Abstract
Thyroid hormones modulate brain structures during neurogenesis and impact cognition and emotions during the lifetime. Hypothyroidism is commonly associated with lower gray matter volume. Fewer studies, however, highlighted significant associations between higher thyroid function and cognitive impairment. Aging is an independent risk factor for cognitive decline and thyroid dysfunction. It is, therefore, important to understand the association of thyroid function with relevant brain structures during the aging process. A subset of 1,010 adults (≥ 50 years) from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) was included. Multivariable linear regression was used. Comparative bilateral volumetric analyses and interaction-based cognition-related stratifications were performed. Females represented 50.00% of included cases, and 43.50% were healthy controls (HC). Thyroid Stimulating Hormone (TSH) levels were lower in the mild cognitive impairment (MCI) group (1.67 vs. 1.81 µIU/mL, p-value = 0.024). A significant positive association between TSH (µIU/mL) and left hippocampus volume (mm(3)) was found in MCI (adj.ß=44.00 [7.50, 81.00], p-value = 0.018). Similar results were found in the right hippocampus, but only in the total study population (adj.ß=29.00 [4.00, 54.00], p-value = 0.023). There was a significant association between TSH (µIU/mL) and left EC volume (mm(3)) in the total study population (adj.ß=31.00 [9.40, 52.00], p-value = 0.005), and after stratification, this association remained statistically significant only in MCI (adj.ß=54.00 [24.00, 84.00], p-value < 0.001). The association between TSH and the amygdala was not statistically significant. It is, therefore, crucial to consider the role of cognitive status and laterality when exploring the thyroid-brain interaction in older adults. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13044-026-00289-4.