Association of Thyroid Dysfunction With Cognitive Function
JAMA Internal Medicine, vol. 181, pp. 1440
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.
Authors 51
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Nicolien A van Vliet corresponding Aachen Department of Internal Medicine Section of Gerontology and Geriatrics
Leiden University Medical Center
Affiliation as printed
Department of Internal Medicine, Section of Gerontology and Geriatrics, Leiden University Medical Center, Leiden, the Netherlands
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Leiden University Medical Center
Affiliation as printed
Department of Internal Medicine, Section of Gerontology and Geriatrics, Leiden University Medical Center, Leiden, the Netherlands
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The University of Western Australia
Affiliation as printed
Medical School, University of Western Australia, Perth, Western Australia, Australia
Western Australian Centre for Health and Ageing, University of Western Australia, Perth, Western Australia, Australia
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Norwegian University of Science and Technology · St Olav's University Hospital
Affiliation as printed
Department of Endocrinology, Clinic of Medicine, St Olav’s Hospital, Trondheim University Hospital, Trondheim, Norway
HUNT Research Center, Department of Public Health and Nursing, NTNU, Norwegian University of Science and Technology, Levanger, Norway
K.G. Jebsen Center for Genetic Epidemiology, Department of Public Health and Nursing, NTNU, Norwegian University of Science and Technology, Trondheim, Norway
Department of Endocrinology, Clinic of Medicine, St Olav's Hospital, Trondheim University Hospital, Trondheim, Norway
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University of Bern · University of Michigan · University Hospital of Bern · VA Ann Arbor Healthcare System · VA Center for Clinical Management Research
Affiliation as printed
Center for Clinical Management Research, Veterans Affairs Ann Arbor Healthcare System, Ann Arbor, Michigan
Department of General Internal Medicine, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland
Institute for Healthcare Policy and Innovation, University of Michigan, Ann Arbor
Institute of Primary Health Care (BIHAM), University of Bern, Bern, Switzerland
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Seoul National University · Seoul National University Bundang Hospital
Affiliation as printed
Department of Neuropsychiatry, Seoul National University Bundang Hospital, Seongnam, South Korea
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Affiliation as printed
Department of Public Health and Primary Care, Cambridge Institute of Public Health, University of Cambridge, Cambridge, United Kingdom
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University of California, San Francisco
Affiliation as printed
Division of General Internal Medicine, School of Medicine, University of California, San Francisco
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Leiden University Medical Center
Affiliation as printed
Department of Internal Medicine, Section of Gerontology and Geriatrics, Leiden University Medical Center, Leiden, the Netherlands
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Affiliation as printed
Department of Public Health and Primary Care, Cambridge Institute of Public Health, University of Cambridge, Cambridge, United Kingdom
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Affiliation as printed
Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia
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University of Parma · Ospedale di Parma
Affiliation as printed
Department of Medicine and Surgery, University of Parma, Unit of Internal Medicine and Oncological Endocrinology, University Hospital of Parma, Parma, Italy
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Amsterdam Public Health · GGZ inGeest · Amsterdam University Medical Centers · Vrije Universiteit Amsterdam
Affiliation as printed
Department of Psychiatry, Amsterdam Public Health research institute, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands
GGZ inGeest Specialized Mental Health Care, Research and Innovation, Amsterdam, the Netherlands
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Université de Bordeaux · Inserm · Bordeaux Population Health
Affiliation as printed
UMR 1219, Bordeaux Population Health Research Center, Inserm, University of Bordeaux, Bordeaux, France
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Affiliation as printed
Department of Public Health and Primary Care, Katholieke Universiteit Leuven, Leuven, Belgium
Institute of Health and Society, Université catholique de Louvain, Brussels, Belgium
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University Medical Center Groningen · University of Groningen
Affiliation as printed
Division of Endocrinology, Department of Internal Medicine, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands
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University Medical Center Groningen · University of Groningen
Affiliation as printed
University Center for Geriatric Medicine, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands
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Leiden University Medical Center · Amsterdam University Medical Centers
Affiliation as printed
Atalmedial Diagnostics Centre, Amsterdam, the Netherlands
Department of Clinical Chemistry and Laboratory Medicine, Leiden University Medical Center, Leiden, the Netherlands
Department of Clinical Chemistry, Amsterdam UMC, Amsterdam, the Netherlands
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Affiliation as printed
Longitudinal Studies Section, Translational Gerontology Branch, Harbor Hospital, Baltimore, Maryland
National Institute on Aging NIA-ASTRA Unit, Baltimore, Maryland
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University of Minnesota · Minneapolis VA Health Care System · Minneapolis VA Medical Center
Affiliation as printed
Department of Medicine, University of Minnesota, Minneapolis
Geriatric Research Education and Clinical Center, VA Healthcare System, Minneapolis, Minnesota
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The University of Western Australia
Affiliation as printed
Medical School, University of Western Australia, Perth, Western Australia, Australia
Western Australian Centre for Health and Ageing, University of Western Australia, Perth, Western Australia, Australia
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Universitätsmedizin Greifswald · German Center for Neurodegenerative Diseases · Universität Greifswald
Affiliation as printed
Department of Psychiatry and Psychotherapy, University Medicine Greifswald, Greifswald, Germany
German Center for Neurodegenerative Diseases (DZNE), Site Rostock/Greifswald, Germany
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Seoul National University · Seoul National University Bundang Hospital
Affiliation as printed
Department of Neuropsychiatry, Seoul National University Bundang Hospital, Seongnam, South Korea
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Université de Bordeaux · Inserm · Bordeaux Population Health
Affiliation as printed
UMR 1219, Bordeaux Population Health Research Center, Inserm, University of Bordeaux, Bordeaux, France
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Amsterdam Public Health · Amsterdam University Medical Centers · Vrije Universiteit Amsterdam
Affiliation as printed
Department of Epidemiology and Biostatistics, Amsterdam Public Health Research Institute, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands
Department of Sociology, VU University Amsterdam, Amsterdam, the Netherlands
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Affiliation as printed
Department of Epidemiology, Erasmus MC, Rotterdam, the Netherlands
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Radiation Effects Research Foundation
Affiliation as printed
Department of Clinical Studies, Radiation Effects Research Foundation, Hiroshima and Nagasaki, Japan
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Amsterdam University Medical Centers
Affiliation as printed
Department of Internal Medicine and Endocrinology, Amsterdam UMC, Amsterdam, the Netherlands
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Leiden University Medical Center · Netherlands Heart Institute
Affiliation as printed
Department of Cardiology, Leiden University Medical Center, Leiden, the Netherlands
Netherlands Heart Institute, Utrecht, the Netherlands
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Seoul National University · Seoul National University Bundang Hospital
Affiliation as printed
Department of Brain and Cognitive Science, Seoul National University College of Natural Sciences, Seoul, South Korea
Department of Neuropsychiatry, Seoul National University Bundang Hospital, Seongnam, South Korea
Department of Psychiatry, Seoul National University, College of Medicine, Seoul, South Korea
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Affiliation as printed
Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania
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Affiliation as printed
Department of Neurology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania
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Leiden University Medical Center
Affiliation as printed
Department of Internal Medicine, Section of Gerontology and Geriatrics, Leiden University Medical Center, Leiden, the Netherlands
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Seoul National University · Seoul National University Bundang Hospital
Affiliation as printed
Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, South Korea
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University of Bern · University Hospital of Bern
Affiliation as printed
Department of General Internal Medicine, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland
Institute of Primary Health Care (BIHAM), University of Bern, Bern, Switzerland
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Universitätsmedizin Greifswald · Universität Greifswald · German Centre for Cardiovascular Research
Affiliation as printed
DZHK (German Centre for Cardiovascular Research), partner site, Greifswald, Germany
Institute of Clinical Chemistry and Laboratory Medicine, University Medicine Greifswald, Greifswald, Germany
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Affiliation as printed
Institute of Clinical Sciences, University of Birmingham, Birmingham, United Kingdom
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Affiliation as printed
Academic Center for Thyroid Diseases, Erasmus MC, Rotterdam, the Netherlands
Department of Internal Medicine, Erasmus MC, Rotterdam, the Netherlands
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Oregon Health & Science University
Affiliation as printed
Division of Endocrinology, Diabetes and Clinical Nutrition, Department of Medicine, Oregon Health & Science University, Portland
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Universitätsmedizin Greifswald · Universität Greifswald
Affiliation as printed
Department of Radiology, University Medicine Greifswald, Greifswald, Germany
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Universitätsmedizin Greifswald · Universität Greifswald
Affiliation as printed
Department of Neurology, University Medicine Greifswald, Greifswald, Germany
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Leiden University Medical Center · Max Planck Institute for Biology of Ageing
Affiliation as printed
Department of Biomedical Data Sciences, Section of Molecular Epidemiology, Leiden University Medical Center, Leiden, the Netherlands
Max Planck Institute for Biology of Ageing, Cologne, Germany
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Norwegian University of Science and Technology · Namsos Hospital
Affiliation as printed
Department of Mental Health, NTNU, Norwegian University of Science and Technology, Trondheim, Norway
Namsos Hospital, Nord-Trøndelag Hospital Trust, Namsos, Norway
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Affiliation as printed
Department of Public Health and Primary Care, Katholieke Universiteit Leuven, Leuven, Belgium
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Universitätsmedizin Greifswald · Universität Greifswald
Affiliation as printed
Institute for Community Medicine, University Medicine Greifswald, Greifswald, Germany
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University of Copenhagen · Leiden University Medical Center
Affiliation as printed
Department of Internal Medicine, Section of Gerontology and Geriatrics, Leiden University Medical Center, Leiden, the Netherlands
Department of Public Health, Section of Epidemiology, Center for Healthy Aging, University of Copenhagen, Copenhagen, Denmark
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Radiation Effects Research Foundation
Affiliation as printed
Department of Clinical Studies, Radiation Effects Research Foundation, Hiroshima and Nagasaki, Japan
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The University of Western Australia · Fiona Stanley Hospital
Affiliation as printed
Department of Endocrinology and Diabetes, Fiona Stanley Hospital, Western Australia, Australia
Medical School, University of Western Australia, Perth, Western Australia, Australia
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University of Bern · University Hospital of Bern
Affiliation as printed
Department of General Internal Medicine, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland
Institute of Primary Health Care (BIHAM), University of Bern, Bern, Switzerland
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Jacobijn Gussekloo Aachen Department of Internal Medicine Section of Gerontology and Geriatrics Department of Public Health and Primary Care
Leiden University Medical Center
Affiliation as printed
Department of Internal Medicine, Section of Gerontology and Geriatrics, Leiden University Medical Center, Leiden, the Netherlands
Department of Public Health and Primary Care, Leiden University Medical Center, Leiden, the Netherlands
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Leiden University Medical Center
Affiliation as printed
Department of Internal Medicine, Section of Gerontology and Geriatrics, Leiden University Medical Center, Leiden, the Netherlands
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