Accelerated Aging after Traumatic Brain Injury: An ENIGMA Multi-Cohort Mega-Analysis

Emily L Dennis^{1

2}, Samantha Vervoordt³, Maheen M Adamson^{4

5}, Amiri Houshang^{6

7}, Erin D Bigler^{1

8}, Karen Caeyenberghs⁹, James H Cole^{10

11}, Kristen Dams-O'Connor^{12

13}, Evelyn M Deutscher⁹, Ekaterina Dobryakova^{14

15}, Helen M Genova^{15

16}, Jordan H Grafman¹⁷, Asta K Håberg^{18

19}, Torgeir Hellstrøm²⁰, Andrei Irimia^{21

22

23}, Vassilis E Koliatsos^{24

25}, Hannah M Lindsey¹, Abigail Livny^{26

27

28}, David K Menon²⁹, Tricia L Merkley^{1

8}, Abdalla Z Mohamed³⁰, Stefania Mondello³¹, Martin M Monti^{32

33}, Virginia Fj Newcombe²⁹, Mary R Newsome^{1

2}, Jennie Ponsford^{34

35}, Amanda Rabinowitz^{36

37}, Hanne Smevik^{38

39}, Gershon Spitz^{34

35

40}, Umesh M Venkatesan^{36

37}, Lars T Westlye^{41

42}, Ross Zafonte^{43

44}, Paul M Thompson^{45

46}, Elisabeth A Wilde^{1

2}, Alexander Olsen^#^{38

39

47}, Frank G Hillary^#³

Affiliations

¹ Department of Neurology, University of Utah, Salt Lake City, UT, USA.
² George E. Whalen Veterans Affairs Medical Center, Salt Lake City, UT, USA.
³ Department of Psychology, Penn State University, State College, PA, USA.
⁴ Women's Operational Military Exposure Network (WOMEN) & Rehabilitation, VA Palo Alto Healthcare System, Palo Alto, CA, USA.
⁵ Neurosurgery, Stanford University School of Medicine, Stanford, CA, USA.
⁶ Neuroscience Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman, Iran.
⁷ Department of Radiology & Nuclear Medicine, Amsterdam UMC, Amsterdam, The Netherlands.
⁸ Department of Psychology and Neuroscience Center, Brigham Young University, Provo, UT, USA.
⁹ Cognitive Neuroscience Unit, School of Psychology, Deakin University, Geelong, Australia.
¹⁰ Centre for Medical Image Computing, Computer Science, University College London, London, UK.
¹¹ Dementia Research Centre, Queen Square Institute of Neurology, University College London, London, UK.
¹² Department of Rehabilitation and Human Performance, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
¹³ Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
¹⁴ Center for Traumatic Brain Injury, Kessler Foundation, East Hanover, NJ, USA.
¹⁵ Rutgers New Jersey Medical School, Newark, NJ, USA.
¹⁶ Center for Neuropsychology and Neuroscience Research, Kessler Foundation, East Hanover, NJ, USA.
¹⁷ Shirley Ryan Ability Lab, Chicago, IL, USA.
¹⁸ Department of Neuromedicine and Movement Science, Faculty of Medicine and Health Sciences, NTNU, Trondheim, Norway.
¹⁹ Department of Radiology and Nuclear Medicine, St. Olavs Hospital, Trondheim University Hospital, Trondheim, Norway.
²⁰ Department of Physical Medicine and Rehabilitation, Oslo University Hospital, Oslo, Norway.
²¹ Ethel Percy Andrus Gerontology Center, Leonard Davis School of Gerontology, University of Southern California, Los Angeles, CA, USA.
²² Alfred E. Mann Department of Biomedical Engineering, Viterbi School of Engineering, University of Southern California, Los Angeles, CA, USA.
²³ Department of Quantitative and Computational Biology, Dornsife College of Arts and Sciences, University of Southern California, Los Angeles, CA, USA.
²⁴ Departments of Pathology (Neuropathology), Neurology, and Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
²⁵ Neuropsychiatry Program, Sheppard and Enoch Pratt Hospital, Baltimore, MD, USA.
²⁶ Division of Diagnostic Imaging, Sheba Medical Center, Tel-Aviv, Israel.
²⁷ Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel.
²⁸ Sagol Neuroscience School, Tel-Aviv University, Tel-Aviv, Israel.
²⁹ Department of Medicine, University of Cambridge, Cambridge, UK.
³⁰ Thompson Institute, University of the Sunshine Coast, Birtinya, Australia.
³¹ Department of Biomedical and Dental Sciences and Morphofunctional Imaging, University of Messina, Messina, Italy.
³² Department of Psychology, UCLA, Los Angeles, CA, USA.
³³ Brain Injury Research Center (BIRC), Department of Neurosurgery, UCLA, Los Angeles, CA, USA.
³⁴ Monash-Epworth Rehabilitation Research Centre, School of Psychological Sciences, Monash University, Melbourne, Australia.
³⁵ School of Psychological Sciences, Monash University, Melbourne, Australia.
³⁶ Moss Rehabilitation Research Institute, Elkins Park, PA, USA.
³⁷ Department of Rehabilitation Medicine, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, PA, USA.
³⁸ Department of Psychology, NTNU, Trondheim, Norway.
³⁹ NorHEAD - Norwegian Centre for Headache Research, NTNU, Trondheim, Norway.
⁴⁰ Department of Neuroscience, Central Clinical School, Monash University, Melbourne, Australia.
⁴¹ Department of Psychology, University of Oslo, Oslo, Norway.
⁴² NORMENT, Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway.
⁴³ Department of Physical Medicine and Rehabilitation, Massachusetts General Hospital/Brigham & Women's Hospital, Boston, MA, USA.
⁴⁴ Spaulding Rehabilitation Hospital, Boston, MA, USA.
⁴⁵ Imaging Genetics Center, Stevens Neuroimaging & Informatics Institute, Keck School of Medicine of USC, Marina del Rey, CA, USA.
⁴⁶ Departments of Neurology, Pediatrics, Psychiatry, Radiology, Engineering, and Ophthalmology, USC, Los Angeles, CA, USA.
⁴⁷ Clinic of Rehabilitation, St. Olavs Hospital, Trondheim University Hospital, Trondheim, Norway.

^# Contributed equally.

PMID: 38845484
DOI: 10.1002/ana.26952

Meta-Analysis

Accelerated Aging after Traumatic Brain Injury: An ENIGMA Multi-Cohort Mega-Analysis

Emily L Dennis et al. Ann Neurol. 2024 Aug.

. 2024 Aug;96(2):365-377.

doi: 10.1002/ana.26952. Epub 2024 Jun 7.

Authors

Affiliations

¹ Department of Neurology, University of Utah, Salt Lake City, UT, USA.
² George E. Whalen Veterans Affairs Medical Center, Salt Lake City, UT, USA.
³ Department of Psychology, Penn State University, State College, PA, USA.
⁴ Women's Operational Military Exposure Network (WOMEN) & Rehabilitation, VA Palo Alto Healthcare System, Palo Alto, CA, USA.
⁵ Neurosurgery, Stanford University School of Medicine, Stanford, CA, USA.
⁶ Neuroscience Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman, Iran.
⁷ Department of Radiology & Nuclear Medicine, Amsterdam UMC, Amsterdam, The Netherlands.
⁸ Department of Psychology and Neuroscience Center, Brigham Young University, Provo, UT, USA.
⁹ Cognitive Neuroscience Unit, School of Psychology, Deakin University, Geelong, Australia.
¹⁰ Centre for Medical Image Computing, Computer Science, University College London, London, UK.
¹¹ Dementia Research Centre, Queen Square Institute of Neurology, University College London, London, UK.
¹² Department of Rehabilitation and Human Performance, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
¹³ Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
¹⁴ Center for Traumatic Brain Injury, Kessler Foundation, East Hanover, NJ, USA.
¹⁵ Rutgers New Jersey Medical School, Newark, NJ, USA.
¹⁶ Center for Neuropsychology and Neuroscience Research, Kessler Foundation, East Hanover, NJ, USA.
¹⁷ Shirley Ryan Ability Lab, Chicago, IL, USA.
¹⁸ Department of Neuromedicine and Movement Science, Faculty of Medicine and Health Sciences, NTNU, Trondheim, Norway.
¹⁹ Department of Radiology and Nuclear Medicine, St. Olavs Hospital, Trondheim University Hospital, Trondheim, Norway.
²⁰ Department of Physical Medicine and Rehabilitation, Oslo University Hospital, Oslo, Norway.
²¹ Ethel Percy Andrus Gerontology Center, Leonard Davis School of Gerontology, University of Southern California, Los Angeles, CA, USA.
²² Alfred E. Mann Department of Biomedical Engineering, Viterbi School of Engineering, University of Southern California, Los Angeles, CA, USA.
²³ Department of Quantitative and Computational Biology, Dornsife College of Arts and Sciences, University of Southern California, Los Angeles, CA, USA.
²⁴ Departments of Pathology (Neuropathology), Neurology, and Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
²⁵ Neuropsychiatry Program, Sheppard and Enoch Pratt Hospital, Baltimore, MD, USA.
²⁶ Division of Diagnostic Imaging, Sheba Medical Center, Tel-Aviv, Israel.
²⁷ Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel.
²⁸ Sagol Neuroscience School, Tel-Aviv University, Tel-Aviv, Israel.
²⁹ Department of Medicine, University of Cambridge, Cambridge, UK.
³⁰ Thompson Institute, University of the Sunshine Coast, Birtinya, Australia.
³¹ Department of Biomedical and Dental Sciences and Morphofunctional Imaging, University of Messina, Messina, Italy.
³² Department of Psychology, UCLA, Los Angeles, CA, USA.
³³ Brain Injury Research Center (BIRC), Department of Neurosurgery, UCLA, Los Angeles, CA, USA.
³⁴ Monash-Epworth Rehabilitation Research Centre, School of Psychological Sciences, Monash University, Melbourne, Australia.
³⁵ School of Psychological Sciences, Monash University, Melbourne, Australia.
³⁶ Moss Rehabilitation Research Institute, Elkins Park, PA, USA.
³⁷ Department of Rehabilitation Medicine, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, PA, USA.
³⁸ Department of Psychology, NTNU, Trondheim, Norway.
³⁹ NorHEAD - Norwegian Centre for Headache Research, NTNU, Trondheim, Norway.
⁴⁰ Department of Neuroscience, Central Clinical School, Monash University, Melbourne, Australia.
⁴¹ Department of Psychology, University of Oslo, Oslo, Norway.
⁴² NORMENT, Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway.
⁴³ Department of Physical Medicine and Rehabilitation, Massachusetts General Hospital/Brigham & Women's Hospital, Boston, MA, USA.
⁴⁴ Spaulding Rehabilitation Hospital, Boston, MA, USA.
⁴⁵ Imaging Genetics Center, Stevens Neuroimaging & Informatics Institute, Keck School of Medicine of USC, Marina del Rey, CA, USA.
⁴⁶ Departments of Neurology, Pediatrics, Psychiatry, Radiology, Engineering, and Ophthalmology, USC, Los Angeles, CA, USA.
⁴⁷ Clinic of Rehabilitation, St. Olavs Hospital, Trondheim University Hospital, Trondheim, Norway.

^# Contributed equally.

PMID: 38845484
DOI: 10.1002/ana.26952

Abstract

Objective: The long-term consequences of traumatic brain injury (TBI) on brain structure remain uncertain. Given evidence that a single significant brain injury event increases the risk of dementia, brain-age estimation could provide a novel and efficient indexing of the long-term consequences of TBI. Brain-age procedures use predictive modeling to calculate brain-age scores for an individual using structural magnetic resonance imaging (MRI) data. Complicated mild, moderate, and severe TBI (cmsTBI) is associated with a higher predicted age difference (PAD), but the progression of PAD over time remains unclear. We sought to examine whether PAD increases as a function of time since injury (TSI) and if injury severity and sex interacted to influence this progression.

Methods: Through the ENIGMA Adult Moderate and Severe (AMS)-TBI working group, we examine the largest TBI sample to date (n = 343), along with controls, for a total sample size of n = 540, to replicate and extend prior findings in the study of TBI brain age. Cross-sectional T1w-MRI data were aggregated across 7 cohorts, and brain age was established using a similar brain age algorithm to prior work in TBI.

Results: Findings show that PAD widens with longer TSI, and there was evidence for differences between sexes in PAD, with men showing more advanced brain age. We did not find strong evidence supporting a link between PAD and cognitive performance.

Interpretation: This work provides evidence that changes in brain structure after cmsTBI are dynamic, with an initial period of change, followed by relative stability in brain morphometry, eventually leading to further changes in the decades after a single cmsTBI. ANN NEUROL 2024;96:365-377.

PubMed Disclaimer

References

1. Graham NS, Sharp DJ. Understanding neurodegeneration after traumatic brain injury: from mechanisms to clinical trials in dementia. J Neurol Neurosurg Psychiatry 2019;90:1221–1233.
1. Amgalan A, Maher AS, Ghosh S, et al. Brain age estimation reveals older adults' accelerated senescence after traumatic brain injury. Geroscience 2022;44:2509–2525.
1. Povlishock JT, Katz DI. Update of neuropathology and neurological recovery after traumatic brain injury. J Head Trauma Rehabil 2005;20:76–94.
1. Graham NSN, Jolly A, Zimmerman K, et al. Diffuse axonal injury predicts neurodegeneration after moderate‐severe traumatic brain injury. Brain 2020;143:3685–3698.
1. Graham NSN, Cole JH, Bourke NJ, et al. Distinct patterns of neurodegeneration after TBI and in Alzheimer's disease. Alzheimers Dement 2023;19:3065–3077.

Publication types

Actions

MeSH terms

Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions

Grants and funding

LinkOut - more resources

Full Text Sources
- Ovid Technologies, Inc.
- Wiley
Medical
- MedlinePlus Health Information
Miscellaneous
- NCI CPTAC Assay Portal

Save citation to file

Email citation

Add to Collections

Add to My Bibliography

Your saved search

Create a file for external citation management software

Your RSS Feed

Accelerated Aging after Traumatic Brain Injury: An ENIGMA Multi-Cohort Mega-Analysis

Affiliations

Accelerated Aging after Traumatic Brain Injury: An ENIGMA Multi-Cohort Mega-Analysis

Authors

Affiliations

Abstract

References

Publication types

MeSH terms

Grants and funding

LinkOut - more resources

Full Text Sources

Medical

Miscellaneous