Apolipoprotein E gene polymorphism, posttraumatic stress disorder, and cognitive function in older U.S. veterans: Results from the National Health and Resilience in Veterans Study

Lynnette A. Averill, Chadi G. Abdallah, Daniel F. Levey, Shizhong Han, Ilan Harpaz-Rotem, Henry R. Kranzler, Steven M. Southwick, John H. Krystal, Joel Gelernter, Robert H. Pietrzak

Research output: Contribution to journalArticlepeer-review

Abstract

Background: Although the ε4 allele of the apolipoprotein E (APOE) gene and posttraumatic stress disorder (PTSD) have been linked to cognitive dysfunction and dementia risk, it is unknown whether they interact to predict cognitive dysfunction. Methods: We analyzed data from European-American (EA) veterans who participated in the National Health and Resilience in Veterans Study (NHRVS): main sample (n = 1,386) and primary replication sample (n = 509). EAs from the Yale–Penn Study cohort (n = 948) served as a second replication sample. Multivariable analyses were conducted to evaluate the predictive effects of ε4 carrier status and PTSD on cognitive functioning, with a focus on whether PTSD moderates the effect of ε4 carrier status. Results: APOE ε4 allele carrier status (d = 0.15 and 0.17 in the main and primary replication NHRVS samples, respectively) and PTSD (d = 0.31 and 0.17, respectively) were independently associated with lower cognitive functioning. ε4 carriers with PTSD scored lower than those without PTSD (d = 0.68 and 1.29, respectively) with the most pronounced differences in executive function (d's = 0.75–1.50) and attention/concentration (d's = 0.62–1.33). A significant interaction was also observed in the Yale–Penn sample, with ε4 carriers with PTSD making more perseverative errors on a measure of executive function than those without PTSD (24.7% vs. 17.6%; d = 0.59). Conclusions: APOE ε4 allele carriers with PTSD have substantially greater cognitive difficulties than ε4 carriers without PTSD. These results underscore the importance of assessing, monitoring, and treating PTSD in trauma-affected individuals who are at genetic risk for cognitive decline and dementia.

Original languageEnglish (US)
Pages (from-to)834-845
Number of pages12
JournalDepression and anxiety
Volume36
Issue number9
DOIs
StatePublished - Sep 1 2019

Keywords

  • APOE
  • PTSD
  • aging
  • cognitive decline
  • genetics
  • veterans

ASJC Scopus subject areas

  • Clinical Psychology
  • Psychiatry and Mental health

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