Alzheimer's disease and related dementias among aging veterans: Examining gene‐by‐environment interactions with post‐traumatic stress disorder and traumatic brain injury

ABSTRACT Introduction Post‐traumatic stress disorder (PTSD) and traumatic brain injury (TBI) confer risk for Alzheimer's disease and related dementias (ADRD). Methods This study from the Million Veteran Program (MVP) evaluated the impact of apolipoprotein E ( APOE ) ε4, PTSD, and TBI on ADRD prevalence in veteran cohorts of European ancestry (EA; n = 11,112 ADRD cases, 170,361 controls) and African ancestry (AA; n = 1443 ADRD cases, 16,191 controls). Additive‐scale interactions were estimated using the relative excess risk due to interaction (RERI) statistic. Results PTSD, TBI, and APOE ε4 showed strong main‐effect associations with ADRD. RERI analysis revealed significant additive APOE ε4 interactions with PTSD and TBI in the EA cohort and TBI in the AA cohort. These additive interactions indicate that ADRD prevalence associated with PTSD and TBI increased with the number of inherited APOE ε4 alleles. Discussion PTSD and TBI history will be an important part of interpreting the results of ADRD genetic testing and doing accurate ADRD risk assessment.