The researchers discovered a larger percentage of ADRD in veterans with PTSD and TBI than in those without, as well as higher rates of ADRD in veterans who inherited the ε4 variation. Using a mathematical model, Logue and his colleagues then investigated for relationships between the ε4 variant, PTSD, and TBI.
European Ancestry Veterans Prone to Post-Traumatic Stress Disorder
The study discovered an increase in PTSD and TBI risk in veterans of European ancestry who acquired the ε4 variation. The impact of PTSD on veterans of African ancestry did not differ as a function of ε4, while the TBI effect and interaction with ε4 was considerably larger. According to other research, ε4 may amplify the consequences 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.”
Advantage of the Veterans Administration’s Million Veteran Program
The researchers conducted the study using data from the veterans Administration’s Million Veteran Program (MVP), one of the world’s largest databases of health and genetic information. MVP aims to discover how genes, lifestyle, and military exposures affect health and sickness, and it currently has over 900,000 veterans participating in its quest to reach 1 million and beyond.
Increase in the Incidence of Dementia in Veterans
With more than 40% of veterans over the age of 75, the number of former service members at risk for Alzheimer’s and other kinds of dementia is increasing. While extensive cohort studies have demonstrated that PTSD and TBI increase the incidence of dementia in veterans, Logue and his colleagues looked into this further by looking at these risk factors in conjunction with the APOE 4 variation. Most people do not inherit that mutation, but those who do so from one (or both) of their parents (two copies).
Research has shown that if you inherit one copy of ε4, you’re at increased risk of Alzheimer’s disease,” he said, “and if you inherit two copies, you are at much higher risk.”
According to Logue, who is also an army veteran and an associate professor at Boston University, the number of four variations a person receives is fixed at birth, but their influence varies 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 ε4 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 ε4 diminishes.”
Increased Risk of Brain Damage
The study found that the risk of PTSD and brain damage was higher for ε4 carriers. According to their estimate, among 80-year-old veterans of European ancestry who did not acquire the ε4 variation, the percentage of ADRD would be 6% higher for those with PTSD compared to those without. However, for 80-year-old veterans of European ancestry who inherited two copies of ε4, the percentage of ADRD with PTSD would be 11% higher than those without.
Association Between Post-Traumatic Stress Disorder and Traumatic Brain Injury and Dementia
Logue was taken aback by the clear evidence of a relationship between PTSD and head trauma and dementia risk.
“I’ve worked in Alzheimer’s disease genetics for over a decade now, and I was used to seeing a clear impact of APOE ε4 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 ε4 from one of your parents.”
Following that, Logue and his colleagues hope to use MVP data to investigate other risk variables important to veterans, to learn how they might interact with Alzheimer’s risk variations. They also intend to conduct genome-wide association scans to identify new Alzheimer’s and dementia risk mutations. According to Logue, the most recent large-scale genome-wide association study of Alzheimer’s discovered about 80 variations connected to the risk of Alzheimer’s, although those variants were rare or had a considerably lesser influence than ε4.
MVP data can be utilized to increase the power of this type of study, he says, but PTSD and TBI history will be critical in interpreting the results of ADRD genetic testing and performing correct ADRD risk assessments.
“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 which 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.”
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