Menu Close

APOE ε4 and the Influence of Sex, Age, Vascular Risk Factors, and Ethnicity on Cognitive Decline

Citation

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, et al. (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), 1863-73. PMCID: PMC7518559

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.

URL

http://dx.doi.org/10.1093/gerona/glaa116

Reference Type

Journal Article

Journal Title

Journals of Gerontology Series A: Biological Sciences and Medical Sciences

Author(s)

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.
Wang, Cuiling
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
Pin Ng, Tze
Gao, Qi
Zin Nyunt, Ma Shwe
Brodaty, Henry
Trollor, Julian N.
Leung, Yvonne
Lo, Jessica W.
Sachdev, Perminder

Year Published

2020

Volume Number

75

Issue Number

10

Pages

1863-73

PMCID

PMC7518559

Reference ID

13289