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.
Original language | English |
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Pages (from-to) | 1440-1450 |
Number of pages | 11 |
Journal | Jama internal medicine |
Volume | 181 |
Issue number | 11 |
Early online date | 7 Sept 2021 |
DOIs | |
Publication status | Published - Nov 2021 |
Funding
Funders | Funder number |
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Becton Dickinson | |
BÄK | |
DGKL | |
Dutch Alzheimer Foundation | |
European Commission Horizon 2020 | |
European Union Interreg | 01ZZ0403, INT-10-0008, 81Z7400171, 01ZZ0103, 01ZZ9603, 81Z7400173 |
GCCR | |
German Federal State of Mecklenburg-West Pomerania | |
German Medical Association | |
ISBER | |
Max Rubner-Institut | |
Netherlands Ministry of Health Welfare and Sports, Directorate of Long-Term Care | |
RERF | RP-A2-16 |
National Institutes of Health | |
U.S. Department of Energy | |
National Institute on Aging | ICS110.1/RF97.71, N01-AG-6-2106, 263 MD, N01-AG-6-2101, R01-AG028050, N01-AG-6-2103 |
National Heart, Lung, and Blood Institute | |
National Institute of Nursing Research | R01-NR012459 |
National Institute of Neurological Disorders and Stroke | R01AG023629 |
National Institute of Arthritis and Musculoskeletal and Skin Diseases | |
AstraZeneca | |
National Center for Advancing Translational Sciences | UL1TR002369, U01 AG027810, U01 AG042140, U01 AG042139, U01 AR066160, U01 AG042124, U01 AG042168, U01 AG042145, UL1 TR000128, U01 AG042143 |
Velux Stiftung | 1156 |
Oregon Clinical and Translational Research Institute | |
Deutsches Zentrum für Herz-Kreislaufforschung | |
Fresenius Medical Care North America | |
European Commission | |
National Health and Medical Research Council | |
Deutsche Forschungsgemeinschaft | |
Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung | 75N92021D00006, HHSN268200800007C, N01HC55222, N01HC85081, U01HL080295, N01HC85082, HHSN268201800001C, N01HC85080, HHSN268201200036C, N01HC85086, N01HC85083, N01HC85079, SNSF 320030-172676, U01HL130114 |
Bundesministerium für Bildung und Forschung | |
Nierstichting | E.033 |
Ministero della Salute | |
Ministry of Health, Labour and Welfare | |
Ministry of Health and Welfare | A092077, HI09C1379 |
Horizon 2020 | 666869 |
European Association for the Study of Diabetes |
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Longitudinal Aging Study Amsterdam
Huisman, M. (Creator), van Tilburg, T. (Creator), Broese Van Groenou, M. (Creator), Suanet, B. (Creator), Visser, M. (Creator), Kok, A. A. L. (Creator), Hoogendijk, E. O. (Creator), Deeg, D. (Creator), Schaap, L. (Creator), Beekman, A. F. T. (Creator) & van Schoor, N. M. (Creator), Amsterdam UMC, 1992
Dataset / Software: Dataset