Abstract
Objectives: Traumatic brain injury (TBI) is associated with sleep deficits, but it is not clear why some report sleep disturbances and others do not. The objective of this study was to assess the associations between axonal injury, sleep, and memory in chronic and acute TBI. Methods: Data were acquired from two independent datasets which included 156 older adult veterans (69.8 years) from the Alzheimer's Disease Neuroimaging Initiative (ADNI) with prior moderate-to-severe TBIs and 90 (69.2 years) controls and 374 (39.6 years) from Transforming Research and Clinical Knowledge in TBI (TRACK-TBI) with a recent mild TBI (mTBI) and 87 controls (39.6 years), all who completed an MRI, memory assessment, and sleep questionnaire. Results: Older adults with a prior TBI had a significant association between axonal injury and sleep disturbances [β = 9.52, 95% CI (4.1, 14.9), p = 0.01]. Axonal injury predicted changes in memory over 1-year in TBI [β = −8.72, 95% CI (−18, −2.7), p = 0.03]. We externally validated those findings in TRACK-TBI where axonal injury within 2 weeks after mTBI was significantly associated with higher sleep disturbances in the TBI group at 2 weeks[β = −7.2, 95% CI (−14, −0.50), p = 0.04], 6 months [β = −16, 95% CI (−24, −7.6), p ≤ 0.01], and 12 months post-injury [β = −11, 95% CI (−19, −0.85), p = 0.03]. These associations were not significant in controls. Interpretations: Axonal injury, specifically to the left anterior internal capsule is robustly associated with sleep disturbances in multiple TBI populations. Early assessment of axonal injury following mTBI could identify those at risk for persistent sleep disturbances following injury.
| Original language | English |
|---|---|
| Journal | Annals of Clinical and Translational Neurology |
| DOIs | |
| State | Accepted/In press - 2024 |
Bibliographical note
Publisher Copyright:© 2024 The Author(s). Annals of Clinical and Translational Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.
Funding
We thank the ADNI/DoD and TRACK\u2010TBI investigators for the use and availability of the data. 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\u201012\u20102\u20100012). 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\u2010Myers Squibb Company; CereSpir, Inc.; Cogstate; Eisai Inc.; Elan Pharmaceuticals, Inc.; Eli Lilly and Company; EuroImmun; F. Hoffmann\u2010La 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. Data used in preparation of this article were obtained from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database ( adni.loni.usc.edu ). As such, the investigators within the ADNI contributed to the design and implementation of ADNI and/or provided data but did not participate in analysis or writing of this report. A complete listing of ADNI investigators can be found at http://adni.loni.usc.edu/wp\u2010content/uploads/how_to_apply/ADNI_Acknowledgement_List.pdf . Other data and/or research tools used in the preparation of this manuscript were obtained and analyzed from the controlled access datasets distributed from the DOD\u2010 and NIH\u2010supported Federal Interagency Traumatic Brain Injury Research (FITBIR) Informatics Systems. FITBIR is a collaborative biomedical informatics system created by the Department of Defense and the National Institutes of Health to provide a national resource to support and accelerate research in TBI. Dataset identifier: NCT01565551. TRACK\u2010TBI was funded by the US National Institutes of Health, National Institute of Neurologic Disorders and Stroke (grant U01 NS1365885) and supported by the US Department of Defense (grant W81XWH\u201014\u20102\u20100176). This manuscript reflects the views of the authors and may not reflect the opinions or views of the DOD, NIH, or of the submitters submitting original data to FITBIR Informatics System. Additionally, this work was completed in part using the Discovery cluster, supported by Northeastern University's Research Computing team.
| Funders | Funder number |
|---|---|
| Alzheimer's Association | |
| BioClinica Inc. | |
| National Institute of Biomedical Imaging and Bioengineering | |
| AbbVie | |
| Biogen IDEC | |
| DoD Alzheimer's Disease Neuroimaging Initiative | |
| Araclon Biotech | |
| DOD ADNI | |
| National Institute on Aging | |
| Northeastern University, China | |
| Alzheimer's Drug Discovery Foundation | |
| National Institutes of Health (NIH) | U01 AG024904 |
| U.S. Department of Defense | W81XWH‐12‐2‐0012, W81XWH‐14‐2‐0176 |
| Institute of Neurological Disorders and Stroke National Advisory Neurological Disorders and Stroke Council | U01 NS1365885 |
ASJC Scopus subject areas
- General Neuroscience
- Clinical Neurology