Currently, the largest health crises in the world are neurodegenerative diseases, which affect millions per year. While studies examine plausible causative agents, associations between neurodegenerative disease and traumatic brain injury have been noted. Motivated by previous studies linking TBI exposure to neurological disease, this study examined TBI and neurodegenerative disease cases from the University of Kansas Medical Center (KUMC) HERON database. Three hundred and thirty-four unique cases were analyzed using Cox hazard regression modeling to characterize patterns in demographics, TBI diagnosis categories, and neurodegenerative disease outcomes for adults with one recorded TBI diagnosis. The Cox hazard model was uninterpretable due to no cases under 30 being identified and loss of variance; therefore, analysis was limited to older adults and focused on exploratory logistic regression analysis as opposed to time-to-event. The majority of associations examined were not statistically robust, but diffuse traumatic brain injury was observed to have a nominally significant association with Lewy Body Dementia. Within the cohort, an individual’s sex was associated with Alzheimer’s disease diagnosis. These findings describe plausible patterns in TBI-exposed older adult populations but should not be viewed as legitimate population pattern estimates.
References
[1]
Kumar, D.R., Aslinia, F., Yale, S.H. and Mazza, J.J. (2010) Jean-Martin Charcot: The Father of Neurology. Clinical Medicine & Research, 9, 46-49. https://doi.org/10.3121/cmr.2009.883
[2]
Partnership to Fight Chronic Disease (2016) U.S. Burden of Neurodegenerative Disease. PFCD. https://www.fightchronicdisease.org/resources/neurodegenerative
[3]
National Institute of Environmental Health Sciences (2022) Neurodegenerative Diseases. National Institute of Environmental Health Sciences. https://www.niehs.nih.gov/research/supported/health/neurodegenerative
[4]
Crooks, S., Carter, G., Wilson, C.B., Wynne, L., Stark, P., Doumas, M., et al. (2023) Exploring Public Perceptions and Awareness of Parkinson’s Disease: A Scoping Review. PLOS ONE, 18, e0291357. https://doi.org/10.1371/journal.pone.0291357
[5]
National Institute of Neurological Disorders and Stroke (2024) Traumatic Brain Injury (TBI). https://www.ninds.nih.gov/health-information/disorders/traumatic-brain-injury-tbi
[6]
Brett, B.L., Gardner, R.C., Godbout, J., Dams-O’Connor, K. and Keene, C.D. (2022) Traumatic Brain Injury and Risk of Neurodegenerative Disorder. Biological Psychiatry, 91, 498-507. https://doi.org/10.1016/j.biopsych.2021.05.025
[7]
Feigin, V.L., Vos, T., Nichols, E., Owolabi, M.O., Carroll, W.M., Dichgans, M., et al. (2020) The Global Burden of Neurological Disorders: Translating Evidence into Policy. The Lancet Neurology, 19, 255-265. https://doi.org/10.1016/s1474-4422(19)30411-9
[8]
Washington, P.M., Villapol, S. and Burns, M.P. (2016) Polypathology and Dementia after Brain Trauma: Does Brain Injury Trigger Distinct Neurodegenerative Diseases, or Should They Be Classified Together as Traumatic Encephalopathy? Experimental Neurology, 275, 381-388. https://doi.org/10.1016/j.expneurol.2015.06.015
[9]
Head Strong (2025) History of CTE. Headstrong Concussion. https://www.headstrongconcussion.com/history-of-cte
[10]
VanItallie, T.B. (2019) Traumatic Brain Injury (TBI) in Collision Sports: Possible Mechanisms of Transformation into Chronic Traumatic Encephalopathy (CTE). Metabolism, 100, Article ID: 153943. https://doi.org/10.1016/j.metabol.2019.07.007
[11]
Dams-O’Connor, K., Guetta, G., Hahn-Ketter, A.E. and Fedor, A. (2016) Traumatic Brain Injury as a Risk Factor for Alzheimer’s Disease: Current Knowledge and Future Directions. Neurodegenerative Disease Management, 6, 417-429. https://doi.org/10.2217/nmt-2016-0017
[12]
Huang, C.H., Lin, C.W., Lee, Y.C., et al. (2018) Is Traumatic Brain Injury a Risk Factor for Neurodegeneration? A Meta-Analysis of Population-Based Studies. BMC Neurology, 18, Article No. 184. https://doi.org/10.1186/s12883-018-1187-0
[13]
Raj, R., Kaprio, J., Korja, M., Mikkonen, E.D., Jousilahti, P. and Siironen, J. (2017) Risk of Hospitalization with Neurodegenerative Disease after Moderate-to-Severe Traumatic Brain Injury in the Working-Age Population: A Retrospective Cohort Study Using the Finnish National Health Registries. PLOS Medicine, 14, e1002316. https://doi.org/10.1371/journal.pmed.1002316
[14]
Chen, Z., Wang, P., Cheng, H., Wang, N., Wu, M., Wang, Z., et al. (2023) Adolescent Traumatic Brain Injury Leads to Incremental Neural Impairment in Middle-Aged Mice: Role of Persistent Oxidative Stress and Neuroinflammation. Frontiers in Neuroscience, 17, Article ID: 1292014. https://doi.org/10.3389/fnins.2023.1292014
[15]
Ruchika, F., Shah, S., Neupane, D., Vijay, R., Mehkri, Y. and Lucke-Wold, B. (2023) Understanding the Molecular Progression of Chronic Traumatic Encephalopathy in Traumatic Brain Injury, Aging and Neurodegenerative Disease. International Journal of Molecular Sciences, 24, Article No. 1847. https://doi.org/10.3390/ijms24031847
[16]
Cantu, R.C. and Bernick, C. (2020) History of Chronic Traumatic Encephalopathy. Seminars in Neurology, 40, 353-358. https://doi.org/10.1055/s-0040-1713622
[17]
National Institute on Aging (2021) What Is Alzheimer’s Disease? National Institute on Aging. https://www.nia.nih.gov/health/alzheimers-and-dementia/what-alzheimers-disease
[18]
Tator, C.H. (2013) Concussions and Their Consequences: Current Diagnosis, Management and Prevention. Canadian Medical Association Journal, 185, 975-979. https://doi.org/10.1503/cmaj.120039
[19]
Shively, S., Scher, A.I., Perl, D.P. and Diaz-Arrastia, R. (2012) Dementia Resulting from Traumatic Brain Injury. Archives of Neurology, 69, 1245-1251. https://doi.org/10.1001/archneurol.2011.3747
[20]
Bianco, A., Antonacci, Y. and Liguori, M. (2023) Sex and Gender Differences in Neurodegenerative Diseases: Challenges for Therapeutic Opportunities. International Journal of Molecular Sciences, 24, Article No. 6354. https://doi.org/10.3390/ijms24076354
[21]
Liu, S., Hu, Y., Liu, J., Luo, Y., Li, T., Liu, Z., et al. (2025) Investigating Sex-Specific Associations of Parkinson’s Disease with Sex Hormones and Sex Hormones-Related Phenotypes Using Mendelian Randomization. Parkinsonism & Related Disorders, 135, Article ID: 107831. https://doi.org/10.1016/j.parkreldis.2025.107831
[22]
Casali, B.T., Lin, L., Benedict, O., Zuppe, H., Marsico, E. and Reed, E.G. (2025) Sex Chromosomes and Gonads Modify Microglial-Mediated Pathology in a Mouse Model of Alzheimer’s Disease. Journal of Neuroinflammation, 22, Article No. 81. https://doi.org/10.1186/s12974-025-03404-8
[23]
Huang, Q., Li, Q. and Guo, J. (2024) Causal Relationship between Sex Hormones and Risk of Developing Common Neurodegenerative Diseases: A Mendelian Randomization Study. Journal of Integrative Neuroscience, 23, Article No. 78. https://doi.org/10.31083/j.jin2304078
[24]
Sanfilippo, C., Giuliano, L., Castrogiovanni, P., Imbesi, R., Ulivieri, M., Fazio, F., et al. (2023) Sex, Age, and Regional Differences in chrm1 and chrm3 Genes Expression Levels in the Human Brain Biopsies: Potential Targets for Alzheimer’s Disease-Related Sleep Disturbances. Current Neuropharmacology, 21, 740-760. https://doi.org/10.2174/1570159x21666221207091209
[25]
Matthews, K.A., Xu, W., Gaglioti, A.H., Holt, J.B., Croft, J.B., Mack, D., et al. (2018) Racial and Ethnic Estimates of Alzheimer’s Disease and Related Dementias in the United States (2015-2060) in Adults Aged ≥ 65 Years. Alzheimer’s & Dementia, 15, 17-24. https://doi.org/10.1016/j.jalz.2018.06.3063
[26]
Patel, A., Mearns, E., Kowal, S., Rosettie, K. and Win, N. (2024) Disease Burden of Neurological Disorders in Underserved Populations across the US in 2022 (s43.007). Neurology, 102, 3658. https://doi.org/10.1212/wnl.0000000000205289
[27]
Butts, B., Huang, H., Hu, W.T., Kehoe, P.G., Miners, J.S., Verble, D.D., et al. (2023) sPDGFRβ and Neuroinflammation Are Associated with AD Biomarkers and Differ by Race: The ASCEND Study. Alzheimer’s & Dementia, 20, 1175-1189. https://doi.org/10.1002/alz.13457
[28]
Thygesen, L.C., Gimsing, L.N., Bautz, A., Hvidt, N.C. and Johansen, C. (2017) Chronic Neurodegenerative Illnesses and Epilepsy in Danish Adventists and Baptists: A Nationwide Cohort Study. Journal of Alzheimer’s Disease, 56, 1429-1435. https://doi.org/10.3233/jad-160710
[29]
Otaiku, A.I. (2022) Religiosity and Risk of Parkinson’s Disease in England and the USA. Journal of Religion and Health, 62, 4192-4208. https://doi.org/10.1007/s10943-022-01603-8
[30]
de Diego-Cordero, R., Martos-Lorite, I. and Vega-Esca？o, J. (2022) Spiritual Dimension in Neurological and Neurodegenerative Diseases: A Systematic Mapping Review. Journal of Religion and Health, 62, 4158-4176. https://doi.org/10.1007/s10943-022-01683-6
[31]
Chen, Z., Wu, H., Wang, X., Zeng, Y., Huang, G., Lv, Y., et al. (2021) Association between Marital Status and Cognitive Impairment Based on a Cross-Sectional Study in China. International Journal of Geriatric Psychiatry, 37, 1-9. https://doi.org/10.1002/gps.5649
[32]
Spataro, R., Volanti, P., Lo Coco, D. and La Bella, V. (2017) Marital Status Is a Prognostic Factor in Amyotrophic Lateral Sclerosis. Acta Neurologica Scandinavica, 136, 624-630. https://doi.org/10.1111/ane.12771
