summary: The risk of developing Alzheimer’s disease and dementia-related symptoms is higher in people with traumatic brain injury and post-traumatic stress disorder who carry the APOE E4 gene.
Source: Veterans Affairs Research Communications
In a study of veterans led by Dr. Mark Logue, a 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 Alzheimer’s disease and related illness. dementia (ADRD).
The medical community has not investigated the simultaneous effect of post-traumatic stress disorder (PTSD), traumatic brain injury (TBI) and genetic risk factors in a large cohort until now. They initially found a higher incidence of ADRD in veterans with PTSD with TBI, than in those without, as well as higher rates of ADRD in veterans who had inherited the ε4 variant. Lugo and his 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 war veterans of European descent who had inherited the ε4 variant. In African-American veterans, the effect of PTSD did not differ as a function of ε4, but the effect of TBI and the interaction with ε4 was 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,” Lugo and colleagues write. “A history of post-traumatic stress disorder (PTSD) and TBI will be an important part of interpreting ADRD genetic test results and making an accurate assessment of ADRD risk.”
Benefit from the VA’s Million Veteran Program
The researchers conducted the study by accessing data from the VA Association’s Million Veteran Program (MVP), one of the largest databases of health and genetic information in the world. MVP aims to learn how genes, lifestyle, and military exposure affect health and disease, with more than 900,000 registered veterans climbing to 1 million and beyond.
With more than 40% of veterans over the age of 75, the number of former service members at risk for Alzheimer’s disease and other forms of dementia is growing. While large cohort studies have shown that post-traumatic stress disorder (PTSD) and TBI increase the risk of dementia in veterans, Lugo and colleagues further investigated by examining these risk factors along with the APOE ε4 variant. Most people do not inherit this variant, but those who do inherit it from either one parent (one copy) or both parents (two copies).
He said, “Research has shown that if you inherit one copy of ε4, you are at increased risk of developing Alzheimer’s disease, and if you inherit two copies, you are at a much higher risk.”
The number of ε4 variants a person inherits is set at birth, but their effect varies with age, according to Lugo, who is also a veteran and associate professor at Boston University.
“The risk of Alzheimer’s disease increases with age for all APOE genotypes,” he said. “But when compared to people with two copies of the common variant, the difference in risk for those with the ε4 copy appears to peak somewhere between ages 65 and 70 and then decline thereafter. Again, this does not mean that your chances of developing Alzheimer’s disease It decreases after that, only that the difference between the risk of Alzheimer’s disease and without Alzheimer’s disease diminishes.”
The study showed that the risk associated with PTSD and head injury was greater for carriers of ε4. Their model led the researchers to predict that for 80-year-old veterans of European ancestry who did not inherit the ε4 variant, the incidence of ADRD would be 6% higher than for those with Those with PTSD compared to those without. But for 80-year-old veterans of European descent who inherited two copies of ε4, the incidence of ADRD would be 11% higher for those with PTSD than for those without PTSD.
The apparent association between PTSD and TBI on dementia may come as a surprise
Lugo was surprised to see such clear evidence of a link between PTSD and head trauma in dementia risk.
“I’ve been working on the genetics of Alzheimer’s disease for over a decade now, and I used to see a clear effect of APOE-4 on Alzheimer’s risk,” he says. “However, in this group, the effects of PTSD and head injury were quite pronounced and seemed similar to the effect of inheriting ε4 from one of your parents.”
Next, Logue and his colleagues want to use the MVP data to search for other risk factors relevant to veterans, with the goal of learning how they interact with Alzheimer’s disease risk variables. They are also looking into genome-wide screenings to try to find new risk variants for Alzheimer’s disease and dementia. The most recent genome-wide association study of Alzheimer’s disease identified about 80 variants associated with Alzheimer’s risk, Lugo said, noting that these variants were rare or had a much smaller effect than ε4.
He added that the MVP data could be used to leverage the power for this type of study, but that a history of post-traumatic stress disorder (PTSD) and TBI would be an important part of interpreting ADRD genetic test results and making accurate assessments of ADRD risk.
“We know that genes play a big role in Alzheimer’s risk, but they don’t tell the whole story,” explained Logie.
“Currently, no genetic test can tell you whether you are certain you have Alzheimer’s disease. The tests can only give an estimate of your likelihood of developing Alzheimer’s disease that may be higher or lower than average. Our study shows that these estimates would be more accurate if they included On more than just age and genes.
“In veterans, a history of head injuries and post-traumatic stress disorder can make a huge difference in dementia risk, so using this information will allow for a more accurate measure of the chances of developing dementia.”
About this research in Neuroscience News
author: Mike Richman
Source: Veterans Affairs Research Communications
communication: Mike Richman – Veterans Affairs Research Communications
picture: The image is in the public domain
Original search: open access.
“Alzheimer’s disease and related dementia among combat veterans: an examination of genetic-environment interactions with post-traumatic stress disorder and traumatic brain injury” by Mark W. Lugo et al. Alzheimer’s disease and dementia
Alzheimer’s disease and related dementia among elderly war veterans: examining genetic-environment interactions with post-traumatic stress disorder and traumatic brain injury.
Post-traumatic stress disorder (PTSD) and traumatic brain injury (TBI) confer the risk of Alzheimer’s disease and related dementia (ADRD).
This study from the Million Veteran Program (MVP) evaluated the effect of apolipoprotein E (APOE) ε4, PTSD, and TBI on the prevalence of ADRD in veteran cohorts of European ancestry (EA; n = 11,112 ADRD cases, 170,361 control groups) and African ancestry (AA; n = 1443 ADRD cases, 16191 controls). Additional measure interactions were estimated using the relative excess risk due to interaction (RERI) statistic.
PTSD and TBI and APOE ε4 showed strong main effect associations with ADRD. RERI analysis revealed an additive of interest APOE ε4 interactions with PTSD and TBI in the EA group and TBI in the AA group. These additive interactions indicate that the prevalence of ADRD associated with PTSD and TBI increased with the number of genotypes. APOE ε4 alleles.
A history of PTSD and TBI will be an important part of interpreting ADRD genetic test results and making an accurate assessment of ADRD risk.
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