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

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Abstract

Background and objective

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.

Methods

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.

Results

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.

Conclusion

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.

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Data availability

Data not provided in the article because of space limitations may be shared (anonymized) at the request of any qualified investigator for purposes of replicating procedures and results.

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Acknowledgements

We are thankful to the authors of the reviewed/included studies in this systematic review who contributed by sharing the relevant data on request.

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M.D., Am.S., A.F., and A.T. contributed to conception and design of the study, M.D., and Ar.S. contributed to data acquisition and analysis, M.D., Ar.S., H.S.M. contributed to drafting a significant portion of the manuscript and figures, A.T., A.F., and V.A. supervised this study, M.D., Ar.S., Am.S., H.S.M., V.A., A.T., A.F., contributed to revising the manuscript and confirmed the final version of the manucript.

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Correspondence to Abbas Tafakhori.

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This study was done in accorance with ethics guidelines of Helsinki. The protocol for this study was registered in the Prospective Register of Systematic Reviews (PROSPERO) website (https://www.crd.york.ac.uk/prospero/) with the following ID: CRD42020078556. It was reviewed and approved by the ethics committee of Tehran University of Medical Sciences and designated the followoing ethics code: IR.TUMS.VCR.REC.1398.559.

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Dolatshahi, M., Salehipour, A., Saghazadeh, A. et al. Thyroid hormone levels in Alzheimer disease: a systematic review and meta-analysis. Endocrine 79, 252–272 (2023). https://doi.org/10.1007/s12020-022-03190-w

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