Head trauma, PTSD may increase impact of genetic variant on Alzheimer’s risk

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

the medical community has never studied the simultaneous impact of post-traumatic stress disorder (PTSD), traumatic brain injury (CCT) and genetic risk factors in a large cohort so far. They first found a higher percentage of ADRD in veterans with PTSD and in those with TBI, compared to those without, as well as higher rates of ADRD in veterans who had inherited from ε4 variant. Logue and his team then searched for interactions between the ε4 variant, PTSD and TBI using a mathematical model.

The study found an increased risk due to PTSD and TBI in veterans of European ancestry who inherited the ε4 variant. In veterans of African descent, the impact of PTSD did not vary with ε4, but the TBI effect and the interaction with ε4 were even stronger. Other studies have suggested that ε4 may amplify the effects of head injury and/or combat-related stress.

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

Capitalize on VA’s Million Veteran Program

Researchers conducted the study by accessing data from the VA’s Million Veteran Program (MVP), one of the world’s largest databases on health and genetic information. MVP aims to learn how genes, lifestyle, and military exposures affect health and disease, with more than 900,000 veterans enrolled in its rise to 1 million and beyond.

With more than 40% of the veteran population over the age of 75, the number of former military personnel at risk of developing Alzheimer’s disease and other forms of dementia is increasing. While large cohort studies have shown that PTSD and TBI increase the risk of dementia in veterans, Logue and his colleagues have taken their research further by studying these risk factors with the APOE ε4 variant. Most people do not inherit this variant, but those who inherit it from one parent (one copy) or from both parents (two copies).

“Research has shown that if you inherit one copy of ε4 you are at increased risk of Alzheimer’s disease,” he said, “and if you inherit two copies you are at much greater risk. raised”.

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 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 risk difference for those with one copy of ε4 appears to peak somewhere between age 65 and 70 and then decline thereafter. Again, this does not mean that your chances of Alzheimer’s disease decreases after that, just that the difference between the risk for those with and without ε4 decreases.”

The study showed that the risk associated with PTSD and head injuries was greater for carriers of ε4. Their model led the researchers to expect that for 80-year-old veterans of European ancestry who did not inherit the ε4 variant, the percentage of SARD would be 6% higher for those with PTSD. only for those who don’t have one. But for 80-year-old veterans of European ancestry who inherited two copies of ε4, the percentage of SARD would be 11% higher for those with PTSD than for those without.

Clear link between PTSD and TBI on dementia may come as a surprise

Logue was very surprised to see such clear evidence of a link between PTSD and head trauma on dementia risk.

“I’ve been working in the area of ​​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 injuries were equally clear and resembled the effect of inheriting ε4 from one of your parents.”

Next, Logue and his colleagues would like to use the MVP data to research other relevant risk factors for veterans, with the goal of learning how they may interact with Alzheimer’s disease risk variants. They are also looking to perform genome-wide association analyzes to try to find new risk variants for Alzheimer’s and dementia. The most recent large-scale genome-wide association study in Alzheimer’s disease identified some 80 variants linked to Alzheimer’s disease risk, Logue said, noting that these variants were rare or had a much lower impact than ε4. .

MVP data can be used to increase the power of this type of study, he added, but history of PTSD and TBI will be an important part of interpreting ADRD genetic test results and performing accurate SARD risk assessments.

“We know that genes play a big role in Alzheimer’s risk, but they don’t tell the whole story,” Logue explained.

“Currently, no genetic test can tell you if you are certain of developing Alzheimer’s disease. Tests can only give an estimate of your likelihood of developing Alzheimer’s disease which may be higher or below 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 trauma and PTSD can also make a big difference in dementia risk , so using this information will allow a more accurate measurement of the risk of developing dementia.

The results are published in the journal Alzheimer’s and dementia.

Provided by Veterans Affairs Research Communications