Thyroid hormone levels in Alzheimer disease: a systematic review and meta-analysis

Thyroid hormone (TH) disturbances are perceived to contribute to cognitive impairment and dementia. However, there is no consensus on the association between TH levels and Alzheimer Disease (AD). In this study, we aimed to compare serum and cerebrospinal fluid (CSF) TH levels in AD patients to controls by performing a meta-analysis.

We systematically searched online databases for papers comparing CSF or serum TH levels in AD patients to controls, and performed a meta-analysis on the extracted data.

Out of 1604 records identified, 32 studies were included. No significant difference in serum TSH (standardized mean difference (SMD): -0.03; 95% confidence interval (CI): -0.22-0.16), total T4 (SMD: 0.10; 95% CI: -0.29-0.49), and free T4 (SMD: 0.25; 95% CI: -0.16-0.69) levels were observed. However, there was significantly lower serum total T3 (SMD: -0.56; 95%CI: -0.97 to -0.15) and free T3 (SMD: -0.47; 95%CI: -0.89 to -0.05) levels in AD group compared to controls. Subgroup analyses on studies including only euthyroid patients did not show any significant difference in either of the thyroid hormone levels. Also, no significant difference in CSF total T4 and total T3/total T4 ratios but significantly lower CSF total T3 (SMD: -2.45; 95% CI: -4.89 to -0.02) in AD group were detected.

Serum total and free T3 and CSF total T3 levels are significantly lower in AD patients compared to controls. The temporality of changes in thyroid hormone levels and AD development should be illustrated by further longitudinal studies.