Supplementary Material for: Thyroid Disorders as a Risk Factor for Neurodegenerative Proteinopathies: A Large-Scale Propensity Score-Matched Analysis

Introduction: The relationship between thyroid disorders and neurodegenerative diseases remains poorly understood. This large-scale retrospective cohort study aimed to investigate the association between thyroid disorders and various neurodegenerative diseases, as well as the potential impact of thyroidectomy. Methods: We analyzed data from 3,719,666 patients with thyroid disorders and 2,945,438 controls from 120 healthcare organizations. After propensity score matching, each group included 2,033,096 patients. We compared the risk of neurodegenerative diseases between these groups and examined the effect of thyroidectomy in a subgroup analysis of 31,753 matched pairs. Results: Patients with thyroid disorders showed significantly higher risks of Alzheimer's disease (RR=1.15, 95%CI: 1.110-1.195), Parkinson's disease (RR=1.25, 95%CI: 1.187-1.318), amyotrophic lateral sclerosis (RR=1.35, 95%CI: 1.131-1.622), frontotemporal dementia (RR=1.44, 95%CI: 1.219-1.702), Lewy body dementia (RR=1.15, 95%CI: 1.107-1.186), progressive supranuclear palsy (RR=1.41, 95%CI: 1.095-1.819), vascular dementia (RR=1.32, 95%CI: 1.266-1.369), Niemann-Pick disease type C (RR=1.34, 95%CI: 1.092-1.638), and Wilson's disease (RR=1.26, 95%CI: 1.056-1.507). Interestingly, the risk of multiple sclerosis was lower (RR=0.80, 95%CI: 0.738-0.862). Thyroidectomy was associated with a 44.2% lower risk of Lewy body dementia (RR=0.558, 95%CI: 0.339-0.919, p=0.020). Conclusion: Thyroid disorders are significantly associated with an increased risk of several neurodegenerative diseases. Thyroidectomy may have a protective effect against Lewy body dementia. These findings suggest a complex relationship between thyroid function and neurodegeneration, emphasizing the need for neurological monitoring in patients with thyroid disorders and further research into thyroid-brain interactions.