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

Background Although the epsilon 4 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 epsilon 4 carrier status and PTSD on cognitive functioning, with a focus on whether PTSD moderates the effect of epsilon 4 carrier status. Results APOE epsilon 4 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. epsilon 4 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 epsilon 4 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 epsilon 4 allele carriers with PTSD have substantially greater cognitive difficulties than epsilon 4 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.