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

IntroductionThyroid 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. MethodsA subset of 1348 older adults from the Alzheimers 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. ResultsFemales 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.{beta}=92 (23, 161), p- value=0.009), while a negative association in dementia participants remained statistically significant ({beta}=-177 (-295, -60), p-value=0.003 and adj.{beta}=-141 (-250, -32), p-value=0.012). There was a significant association between TSH and total Entorhinal cortex volume in the total study population ({beta}=44 (3.9, 85), p-value=0.032 and adj.{beta}=40 (5.1, 75), p-value=0.025). Stratification showed significant associations only in MCI ({beta}=80 (21, 138), p-value=0.007, and adj.{beta}=83 (27, 138), p-value=0.003), and males (adj.{beta}=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 ({beta}=37 (1.6, 73), p- value=0.041) and negative in dementia participants ({beta}=-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. ConclusionsDepending 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. HighlightsO_LIHigher TSH levels are associated with lower Hippocampus volume on both sides in the dementia group. C_LIO_LILower TSH levels are associated with lower left Entorhinal cortex volume in the mild cognitive impairment and male strata. C_LIO_LIHigher TSH levels are associated with lower right Amygdala volume in the dementia group. C_LI Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=113 SRC="FIGDIR/small/24314757v1_ufig1.gif" ALT="Figure 1"> View larger version (67K): org.highwire.dtl.DTLVardef@1fc4bd8org.highwire.dtl.DTLVardef@d76a84org.highwire.dtl.DTLVardef@922fbaorg.highwire.dtl.DTLVardef@17b7e7b_HPS_FORMAT_FIGEXP M_FIG C_FIG