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

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2168-6106

Name of journal: JAMA internal medicineAbstract: Conclusions and Relevance: In this individual participant data analysis of more than 74000 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.Design, Setting, and Participants: This multicohort individual participant data analysis assessed 114267 person-years (median, 1.7-11.3 years) of follow-up for cognitive function and 525222 person-years (median, 3.8-15.3 years) for dementia between 1989 and 2017. Analyses on cognitive function included 21 cohorts comprising 38144 participants. Analyses on dementia included eight cohorts with a total of 2033 cases with dementia and 44573 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.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.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.Objective: To assess cross-sectional and longitudinal associations of baseline thyroid dysfunction with cognitive function and dementia.Results: Among 74565 total participants, 66567 (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; 42847 (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.All authors: Almeida OP, Asvold BO, Aubert CE, Bae JB, Barnes LE, Bauer DC, Blauw GJ, Brayne C, Cappola AR, Ceresini G, Comijs HC, Dartigues JF, de Jongh RT, Degryse JM, den Elzen WPJ, Dullaart RPF, Ferrucci L, Fink HA, Flicker L, Grabe HJ, Gussekloo J, Han JW, Helmer C, Huisman M, Ikram MA, Imaizumi M, Jukema JW, Kim KW, Kuller LH, Lopez OL, Mooijaart SP, Moon JH, Moutzouri E, Nauck M, Parle J, Peeters RP, Rodondi N, Samuels MH, Schmidt CO, Schminke U, Slagboom PE, Stordal E, Thyroid Studies Collaboration, Trompet S, Vaes B, van Eersel MEA, van Heemst D, van Vliet NA, Volzke H, Westendorp RGJ, Yamada M, Yeap BBOriginally published: JAMA Internal Medicine. 2021 Sep 07JAMA Internal Medicine. 181(11):1440-1450, 2021 11 01.Fiscal year: FY2022Fiscal year of original publication: FY2022Digital Object Identifier:

https://dx.doi.org/10.1001/jamainternmed.2021.5078

Date added to catalog: 2021-11-01

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Holdings
Item type	Current library	Collection	Call number	Status	Date due	Barcode
Journal Article	MedStar Authors Catalog	Article	34491268	Available		34491268

Conclusions and Relevance: In this individual participant data analysis of more than 74000 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.

Design, Setting, and Participants: This multicohort individual participant data analysis assessed 114267 person-years (median, 1.7-11.3 years) of follow-up for cognitive function and 525222 person-years (median, 3.8-15.3 years) for dementia between 1989 and 2017. Analyses on cognitive function included 21 cohorts comprising 38144 participants. Analyses on dementia included eight cohorts with a total of 2033 cases with dementia and 44573 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.

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.

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.

Objective: To assess cross-sectional and longitudinal associations of baseline thyroid dysfunction with cognitive function and dementia.

Results: Among 74565 total participants, 66567 (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; 42847 (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.

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