Interactive association of posttraumatic stress disorder, apolipoprotein ε4 genotype, and age on cognitive functioning

Background: The epsilon 4 allele of the apolipoprotein (APOE) gene and posttraumatic stress disorder (PTSD) are associated with cognitive deficits. Both associations may vary depending on age. No previous study has examined a possible three-way interaction between APOE epsilon 4, PTSD, and age on cognitive functioning.Methods: Data were analyzed from 1244 European-American U.S. military veterans who participated in the 2011 National Health and Resilience in Veterans Study (NHRVS). Analyses of covariance were used to examine the main effects and interactions of APOE epsilon 4, PTSD, and age on learning/working memory (LWM) and attention/psychomotor (APM) performance.Results: A significant three-way interaction between APOE epsilon 4, PTSD, and age on the LWM composite (eta(2)(p) = 0.011) was observed such that the main effect of APOE epsilon 4 on LWM was only significant for older participants with PTSD. A significant two-way interaction between PTSD and age on the APM composite (eta(2)(p) = 0.011) was observed such that the main effect of PTSD on APM was only significant in older participants.Conclusion: Older APOE epsilon 4 carriers with probable PTSD showed poorer LWM performance relative to other groups. Aging-related associations on APM performance were most pronounced in veterans with PTSD. These data are preliminary evidence that identification and treatment of PTSD may be beneficial for individuals at risk for age-related cognitive impairment.