Subclinical Thyroid Dysfunction and Cognitive Decline in Old Age
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BACKGROUND: Subclinical thyroid dysfunction has been implicated as a risk factor for cognitive decline in old age, but results are inconsistent. We investigated the association between subclinical thyroid dysfunction and cognitive decline in the PROspective Study of Pravastatin in the Elderly at Risk (PROSPER). METHODS: Prospective longitudinal study of men and women aged 70-82 years with pre-existing vascular disease or more than one risk factor to develop this condition (N = 5,154). Participants taking antithyroid medications, thyroid hormone supplementation and/or amiodarone were excluded. Thyroid function was measured at baseline: subclinical hyper- and hypothyroidism were defined as thyroid stimulating hormones (TSH) <0.45 mU/L or >4.50 mU/L respectively, with normal levels of free thyroxine (FT4). Cognitive performance was tested at baseline and at four subsequent time points during a mean follow-up of 3 years, using five neuropsychological performance tests. RESULTS: Subclinical hyperthyroidism and hypothyroidism were found in 65 and 161 participants, respectively. We found no consistent association of subclinical hyper- or hypothyroidism with altered cognitive performance compared to euthyroid participants on the individual cognitive tests. Similarly, there was no association with rate of cognitive decline during follow-up. CONCLUSION: We found no consistent evidence that subclinical hyper- or hypothyroidism contribute to cognitive impairment or decline in old age. Although our data are not in support of treatment of subclinical thyroid dysfunction to prevent cognitive dysfunction in later life, only large randomized controlled trials can provide definitive evidence.
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Two recent prospective studies did not find an association between low serum TSH levels and the risk of cognitive impairment and dementia or decreased functional capacity in the elderly.
“At variance, two recent prospective studies did not find an association between low serum TSH levels and the risk of cognitive impairment and dementia or decreased functional capacity in the elderly [61,62] .”
From The 2015 European Thyroid Association Guidelines on Diagnosis and Treatment of Endogenous Subclinical Hyperthyroidism (2015) · cites this paper as [61]
The Discussion reports no association between subclinical thyroid dysfunction and cognitive performance or decline in participants aged 70–82 with vascular disease or risk factors. The Methods define low TSH as subclinical hyperthyroidism, so this supports the cognitive portion of the claim. The study did not report prospective risks of dementia or decreased functional capacity; its functional-capacity scores appear only as baseline characteristics in the Results. (LLM, conf=0.86)
Experimental — accuracy not yet measuredA large body of literature has investigated possible correlations between SH and cognitive decline.
“A large body of literature has investigated possible correlations between SH and cognitive decline [reviewed by Gan and Pearce (418), with more recent studies by others (419,420)].”
From 2016 American Thyroid Association Guidelines for Diagnosis and Management of Hyperthyroidism and Other Causes of Thyrotoxicosis (2016) · cites this paper as [419]
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- Authors
- Wijsman, L. W., de Craen, A. J. M., Trompet, S., Gussekloo, J., Stott, D. J., Rodondi, N., Welsh, P., Jukema, J. W., Westendorp, R. G. J., & Mooijaart, S. P.
- Affiliations
- Leiden University Medical Center (NL)
- University of Glasgow (GB)
- University of Bern (CH)
- Corresponding author
- Mooijaart, Simon P.
- ORCID
- Venue
- PLoS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2013-03-12
- Volume
- 8
- Issue
- 3
- Pages
- e59199
- ISSN
- 1932-6203 (ISSN-L)
- PMC
- PMC3595244
- OpenAlex
- W2073488774
- Cited by
- 68
- References
- 42
- Citations by year
- 2025: 3 · 2024: 2 · 2023: 2 · 2022: 3 · 2021: 3 · 2020: 5 · 2019: 3 · 2018: 6 · 2017: 12 · 2016: 11 · 2015: 10 · 2014: 6 · 2013: 2
- FWCI
- 7.60
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- PLoS ONE (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, other-oa)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- ENLIGHTEN (Jurnal Bimbingan dan Konseling Islam) (acceptedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Leiden Repository (Leiden University) (submittedVersion)
- BORIS (University Library Bern) (submittedVersion, cc-by)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Open Access CRIS of the University of Bern
- Funders
- National Science Foundation
- Bristol-Myers Squibb
- Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (138267, 320030)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Disorders and Treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Menopause: Health Impacts and Treatments
- Keywords
- subclinical hyperthyroidism, subclinical hypothyroidism, subclinical thyroid dysfunction, cognitive decline, cognitive impairment, older adults, thyroid-stimulating hormone, free thyroxine, PROSPER trial, vascular risk
- MeSH terms
- Aged, Aged, 80 and over, Aging, Cognition Disorders, Female, Humans, Hyperthyroidism, Hypothyroidism, Longitudinal Studies, Male, Neuropsychological Tests, Risk Factors, Thyroid Function Tests, Thyroid Gland, Thyrotropin, Thyroxine
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