Sex-specific impacts of obesity on long-term prognosis of traumatic brain injury: a multicenter prospective study

Our investigation delves into the nuanced interplay between obesity and sex on the long-term outcomes of traumatic brain injury (TBI), a relationship that previous studies have hinted at but not thoroughly elucidated. Acknowledging the divergent recovery paths of males and females post-TBI, we aimed to elucidate whether obesity’s prognostic impact on TBI prognosis is indeed sex-dependent. This study was a prospective multi-center cohort study conducted on adult TBI patients, with intracranial hemorrhage or diffuse axonal injury confirmed by radiological examination, admitted to five participating emergency departments (EDs) from December 2018 to March 2023. The study outcomes were 6-month disability and mortality. The primary exposure was obesity, defined as body mass index (BMI) over 25. Multi-level logistic regression analysis was performed to estimate the association between obesity and the study outcomes. We conducted a stratified analysis by sex to investigate whether the association between obesity and TBI outcomes differs between sex. Our multilevel logistic regression analysis, using the normal weight group as a reference, indicated that higher BMI categories over 25 did not significantly alter the risk of 6-month disability or mortality when compared to the normal weight group. Our study revealed a higher one-month disability rate in female TBI patients with a BMI over 30 compared to those with a normal BMI, highlighting the need for gender-specific approaches in managing and rehabilitating TBI outcomes.

Sex; Obesity; TBI

[1] Maas AIR, Menon DK, Adelson PD, Andelic N, Bell MJ, Belli A, et al. Traumatic brain injury: integrated approaches to improve prevention, clinical care, and research. The Lancet Neurology. 2017; 16: 987–1048.

[2] Peterson AB, Xu L, Daugherty J, Breiding MJ. Surveillance report of traumatic brain injury-related emergency department visits, hospitalizations, and deaths, United States, 2014 (5814). Atlanta: 10 December. 2019.

[3] Abdul-Muneer PM, Chandra N, Haorah J. Interactions of oxidative stress and neurovascular inflammation in the pathogenesis of traumatic brain injury. Molecular Neurobiology. 2015; 51: 966–979.

[4] Redpath SJ, Williams WH, Hanna D, Linden MA, Yates P, Harris A. Healthcare professionals’ attitudes towards traumatic brain injury (TBI): the influence of profession, experience, aetiology and blame on prejudice towards survivors of brain injury. Brain Injury. 2010; 24: 802–811.

[5] Binder S, Corrigan JD, Langlois JA. The public health approach to traumatic brain injury. Journal of Head Trauma Rehabilitation. 2005; 20: 189–195.

[6] Youse KM, Le KN, Cannizzaro MS, Coelho CA. Traumatic brain injury: a primer for professionals. The ASHA Leader. 2002; 7: 4–7.

[7] Andelic N, Sigurdardottir S, Schanke A, Sandvik L, Sveen U, Roe C. Disability, physical health and mental health 1 year after traumatic brain injury. Disability and Rehabilitation. 2010; 32: 1122–1131.

[8] Zaloshnja E, Miller T, Langlois JA, Selassie AW. Prevalence of long-term disability from traumatic brain injury in the civilian population of the United States, 2005. Journal of Head Trauma Rehabilitation. 2008; 23: 394–400.

[9] Galgano M, Toshkezi G, Qiu X, Russell T, Chin L, Zhao L. Traumatic brain injury: current treatment strategies and future endeavors. Cell Transplantation. 2017; 26: 1118–1130.

[10] Crupi R, Cordaro M, Cuzzocrea S, Impellizzeri D. Management of traumatic brain injury: from present to future. Antioxidants. 2020; 9: 297.

[11] Jourdan C, Bosserelle V, Azerad S, Ghout I, Bayen E, Aegerter P, et al. Predictive factors for 1-year outcome of a cohort of patients with severe traumatic brain injury (TBI): results from the PariS-TBI study. Brain Injury. 2013; 27: 1000–1007.

[12] Kulesza B, Nogalski A, Kulesza T, Prystupa A. Prognostic factors in traumatic brain injury and their association with outcome. Journal of Pre-Clinical and Clinical Research. 2015; 9: 163–166.

[13] Roozenbeek B, Maas AIR, Menon DK. Changing patterns in the epidemiology of traumatic brain injury. Nature Reviews Neurology. 2013; 9: 231–236.

[14] Yue JK, Vassar MJ, Lingsma HF, Cooper SR, Okonkwo DO, Valadka AB, et al. Transforming research and clinical knowledge in traumatic brain injury pilot: multicenter implementation of the common data elements for traumatic brain injury. Journal of Neurotrauma. 2013; 30: 1831–1844.

[15] Brown CVR, Rhee P, Neville AL, Sangthong B, Salim A, Demetriades D. Obesity and traumatic brain injury. The Journal of Trauma and Acute Care Surgery. 2006; 61: 572–576.

[16] McGlennon TW, Buchwald JN, Pories WJ, Yu F, Roberts A, Ahnfeldt EP, et al. Bypassing TBI: metabolic surgery and the link between obesity and traumatic brain injury—a review. Obesity Surgery. 2020; 30: 4704–4714.

[17] Sherman M, Liu M, Birnbaum S, Wolf SE, Minei JP, Gatson JW. Adult obese mice suffer from chronic secondary brain injury after mild TBI. Journal of Neuroinflammation. 2016; 13: 171.

[18] Mishra R, Galwankar S, Konar S, Shrivastava A, Raj S, Choksey P, et al. Obesity as a predictor of outcome following traumatic brain injury: a systematic review and meta-analysis. Clinical Neurology and Neurosurgery. 2022; 217: 107260.

[19] Gupte RP, Brooks WM, Vukas RR, Pierce JD, Harris JL. Sex Differences in traumatic brain injury: what we know and what we should know. Journal of Neurotrauma. 2019; 36: 3063–3091.

[20] Mollayeva T, Mollayeva S, Colantonio A. Traumatic brain injury: sex, gender and intersecting vulnerabilities. Nature Reviews Neurology. 2018; 14: 711–722.

[21] Kim KH, Ro YS, Yoon H, Lee SGW, Jung E, Moon SB, et al. Serum zinc and long-term prognosis after acute traumatic brain injury with intracranial injury: a multicenter prospective study. Journal of Clinical Medicine. 2022; 11: 6496.

[22] Lockhart TE, Frames CW, Soangra R, Lieberman A. Effects of obesity and fall risk on gait and posture of community-dwelling older adults. International Journal of Prognostics and Health Management. 2019; 10: 019.

[23] Dreer LE, Ketchum JM, Novack TA, Bogner J, Felix ER, Corrigan JD, et al. Obesity and overweight problems among individuals 1 to 25 years following acute rehabilitation for traumatic brain injury: a NIDILRR traumatic brain injury model systems study. Journal of Head Trauma Rehabilitation. 2018; 33: 246–256.

[24] Kumar RG, Juengst SB, Wang Z, Dams-O’Connor K, Dikmen SS, O’Neil-Pirozzi TM, et al. Epidemiology of comorbid conditions among adults 50 years and older with traumatic brain injury. Journal of Head Trauma Rehabilitation. 2018; 33: 15–24.

[25] Eagle SR, Puccio AM, Nelson LD, McCrea M, Giacino J, Diaz-Arrastia R, et al. Association of obesity with mild traumatic brain injury symptoms, inflammatory profile, quality of life and functional outcomes: a TRACK-TBI Study. Journal of Neurology, Neurosurgery & Psychiatry. 2023; 94: 1012–1017.

[26] Mishra R, Galwankar S, Konar S, Shrivastava A, Raj S, Choksey P, et al. Obesity as a predictor of outcome following traumatic brain injury: a systematic review and meta-analysis. Clinical Neurology and Neurosurgery. 2022; 217: 107260.

[27] Mou Y, Du Y, Zhou L, Yue J, Hu X, Liu Y, et al. Gut microbiota interact with the brain through systemic chronic inflammation: Implications on neuroinflammation, neurodegeneration, and aging. Frontiers in Immunology. 2022; 13: 796288.

[28] Kim N, Lee J, Song HS, Oh YJ, Kwon M, Yun M, et al. Kimchi intake alleviates obesity-induced neuroinflammation by modulating the gut-brain axis. Food Research International. 2022; 158: 111533.

[29] Dong Q, Yang S, Liao H, He Q, Xiao J. Preclinical findings reveal the pharmacological targets of ferulic acid in the treatment of traumatic brain injury. Food Science & Nutrition. 2022; 10: 4403–4410.

[30] Standen EC, Finch LE, Tiongco-Hofschneider L, Schopp E, Lee KM, Parker JE, et al. Healthy versus unhealthy comfort eating for psychophysiological stress recovery in low-income Black and Latinx adults. Appetite. 2022; 176: 106140.

[31] Di Polito N, Stylianakis AA, Richardson R, Baker KD. Real-world intake of dietary sugars is associated with reduced cortisol reactivity following an acute physiological stressor. Nutrients. 2023; 15: 209.