Association of Amygdala, Hippocampus, and Entorhinal cortex with thyroid function in older adults: Stratification’s value and relevance of bilateral volumetric analyses

Introduction

Thyroid hormones modulate the brain structure during neurogenesis and impact cognition and emotions during the lifetime. It is, therefore, important to understand their association with relevant brain structures during the aging process.

Methods

A subset of 1348 older adults from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) was included. Linear regression was used to study the association between serum thyroid stimulating hormone (TSH) and the Amygdala, Hippocampus, and Entorhinal cortex volumes. Sex and neurodegeneration-related stratifications and comparative bilateral volumetric analyses were performed.

Results

Females represented 667 (49%) of included cases, and 522 (38.72 %) were healthy controls (HC). A significant positive association was observed between TSH and total Hippocampus volume in mild cognitive impairment (MCI) (adj. ß =92 (23, 161), p- value =0.009), while a negative association in dementia participants remained statistically significant ( ß =-177 (−295, −60), p-value =0.003 and adj. ß =-141 (−250, −32), p-value =0.012). There was a significant association between TSH and total Entorhinal cortex volume in the total study population ( ß =44 (3.9, 85), p-value =0.032 and adj. ß =40 (5.1, 75), p-value =0.025). Stratification showed significant associations only in MCI ( ß =80 (21, 138), p-value =0.007, and adj. ß =83 (27, 138), p-value =0.003), and males (adj. ß =54 (1.9, 106), p-value =0.042). Similar statistically significant associations were found only in the left Entorhinal cortex. The association between TSH and total Amygdala volume was positive in HC ( ß =37 (1.6, 73), p- value =0.041) and negative in dementia participants ( ß =-67 (−128, −6.4), p-value =0.030). None of those results remained statistically significant after adjusting the models. The bilateral volumetric analysis showed significant results only in the right Amygdala and dementia group.

Conclusions

Depending on the stratum and side of the volumetric analysis, significant associations were observed between TSH and Hippocampus, Amygdala, and Entorhinal cortex volumes. It is, therefore, crucial to consider the role of sex, neurodegeneration, and laterality when exploring the thyroid-brain interaction in older adults.

Highlights

• Higher TSH levels are associated with lower Hippocampus volume on both sides in the dementia group.

• Lower TSH levels are associated with lower left Entorhinal cortex volume in the mild cognitive impairment and male strata.

• Higher TSH levels are associated with lower right Amygdala volume in the dementia group.