Head Trauma and PTSD May Increase Genetic Variant’s Impact on Alzheimer’s Risk

Summary: Those with TBI and PTSD who carry the APOE E4 gene are at higher risk of developing symptoms associated with Alzheimer’s disease and dementia.

Source: Veterans Affairs Research Communications

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

Until now, the medical community has never investigated the concurrent impact of post-traumatic stress disorder (PTSD), traumatic brain injury (TBI), and genetic risk factors in a large cohort. First, they found a greater percentage of ADRD in Veterans with PTSD and those without TBD, as well as higher rates of ADRD in Veterans who inherited the ε4 variant. Logue and her team then looked for interactions between the ε4 variant, PTSD, and TBI using a mathematical model.

The study found an increased risk for PTSD and TBI in Veterans of European descent who inherited the ε4 variant. In African Veterans, the effect of PTSD did not change as a function of ε4, but the effect of TBI and its 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.

“These additional interactions suggest that the prevalence of ADRD associated with PTSD and TBI increases with the number of heritable APOE ε4 alleles,” Logue and colleagues wrote. “PTSD and TBI history will be an important part of interpreting the results of ADRD genetic testing and performing accurate ADRD risk assessment.”

Benefiting from the VA’s Million Veteran Program

The researchers conducted the study by accessing data from the VA’s Million Veterans Program (MVP), one of the world’s largest databases of health and genetic information. With more than 900,000 registered Veterans climbing to 1 million and beyond, MVP aims to learn how genes, lifestyle and military risks affect health and disease.

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With more than 40% of the senior population over the age of 75, the number of former Service Members at risk for Alzheimer’s and other forms of dementia is increasing. While large cohort studies have shown that PTSD and TBH increase the risk of dementia in Veterans, Logue and colleagues conducted further research examining these risk factors in conjunction with the APOE ε4 variant. Most people do not inherit this variant, but those who inherit it from one parent (one copy) or both parents (two copies).

“Studies have shown that if you inherit one copy of ε4, you have an 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 associate professor at Boston University, the number of ε4 variants a person inherits is fixed at birth, but their effects vary with age.

“The risk of Alzheimer’s disease increases with age for all APOE genotypes,” he said. “However, the difference in risk between people with the ε4 copy, compared with people with two copies of the common variant, seems to peak between the ages of 65 and 70 and decline thereafter. Again, that doesn’t mean your chances of getting Alzheimer’s decrease after that, just those with and without ε4. This means that the difference in risk between

The study showed that the risk associated with PTSD and head injury was greater for ε4 carriers. Their model led the researchers to expect that for 80-year-old Veterans of European descent who did not inherit the ε4 variant, the percentage of ADRD would be 6% higher in those with PTSD than in those without. However, for 80-year-old Veterans of European descent who inherited two copies of ε4, the percentage of ADRD would be 11% higher for those with PTSD than for those without.

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Clear link between PTSD and TBI in dementia risks surprise

Logue was surprised to see such clear evidence of such a clear link between PTSD and head injury for dementia risk.

“I have been working in the genetics of Alzheimer’s disease for over a decade and am used to seeing the clear impact of APOE ε4 on Alzheimer’s risk,” he says. “However, the effects of PTSD and head injury in this cohort were just as clear and similar to the effect of getting an ε4 from one of your parents.”

It shows a brain
The study found an increased risk for PTSD and TBI in Veterans of European descent who inherited the ε4 variant. Image is in the public domain

Next, Logue and colleagues want to use the MVP data to explore other Veterans-related risk factors to learn how they might interact with Alzheimer’s risk variants. They also want to perform genome-wide association scans to try to find new Alzheimer’s and dementia risk variants. The latest large-scale genome-wide association study of Alzheimer’s has identified about 80 variants linked to Alzheimer’s risk, Logue said, noting that these variants are rare or have a much smaller effect than ε4.

He added that MVP data can be used to increase power for this type of study, but that PTSD and TBI history will be an important part of interpreting the results of ADRD genetic testing and conducting accurate ADRD risk assessments.

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

“Currently, no genetic test can tell you whether you will develop Alzheimer’s disease. The 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 would be more accurate if they included more than just age and genetics.

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see also

It shows a brain

“In veterans, a history of head injury and PTSD can also make a big difference in dementia risk, so using this information will provide a more accurate measure of the chances of developing dementia.”

About this neurology research news

Author: Mike Richman
Source: Veterans Affairs Research Communications
To contact: Mike Richman – Veterans Affairs Research Communications
Picture: the image is in the public domain

Original research: Open Access.
“Alzheimer’s disease and related dementias among aging veterans: Examination of gene-environment interactions with post-traumatic stress disorder and traumatic brain injury” by Mark W. Logue et al et al. Alzheimer’s and Dementia


Abstract

Alzheimer’s disease and related dementias among aging veterans: Examination of gene-environment interactions with post-traumatic stress disorder and traumatic brain injury.

Login

Post-traumatic stress disorder (PTSD) and traumatic brain injury (TBI) pose risks for Alzheimer’s disease and related dementias (ADRD).

Methods

This study from the Million Veteran Program (MVP) demonstrated that apolipoprotein E (APOE) ε4, PTSD and TBD (EA; n = 11,112 ADRD cases, 170.361 controls) and African descent (AA; n = 1443 ADRD cases, 16,191 controls). Additive-scale interactions were estimated using the relative extreme risk due to interaction (RERI) statistic.

Results

PTSD, TBI and APOE ε4 showed strong main effect relationships with ADRD. RERI analysis reveals key additive APOE Interactions of PTSD and TBI in the EA cohort and TBI with ε4 in the AA cohort. These additive interactions suggest that the prevalence of PTSD and TBI-associated ADRD increases with the number of inherited diseases. APOE ε4 allele.

Argument

A history of PTSD and TBI will be an important part of interpreting the results of ADRD genetic testing and making an accurate ADRD risk assessment.

Source

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