Associations of thyroid hormone serum levels with in-vivo Alzheimer's disease pathologies

Background: The present study investigated the relationships between thyroid hormone serum levels or thyroid-stimulating hormone (TSH) and two Alzheimer's disease (AD)-specific biomarkers, cerebral amyloid beta (A beta) burden and glucose metabolism, in AD-signature brain regions in cognitively normal (CN) middle-aged and older individuals. Methods: This study assessed 148 CN individuals who received comprehensive clinical and neuropsychological assessments that included C-11-Pittsburgh Compound B (PiB)-positron emission tomography (PET) scans, F-18-deoxyglucose (FDG)-PET scans, and the quantification of serum triiodothyronine (T3), free T3, free thyroxine (fT4), and TSH levels. Results: All participants were clinically euthyroid. Independent negative associations were found between serum fT4 levels and global cerebral A beta deposition after controlling for the effects of age, gender, and the apolipoprotein E epsilon 4 (APOE epsilon 4) genotype. Although serum TSH levels were not associated with global cerebral A beta deposition, they had a significant negative association with glucose metabolism in the precuneus/posterior cingulate cortex after controlling for age, gender, and the APOEe4 genotype. No other thyroid hormones exhibited relationships with either brain A beta burden or glucose metabolism. Conclusions: Even in a clinical euthyroid state, low serum fT4 and high serum TSH levels appear to be differentially associated with AD-specific brain changes.