Beyond peripheral symptoms: Hyperthyroidism as a risk factor for neurodegenerative disorders

Hyperthyroidism affects 0.5–1.3% of the global population and may contribute to neurodegenerative disorders through multiple pathways including oxidative stress, neuroinflammation, and altered neural connectivity. This review examines the relationship between elevated thyroid hormone levels and neurodegenerative processes, focusing on clinical features, epidemiological associations, molecular pathways, and therapeutic interventions. Clinical and epidemiological studies demonstrate significant associations between hyperthyroidism and cognitive impairment, Alzheimer’s disease, and Parkinson’s disease. Meta-analyses reveal a J-shaped relationship between thyroid function and dementia risk, with hyperthyroidism showing stronger associations than hypothyroidism. Mechanistic studies identify key pathways including increased oxidative stress, mitochondrial dysfunction, neuroinflammation, altered protein aggregation, and disrupted neural networks. Neuroimaging studies show structural brain changes affecting the hippocampus and prefrontal cortex, with disrupted functional connectivity in cognitive networks. Evidence supports that hyperthyroidism is associated with increased risk for neurodegeneration through multiple molecular mechanisms. Early detection and appropriate management of thyroid dysfunction may help preserve cognitive function and potentially modify the course of neurodegenerative disorders.