Association of Thyroid Dysfunction With Cognitive Function: An Individual Participant Data Analysis.
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Authors
van Vliet, Nicolien A
van Heemst, Diana
Almeida, Osvaldo P
Åsvold, Bjørn O
Aubert, Carole E
Bae, Jong Bin
Bauer, Douglas C
Blauw, Gerard J
Cappola, Anne R
Ceresini, Graziano
Comijs, Hannie C
Dartigues, Jean-Francois
Degryse, Jean-Marie
Dullaart, Robin PF
van Eersel, Marlise EA
den Elzen, Wendy PJ
Ferrucci, Luigi
Fink, Howard A
Flicker, Leon
Grabe, Hans J
Han, Ji Won
Helmer, Catherine
Huisman, Martijn
Ikram, M Arfan
Imaizumi, Misa
de Jongh, Renate T
Jukema, J Wouter
Kim, Ki Woong
Kuller, Lewis H
Lopez, Oscar L
Mooijaart, Simon P
Moon, Jae Hoon
Moutzouri, Elisavet
Nauck, Matthias
Parle, Jim
Peeters, Robin P
Samuels, Mary H
Schmidt, Carsten O
Schminke, Ulf
Slagboom, P Eline
Stordal, Eystein
Vaes, Bert
Völzke, Henry
Westendorp, Rudi GJ
Yamada, Michiko
Yeap, Bu B
Rodondi, Nicolas
Gussekloo, Jacobijn
Trompet, Stella
Thyroid Studies Collaboration
Publication Date
2021-11-01Journal Title
JAMA Internal Medicine
ISSN
2168-6106
Publisher
American Medical Association
Volume
181
Issue
11
Pages
1440-1450
Type
Article
This Version
VoR
Physical Medium
Print
Metadata
Show full item recordCitation
van Vliet, N. A., van Heemst, D., Almeida, O. P., Åsvold, B. O., Aubert, C. E., Bae, J. B., Barnes, L., et al. (2021). Association of Thyroid Dysfunction With Cognitive Function: An Individual Participant Data Analysis.. JAMA Internal Medicine, 181 (11), 1440-1450. https://doi.org/10.1001/jamainternmed.2021.5078
Abstract
Importance: In clinical guidelines, overt and subclinical thyroid dysfunction are mentioned as causal and treatable factors for cognitive decline. However, the scientific literature on these associations shows inconsistent findings. Objective: To assess cross-sectional and longitudinal associations of baseline thyroid dysfunction with cognitive function and dementia. Design, Setting, and Participants: This multicohort individual participant data analysis assessed 114 267 person-years (median, 1.7-11.3 years) of follow-up for cognitive function and 525 222 person-years (median, 3.8-15.3 years) for dementia between 1989 and 2017. Analyses on cognitive function included 21 cohorts comprising 38 144 participants. Analyses on dementia included eight cohorts with a total of 2033 cases with dementia and 44 573 controls. Data analysis was performed from December 2016 to January 2021. Exposures: Thyroid function was classified as overt hyperthyroidism, subclinical hyperthyroidism, euthyroidism, subclinical hypothyroidism, and overt hypothyroidism based on uniform thyrotropin cutoff values and study-specific free thyroxine values. Main Outcomes and Measures: The primary outcome was global cognitive function, mostly measured using the Mini-Mental State Examination. Executive function, memory, and dementia were secondary outcomes. Analyses were first performed at study level using multivariable linear regression and multivariable Cox regression, respectively. The studies were combined with restricted maximum likelihood meta-analysis. To overcome the use of different scales, results were transformed to standardized mean differences. For incident dementia, hazard ratios were calculated. Results: Among 74 565 total participants, 66 567 (89.3%) participants had normal thyroid function, 577 (0.8%) had overt hyperthyroidism, 2557 (3.4%) had subclinical hyperthyroidism, 4167 (5.6%) had subclinical hypothyroidism, and 697 (0.9%) had overt hypothyroidism. The study-specific median age at baseline varied from 57 to 93 years; 42 847 (57.5%) participants were women. Thyroid dysfunction was not associated with global cognitive function; the largest differences were observed between overt hypothyroidism and euthyroidism-cross-sectionally (-0.06 standardized mean difference in score; 95% CI, -0.20 to 0.08; P = .40) and longitudinally (0.11 standardized mean difference higher decline per year; 95% CI, -0.01 to 0.23; P = .09). No consistent associations were observed between thyroid dysfunction and executive function, memory, or risk of dementia. Conclusions and Relevance: In this individual participant data analysis of more than 74 000 adults, subclinical hypothyroidism and hyperthyroidism were not associated with cognitive function, cognitive decline, or incident dementia. No rigorous conclusions can be drawn regarding the role of overt thyroid dysfunction in risk of dementia. These findings do not support the practice of screening for subclinical thyroid dysfunction in the context of cognitive decline in older adults as recommended in current guidelines.
Keywords
Thyroid Studies Collaboration
Sponsorship
Medical Research Council (G0601022)
Medical Research Council (G9901400)
Identifiers
External DOI: https://doi.org/10.1001/jamainternmed.2021.5078
This record's URL: https://www.repository.cam.ac.uk/handle/1810/336272
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