Thyroid Hormones Are Associated with Poorer Cognition in Mild Cognitive Impairment

Abstract

Background: Alterations in interrelated endocrine axes may be related to the pathogenesis of mild cognitive impairment (MCI) and dementia. Methods: Salivary cortisol before and after a 0.5-mg dexamethasone test, and serum levels of thyroid-stimulating hormone, total thyroxine (T₄), free T₄, total triiodothyronine (TT₃), estradiol, testosterone and insulin-like growth factor 1 were measured in 43 MCI cases and 26 healthy controls. All participants underwent a comprehensive neuropsychological test battery covering the cognitive domains of speed/attention, memory, visuospatial functions, language and executive functions. Results: The MCI group did not differ in basal levels of endocrine markers compared to controls. Among those with MCI, TT₃ levels were inversely associated with cognitive performance across all domains. After stratifying MCI cases according to TT₃ levels, those with relatively high TT₃ levels showed impairment in memory as well as in visuospatial and executive functions. Those with TT₃ levels at or below the lower boundary of the normal range performed comparably to healthy controls. Other endocrine markers were not related to cognitive performance. Conclusions: Among those with MCI, TT₃ was associated with a neuropsychological profile typical of prodromal Alzheimer’s disease. While the mechanisms remain unclear, optimal levels of thyroid hormone under a compromising condition such as MCI and related neuropathology need reconsideration.