APOE ε4 and the influence of sex, age, vascular risk factors, and ethnicity on cognitive decline
Steve R Makkar
(1)
,
Darren M Lipnicki
(1)
,
John D Crawford
(1)
,
Nicole A Kochan
(1)
,
Erico Castro-Costa
(2)
,
Maria Fernanda Lima-Costa
(2)
,
Breno Satler Diniz
(3, 4)
,
Carol Brayne
(5)
,
Blossom Stephan
(6)
,
Fiona Matthews
(6)
,
Juan J Llibre-Rodriguez
(7)
,
Jorge J Llibre-Guerra
(8)
,
Adolfo J Valhuerdi-Cepero
(9)
,
Richard B Lipton
(10)
,
Mindy J Katz
(10)
,
Cuiling Wang
(10)
,
Karen Ritchie
(11, 12)
,
Sophie Carles
(13, 14)
,
Isabelle Carriere
(11, 12)
,
Nikolaos Scarmeas
(15, 16)
,
Mary Yannakoulia
(17)
,
Mary Kosmidis
(18)
,
Linda Lam
(19)
,
Wai Chi Chan
(19)
,
Ada Fung
(20)
,
Antonio Guaita
(21)
,
Roberta Vaccaro
(21)
,
Annalisa Davin
(21)
,
Ki Woong Kim
(22, 23)
,
Ji Won Han
(23)
,
Seung Wan Suh
(23)
,
Steffi G Riedel-Heller
(24)
,
Susanne Roehr
(24)
,
Alexander Pabst
(24)
,
Mary Ganguli
(25)
,
Tiffany F Hughes
(26)
,
Beth Snitz
(25)
,
Kaarin J Anstey
(27, 28)
,
Nicolas Cherbuin
(28)
,
Simon Easteal
(28)
,
Mary N Haan
(8)
,
Allison E Aiello
(29)
,
Kristina Dang
(8)
,
Tze Pin Ng
(30)
,
Qi Gao
(30)
,
Ma Shwe Zin Nyunt
(30)
,
Henry Brodaty
(1)
,
Julian N Trollor
(1)
,
Yvonne Leung
(31)
,
Jessica W Lo
(1)
,
Perminder Sachdev
(1)
1
UNSW -
University of New South Wales [Sydney]
2 FIOCRUZ - Fundação Oswaldo Cruz / Oswaldo Cruz Foundation
3 University of Toronto
4 Center For Addiction and Mental Health
5 CAM - University of Cambridge [UK]
6 Newcastle University [Newcastle]
7 UH - University of Havana (Universidad de la Habana)
8 UC San Francisco - University of California [San Francisco]
9 Universidad de Matanzas
10 Yeshiva University
11 PSNREC - Neuropsychiatrie : recherche épidémiologique et clinique
12 Hôpital la Colombière [CHU Montpellier]
13 CRESS (U1153 / UMR_A 1125) - Centre for Research in Epidemiology and Statistics | Centre de Recherche Épidémiologie et Statistiques
14 UPD5 - Université Paris Descartes - Paris 5
15 NKUA - National and Kapodistrian University of Athens
16 Columbia University [New York]
17 Harokopio University of Athens
18 Aristotle University of Thessaloniki
19 CUHK - The Chinese University of Hong Kong [Hong Kong]
20 POLYU - The Hong Kong Polytechnic University [Hong Kong]
21 Golgi Cenci Foundation
22 SNU - Seoul National University [Seoul]
23 Seoul National University Hospital
24 Leipzig University / Universität Leipzig
25 University of Pittsburgh School of Medicine
26 YSU - Youngstown State University
27 NeuRA - Neuroscience Research Australia
28 ANU - Australian National University
29 UNC - University of North Carolina [Chapel Hill]
30 NUS - National University of Singapore
31 University of Nottingham Malaysia Campus
2 FIOCRUZ - Fundação Oswaldo Cruz / Oswaldo Cruz Foundation
3 University of Toronto
4 Center For Addiction and Mental Health
5 CAM - University of Cambridge [UK]
6 Newcastle University [Newcastle]
7 UH - University of Havana (Universidad de la Habana)
8 UC San Francisco - University of California [San Francisco]
9 Universidad de Matanzas
10 Yeshiva University
11 PSNREC - Neuropsychiatrie : recherche épidémiologique et clinique
12 Hôpital la Colombière [CHU Montpellier]
13 CRESS (U1153 / UMR_A 1125) - Centre for Research in Epidemiology and Statistics | Centre de Recherche Épidémiologie et Statistiques
14 UPD5 - Université Paris Descartes - Paris 5
15 NKUA - National and Kapodistrian University of Athens
16 Columbia University [New York]
17 Harokopio University of Athens
18 Aristotle University of Thessaloniki
19 CUHK - The Chinese University of Hong Kong [Hong Kong]
20 POLYU - The Hong Kong Polytechnic University [Hong Kong]
21 Golgi Cenci Foundation
22 SNU - Seoul National University [Seoul]
23 Seoul National University Hospital
24 Leipzig University / Universität Leipzig
25 University of Pittsburgh School of Medicine
26 YSU - Youngstown State University
27 NeuRA - Neuroscience Research Australia
28 ANU - Australian National University
29 UNC - University of North Carolina [Chapel Hill]
30 NUS - National University of Singapore
31 University of Nottingham Malaysia Campus
John D Crawford
- Fonction : Auteur
- PersonId : 811551
- ORCID : 0000-0001-5141-0673
Erico Castro-Costa
- Fonction : Auteur
- PersonId : 798923
- ORCID : 0000-0003-0792-5439
Carol Brayne
- Fonction : Auteur
- PersonId : 766057
- ORCID : 0000-0001-5307-663X
Blossom Stephan
- Fonction : Auteur
- PersonId : 778033
- ORCID : 0000-0002-1235-360X
Jorge J Llibre-Guerra
- Fonction : Auteur
- PersonId : 811552
- ORCID : 0000-0002-2137-7750
Sophie Carles
- Fonction : Auteur
- PersonId : 749166
- IdHAL : sophiecarles
- ORCID : 0000-0003-0792-1104
Nikolaos Scarmeas
- Fonction : Auteur
- PersonId : 761369
- ORCID : 0000-0001-6453-8908
Ji Won Han
- Fonction : Auteur
- PersonId : 798924
- ORCID : 0000-0003-2418-4257
Susanne Roehr
- Fonction : Auteur
- PersonId : 803840
- ORCID : 0000-0001-9385-0669
Alexander Pabst
- Fonction : Auteur
- PersonId : 794546
- ORCID : 0000-0003-0432-5681
Kaarin J Anstey
- Fonction : Auteur
- PersonId : 807421
- ORCID : 0000-0002-9706-9316
Mary N Haan
- Fonction : Auteur
- PersonId : 811553
- ORCID : 0000-0001-9312-4501
Yvonne Leung
- Fonction : Auteur
- PersonId : 798952
- ORCID : 0000-0001-9110-7054
Perminder Sachdev
- Fonction : Auteur
- PersonId : 778032
- ORCID : 0000-0002-9595-3220
- IdRef : 076727041
Résumé
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.
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