols; Renaud La Joie; Kaitlin B. Casaletto; Raj G. Kumar; Kristen Dams-O'Connor; Priya Palta; Kristen M. George; Claudia L. Satizabal; Lisa L. Barnes; Julie A. Schneider; Alexa Pichette Binet; Sylvia Villeneuve; Judy Pa; Adam M. Brickman; Sandra E. Black; Jennifer S. Rabin

doi:10.1002/alz.13036

Sex differences in associations between APOE ε2 and longitudinal cognitive decline

Madeline E. Wood, Lisa Y. Xiong, Yuen Yan Wong, Rachel F. Buckley, Walter Swardfager, Mario Masellis, Andrew S.P. Lim, Emma Nichols, Renaud La Joie, Kaitlin B. Casaletto, Raj G. Kumar, Kristen Dams-O'Connor, Priya Palta, Kristen M. George, Claudia L. Satizabal, Lisa L. Barnes, Julie A. Schneider, Alexa Pichette Binet, Sylvia Villeneuve, Judy PaAdam M. Brickman, Sandra E. Black, Jennifer S. Rabin

Research output: Contribution to journal › Article › peer-review

5 Scopus citations

Abstract

INTRODUCTION: We examined whether sex modifies the association between APOE ε2 and cognitive decline in two independent samples. METHODS: We used observational data from cognitively unimpaired non-Hispanic White (NHW) and non-Hispanic Black (NHB) adults. Linear mixed models examined interactive associations of APOE genotype (ε2 or ε4 carrier vs. ε3/ε3) and sex on cognitive decline in NHW and NHB participants separately. RESULTS: In both Sample 1 (N = 9766) and Sample 2 (N = 915), sex modified the association between APOE ε2 and cognitive decline in NHW participants. Specifically, relative to APOE ε3/ε3, APOE ε2 protected against cognitive decline in men but not women. Among APOE ε2 carriers, men had slower decline than women. Among APOE ε3/ε3 carriers, cognitive trajectories did not differ between sexes. There were no sex-specific associations of APOE ε2 with cognition in NHB participants (N = 2010). DISCUSSION: In NHW adults, APOE ε2 may protect men but not women against cognitive decline. Highlights: We studied sex-specific apolipoprotein E (APOE) ε2 effects on cognitive decline. In non-Hispanic White (NHW) adults, APOE ε2 selectively protects men against decline. Among men, APOE ε2 was more protective than APOE ε3/ε3. In women, APOE ε2 was no more protective than APOE ε3/ε3. Among APOE ε2 carriers, men had slower decline than women. There were no sex-specific APOE ε2 effects in non-Hispanic Black (NHB) adults.

Original language	English (US)
Pages (from-to)	4651-4661
Number of pages	11
Journal	Alzheimer's and Dementia
Volume	19
Issue number	10
DOIs	https://doi.org/10.1002/alz.13036
State	Published - Oct 2023

Keywords

APOE
Alzheimer's disease
cognitive decline
race/ethnicity
sex differences

ASJC Scopus subject areas

Epidemiology
Health Policy
Developmental Neuroscience
Clinical Neurology
Geriatrics and Gerontology
Cellular and Molecular Neuroscience
Psychiatry and Mental health

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10.1002/alz.13036

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Wood, M. E., Xiong, L. Y., Wong, Y. Y., Buckley, R. F., Swardfager, W., Masellis, M., Lim, A. S. P., Nichols, E., Joie, R. L., Casaletto, K. B., Kumar, R. G., Dams-O'Connor, K., Palta, P., George, K. M., Satizabal, C. L., Barnes, L. L., Schneider, J. A., Binet, A. P., Villeneuve, S., ... Rabin, J. S. (2023). Sex differences in associations between APOE ε2 and longitudinal cognitive decline. Alzheimer's and Dementia, 19(10), 4651-4661. https://doi.org/10.1002/alz.13036

Wood, ME, Xiong, LY, Wong, YY, Buckley, RF, Swardfager, W, Masellis, M, Lim, ASP, Nichols, E, Joie, RL, Casaletto, KB, Kumar, RG, Dams-O'Connor, K, Palta, P, George, KM, Satizabal, CL, Barnes, LL, Schneider, JA, Binet, AP, Villeneuve, S, Pa, J, Brickman, AM, Black, SE & Rabin, JS 2023, 'Sex differences in associations between APOE ε2 and longitudinal cognitive decline', Alzheimer's and Dementia, vol. 19, no. 10, pp. 4651-4661. https://doi.org/10.1002/alz.13036

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title = "Sex differences in associations between APOE ε2 and longitudinal cognitive decline",

abstract = "INTRODUCTION: We examined whether sex modifies the association between APOE ε2 and cognitive decline in two independent samples. METHODS: We used observational data from cognitively unimpaired non-Hispanic White (NHW) and non-Hispanic Black (NHB) adults. Linear mixed models examined interactive associations of APOE genotype (ε2 or ε4 carrier vs. ε3/ε3) and sex on cognitive decline in NHW and NHB participants separately. RESULTS: In both Sample 1 (N = 9766) and Sample 2 (N = 915), sex modified the association between APOE ε2 and cognitive decline in NHW participants. Specifically, relative to APOE ε3/ε3, APOE ε2 protected against cognitive decline in men but not women. Among APOE ε2 carriers, men had slower decline than women. Among APOE ε3/ε3 carriers, cognitive trajectories did not differ between sexes. There were no sex-specific associations of APOE ε2 with cognition in NHB participants (N = 2010). DISCUSSION: In NHW adults, APOE ε2 may protect men but not women against cognitive decline. Highlights: We studied sex-specific apolipoprotein E (APOE) ε2 effects on cognitive decline. In non-Hispanic White (NHW) adults, APOE ε2 selectively protects men against decline. Among men, APOE ε2 was more protective than APOE ε3/ε3. In women, APOE ε2 was no more protective than APOE ε3/ε3. Among APOE ε2 carriers, men had slower decline than women. There were no sex-specific APOE ε2 effects in non-Hispanic Black (NHB) adults.",

keywords = "APOE, Alzheimer's disease, cognitive decline, race/ethnicity, sex differences",

author = "Wood, {Madeline E.} and Xiong, {Lisa Y.} and Wong, {Yuen Yan} and Buckley, {Rachel F.} and Walter Swardfager and Mario Masellis and Lim, {Andrew S.P.} and Emma Nichols and Joie, {Renaud La} and Casaletto, {Kaitlin B.} and Kumar, {Raj G.} and Kristen Dams-O'Connor and Priya Palta and George, {Kristen M.} and Satizabal, {Claudia L.} and Barnes, {Lisa L.} and Schneider, {Julie A.} and Binet, {Alexa Pichette} and Sylvia Villeneuve and Judy Pa and Brickman, {Adam M.} and Black, {Sandra E.} and Rabin, {Jennifer S.}",

note = "Publisher Copyright: {\textcopyright} 2023 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.",

year = "2023",

month = oct,

doi = "10.1002/alz.13036",

language = "English (US)",

volume = "19",

pages = "4651--4661",

journal = "Alzheimer's and Dementia",

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TY - JOUR

T1 - Sex differences in associations between APOE ε2 and longitudinal cognitive decline

AU - Wood, Madeline E.

AU - Xiong, Lisa Y.

AU - Wong, Yuen Yan

AU - Buckley, Rachel F.

AU - Swardfager, Walter

AU - Masellis, Mario

AU - Lim, Andrew S.P.

AU - Nichols, Emma

AU - Joie, Renaud La

AU - Casaletto, Kaitlin B.

AU - Kumar, Raj G.

AU - Dams-O'Connor, Kristen

AU - Palta, Priya

AU - George, Kristen M.

AU - Satizabal, Claudia L.

AU - Barnes, Lisa L.

AU - Schneider, Julie A.

AU - Binet, Alexa Pichette

AU - Villeneuve, Sylvia

AU - Pa, Judy

AU - Brickman, Adam M.

AU - Black, Sandra E.

AU - Rabin, Jennifer S.

PY - 2023/10

Y1 - 2023/10

N2 - INTRODUCTION: We examined whether sex modifies the association between APOE ε2 and cognitive decline in two independent samples. METHODS: We used observational data from cognitively unimpaired non-Hispanic White (NHW) and non-Hispanic Black (NHB) adults. Linear mixed models examined interactive associations of APOE genotype (ε2 or ε4 carrier vs. ε3/ε3) and sex on cognitive decline in NHW and NHB participants separately. RESULTS: In both Sample 1 (N = 9766) and Sample 2 (N = 915), sex modified the association between APOE ε2 and cognitive decline in NHW participants. Specifically, relative to APOE ε3/ε3, APOE ε2 protected against cognitive decline in men but not women. Among APOE ε2 carriers, men had slower decline than women. Among APOE ε3/ε3 carriers, cognitive trajectories did not differ between sexes. There were no sex-specific associations of APOE ε2 with cognition in NHB participants (N = 2010). DISCUSSION: In NHW adults, APOE ε2 may protect men but not women against cognitive decline. Highlights: We studied sex-specific apolipoprotein E (APOE) ε2 effects on cognitive decline. In non-Hispanic White (NHW) adults, APOE ε2 selectively protects men against decline. Among men, APOE ε2 was more protective than APOE ε3/ε3. In women, APOE ε2 was no more protective than APOE ε3/ε3. Among APOE ε2 carriers, men had slower decline than women. There were no sex-specific APOE ε2 effects in non-Hispanic Black (NHB) adults.

AB - INTRODUCTION: We examined whether sex modifies the association between APOE ε2 and cognitive decline in two independent samples. METHODS: We used observational data from cognitively unimpaired non-Hispanic White (NHW) and non-Hispanic Black (NHB) adults. Linear mixed models examined interactive associations of APOE genotype (ε2 or ε4 carrier vs. ε3/ε3) and sex on cognitive decline in NHW and NHB participants separately. RESULTS: In both Sample 1 (N = 9766) and Sample 2 (N = 915), sex modified the association between APOE ε2 and cognitive decline in NHW participants. Specifically, relative to APOE ε3/ε3, APOE ε2 protected against cognitive decline in men but not women. Among APOE ε2 carriers, men had slower decline than women. Among APOE ε3/ε3 carriers, cognitive trajectories did not differ between sexes. There were no sex-specific associations of APOE ε2 with cognition in NHB participants (N = 2010). DISCUSSION: In NHW adults, APOE ε2 may protect men but not women against cognitive decline. Highlights: We studied sex-specific apolipoprotein E (APOE) ε2 effects on cognitive decline. In non-Hispanic White (NHW) adults, APOE ε2 selectively protects men against decline. Among men, APOE ε2 was more protective than APOE ε3/ε3. In women, APOE ε2 was no more protective than APOE ε3/ε3. Among APOE ε2 carriers, men had slower decline than women. There were no sex-specific APOE ε2 effects in non-Hispanic Black (NHB) adults.

KW - APOE

KW - Alzheimer's disease

KW - cognitive decline

KW - race/ethnicity

KW - sex differences

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Sex differences in associations between APOE ε2 and longitudinal cognitive decline

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