Surface-based morphometry reveals divergent aging trajectories in veterans with and without traumatic brain injury

doi:10.1007/s11357-025-01893-2

Surface-based morphometry reveals divergent aging trajectories in veterans with and without traumatic brain injury

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Abstract

This study investigates how traumatic brain injury (TBI) alters cortical aging by comparing cortical thickness (CT) and surface area (SA) in 34 brain regions between TBI survivors and age-matched controls. Using a cross-sectional retrospective design, 105 Vietnam Veterans (32 with moderate-to-severe TBI, 73 controls) were analyzed via surface-based morphometry. Principal Component Analysis (PCA) reduced dimensionality, and Multivariate Analysis of Covariance tested group differences while controlling for age, education, depression, Post-Traumatic Stress Disorder, and intracranial volume. Findings revealed divergent morphometric signatures of aging: the proportion of SA variance explained by the first principal component (PC1) was lower in the TBI cohort compared to controls, particularly in parietal and limbic regions. Conversely, CT variance explained by PC1 was higher in TBI compared to controls, with fewer factor loadings in frontal and occipital regions, suggesting differential structural aging patterns due to TBI. Regression analysis demonstrated a stronger association of SA with age in TBI (R² = 0.619, p = 0.01), while CT exhibited significant negative age-related thinning in TBI-specific regions (R² = 0.450, p < 0.001). Together, these results suggest that TBI survivors exhibit structured, yet distinct, cortical remodeling, contrasting with the more diffuse patterns seen in normal aging. The differentiated organization of brain areas based on CT and SA points to brain morphology-based biomarkers capable of distinguishing pathological from normative aging trajectories. These biomarkers hold translational potential for refining diagnostic models of brain age and informing targeted neuromodulation or rehabilitation strategies to support cognitive and functional resilience in older adults with TBI.

Original language	English
Pages (from-to)	4327-4348
Number of pages	22
Journal	GeroScience
Volume	48
Issue number	3
DOIs	https://doi.org/10.1007/s11357-025-01893-2
State	Published - Jun 2026

Bibliographical note

Publisher Copyright:
© The Author(s) 2025.

Funding

Data collection and sharing for this project was funded by the Alzheimer's Disease Neuroimaging Initiative (ADNI) (National Institutes of Health Grant U01 AG024904) and DOD ADNI (Department of Defense award number W81XWH-12-2-0012). ADNI is funded by the National Institute on Aging, the National Institute of Biomedical Imaging and Bioengineering, and through generous contributions from the following: AbbVie, Alzheimer’s Association; Alzheimer’s Drug Discovery Foundation; Araclon Biotech; BioClinica, Inc.; Biogen; Bristol-Myers Squibb Company; CereSpir, Inc.; Cogstate; Eisai Inc.; Elan Pharmaceuticals, Inc.; Eli Lilly and Company; EuroImmun; F. Hoffmann-La Roche Ltd and its affiliated company Genentech, Inc.; Fujirebio; GE Healthcare; IXICO Ltd.; Janssen Alzheimer Immunotherapy Research & Development, LLC.; Johnson & Johnson Pharmaceutical Research & Development LLC.; Lumosity; Lundbeck; Merck & Co., Inc.; Meso Scale Diagnostics, LLC.; NeuroRx Research; Neurotrack Technologies; Novartis Pharmaceuticals Corporation; Pfizer Inc.; Piramal Imaging; Servier; Takeda Pharmaceutical Company; and Transition Therapeutics. The Canadian Institutes of Health Research is providing funds to support ADNI clinical sites in Canada. Private sector contributions are facilitated by the Foundation for the National Institutes of Health ( www.fnih.org ). The grantee organization is the Northern California Institute for Research and Education, and the study is coordinated by the Alzheimer’s Therapeutic Research Institute at the University of Southern California. ADNI data are disseminated by the Laboratory for Neuro Imaging at the University of Southern California.

Funders	Funder number
DoD Alzheimer's Disease Neuroimaging Initiative
National Institute of Biomedical Imaging and Bioengineering
U.S. Department of Health & Human Services \| NIH \| National Institute on Aging (U.S. National Institute on Aging)
National Institutes of Health (NIH)	U01 AG024904
U.S. Department of Defense	W81XWH-12-2-0012

Keywords

Aging
Cortical thickness
Neurodegeneration
Surface area
Traumatic brain injury

ASJC Scopus subject areas

Aging
Veterinary (miscellaneous)
Complementary and alternative medicine
Geriatrics and Gerontology
Cardiology and Cardiovascular Medicine

Access to Document

10.1007/s11357-025-01893-2

Cite this

@article{d7ee0f48ef174ba3a1632571477fb861,

title = "Surface-based morphometry reveals divergent aging trajectories in veterans with and without traumatic brain injury",

abstract = "This study investigates how traumatic brain injury (TBI) alters cortical aging by comparing cortical thickness (CT) and surface area (SA) in 34 brain regions between TBI survivors and age-matched controls. Using a cross-sectional retrospective design, 105 Vietnam Veterans (32 with moderate-to-severe TBI, 73 controls) were analyzed via surface-based morphometry. Principal Component Analysis (PCA) reduced dimensionality, and Multivariate Analysis of Covariance tested group differences while controlling for age, education, depression, Post-Traumatic Stress Disorder, and intracranial volume. Findings revealed divergent morphometric signatures of aging: the proportion of SA variance explained by the first principal component (PC1) was lower in the TBI cohort compared to controls, particularly in parietal and limbic regions. Conversely, CT variance explained by PC1 was higher in TBI compared to controls, with fewer factor loadings in frontal and occipital regions, suggesting differential structural aging patterns due to TBI. Regression analysis demonstrated a stronger association of SA with age in TBI (R2 = 0.619, p = 0.01), while CT exhibited significant negative age-related thinning in TBI-specific regions (R2 = 0.450, p < 0.001). Together, these results suggest that TBI survivors exhibit structured, yet distinct, cortical remodeling, contrasting with the more diffuse patterns seen in normal aging. The differentiated organization of brain areas based on CT and SA points to brain morphology-based biomarkers capable of distinguishing pathological from normative aging trajectories. These biomarkers hold translational potential for refining diagnostic models of brain age and informing targeted neuromodulation or rehabilitation strategies to support cognitive and functional resilience in older adults with TBI.",

keywords = "Aging, Cortical thickness, Neurodegeneration, Surface area, Traumatic brain injury",

author = "Eliason, \{Michelle C.\} and Nagella, \{Amrutha Bindu\} and Cristian Cuadra and Wack, \{David S.\} and Saleem, \{Ghazala T.\} and Raj, \{Balebail Ashok\} and Kristin Fargher and Amanda Smith and Lisa Raudin and Gloria Chaing and Norman Relkin and Smith, \{Karen Elizabeth\} and Hyungsub Shim and Ponto, \{Laura L.Boles\} and Schultz, \{Susan K.\} and Antero Sarrael and Raymundo Hernando and Nunzio Pomara and Dick Drost and Andrew Kertesz and John Rogers and Irina Rachinsky and Stephen Pasternak and Elizabether Finger and David Bachman and Kenneth Spicer and Jacobo Mintzer and Miller, \{Bruce L.\} and Rosen, \{Howard J.\} and Stephen Correia and Paul Malloy and Stephen Salloway and Geoffrey Tremont and Henry Querfurth and Ott, \{Brian R.\} and Franklin Watkins and Pradeep Garg and Williamson, \{Jeff D.\} and SinkS, \{Kaycee M.\} and Schwartz, \{Eben S.\} and Kitzmiller, \{Tamar J.\} and Santulli, \{Robert B.\} and Karen Anderson and Karen Blank and Pearlson, \{Godfrey D.\} and Brown, \{Alice D.\} and Dzintra Celmins and Richard King and Greg Jicha and Scott Neu",

note = "Publisher Copyright: {\textcopyright} The Author(s) 2025.",

year = "2026",

month = jun,

doi = "10.1007/s11357-025-01893-2",

language = "English",

volume = "48",

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AU - Eliason, Michelle C.

AU - Nagella, Amrutha Bindu

AU - Cuadra, Cristian

AU - Wack, David S.

AU - Saleem, Ghazala T.

AU - Raj, Balebail Ashok

AU - Fargher, Kristin

AU - Smith, Amanda

AU - Raudin, Lisa

AU - Chaing, Gloria

AU - Relkin, Norman

AU - Smith, Karen Elizabeth

AU - Shim, Hyungsub

AU - Ponto, Laura L.Boles

AU - Schultz, Susan K.

AU - Sarrael, Antero

AU - Hernando, Raymundo

AU - Pomara, Nunzio

AU - Drost, Dick

AU - Kertesz, Andrew

AU - Rogers, John

AU - Rachinsky, Irina

AU - Pasternak, Stephen

AU - Finger, Elizabether

AU - Bachman, David

AU - Spicer, Kenneth

AU - Mintzer, Jacobo

AU - Miller, Bruce L.

AU - Rosen, Howard J.

AU - Correia, Stephen

AU - Malloy, Paul

AU - Salloway, Stephen

AU - Tremont, Geoffrey

AU - Querfurth, Henry

AU - Ott, Brian R.

AU - Watkins, Franklin

AU - Garg, Pradeep

AU - Williamson, Jeff D.

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AU - Schwartz, Eben S.

AU - Kitzmiller, Tamar J.

AU - Santulli, Robert B.

AU - Anderson, Karen

AU - Blank, Karen

AU - Pearlson, Godfrey D.

AU - Brown, Alice D.

AU - Celmins, Dzintra

AU - King, Richard

AU - Jicha, Greg

AU - Neu, Scott

PY - 2026/6

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N2 - This study investigates how traumatic brain injury (TBI) alters cortical aging by comparing cortical thickness (CT) and surface area (SA) in 34 brain regions between TBI survivors and age-matched controls. Using a cross-sectional retrospective design, 105 Vietnam Veterans (32 with moderate-to-severe TBI, 73 controls) were analyzed via surface-based morphometry. Principal Component Analysis (PCA) reduced dimensionality, and Multivariate Analysis of Covariance tested group differences while controlling for age, education, depression, Post-Traumatic Stress Disorder, and intracranial volume. Findings revealed divergent morphometric signatures of aging: the proportion of SA variance explained by the first principal component (PC1) was lower in the TBI cohort compared to controls, particularly in parietal and limbic regions. Conversely, CT variance explained by PC1 was higher in TBI compared to controls, with fewer factor loadings in frontal and occipital regions, suggesting differential structural aging patterns due to TBI. Regression analysis demonstrated a stronger association of SA with age in TBI (R2 = 0.619, p = 0.01), while CT exhibited significant negative age-related thinning in TBI-specific regions (R2 = 0.450, p < 0.001). Together, these results suggest that TBI survivors exhibit structured, yet distinct, cortical remodeling, contrasting with the more diffuse patterns seen in normal aging. The differentiated organization of brain areas based on CT and SA points to brain morphology-based biomarkers capable of distinguishing pathological from normative aging trajectories. These biomarkers hold translational potential for refining diagnostic models of brain age and informing targeted neuromodulation or rehabilitation strategies to support cognitive and functional resilience in older adults with TBI.

AB - This study investigates how traumatic brain injury (TBI) alters cortical aging by comparing cortical thickness (CT) and surface area (SA) in 34 brain regions between TBI survivors and age-matched controls. Using a cross-sectional retrospective design, 105 Vietnam Veterans (32 with moderate-to-severe TBI, 73 controls) were analyzed via surface-based morphometry. Principal Component Analysis (PCA) reduced dimensionality, and Multivariate Analysis of Covariance tested group differences while controlling for age, education, depression, Post-Traumatic Stress Disorder, and intracranial volume. Findings revealed divergent morphometric signatures of aging: the proportion of SA variance explained by the first principal component (PC1) was lower in the TBI cohort compared to controls, particularly in parietal and limbic regions. Conversely, CT variance explained by PC1 was higher in TBI compared to controls, with fewer factor loadings in frontal and occipital regions, suggesting differential structural aging patterns due to TBI. Regression analysis demonstrated a stronger association of SA with age in TBI (R2 = 0.619, p = 0.01), while CT exhibited significant negative age-related thinning in TBI-specific regions (R2 = 0.450, p < 0.001). Together, these results suggest that TBI survivors exhibit structured, yet distinct, cortical remodeling, contrasting with the more diffuse patterns seen in normal aging. The differentiated organization of brain areas based on CT and SA points to brain morphology-based biomarkers capable of distinguishing pathological from normative aging trajectories. These biomarkers hold translational potential for refining diagnostic models of brain age and informing targeted neuromodulation or rehabilitation strategies to support cognitive and functional resilience in older adults with TBI.

KW - Aging

KW - Cortical thickness

KW - Neurodegeneration

KW - Surface area

KW - Traumatic brain injury

UR - https://www.scopus.com/pages/publications/105018470129

UR - https://www.scopus.com/pages/publications/105018470129#tab=citedBy

U2 - 10.1007/s11357-025-01893-2

DO - 10.1007/s11357-025-01893-2

M3 - Article

C2 - 41023330

AN - SCOPUS:105018470129

SN - 2509-2715

VL - 48

SP - 4327

EP - 4348

JO - GeroScience

JF - GeroScience

IS - 3

ER -

Surface-based morphometry reveals divergent aging trajectories in veterans with and without traumatic brain injury

Abstract

Bibliographical note

Funding

Keywords

ASJC Scopus subject areas

Access to Document

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