Association of Thyroid Dysfunction With Cognitive Function: An Individual Participant Data Analysis.
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van Vliet Nicolien A, van Heemst Diana, Almeida Osvaldo P, Åsvold Bjørn O, Aubert Carole E, Bae Jong Bin, Barnes Linda E, Bauer Douglas C, Blauw Gerard J, Brayne Carol, Cappola Anne R, Ceresini Graziano, Comijs Hannie C, Dartigues Jean-Francois, Degryse Jean-Marie, Dullaart Robin P F, van Eersel Marlise E A, den Elzen Wendy P J, 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 G J, Yamada Michiko, Yeap Bu B, Rodondi Nicolas, Gussekloo Jacobijn, Trompet Stella, Thyroid Studies Collaboration
Аннотация
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.