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Alzheimer's disease and related dementias among aging veterans: Examining gene‐by‐environment interactions with post‐traumatic stress disorder and traumatic brain injury
Open accessAbstract
Introduction: Post‐traumatic stress disorder (PTSD) and traumatic brain injury (TBI) confer risk for Alzheimer's disease and related dementias (ADRD). Methods: This study from the Million Veteran Program (MVP) evaluated the impact of apolipoprotein E ( APOE ) ε4, PTSD, and TBI on ADRD prevalence in veteran cohorts of European ancestry (EA; n = 11,112 ADRD cases, 170,361 controls) and African ancestry (AA; n = 1443 ADRD cases, 16,191 controls). Additive‐scale interactions were estimated using the relative excess risk due to interaction (RERI) statistic. Results: PTSD, TBI, and APOE ε4 showed strong main‐effect associations with ADRD. RERI analysis revealed significant additive APOE ε4 interactions with PTSD and TBI in the EA cohort and TBI in the AA cohort. These additive interactions indicate that ADRD prevalence associated with PTSD and TBI increased with the number of inherited APOE ε4 alleles. Discussion: PTSD and TBI history will be an important part of interpreting the results of ADRD genetic testing and doing accurate ADRD risk assessment.
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The specific ICD-code-based definitions used for MDD and AD/ADRD were validated or used in multiple previous studies.
“However, the specific ICD-codebased definitions we used were validated or used in multiple previous studies for MDD 9 and AD/ADRD. 12-14”
From Antidepressant exposure and long‐term dementia risk in a nationwide retrospective study on US veterans with midlife major depressive disorder (2024) · cites this paper as [13]
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Ramos‐Cejudo, J., Corrigan, J. K., Zheng, C., Swinnerton, K. N., Jacobson, S. R., La, J., Betensky, R. A., Osorio, R. S., Madanes, S., Pomara, N., et al. (2024) · Alzheimer's & Dementia · doi:10.1002/alz.13853 · Cited by 11
Metadata
- Authors
- Logue, M. W., Miller, M. W., Sherva, R., Zhang, R., Harrington, K. M., Fonda, J. R., Merritt, V. C., Panizzon, M. S., Hauger, R. L., Wolf, E. J., Neale, Z., Gaziano, J. M., & Program, T. M. V.
- Affiliations
- Boston University (US)
- VA Boston Healthcare System (US)
- University of California San Diego (US)
- Brigham and Women's Hospital (US)
- Corresponding author
- Logue, Mark W.
- ORCID
- Venue
- Alzheimer's & Dementia
- Publisher
- Wiley
- Published
- 2022-12-22
- Volume
- 19
- Issue
- 6
- Pages
- 2549-2559
- ISSN
- 1552-5260 (ISSN-L)
- 1552-5279
- PMC
- PMC10271966
- OpenAlex
- W4312093956
- Cited by
- 35
- References
- 16
- Citations by year
- 2026: 14 · 2025: 3 · 2024: 14 · 2023: 4
- FWCI
- 2.88
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Alzheimer s & Dementia (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- U.S. Department of Veterans Affairs (I01 BX004192, BX004192, 1ik2cx002192-01a2, 1 I01, IK2 CX002192, I01 CX001727)
- Office of Research and Development
- National Institute of Mental Health (T32MH019836)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Clinical Neurology › Traumatic Brain Injury Research
- Keywords
- Alzheimer's disease and related dementias, post-traumatic stress disorder
- MeSH terms
- Brain Injuries, Traumatic, Aging, Alzheimer Disease, Humans, Stress Disorders, Post-Traumatic, Veterans, Apolipoprotein E4, Gene-Environment Interaction
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