Dataset Information

Association of Thyroid Dysfunction With Cognitive Function: An Individual Participant Data Analysis.

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.

SUBMITTER: van Vliet NA

PROVIDER: S-EPMC8424529 | biostudies-literature | 2021 Nov

REPOSITORIES: biostudies-literature

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Publications

Association of Thyroid Dysfunction With Cognitive Function: An Individual Participant Data Analysis.

van Vliet Nicolien A NA van Heemst Diana D Almeida Osvaldo P OP Åsvold Bjørn O BO Aubert Carole E CE Bae Jong Bin JB Barnes Linda E LE Bauer Douglas C DC Blauw Gerard J GJ Brayne Carol C Cappola Anne R AR Ceresini Graziano G Comijs Hannie C HC Dartigues Jean-Francois JF Degryse Jean-Marie JM Dullaart Robin P F RPF van Eersel Marlise E A MEA den Elzen Wendy P J WPJ Ferrucci Luigi L Fink Howard A HA Flicker Leon L Grabe Hans J HJ Han Ji Won JW Helmer Catherine C Huisman Martijn M Ikram M Arfan MA Imaizumi Misa M de Jongh Renate T RT Jukema J Wouter JW Kim Ki Woong KW Kuller Lewis H LH Lopez Oscar L OL Mooijaart Simon P SP Moon Jae Hoon JH Moutzouri Elisavet E Nauck Matthias M Parle Jim J Peeters Robin P RP Samuels Mary H MH Schmidt Carsten O CO Schminke Ulf U Slagboom P Eline PE Stordal Eystein E Vaes Bert B Völzke Henry H Westendorp Rudi G J RGJ Yamada Michiko M Yeap Bu B BB Rodondi Nicolas N Gussekloo Jacobijn J Trompet Stella S

JAMA internal medicine 20211101 11

<h4>Importance</h4>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.<h4>Objective</h4>To assess cross-sectional and longitudinal associations of baseline thyroid dysfunction with cognitive function and dementia.<h4>Design, setting, and participants</h4>This multicohort individual participant data analysis assessed 114 267 perso ...[more]

PMID: 34491268

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Project description:BackgroundAdequate maternal thyroid function is important for an uncomplicated pregnancy. Although multiple observational studies have evaluated the association between thyroid dysfunction and hypertensive disorders of pregnancy, the methods and definitions of abnormalities in thyroid function tests were heterogeneous, and the results were conflicting. We aimed to examine the association between abnormalities in thyroid function tests and risk of gestational hypertension and pre-eclampsia.MethodsIn this systematic review and meta-analysis of individual-participant data, we searched MEDLINE (Ovid), Embase, Scopus, and the Cochrane Database of Systematic Reviews from date of inception to Dec 27, 2019, for prospective cohort studies with data on maternal concentrations of thyroid-stimulating hormone (TSH), free thyroxine (FT4), thyroid peroxidase (TPO) antibodies, individually or in combination, as well as on gestational hypertension, pre-eclampsia, or both. We issued open invitations to study authors to participate in the Consortium on Thyroid and Pregnancy and to share the individual-participant data. We excluded participants who had pre-existing thyroid disease or multifetal pregnancy, or were taking medications that affect thyroid function. The primary outcomes were documented gestational hypertension and pre-eclampsia. Individual-participant data were analysed using logistic mixed-effects regression models adjusting for maternal age, BMI, smoking, parity, ethnicity, and gestational age at blood sampling. The study protocol was registered with PROSPERO, CRD42019128585.FindingsWe identified 1539 published studies, of which 33 cohorts met the inclusion criteria and 19 cohorts were included after the authors agreed to participate. Our study population comprised 46 528 pregnant women, of whom 39 826 (85·6%) women had sufficient data (TSH and FT4 concentrations and TPO antibody status) to be classified according to their thyroid function status. Of these women, 1275 (3·2%) had subclinical hypothyroidism, 933 (2·3%) had isolated hypothyroxinaemia, 619 (1·6%) had subclinical hyperthyroidism, and 337 (0·8%) had overt hyperthyroidism. Compared with euthyroidism, subclinical hypothyroidism was associated with a higher risk of pre-eclampsia (2·1% vs 3·6%; OR 1·53 [95% CI 1·09-2·15]). Subclinical hyperthyroidism, isolated hypothyroxinaemia, or TPO antibody positivity were not associated with gestational hypertension or pre-eclampsia. In continuous analyses, both a higher and a lower TSH concentration were associated with a higher risk of pre-eclampsia (p=0·0001). FT4 concentrations were not associated with the outcomes measured.InterpretationCompared with euthyroidism, subclinical hypothyroidism during pregnancy was associated with a higher risk of pre-eclampsia. There was a U-shaped association of TSH with pre-eclampsia. These results quantify the risks of gestational hypertension or pre-eclampsia in women with thyroid function test abnormalities, adding to the total body of evidence on the risk of adverse maternal and fetal outcomes of thyroid dysfunction during pregnancy. These findings have potential implications for defining the optimal treatment target in women treated with levothyroxine during pregnancy, which needs to be assessed in future interventional studies.FundingArkansas Biosciences Institute and Netherlands Organization for Scientific Research.

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Dataset Information

Association of Thyroid Dysfunction With Cognitive Function: An Individual Participant Data Analysis.

Importance

Objective

Design, setting, and participants

Exposures

Main outcomes and measures

Results

Conclusions and relevance

Publications

Association of Thyroid Dysfunction With Cognitive Function: An Individual Participant Data Analysis.

Similar Datasets

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