Low serum concentration of free triiodothyronine (FT3) is associated with increased risk of Alzheimer's disease

Background: In epidemiological studies, thyroid hormones (THs) have been associated with the risk of dementia. However, little is known of the relation between THs and risk of Alzheimer's disease (AD) or vascular dementia (VaD) in a memory clinic population. Methods: In a mono-center study, serum concentrations of thyroid-stimulating hormone (TSH), free thyroxine (FT4), and free triiodothyronine (FT3) were assessed in 302 patients. All patients had subjective or objective mild cognitive impairment and none received treatment with THs. Cox proportional hazards regression analyses was used to determine whether THs at baseline were associated with the risk of conversion to all-cause dementia, AD or VaD. Results: During the follow-up (mean 2.8 years), 82 (28%) of the patients progressed to dementia [AD, n = 55 (18%) and VaD, n = 17 (6%)]. Serum concentrations of TSH, FT4, and FT3 did not associate with all-cause dementia or VaD. Higher serum FT3 was associated with lower risk of conversion to AD [hazard ratio (HR) = 054; 95% confidence interval (CI): 0.32-0.92 per 1 pmol/L increase]. Furthermore, patients in the lowest serum FT3 quartile had a twofold increased risk of AD compared to those in the highest quartile (HR = 2.63; 95% CI: 1.06-6.47). These associations remained after adjustment for multiple covariates. Conclusions: In a memory clinic population, there was an inverse, linear association between serum FT3 and risk of AD whereas THs did not associate with all-cause dementia or VaD. Further studies are needed to determine the underlying mechanisms as well as the clinical significance of these findings.