Associations of history of traumatic brain injury with markers of brain health among older men in the Vietnam Era Twin Study of Aging

Background: Traumatic brain injury (TBI) is associated with increased risk of dementia, but it is unclear how earlier life TBI is related to brain health in older age. Methods: This cross-sectional study compared 517 male Vietnam Era Twin Study of Aging participants with and without a history of TBI...

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Main Authors: Alexander Ivan B. Posis, Jeremy A. Elman, John E. Alcaraz, Humberto Parada, Jr., Aladdin H. Shadyab, Christine Fennema-Notestine, Donald J. Hagler, Jr., Michael J. Lyons, Matthew S. Panizzon, Chandra A. Reynolds, Carol E. Franz, William S. Kremen, Linda K. McEvoy
Format: Article
Language:English
Published: Elsevier 2025-01-01
Series:NeuroImage: Clinical
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Online Access:http://www.sciencedirect.com/science/article/pii/S2213158225001019
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author Alexander Ivan B. Posis
Jeremy A. Elman
John E. Alcaraz
Humberto Parada, Jr.
Aladdin H. Shadyab
Christine Fennema-Notestine
Donald J. Hagler, Jr.
Michael J. Lyons
Matthew S. Panizzon
Chandra A. Reynolds
Carol E. Franz
William S. Kremen
Linda K. McEvoy
author_facet Alexander Ivan B. Posis
Jeremy A. Elman
John E. Alcaraz
Humberto Parada, Jr.
Aladdin H. Shadyab
Christine Fennema-Notestine
Donald J. Hagler, Jr.
Michael J. Lyons
Matthew S. Panizzon
Chandra A. Reynolds
Carol E. Franz
William S. Kremen
Linda K. McEvoy
author_sort Alexander Ivan B. Posis
collection DOAJ
description Background: Traumatic brain injury (TBI) is associated with increased risk of dementia, but it is unclear how earlier life TBI is related to brain health in older age. Methods: This cross-sectional study compared 517 male Vietnam Era Twin Study of Aging participants with and without a history of TBI (34 % with TBI; median age = 68 [range = 61–72] years). Validated brain age models were used to calculate predicted brain age difference (PBAD and Brain-PAD) scores. A multichannel segmentation approach was used to quantify abnormal white matter signal intensities (AWM). Restriction spectrum imaging (RSI) was used to model multishell diffusion in restricted (intracellular) and free water compartments. Multivariable linear mixed-effects models estimated associations of TBI with PBAD, Brain-PAD, AWM, and RSI outcomes. We assessed moderation in associations of TBI with PBAD, Brain-PAD, AWM, and RSI outcomes by apolipoprotein E epsilon 4 (APOE-ε4) status, depressive and posttraumatic stress symptom severity, and loneliness. Results: PBAD, Brain-PAD, AWM, and global white matter RSI measures did not differ by TBI status but those with history of TBI showed lower restricted diffusion in the inferior longitudinal fasciculus bilaterally and the left inferior occipital fasciculus compared to those without TBI, after adjusting for age and scanner (p-values < 0.05). Results did not differ by APOE-ε4 status, psychiatric symptoms, or loneliness for any primary outcome. Conclusions: There may be subtle white matter microstructural changes after a TBI event that persist even after over four decades after initial injury. Further research is needed to determine if these differences relate to increased TBI-associated risk of dementia.
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spelling doaj-art-8b7323a780cf4101ac7ddf4dc8b9bc882025-08-20T03:32:22ZengElsevierNeuroImage: Clinical2213-15822025-01-014710383110.1016/j.nicl.2025.103831Associations of history of traumatic brain injury with markers of brain health among older men in the Vietnam Era Twin Study of AgingAlexander Ivan B. Posis0Jeremy A. Elman1John E. Alcaraz2Humberto Parada, Jr.3Aladdin H. Shadyab4Christine Fennema-Notestine5Donald J. Hagler, Jr.6Michael J. Lyons7Matthew S. Panizzon8Chandra A. Reynolds9Carol E. Franz10William S. Kremen11Linda K. McEvoy12Herbert Wertheim School of Public Health and Human Longevity Science, University of California San Diego, La Jolla, CA, USA; School of Public Health, San Diego State University, San Diego, CA, USA; Corresponding author at: Department of Public Health Sciences, University of California, Davis, CA, USA.Department of Psychiatry, University of California San Diego, La Jolla, CA, USA; Center for Behavior Genetics of Aging, University of California San Diego, La Jolla, CA, USASchool of Public Health, San Diego State University, San Diego, CA, USASchool of Public Health, San Diego State University, San Diego, CA, USA; Moores Cancer Center, UC San Diego Health, La Jolla, CA, USA; Department of Radiation Medicine &amp; Applied Science, University of California, San Diego, La Jolla, CA, USAHerbert Wertheim School of Public Health and Human Longevity Science, University of California San Diego, La Jolla, CA, USADepartment of Psychiatry, University of California San Diego, La Jolla, CA, USA; Center for Behavior Genetics of Aging, University of California San Diego, La Jolla, CA, USA; Department of Radiology, University of California San Diego, La Jolla, CA, USAJ. Craig Venter Research Institute, La Jolla, CA, USADepartment of Psychological and Brain Sciences, Boston University, Boston, MA, USADepartment of Psychiatry, University of California San Diego, La Jolla, CA, USA; Center for Behavior Genetics of Aging, University of California San Diego, La Jolla, CA, USAInstitute for Behavioral Genetics, University of Colorado Boulder, Boulder, CO, USADepartment of Psychiatry, University of California San Diego, La Jolla, CA, USA; Center for Behavior Genetics of Aging, University of California San Diego, La Jolla, CA, USADepartment of Psychiatry, University of California San Diego, La Jolla, CA, USA; Center for Behavior Genetics of Aging, University of California San Diego, La Jolla, CA, USAHerbert Wertheim School of Public Health and Human Longevity Science, University of California San Diego, La Jolla, CA, USA; Kaiser Permanente Washington Health Research Institute, Seattle, WA, USABackground: Traumatic brain injury (TBI) is associated with increased risk of dementia, but it is unclear how earlier life TBI is related to brain health in older age. Methods: This cross-sectional study compared 517 male Vietnam Era Twin Study of Aging participants with and without a history of TBI (34 % with TBI; median age = 68 [range = 61–72] years). Validated brain age models were used to calculate predicted brain age difference (PBAD and Brain-PAD) scores. A multichannel segmentation approach was used to quantify abnormal white matter signal intensities (AWM). Restriction spectrum imaging (RSI) was used to model multishell diffusion in restricted (intracellular) and free water compartments. Multivariable linear mixed-effects models estimated associations of TBI with PBAD, Brain-PAD, AWM, and RSI outcomes. We assessed moderation in associations of TBI with PBAD, Brain-PAD, AWM, and RSI outcomes by apolipoprotein E epsilon 4 (APOE-ε4) status, depressive and posttraumatic stress symptom severity, and loneliness. Results: PBAD, Brain-PAD, AWM, and global white matter RSI measures did not differ by TBI status but those with history of TBI showed lower restricted diffusion in the inferior longitudinal fasciculus bilaterally and the left inferior occipital fasciculus compared to those without TBI, after adjusting for age and scanner (p-values < 0.05). Results did not differ by APOE-ε4 status, psychiatric symptoms, or loneliness for any primary outcome. Conclusions: There may be subtle white matter microstructural changes after a TBI event that persist even after over four decades after initial injury. Further research is needed to determine if these differences relate to increased TBI-associated risk of dementia.http://www.sciencedirect.com/science/article/pii/S2213158225001019Traumatic brain injuryRestriction spectrum imagingWhite matter
spellingShingle Alexander Ivan B. Posis
Jeremy A. Elman
John E. Alcaraz
Humberto Parada, Jr.
Aladdin H. Shadyab
Christine Fennema-Notestine
Donald J. Hagler, Jr.
Michael J. Lyons
Matthew S. Panizzon
Chandra A. Reynolds
Carol E. Franz
William S. Kremen
Linda K. McEvoy
Associations of history of traumatic brain injury with markers of brain health among older men in the Vietnam Era Twin Study of Aging
NeuroImage: Clinical
Traumatic brain injury
Restriction spectrum imaging
White matter
title Associations of history of traumatic brain injury with markers of brain health among older men in the Vietnam Era Twin Study of Aging
title_full Associations of history of traumatic brain injury with markers of brain health among older men in the Vietnam Era Twin Study of Aging
title_fullStr Associations of history of traumatic brain injury with markers of brain health among older men in the Vietnam Era Twin Study of Aging
title_full_unstemmed Associations of history of traumatic brain injury with markers of brain health among older men in the Vietnam Era Twin Study of Aging
title_short Associations of history of traumatic brain injury with markers of brain health among older men in the Vietnam Era Twin Study of Aging
title_sort associations of history of traumatic brain injury with markers of brain health among older men in the vietnam era twin study of aging
topic Traumatic brain injury
Restriction spectrum imaging
White matter
url http://www.sciencedirect.com/science/article/pii/S2213158225001019
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