Alzheimer's disease and related dementias among aging veterans: Examining gene-by-environment interactions with post-traumatic stress disorder and traumatic brain injury.
Level 4 - case-series / case-control
Cross-sectional case-control association study nested within a cohort.
PubMed 36546606 · doi:10.1002/alz.12870
What was done
Using data from the Million Veteran Program (MVP), researchers assessed whether apolipoprotein E (APOE) ε4 status interacts with post-traumatic stress disorder (PTSD) and traumatic brain injury (TBI) to influence Alzheimer's disease and related dementias (ADRD) prevalence. The study evaluated cohorts of European ancestry (EA; 11,112 ADRD cases, 170,361 controls) and African ancestry (AA; 1,443 ADRD cases, 16,191 controls). Additive-scale gene-environment interactions were evaluated using relative excess risk due to interaction (RERI) statistics.
What was found
PTSD, TBI, and APOE ε4 each showed strong main-effect associations with ADRD. Significant additive interactions were found between APOE ε4 and both PTSD and TBI in the EA cohort, and between APOE ε4 and TBI in the AA cohort. ADRD prevalence associated with PTSD and TBI rose with the number of inherited APOE ε4 alleles. Specific numerical effect sizes, RERI statistics, odds ratios, and confidence intervals were not reported in the abstract.
Why it matters
The findings indicate that physical and psychological trauma compound genetic susceptibility to ADRD. A history of PTSD and TBI is therefore essential context when interpreting ADRD genetic testing and conducting clinical risk assessments.
Limits
The abstract reports no numerical values, effect sizes, or confidence intervals. The sample comprises US military veterans, which may limit generalizability to non-veteran and female populations. The case-control prevalence design restricts causal and temporal inference.
Cited by
- supports Individuals with traumatic brain injury who carry the APOE4 allele have a 10 to 20 times increased risk of developing Alzheimer's disease depending on allele count.