Age‐dependent white matter disruptions after military traumatic brain injury: Multivariate analysis results from ENIGMA brain injury

Abstract

Mild Traumatic brain injury (mTBI) is a signature wound in military personnel, and repetitive mTBI has been linked to age‐related neurogenerative disorders that affect white matter (WM) in the brain. However, findings of injury to specific WM tracts have been variable and inconsistent. This may be due to the heterogeneity of mechanisms, etiology, and comorbid disorders related to mTBI. Non‐negative matrix factorization (NMF) is a data‐driven approach that detects covarying patterns (components) within high‐dimensional data. We applied NMF to diffusion imaging data from military Veterans with and without a self‐reported TBI history. NMF identified 12 independent components derived from fractional anisotropy (FA) in a large dataset (n = 1,475) gathered through the ENIGMA (Enhancing Neuroimaging Genetics through Meta‐Analysis) Military Brain Injury working group. Regressions were used to examine TBI‐ and mTBI‐related associations in NMF‐derived components while adjusting for age, sex, post‐traumatic stress disorder, depression, and data acquisition site/scanner. We found significantly stronger age‐dependent effects of lower FA in Veterans with TBI than Veterans without in four components (q < 0.05), which are spatially unconstrained by traditionally defined WM tracts. One component, occupying the most peripheral location, exhibited significantly stronger age‐dependent differences in Veterans with mTBI. We found NMF to be powerful and effective in detecting covarying patterns of FA associated with mTBI by applying standard parametric regression modeling. Our results highlight patterns of WM alteration that are differentially affected by TBI and mTBI in younger compared to older military Veterans.

Document Details

Document Type
Pub Defense Publication
Publication Date
Mar 15, 2022
Source ID
10.1002/hbm.25811

Entities

People

  • Andrei Irimia
  • Annelise Silva
  • Aristeidis Sotiras
  • Carmen Velez
  • Carol E Franz
  • David F Tate
  • Delin Sun
  • Elbert Geuze
  • Elisabeth A Wilde
  • Emily L Dennis
  • Gerald Grant
  • Heather C. Bouchard
  • Inga K. Koerte
  • Jeremy A. Elman
  • Lori Shutter
  • M. Wright Williams
  • Maheen M. Adamson
  • Mark S. George
  • Martha E. Shenton
  • Mary R. Newsome
  • Michael J. Coleman
  • Murray B. Stein
  • Nicholas D Davenport
  • Paul M. Thompson
  • Rajendra A Morey
  • Raul Coimbra
  • Ross Zafonte
  • Scott R Sponheim
  • Seth G Disner
  • Thomas W. McAllister
  • William S. Kremen

Organizations

  • Baylor College of Medicine
  • Cancer Genomics Centre
  • Durham VA Medical Center
  • Geisel School of Medicine
  • Harvard Medical School
  • Medical University of South Carolina
  • National Institute of Neurological Disorders and Stroke
  • National Institutes of Health
  • Stanford University
  • United States Army Medical Research and Development Command
  • United States Department of Defense
  • United States Department of Veterans Affairs
  • University of California, San Diego
  • University of Minnesota
  • University of Nebraska–Lincoln
  • University of Pittsburgh
  • University of Southern California
  • University of Utah
  • Veterans Health Administration
  • Washington University in St. Louis

Tags

Readers

  • Mental Health of Military Veterans with Posttraumatic Stress Disorder (PTSD): Risk Factors, Prevalence, Symptoms, and Treatment.
  • Neurotrauma and Rehabilitation Medicine.

Technology Areas

  • Biotechnology