The medical community has never researched the simultaneous impact of post-traumatic stress disorder (PTSD), traumatic brain injury (TBI), and genetic risk factors in a large cohort … until now.

In a study of Veterans led by Dr. Mark Logue, a statistician in the National Center for PTSD at the VA Boston Healthcare System, researchers concluded that PTSD, TBI, and the ε4 variant of the APOE gene showed strong associations with Alzheimer’s Disease and related dementias (ADRD).

The researchers first found a greater percentage of ADRD in Veterans with PTSD and in those with TBI, relative to those without, as well as higher rates of ADRD in Veterans who had inherited the ε4 variant. Logue and his team then looked for interactions between the ε4 variant, PTSD, and TBI using a mathematical model.

The study found an increase in risk due to PTSD and TBI in Veterans of European ancestry who inherited the ε4 variant. In Veterans of African ancestry, the impact of PTSD didn’t vary as a function of ε4, but the TBI effect and interaction with ε4 was even stronger. Other studies have suggested that ε4 may magnify the effects of a head injury and/or combat-related stress.

“These additive interactions indicate that ADRD prevalence associated with PTSD and TBI increased with the number of inherited APOE ε4 alleles,” Logue and his colleagues wrote. “PTSD and TBI history will be an important part of interpreting the results of ADRD genetic testing and doing accurate ADRD risk assessment.”

Capitalizing on VA’s Million Veteran Program

The researchers carried out the study by accessing data from VA’s Million Veteran Program (MVP), one of the world’s largest databases of health and genetic information. MVP is aimed at learning how genes, lifestyle, and military exposures affect health and illness, with more than 900,000 Veterans enrolled in its climb to 1 million and beyond.

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