Washington: Researchers have identified a genetic variant that increases the risk of post-traumatic stress disorder (PTSD) and head injury associated with Alzheimer’s disease and related dementia (ADRD).
In a study of people at the Department of Veterans Affairs (VA), US, researchers first found a higher percentage of ADRD in veterans with PTSD and those with traumatic brain injury (TBI) than those without.
They also found higher rates of ADRD in veterans who inherited the e4 variant.
The findings appear in Alzheimer & Dementia: The Journal of the Alzheimer’s Association.
The researchers used mathematical modeling to look for associations between the e4 variant, PTSD, and TBI.
Until now, the medical community has not studied the concurrent impact of PTSD, TBI, and genetic risk factors in a large cohort.
The study, led by Dr. Mark Locke, a statistician at the National Center for PTSD at the Veterans Affairs (VA) Boston Healthcare System, found an increased risk of PTSD and TBI in veterans of European descent who carried the e4 variant.
Among veterans of African descent, the effect of PTSD did not change as a function of e4, but the association with TBI effect and e4 was still strong. Other studies have suggested that e4 may magnify the effects of head injury and/or combat-related stress, the study said.
“These additive interactions indicate that the prevalence of ADRD associated with PTSD and TBI increased with the number of inherited APOE e4 alleles,” Locke and his colleagues wrote.
“His history of PTSD and TBI can be an important part of interpreting the results of ATRT genetic testing and making an accurate ATRT risk assessment.”
Researchers conducted the study by accessing data from the VA’s Million Veteran Program (MVP), one of the world’s largest databases of health and genetic information. MVP aims to learn how genes, lifestyle and military exposures influence health and disease, with more than 900,000 veterans joining the 1 million and beyond.
According to the study, more than 40 percent of the senior population is over age 75, with a growing number of former service members at risk for Alzheimer’s and other dementias. While large cohort studies have shown that PTSD and TBI increase the risk of dementia in veterans, Locke and his colleagues further investigated these risk factors by studying the APOE e4 variant.
Most people do not inherit the variant, but get it from one parent (one copy) or from both of their parents (two copies), the study said.
“Research shows that if you inherit one copy of e4, you have a higher risk of developing Alzheimer’s disease, and if you inherit two copies, you’re at a higher risk,” he said.
A person’s number of e4 types is fixed at birth, but their impact varies with age, says Locke, an Army veteran and associate professor at Boston University.
“The risk of Alzheimer’s disease increases with age for all APOE genotypes,” he said. “But compared to people with two copies of the common variant, the difference in risk for people with a copy of e4 appears to peak somewhere between the ages of 65 and 70 and declines thereafter.
“Again, that doesn’t mean the chances of getting Alzheimer’s are reduced, just that the risk is reduced in people with e4 and those without,” Locke said.
For 80-year-old veterans of European descent who did not carry the e4 variant, the researchers expected the percentage of ADRD to be 6 percent higher compared to those without PTSD. But for 80-year-old veterans of European descent who had two copies of e4, the percentage of ADRD was 11 percent higher in those with PTSD than in those without.
“I’ve been working in Alzheimer’s disease genetics for over a decade now, and I’m used to seeing a clear impact of APOE e4 on Alzheimer’s risk,” he said. “However, in this cohort, the effects of PTSD and head injury were clear and similar to the effect of having e4 from one of your parents.”