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August 16, 2022; 99 (7) Research Articles

Thyroid Disorders and Dementia Risk

A Nationwide Population-Based Case-Control Study

Daniel R. Wieland, Julia R. Wieland, Han Wang, Yi-Huei Chen, Ching-Heng Lin, Jing-Jie Wang, View ORCID ProfileChien-Hsiang Weng
First published July 6, 2022, DOI: https://doi.org/10.1212/WNL.0000000000200740
Daniel R. Wieland
From the University of Arizona (D.R.W., J.R.W.), Tucson; Department of Neurology (H.W.), Mayo Clinic College of Medicine & Science, Rochester, MN; Department of Neurology (H.W.), Mayo Clinic Health System, Mankato, MN; Departments of Medical Research (Y.-H.C., C.-H.L.) and Otolaryngology (J.-J.W.), Taichung Veterans General Hospital; Institute of Medicine (J.-J.W.), Chung Shan Medical University, Taichung, Taiwan; Department of Family Medicine (C.-H.W.), Brown University Warren Alpert Medical School, Providence, RI; and Coastal Medical Hillside Family Medicine (C.-H.W.), Pawtucket, RI.
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Julia R. Wieland
From the University of Arizona (D.R.W., J.R.W.), Tucson; Department of Neurology (H.W.), Mayo Clinic College of Medicine & Science, Rochester, MN; Department of Neurology (H.W.), Mayo Clinic Health System, Mankato, MN; Departments of Medical Research (Y.-H.C., C.-H.L.) and Otolaryngology (J.-J.W.), Taichung Veterans General Hospital; Institute of Medicine (J.-J.W.), Chung Shan Medical University, Taichung, Taiwan; Department of Family Medicine (C.-H.W.), Brown University Warren Alpert Medical School, Providence, RI; and Coastal Medical Hillside Family Medicine (C.-H.W.), Pawtucket, RI.
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Han Wang
From the University of Arizona (D.R.W., J.R.W.), Tucson; Department of Neurology (H.W.), Mayo Clinic College of Medicine & Science, Rochester, MN; Department of Neurology (H.W.), Mayo Clinic Health System, Mankato, MN; Departments of Medical Research (Y.-H.C., C.-H.L.) and Otolaryngology (J.-J.W.), Taichung Veterans General Hospital; Institute of Medicine (J.-J.W.), Chung Shan Medical University, Taichung, Taiwan; Department of Family Medicine (C.-H.W.), Brown University Warren Alpert Medical School, Providence, RI; and Coastal Medical Hillside Family Medicine (C.-H.W.), Pawtucket, RI.
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Yi-Huei Chen
From the University of Arizona (D.R.W., J.R.W.), Tucson; Department of Neurology (H.W.), Mayo Clinic College of Medicine & Science, Rochester, MN; Department of Neurology (H.W.), Mayo Clinic Health System, Mankato, MN; Departments of Medical Research (Y.-H.C., C.-H.L.) and Otolaryngology (J.-J.W.), Taichung Veterans General Hospital; Institute of Medicine (J.-J.W.), Chung Shan Medical University, Taichung, Taiwan; Department of Family Medicine (C.-H.W.), Brown University Warren Alpert Medical School, Providence, RI; and Coastal Medical Hillside Family Medicine (C.-H.W.), Pawtucket, RI.
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Ching-Heng Lin
From the University of Arizona (D.R.W., J.R.W.), Tucson; Department of Neurology (H.W.), Mayo Clinic College of Medicine & Science, Rochester, MN; Department of Neurology (H.W.), Mayo Clinic Health System, Mankato, MN; Departments of Medical Research (Y.-H.C., C.-H.L.) and Otolaryngology (J.-J.W.), Taichung Veterans General Hospital; Institute of Medicine (J.-J.W.), Chung Shan Medical University, Taichung, Taiwan; Department of Family Medicine (C.-H.W.), Brown University Warren Alpert Medical School, Providence, RI; and Coastal Medical Hillside Family Medicine (C.-H.W.), Pawtucket, RI.
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Jing-Jie Wang
From the University of Arizona (D.R.W., J.R.W.), Tucson; Department of Neurology (H.W.), Mayo Clinic College of Medicine & Science, Rochester, MN; Department of Neurology (H.W.), Mayo Clinic Health System, Mankato, MN; Departments of Medical Research (Y.-H.C., C.-H.L.) and Otolaryngology (J.-J.W.), Taichung Veterans General Hospital; Institute of Medicine (J.-J.W.), Chung Shan Medical University, Taichung, Taiwan; Department of Family Medicine (C.-H.W.), Brown University Warren Alpert Medical School, Providence, RI; and Coastal Medical Hillside Family Medicine (C.-H.W.), Pawtucket, RI.
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Chien-Hsiang Weng
From the University of Arizona (D.R.W., J.R.W.), Tucson; Department of Neurology (H.W.), Mayo Clinic College of Medicine & Science, Rochester, MN; Department of Neurology (H.W.), Mayo Clinic Health System, Mankato, MN; Departments of Medical Research (Y.-H.C., C.-H.L.) and Otolaryngology (J.-J.W.), Taichung Veterans General Hospital; Institute of Medicine (J.-J.W.), Chung Shan Medical University, Taichung, Taiwan; Department of Family Medicine (C.-H.W.), Brown University Warren Alpert Medical School, Providence, RI; and Coastal Medical Hillside Family Medicine (C.-H.W.), Pawtucket, RI.
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  • ORCID record for Chien-Hsiang Weng
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Thyroid Disorders and Dementia Risk
A Nationwide Population-Based Case-Control Study
Daniel R. Wieland, Julia R. Wieland, Han Wang, Yi-Huei Chen, Ching-Heng Lin, Jing-Jie Wang, Chien-Hsiang Weng
Neurology Aug 2022, 99 (7) e679-e687; DOI: 10.1212/WNL.0000000000200740

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Abstract

Background and Objectives Dementia has been gaining attention in aging societies and is estimated to affect 50 million adults globally in 2020, and 12% of the US population may develop a thyroid disorder in their lifetime. There have been limited studies investigating the correlation between thyroid disorder and dementia in the Asian population.

Methods Our large nationwide population-based case-control study used the Taiwanese National Health Insurance Research Database. A total of 7,843 adults with newly diagnosed dementia without a history of dementia or neurodegenerative disease between 2006 and 2013 were identified and included in our study. In addition, 7,843 adults without dementia diagnosis before the index date were age and sex-matched as controls. Diagnosis of hyperthyroidism or hypothyroidism before the diagnosis of dementia or the same index date was identified. Results were obtained from logistic regression models and adjusted for sex, age, history of hypertension, diabetes, coronary artery disease, depression, hyperlipidemia, alcohol dependence syndrome, tinnitus, hearing loss, and radioactive iodine treatment.

Results A total of 15,686 patients were included in the study. Both case and control groups were slightly predominantly female (4,066 [51.8%]). The mean (SD) age for those with dementia was 74.9 (11.3) years and for those without dementia was 74.5 (11.3) years. Among patients aged 65 years or older, a history of hypothyroidism was associated with an increased risk of being diagnosed with dementia (adjusted odds ratio [aOR] 1.81; 95% CI 1.14–2.87; p = 0.011), which was an association not present in patients older than 50 years but younger than 65 years. We found that this association was most significant among patients aged 65 years or older with a history of hypothyroidism who received hypothyroidism medication (aOR 3.17; 95% CI 1.04–9.69; p = 0.043).

Discussion Our large-scale case-control study found that among people aged 65 years or older, those with a history of hypothyroidism were associated with an 81% increased risk of having dementia and among those, there was a more than 3-fold increased dementia risk with thyroid conditions that required thyroid hormone replacement treatment. Future well-controlled prospective longitudinal studies should be conducted to elucidate these potential mechanisms and relationships.

Classification of Evidence This study provides Class III evidence that among patients aged 65 years or older, a history of hypothyroidism was associated with an increased risk of being diagnosed with dementia.

Glossary

AD=
Alzheimer disease;
aOR=
adjusted odds ratio;
APP=
β-amyloid precursor protein;
ICD-9-CM=
International Classification of Diseases, Ninth Revision, Clinical Modification;
LHID=
Longitudinal Health Insurance Database;
NHIRD=
National Health Insurance Research Database;
T3=
3,5,3′-triiodo-l-thyronine;
T4=
3,5,3′,5′-tetraiodo-l-thyronine;
TH=
thyroid hormone;
TSH=
thyroid-stimulating hormone

Footnotes

  • Go to Neurology.org/N for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.

  • ↵* These authors contributed equally as co-first authors to this article.

  • ↵† These authors contributed as co-senior authors to this article.

  • Submitted and externally peer reviewed. The handling editor was Linda Hershey, MD, PhD, FAAN.

  • Class of Evidence NPub.org/coe

  • Received December 5, 2021.
  • Accepted in final form March 31, 2022.
  • © 2022 American Academy of Neurology
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