APOE ε4 and the influence of sex, age, vascular risk factors, and ethnicity on cognitive decline

Steve R. Makkar; Darren M. Lipnicki; John D. Crawford; Nicole A. Kochan; Erico Castro-Costa; Maria Fernanda Lima-Costa; Breno Satler Diniz; Carol Brayne; Blossom Stephan; Fiona Matthews; Juan J. Llibre-Rodriguez; Jorge J. Llibre-Guerra; Adolfo J. Valhuerdi-Cepero; Richard B. Lipton; Mindy J. Katz; CuilingWang; Karen Ritchie; Sophie Carles; Isabelle Carriere; Nikolaos Scarmeas; Mary Yannakoulia; Mary Kosmidis; Linda Lam; Wai Chi Chan; Ada Fung; Antonio Guaita; Roberta Vaccaro; Annalisa Davin; Ki Woong Kim; Ji Won Han; Seung Wan Suh; Steffi G. Riedel-Heller; Susanne Roehr; Alexander Pabst; Mary Ganguli; Tiffany F. Hughes; Beth Snitz; Kaarin J. Anstey; Nicolas Cherbuin; Simon Easteal; Mary N. Haan; Allison E. Aiello; Kristina Dang; Tze Pin Ng; Qi Gao; Ma Shwe Zin Nyunt; Henry Brodaty; Julian N. Trollor; Yvonne Leung; Jessica W. Lo; Perminder Sachdev

doi:10.1093/gerona/glaa116

APOE ε4 and the influence of sex, age, vascular risk factors, and ethnicity on cognitive decline

Steve R. Makkar, Darren M. Lipnicki, John D. Crawford, Nicole A. Kochan, Erico Castro-Costa, Maria Fernanda Lima-Costa, Breno Satler Diniz, Carol Brayne, Blossom Stephan, Fiona Matthews, Juan J. Llibre-Rodriguez, Jorge J. Llibre-Guerra, Adolfo J. Valhuerdi-Cepero, Richard B. Lipton, Mindy J. Katz, CuilingWang, Karen Ritchie, Sophie Carles, Isabelle Carriere, Nikolaos ScarmeasMary Yannakoulia, Mary Kosmidis, Linda Lam, Wai Chi Chan, Ada Fung, Antonio Guaita, Roberta Vaccaro, Annalisa Davin, Ki Woong Kim, Ji Won Han, Seung Wan Suh, Steffi G. Riedel-Heller, Susanne Roehr, Alexander Pabst, Mary Ganguli, Tiffany F. Hughes, Beth Snitz, Kaarin J. Anstey, Nicolas Cherbuin, Simon Easteal, Mary N. Haan, Allison E. Aiello, Kristina Dang, Tze Pin Ng, Qi Gao, Ma Shwe Zin Nyunt, Henry Brodaty, Julian N. Trollor, Yvonne Leung, Jessica W. Lo, Perminder Sachdev

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

11 Scopus citations

Abstract

We aimed to examine the relationship between Apolipoprotein E ε4 (APOE*4) carriage on cognitive decline, and whether these associations were moderated by sex, baseline age, ethnicity, and vascular risk factors. Participants were 19,225 individuals aged 54–103 years from 15 longitudinal cohort studies with a mean follow-up duration ranging between 1.2 and 10.7 years. Two-step individual participant data meta-analysis was used to pool results of study-wise analyses predicting memory and general cognitive decline from carriage of one or two APOE*4 alleles, and moderation of these associations by age, sex, vascular risk factors, and ethnicity. Separate pooled estimates were calculated in both men and women who were younger (ie, 62 years) and older (ie, 80 years) at baseline. Results showed that APOE*4 carriage was related to faster general cognitive decline in women, and faster memory decline in men. A stronger dose-dependent effect was observed in older men, with faster general cognitive and memory decline in those carrying two versus one APOE*4 allele. Vascular risk factors were related to an increased effect of APOE*4 on memory decline in younger women, but a weaker effect of APOE*4 on general cognitive decline in older men. The relationship between APOE*4 carriage and memory decline was larger in older-aged Asians than Whites. In sum, APOE*4 is related to cognitive decline in men and women, although these effects are enhanced by age and carriage of two APOE*4 alleles in men, a higher numbers of vascular risk factors during the early stages of late adulthood in women, and Asian ethnicity.

Original language	English
Pages (from-to)	1863-1873
Number of pages	11
Journal	Journals of Gerontology - Series A Biological Sciences and Medical Sciences
Volume	75
Issue number	10
DOIs	https://doi.org/10.1093/gerona/glaa116
State	Published - Oct 1 2020

Keywords

APOE genotype
Cognitive decline
Epidemiology
Ethnicity
Sex

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10.1093/gerona/glaa116

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Makkar, S. R., Lipnicki, D. M., Crawford, J. D., Kochan, N. A., Castro-Costa, E., Lima-Costa, M. F., Diniz, B. S., Brayne, C., Stephan, B., Matthews, F., Llibre-Rodriguez, J. J., Llibre-Guerra, J. J., Valhuerdi-Cepero, A. J., Lipton, R. B., Katz, M. J., CuilingWang, Ritchie, K., Carles, S., Carriere, I., ... Sachdev, P. (2020). APOE ε4 and the influence of sex, age, vascular risk factors, and ethnicity on cognitive decline. Journals of Gerontology - Series A Biological Sciences and Medical Sciences, 75(10), 1863-1873. https://doi.org/10.1093/gerona/glaa116

Makkar, Steve R. ; Lipnicki, Darren M. ; Crawford, John D. ; Kochan, Nicole A. ; Castro-Costa, Erico ; Lima-Costa, Maria Fernanda ; Diniz, Breno Satler ; Brayne, Carol ; Stephan, Blossom ; Matthews, Fiona ; Llibre-Rodriguez, Juan J. ; Llibre-Guerra, Jorge J. ; Valhuerdi-Cepero, Adolfo J. ; Lipton, Richard B. ; Katz, Mindy J. ; CuilingWang ; Ritchie, Karen ; Carles, Sophie ; Carriere, Isabelle ; Scarmeas, Nikolaos ; Yannakoulia, Mary ; Kosmidis, Mary ; Lam, Linda ; Chan, Wai Chi ; Fung, Ada ; Guaita, Antonio ; Vaccaro, Roberta ; Davin, Annalisa ; Kim, Ki Woong ; Han, Ji Won ; Suh, Seung Wan ; Riedel-Heller, Steffi G. ; Roehr, Susanne ; Pabst, Alexander ; Ganguli, Mary ; Hughes, Tiffany F. ; Snitz, Beth ; Anstey, Kaarin J. ; Cherbuin, Nicolas ; Easteal, Simon ; Haan, Mary N. ; Aiello, Allison E. ; Dang, Kristina ; Ng, Tze Pin ; Gao, Qi ; Nyunt, Ma Shwe Zin ; Brodaty, Henry ; Trollor, Julian N. ; Leung, Yvonne ; Lo, Jessica W. ; Sachdev, Perminder. / APOE ε4 and the influence of sex, age, vascular risk factors, and ethnicity on cognitive decline. In: Journals of Gerontology - Series A Biological Sciences and Medical Sciences. 2020 ; Vol. 75, No. 10. pp. 1863-1873.

@article{324854b308b84d159ca5a074aad22c41,

title = "APOE ε4 and the influence of sex, age, vascular risk factors, and ethnicity on cognitive decline",

abstract = "We aimed to examine the relationship between Apolipoprotein E ε4 (APOE*4) carriage on cognitive decline, and whether these associations were moderated by sex, baseline age, ethnicity, and vascular risk factors. Participants were 19,225 individuals aged 54–103 years from 15 longitudinal cohort studies with a mean follow-up duration ranging between 1.2 and 10.7 years. Two-step individual participant data meta-analysis was used to pool results of study-wise analyses predicting memory and general cognitive decline from carriage of one or two APOE*4 alleles, and moderation of these associations by age, sex, vascular risk factors, and ethnicity. Separate pooled estimates were calculated in both men and women who were younger (ie, 62 years) and older (ie, 80 years) at baseline. Results showed that APOE*4 carriage was related to faster general cognitive decline in women, and faster memory decline in men. A stronger dose-dependent effect was observed in older men, with faster general cognitive and memory decline in those carrying two versus one APOE*4 allele. Vascular risk factors were related to an increased effect of APOE*4 on memory decline in younger women, but a weaker effect of APOE*4 on general cognitive decline in older men. The relationship between APOE*4 carriage and memory decline was larger in older-aged Asians than Whites. In sum, APOE*4 is related to cognitive decline in men and women, although these effects are enhanced by age and carriage of two APOE*4 alleles in men, a higher numbers of vascular risk factors during the early stages of late adulthood in women, and Asian ethnicity.",

keywords = "APOE genotype, Cognitive decline, Epidemiology, Ethnicity, Sex",

author = "Makkar, {Steve R.} and Lipnicki, {Darren M.} and Crawford, {John D.} and Kochan, {Nicole A.} and Erico Castro-Costa and Lima-Costa, {Maria Fernanda} and Diniz, {Breno Satler} and Carol Brayne and Blossom Stephan and Fiona Matthews and Llibre-Rodriguez, {Juan J.} and Llibre-Guerra, {Jorge J.} and Valhuerdi-Cepero, {Adolfo J.} and Lipton, {Richard B.} and Katz, {Mindy J.} and CuilingWang and Karen Ritchie and Sophie Carles and Isabelle Carriere and Nikolaos Scarmeas and Mary Yannakoulia and Mary Kosmidis and Linda Lam and Chan, {Wai Chi} and Ada Fung and Antonio Guaita and Roberta Vaccaro and Annalisa Davin and Kim, {Ki Woong} and Han, {Ji Won} and Suh, {Seung Wan} and Riedel-Heller, {Steffi G.} and Susanne Roehr and Alexander Pabst and Mary Ganguli and Hughes, {Tiffany F.} and Beth Snitz and Anstey, {Kaarin J.} and Nicolas Cherbuin and Simon Easteal and Haan, {Mary N.} and Aiello, {Allison E.} and Kristina Dang and Ng, {Tze Pin} and Qi Gao and Nyunt, {Ma Shwe Zin} and Henry Brodaty and Trollor, {Julian N.} and Yvonne Leung and Lo, {Jessica W.} and Perminder Sachdev",

year = "2020",

month = oct,

day = "1",

doi = "10.1093/gerona/glaa116",

language = "English",

volume = "75",

pages = "1863--1873",

journal = "Journals of Gerontology - Series A Biological Sciences and Medical Sciences",

issn = "1079-5006",

number = "10",

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Makkar, SR, Lipnicki, DM, Crawford, JD, Kochan, NA, Castro-Costa, E, Lima-Costa, MF, Diniz, BS, Brayne, C, Stephan, B, Matthews, F, Llibre-Rodriguez, JJ, Llibre-Guerra, JJ, Valhuerdi-Cepero, AJ, Lipton, RB, Katz, MJ, CuilingWang, Ritchie, K, Carles, S, Carriere, I, Scarmeas, N, Yannakoulia, M, Kosmidis, M, Lam, L, Chan, WC, Fung, A, Guaita, A, Vaccaro, R, Davin, A, Kim, KW, Han, JW, Suh, SW, Riedel-Heller, SG, Roehr, S, Pabst, A, Ganguli, M, Hughes, TF, Snitz, B, Anstey, KJ, Cherbuin, N, Easteal, S, Haan, MN, Aiello, AE, Dang, K, Ng, TP, Gao, Q, Nyunt, MSZ, Brodaty, H, Trollor, JN, Leung, Y, Lo, JW & Sachdev, P 2020, 'APOE ε4 and the influence of sex, age, vascular risk factors, and ethnicity on cognitive decline', Journals of Gerontology - Series A Biological Sciences and Medical Sciences, vol. 75, no. 10, pp. 1863-1873. https://doi.org/10.1093/gerona/glaa116

APOE ε4 and the influence of sex, age, vascular risk factors, and ethnicity on cognitive decline. / Makkar, Steve R.; Lipnicki, Darren M.; Crawford, John D.; Kochan, Nicole A.; Castro-Costa, Erico; Lima-Costa, Maria Fernanda; Diniz, Breno Satler; Brayne, Carol; Stephan, Blossom; Matthews, Fiona; Llibre-Rodriguez, Juan J.; Llibre-Guerra, Jorge J.; Valhuerdi-Cepero, Adolfo J.; Lipton, Richard B.; Katz, Mindy J.; CuilingWang; Ritchie, Karen; Carles, Sophie; Carriere, Isabelle; Scarmeas, Nikolaos; Yannakoulia, Mary; Kosmidis, Mary; Lam, Linda; Chan, Wai Chi; Fung, Ada; Guaita, Antonio; Vaccaro, Roberta; Davin, Annalisa; Kim, Ki Woong; Han, Ji Won; Suh, Seung Wan; Riedel-Heller, Steffi G.; Roehr, Susanne; Pabst, Alexander; Ganguli, Mary; Hughes, Tiffany F.; Snitz, Beth; Anstey, Kaarin J.; Cherbuin, Nicolas; Easteal, Simon; Haan, Mary N.; Aiello, Allison E.; Dang, Kristina; Ng, Tze Pin; Gao, Qi; Nyunt, Ma Shwe Zin; Brodaty, Henry; Trollor, Julian N.; Leung, Yvonne; Lo, Jessica W.; Sachdev, Perminder.

In: Journals of Gerontology - Series A Biological Sciences and Medical Sciences, Vol. 75, No. 10, 01.10.2020, p. 1863-1873.

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

TY - JOUR

T1 - APOE ε4 and the influence of sex, age, vascular risk factors, and ethnicity on cognitive decline

AU - Makkar, Steve R.

AU - Lipnicki, Darren M.

AU - Crawford, John D.

AU - Kochan, Nicole A.

AU - Castro-Costa, Erico

AU - Lima-Costa, Maria Fernanda

AU - Diniz, Breno Satler

AU - Brayne, Carol

AU - Stephan, Blossom

AU - Matthews, Fiona

AU - Llibre-Rodriguez, Juan J.

AU - Llibre-Guerra, Jorge J.

AU - Valhuerdi-Cepero, Adolfo J.

AU - Lipton, Richard B.

AU - Katz, Mindy J.

AU - CuilingWang,

AU - Ritchie, Karen

AU - Carles, Sophie

AU - Carriere, Isabelle

AU - Scarmeas, Nikolaos

AU - Yannakoulia, Mary

AU - Kosmidis, Mary

AU - Lam, Linda

AU - Chan, Wai Chi

AU - Fung, Ada

AU - Guaita, Antonio

AU - Vaccaro, Roberta

AU - Davin, Annalisa

AU - Kim, Ki Woong

AU - Han, Ji Won

AU - Suh, Seung Wan

AU - Riedel-Heller, Steffi G.

AU - Roehr, Susanne

AU - Pabst, Alexander

AU - Ganguli, Mary

AU - Hughes, Tiffany F.

AU - Snitz, Beth

AU - Anstey, Kaarin J.

AU - Cherbuin, Nicolas

AU - Easteal, Simon

AU - Haan, Mary N.

AU - Aiello, Allison E.

AU - Dang, Kristina

AU - Ng, Tze Pin

AU - Gao, Qi

AU - Nyunt, Ma Shwe Zin

AU - Brodaty, Henry

AU - Trollor, Julian N.

AU - Leung, Yvonne

AU - Lo, Jessica W.

AU - Sachdev, Perminder

PY - 2020/10/1

Y1 - 2020/10/1

N2 - We aimed to examine the relationship between Apolipoprotein E ε4 (APOE*4) carriage on cognitive decline, and whether these associations were moderated by sex, baseline age, ethnicity, and vascular risk factors. Participants were 19,225 individuals aged 54–103 years from 15 longitudinal cohort studies with a mean follow-up duration ranging between 1.2 and 10.7 years. Two-step individual participant data meta-analysis was used to pool results of study-wise analyses predicting memory and general cognitive decline from carriage of one or two APOE*4 alleles, and moderation of these associations by age, sex, vascular risk factors, and ethnicity. Separate pooled estimates were calculated in both men and women who were younger (ie, 62 years) and older (ie, 80 years) at baseline. Results showed that APOE*4 carriage was related to faster general cognitive decline in women, and faster memory decline in men. A stronger dose-dependent effect was observed in older men, with faster general cognitive and memory decline in those carrying two versus one APOE*4 allele. Vascular risk factors were related to an increased effect of APOE*4 on memory decline in younger women, but a weaker effect of APOE*4 on general cognitive decline in older men. The relationship between APOE*4 carriage and memory decline was larger in older-aged Asians than Whites. In sum, APOE*4 is related to cognitive decline in men and women, although these effects are enhanced by age and carriage of two APOE*4 alleles in men, a higher numbers of vascular risk factors during the early stages of late adulthood in women, and Asian ethnicity.

AB - We aimed to examine the relationship between Apolipoprotein E ε4 (APOE*4) carriage on cognitive decline, and whether these associations were moderated by sex, baseline age, ethnicity, and vascular risk factors. Participants were 19,225 individuals aged 54–103 years from 15 longitudinal cohort studies with a mean follow-up duration ranging between 1.2 and 10.7 years. Two-step individual participant data meta-analysis was used to pool results of study-wise analyses predicting memory and general cognitive decline from carriage of one or two APOE*4 alleles, and moderation of these associations by age, sex, vascular risk factors, and ethnicity. Separate pooled estimates were calculated in both men and women who were younger (ie, 62 years) and older (ie, 80 years) at baseline. Results showed that APOE*4 carriage was related to faster general cognitive decline in women, and faster memory decline in men. A stronger dose-dependent effect was observed in older men, with faster general cognitive and memory decline in those carrying two versus one APOE*4 allele. Vascular risk factors were related to an increased effect of APOE*4 on memory decline in younger women, but a weaker effect of APOE*4 on general cognitive decline in older men. The relationship between APOE*4 carriage and memory decline was larger in older-aged Asians than Whites. In sum, APOE*4 is related to cognitive decline in men and women, although these effects are enhanced by age and carriage of two APOE*4 alleles in men, a higher numbers of vascular risk factors during the early stages of late adulthood in women, and Asian ethnicity.

KW - APOE genotype

KW - Cognitive decline

KW - Epidemiology

KW - Ethnicity

KW - Sex

UR - http://www.scopus.com/inward/record.url?scp=85087430028&partnerID=8YFLogxK

U2 - 10.1093/gerona/glaa116

DO - 10.1093/gerona/glaa116

M3 - Article

C2 - 32396611

AN - SCOPUS:85087430028

VL - 75

SP - 1863

EP - 1873

JO - Journals of Gerontology - Series A Biological Sciences and Medical Sciences

JF - Journals of Gerontology - Series A Biological Sciences and Medical Sciences

SN - 1079-5006

IS - 10

ER -

APOE ε4 and the influence of sex, age, vascular risk factors, and ethnicity on cognitive decline

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