The consequences of traumatic brain injury (TBI), post-traumatic stress disorder (PTSD), and genetic risk factors in a significant cohort have never been studied by the medical community. Dr. Mark Logue, a statistician at the National Center for PTSD at the VA Boston Healthcare System, conducted a study of Veterans and discovered that PTSD, TBI, and the e4 variant of the APOE gene showed strong connections with Alzheimer’s disease and related dementias (ADRD). First, the researchers discovered higher rates of ADRD in Veterans who had inherited the e4 variation as well as higher rates of ADRD in Veterans with PTSD and TBI in comparison to those without.
Then, using a mathematical model, Logue and his group investigated for relationships between the e4 variation, PTSD, and TBI. In Veterans of European ancestry who acquired the e4 mutation, the study discovered an increase in risk for PTSD and TBI. The effect of PTSD in veterans with African ancestry was unaffected by e4, while the effect and interaction of TBI with e4 was considerably more pronounced. e4 may amplify the consequences of a brain injury and/or combat-related stress, according to certain other research.
“These additive interactions indicate that ADRD prevalence associated with PTSD and TBI increased with the number of inherited APOE e4 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.”
One of the largest databases of health and genetic data in the world, the VA’s Million Veteran Program (MVP), provided the researchers all the information they needed to conduct their study. With more than 900,000 Veterans participating in its ascent to 1 million and beyond, MVP seeks to understand how genes, lifestyle, and military experiences impact health and sickness.
The number of former Service Members at risk for Alzheimer’s and other kinds of dementia is growing since more than 40% of Veterans are over the age of 75. Logue and his colleagues looked into this further by examining these risk variables combined with the APOE e4 mutation. Large cohort studies have demonstrated that PTSD and TBI increase the incidence of dementia in Veterans.
The majority of people don’t acquire the mutation, but those who do do so from either one or both of their parents (one copy) (two copies).
“Research has shown that if you inherit one copy of e4, you’re at increased risk of Alzheimer’s disease,” he said, “and if you inherit two copies, you are at much higher risk.”
The amount of e4 variations a person inherits is set at birth, but Logue, an associate professor at Boston University and an Army veteran, claims that the impact of these variants changes with age.
“The risk of Alzheimer’s disease increases with age for all of the APOE genotypes,” he said. “But when compared to people with two copies of the common variant, the difference in risk for those with a copy of e4 appears to peak somewhere between age 65 and 70 and then decrease after that. Again, that doesn’t mean that your chances of Alzheimer’s decrease after that, just that the difference between the risk for those with and without e4 diminishes.”
The study revealed that e4 carriers had a higher chance of developing PTSD and suffering a head injury. Using their model, the researchers predicted that the percentage of ADRD would be 6% higher for 80-year-old Veterans of European ancestry who didn’t receive the e4 variation.
However, the probability of ADRD for 80-year-old Veterans of European ancestry who inherited two copies of e4 would be 11% greater for those with PTSD than for those without. There is no doubt that PTSD and TBI increase the risk of dementia. Logue was astonished to see such convincing proof of a connection between PTSD and head trauma risk for dementia.
“I’ve worked in Alzheimer’s disease genetics for over a decade now, and I was used to seeing a clear impact of APOE e4 on Alzheimer’s risk,” he says. “However, in this cohort, the effects of PTSD and head injury were just as clear and looked similar to the effect of inheriting e4 from one of your parents.”
Logue and his coworkers will next utilise the MVP data to investigate additional risk variables that are pertinent to Veterans in order to understand how they could interact with Alzheimer’s risk variations. Additionally, they want to conduct genome-wide association studies to hunt for fresh dementia and Alzheimer’s risk mutations.
About 80 variations were found to be associated with the risk of Alzheimer’s in the most recent large-scale genome-wide association analysis, according to Logue, who noted that these variants were uncommon or had a far lesser influence than e4. MVP data can be utilised to increase the power of this sort of study, he continued, but accurate ADRD risk assessments depend heavily on the interpretation of the results of ADRD genetic testing and the history of PTSD and TBI.
“We know that genes play a large role in Alzheimer’s risk, but they don’t tell the whole story,” Logue explained. “Right now, no genetic test can tell you if you’re certain to develop Alzheimer’s disease. Tests can only give an estimate of your likelihood of developing Alzheimer’s that may be higher or lower than average. Our study shows that these estimates will be more accurate if they incorporate more than just age and genetics. In Veterans, a history of head injuries and PTSD can also make a large difference in dementia risk, so using that information will allow for more accurate measurement of the chances of developing dementia.”
