Real-World Evidence on Statin Use for Traumatic Brain Injury Associated Degenerative Neurological Disorders

Yu-Hui Lin,1,* I-Ju Tsai,2,* Yu-Ang Chang,3 Ching-Hui Huang,4– 6,* Chia-Chu Chang7,8,* 1Division of Integrated Dementia Care, Department of Neurology, Kuang Tien General Hospital, Taichung, Taiwan; 2Department of Medical Research, Kuang Tien General Hospital, Taichung, Taiwan; 3Department of Medical Education, Taipei Medical University Hospital, Taipei, Taiwan; 4Division of Cardiology, Department of Internal Medicine, Changhua Christian Hospital, Changhua, Taiwan; 5Department of Mathematics, National Changhua University of Education, Changhua, Taiwan; 6Department of Beauty Science and Graduate Institute of Beauty Science Technology, Chienkuo Technology University, Changhua, Taiwan; 7Department of Internal Medicine, Kuang Tien General Hospital, Taichung, Taiwan; 8Department of Nutrition, Hungkuang University, Taichung, Taiwan*These authors contributed equally to this workCorrespondence: Chia-Chu Chang, Department of Internal Medicine, Kuang Tien General Hospital, No. 127, Sec. 7, Xiangshang Road, Shalu District, Taichung City, 433, Taiwan, Tel +886 4 2662 5111, Email [email protected] Ching-Hui Huang, Division of Cardiology, Department of Internal Medicine, Changhua Christian Hospital, No. 135, Nian-Siau Street, Changhua City, Changhua, 500, Taiwan, Email [email protected]: Traumatic brain injury (TBI) is a major risk factor for subsequent neurodegenerative disorders. Emerging evidence suggests that statins may mitigate neuroinflammation and lipid dysregulation after TBI. This study aimed to evaluate the association between statin use and the risk of post-TBI degenerative neurological disorders in a global, real-world population.Methods: We conducted a retrospective cohort study using the TriNetX global research network and a 1:1 propensity score matching procedure to balance demographic, clinical, and medication covariates. Patients with the first TBI diagnosis from 2000 onward were included. Individuals with continuous statin use every year from 1 year before to 5 years after the index date were classified as the statin treated group, whereas those with no statin prescriptions during the same period were categorized as the untreated group. Patients younger than 18 years and those with pre-index dementia, stroke, or CNS infection were excluded. A 1:1 propensity score matching procedure was applied to balance demographic, clinical, and medication covariates. Cox proportional hazards models estimated hazard ratios (HRs) for vascular dementia, non-vascular dementia, stroke, depression, and Parkinson’s disease during the 5-year follow-up.Results: After matching, 21,427 patients were included in each group. Statin-treated patients demonstrated higher risks of all neurologic outcomes compared with untreated individuals, including vascular dementia (HR 2.47; 95% CI, 1.83– 3.34), non-vascular dementia (HR 1.45; 95% CI, 1.30– 1.61), stroke (HR 1.80; 95% CI, 1.70– 1.89), depression (HR 1.91; 95% CI, 1.79– 2.04), and Parkinson’s disease (HR 1.63; 95% CI, 1.34– 1.98). Subgroup analyses showed consistent risk elevations across sex and age categories.Conclusion: The current Real-World data do not provide evidence supporting the use of statins primarily for neuroprotection after TBI. These findings underscore the importance of pursuing alternative therapeutic strategies that directly target TBI-associated neurodegenerative mechanisms. Keywords: traumatic brain injury, TBI, statins, neurodegenerative disease, real-world data, TriNetX