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

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 (R<sup>2</sup> = 0.619, p = 0.01), while CT exhibited significant negative age-related thinning in TBI-specific regions (R<sup>2</sup> = 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.

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Journal
GeroScience
Published
2025-09-29
DOI
https://doi.org/10.1007/s11357-025-01893-2
Primary Topic
Traumatic Brain Injury Research
Type
article
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article

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

Reisa Anne Sperling, Stephen Salloway, Effie Mitsis, Pierre N. Tariot et al.
GeroScience
Traumatic Brain Injury Research
article

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

Reisa Anne Sperling, Stephen Salloway, Effie Mitsis, Pierre N. Tariot, Lawrence S. Honig, Amanda Smith, Clifford R. Jack, Brandy R. Matthews, Magdalena Korecka, Robert B. Santulli, John Olichney, Kristine Lipowski, Gregory A. Jicha, Maria T. Greig, Donna Munic, Dana M. Pogorelec, Dana Nguyen, Cristian Cuadra, Robert Bartha, Godfrey D. Pearlson, Jason Karlawish, Richard E. Carson, Ann Marie Hake, Maria Carroll, Karen L. Bell, John Brockington, Enchi Liu, Arthur W. Toga, Stephen Pasternak, Teresa Villena, Kaycee M. SinkS, Lisa Raudin, Susan K. Schultz, Catherine Mc Adams Ortiz, Lisa Taylor Reinwald, Balebail Ashok Raj, S. J. Wolk, Gus Jiminez, Karen Crawford, Carl Sadowsky, Michelle Rainka, Raj C. Shah, Judith L. Heidebrink, Neil W. Kowall, Peggy Roberts, Marilyn Albert, Henry Rusinek, Allan I. Levey, Jerome A. Yesavage, John Q. Trojanowki, Kristin Fargher, Antero Sarrael, Lidia Glodzik, Andrew J. Saykin, Dzintra Celmins, Kenneth Spicer, Randall Griffith, Chester A. Mathis, Heather S. Anderson, Heather Johnson, Angela OliverNG, Peter Hardy, Sonia Pawluczyk, Helen Vanderswag, Michael Donohue, Tom Montine, Yaakov Stern, Erin Householder, Joanne Lord, MaryAnn Oakley, Ronald Killiany, Sherye A. Sirrel, Susan De Santi, Anton P. Porsteinsson, Raina Carter, Liana G. Apostolova, Irina Rachinsky, Norman Relkin, Paul S. S Aisen, Henry Querfurth, Dick Trost, Barton Lane, Alexander Norbash, Nunzio Pomara, Andrew E. Budson, Mauricio Beccera, Meghan Frey, Adrian Preda, Danielle Harvey, Kathleen Tingus, Kim Martin, Daniel Silverman, Ronald G. Thomas, Jeffrey Kaye, Sandra E. Black, Liberty Teodoro, Sandra A. Jacobson, Cynthia Hunt, Bojana Stefanovic, Bonnie S. Goldstein, Prashanthi Vemuri, Norbert Schuff, Charles Bernick, Michal Figurski, Ronald Carl Petersen, Sarah Walter, Kris Johnson, Howard Bergman, Bruce L. Miller, Chiadi U. Onyike, Eric M. Reiman, Karen E. L. Smith, Joseph Quinn, Maria Kataki, Ellen Woo, Russell Howard Swerdlow, Christina A. Michel, Myron Weiner, Matthew L. Senjem, Steven G. Potkin, Saba Wolday, Kathleen Johnson, Kristen Martin Cook, Jeff D. Williamson, Sara S. Mason, Brian R. Ott, Bret Borowski, Geoffrey Tremont, Colleen S. Albers, Owen Carmichael, Karen Blank, Kelly M. Makino, Zaven Kachaturian, Gloria Chaing, Adam Fleisher, Neill R. Graff Radford, Kyle Womack, Javier Villanueva Meyer, Hillel Grossman, Partha Sinha, Lon S. Schneider, David S. Knopman, Laurel Beckett, Brigid Reynolds, Christine M. Belden, Ging‐Yuek Robin Hsiung, David S. Wack, Alan J. Lerner, M. Saleem Ismail, John C. Morris, David Geldmacher, Stephen Correia, T. Y. Lee, Martha G. MacAvoy, Chuang Wu, Virginia M.‐Y. Lee, Jeffrey Murray Burns, Chris Hosein, Michael Borrie, Rachelle S. Doody, Sue Leon, Sara Dolen, Michael D. Devous, Paula Ogrocki, Martin R. Farlow, Ramon Diaz Arrastia, Nick J. Fox, Joy L. Taylor, Howard J. Rosen, Elizabeth C. Finger, Stacy Schneider, Thomas O. Obisesan, Raymundo Hernando, Benita Mudge, George Bartzokis, Beau M. Ances, Ghazala T. Saleem, Mark A. Mintun, Kejal Kantarci, Scott Herring, Terence Z. Wong, Brittany Cerbone, James J. Lah, Jeffrey R. Petrella, Connie Brand, Christopher H. van Dyck, Betty Lind, Tracy Kendall, Paul Malloy, Erik D. Roberson, Robert A. Koeppe, James E. Galvin, Elizabeth Oates, Sterling C. Johnson, Francine ParfittH, Matt A. Bernstein, Diana Kerwin, Peter J. Snyder, Kwangsik Nho, Raymond Scott Turner, Howard Chertkow, Marwan N. Sabbagh, Steven Edward Arnold, David Bachman, Keith A. Johnson, Douglas W. Scharre, Evan Fletcher, Tamar J. Kitzmiller, Kewei Chen, Paul M. Thompson, Oscar L. López, Sungeun Kim, David G. Clark, Leslie M. Shaw, Walter Martínez, Karen Anderson, Robert C. Green, Daniel Varon, David Jones, Laura L. Boles Ponto, Stephanie Kielb, Mony J. de Leon, Bryan M. Spann, Andrew Kertesz, Michael Weiner, Pradeep Garg, Norm Foster, Sanjay Asthana, Vernice Bates, Jared Tinklenberg, Nigel J. Cairns, Charles D. Smith, Janet S. Cellar, Tamie Sather, Michelle C. Eliason, Li Shen, Eben S. Schwartz, Steven Potkin, Curtis Caldwell, Patricia Lynn Johnson, Tatiana M. Foroud, William Jagust, James Brewer, Devon Gessert, Ranjan Duara, Scott Neu, Joanne Allard, Susan Molchan, Smita Kittur, Alice D. Brown, Allyson Rosen, Richard King, Dick Drost, Anahita Adeli, John Rogers, R.T. Frank, Mary Quiceno, Po H. Lu, Stephanie Reeder, Cynthia M. Carlsson, Leon Hudson, Hyungsub Shim, Nancy Johnson, Dana Mathews, P. Murali Doraiswamy, Munir Chowdhury, Howard J. Feldman, Horacio Capote, Gary Conrad, Susan Rountree, Marek Marsel Mesulam, Chad Ward, Earl A. Zimmerman, Donna M. Simpson, Jeff Gunter, Ruth A. Mulnard, Leyla deToledo‐Morrell, Jacobo Mintzer, Franklin Watkins, Gaby Thai, Mimi Dang, Michele Assaly Past, Kelley Faber, Susan M. Landau, Gad Marshall, II Agostino, Amrutha Bindu Nagella
article en

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 (R<sup>2</sup> = 0.619, p = 0.01), while CT exhibited significant negative age-related thinning in TBI-specific regions (R<sup>2</sup> = 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.

GeroScience
Universidad Andrés Bello (CL), VA Western New York Healthcare System (US), University at Buffalo, State University of New York (US)
Openalex Percentile: Top 64%
Traumatic Brain Injury Research
DOIOpen Access PDFOpenAlex
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