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.
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.
With more than 40% of the Veteran population above the age of 75, the number of former Service Members at risk for Alzheimer's and other forms of dementia is rising. While large cohort studies have shown that PTSD and TBI increase the risk of dementia in Veterans, Logue and his colleagues investigated further by studying these risk factors along with the APOE ε4 variant. Most people don’t inherit that variant, but those who do inherit it from one parent (one copy) or both of their parents (two copies).
The number of ε4 variants a person inherits is fixed at birth, but their impact differs with age, according to Logue, who is also an Army Veteran and an associate professor at Boston University.
The study showed that the risk associated with PTSD and head injury was larger for ε4 carriers. Their model led the researchers to expect that for 80-year-old Veterans of European ancestry who didn’t inherit the ε4 variant, the percentage of ADRD would be 6% greater for those with PTSD compared to those without. But for 80-year-old Veterans of European ancestry who inherited two copies of ε4, the percentage of ADRD would be 11% higher for those with PTSD than those without.
The findings appeared on December 22, 2022, in Alzheimer’s & Dementia: The Journal of the Alzheimer’s Association.
