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van Vliet NA, van Heemst D, Almeida OP, et al. Association of Thyroid Dysfunction With Cognitive Function: An Individual Participant Data Analysis. JAMA Intern Med. 2021;181(11):1440-1450doi: 10.1001/jamainternmed.2021.5078.
van Vliet, N. A., van Heemst, D., Almeida, O. P., Åsvold, B. O., Aubert, C. E., Bae, J. B., Barnes, L. E., Bauer, D. C., Blauw, G. J., Brayne, C., Cappola, A. R., Ceresini, G., Comijs, H. C., Dartigues, J. F., Degryse, J. M., Dullaart, R. P. F., van Eersel, M. E. A., den Elzen, W. P. J., Ferrucci, L., Fink, H. A., Flicker, L., Grabe, H. J., Han, J. W., Helmer, C., Huisman, M., Ikram, M. A., Imaizumi, M., de Jongh, R. T., Jukema, J. W., Kim, K. W., Kuller, L. H., Lopez, O. L., Mooijaart, S. P., Moon, J. H., Moutzouri, E., Nauck, M., Parle, J., Peeters, R. P., Samuels, M. H., Schmidt, C. O., Schminke, U., Slagboom, P. E., Stordal, E., Vaes, B., Völzke, H., Westendorp, R. G. J., Yamada, M., Yeap, B. B., Rodondi, N., Gussekloo, J., Trompet, S. (2021). Association of Thyroid Dysfunction With Cognitive Function: An Individual Participant Data Analysis. JAMA internal medicine, 181(11), 1440-1450. https://doi.org/10.1001/jamainternmed.2021.5078
van Vliet, Nicolien A, et al. "Association of Thyroid Dysfunction With Cognitive Function: An Individual Participant Data Analysis." JAMA internal medicine vol. 181,11 (2021): 1440-1450. doi: https://doi.org/10.1001/jamainternmed.2021.5078
van Vliet NA, van Heemst D, Almeida OP, Åsvold BO, Aubert CE, Bae JB, Barnes LE, Bauer DC, Blauw GJ, Brayne C, Cappola AR, Ceresini G, Comijs HC, Dartigues JF, Degryse JM, Dullaart RPF, van Eersel MEA, den Elzen WPJ, Ferrucci L, Fink HA, Flicker L, Grabe HJ, Han JW, Helmer C, Huisman M, Ikram MA, Imaizumi M, de Jongh RT, Jukema JW, Kim KW, Kuller LH, Lopez OL, Mooijaart SP, Moon JH, Moutzouri E, Nauck M, Parle J, Peeters RP, Samuels MH, Schmidt CO, Schminke U, Slagboom PE, Stordal E, Vaes B, Völzke H, Westendorp RGJ, Yamada M, Yeap BB, Rodondi N, Gussekloo J, Trompet S. Association of Thyroid Dysfunction With Cognitive Function: An Individual Participant Data Analysis. JAMA Intern Med. 2021 Nov 01;181(11):1440-1450. doi: 10.1001/jamainternmed.2021.5078. PMID: 34491268; PMCID: PMC8424529.
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JAMA Intern Med. 2021 Nov 01;181(11):1440-1450. doi: 10.1001/jamainternmed.2021.5078.

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

JAMA internal medicine

Nicolien A van Vliet, Diana van Heemst, Osvaldo P Almeida, Bjørn O Åsvold, Carole E Aubert, Jong Bin Bae, Linda E Barnes, Douglas C Bauer, Gerard J Blauw, Carol Brayne, Anne R Cappola, Graziano Ceresini, Hannie C Comijs, Jean-Francois Dartigues, Jean-Marie Degryse, Robin P F Dullaart, Marlise E A van Eersel, Wendy P J den Elzen, Luigi Ferrucci, Howard A Fink, Leon Flicker, Hans J Grabe, Ji Won Han, Catherine Helmer, Martijn Huisman, M Arfan Ikram, Misa Imaizumi, Renate T de Jongh, J Wouter Jukema, Ki Woong Kim, Lewis H Kuller, Oscar L Lopez, Simon P Mooijaart, Jae Hoon Moon, Elisavet Moutzouri, Matthias Nauck, Jim Parle, Robin P Peeters, Mary H Samuels, Carsten O Schmidt, Ulf Schminke, P Eline Slagboom, Eystein Stordal, Bert Vaes, Henry Völzke, Rudi G J Westendorp, Michiko Yamada, Bu B Yeap, Nicolas Rodondi, Jacobijn Gussekloo, Stella Trompet,

Affiliations

  1. Department of Internal Medicine, Section of Gerontology and Geriatrics, Leiden University Medical Center, Leiden, the Netherlands.
  2. Medical School, University of Western Australia, Perth, Western Australia, Australia.
  3. Western Australian Centre for Health and Ageing, University of Western Australia, Perth, Western Australia, Australia.
  4. K.G. Jebsen Center for Genetic Epidemiology, Department of Public Health and Nursing, NTNU, Norwegian University of Science and Technology, Trondheim, Norway.
  5. Department of Endocrinology, Clinic of Medicine, St Olav's Hospital, Trondheim University Hospital, Trondheim, Norway.
  6. HUNT Research Center, Department of Public Health and Nursing, NTNU, Norwegian University of Science and Technology, Levanger, Norway.
  7. Department of General Internal Medicine, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.
  8. Institute of Primary Health Care (BIHAM), University of Bern, Bern, Switzerland.
  9. Center for Clinical Management Research, Veterans Affairs Ann Arbor Healthcare System, Ann Arbor, Michigan.
  10. Institute for Healthcare Policy and Innovation, University of Michigan, Ann Arbor.
  11. Department of Neuropsychiatry, Seoul National University Bundang Hospital, Seongnam, South Korea.
  12. Department of Public Health and Primary Care, Cambridge Institute of Public Health, University of Cambridge, Cambridge, United Kingdom.
  13. Division of General Internal Medicine, School of Medicine, University of California, San Francisco.
  14. Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia.
  15. Department of Medicine and Surgery, University of Parma, Unit of Internal Medicine and Oncological Endocrinology, University Hospital of Parma, Parma, Italy.
  16. Department of Psychiatry, Amsterdam Public Health research institute, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands.
  17. GGZ inGeest Specialized Mental Health Care, Research and Innovation, Amsterdam, the Netherlands.
  18. UMR 1219, Bordeaux Population Health Research Center, Inserm, University of Bordeaux, Bordeaux, France.
  19. Department of Public Health and Primary Care, Katholieke Universiteit Leuven, Leuven, Belgium.
  20. Institute of Health and Society, Université catholique de Louvain, Brussels, Belgium.
  21. Division of Endocrinology, Department of Internal Medicine, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
  22. University Center for Geriatric Medicine, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
  23. Department of Clinical Chemistry and Laboratory Medicine, Leiden University Medical Center, Leiden, the Netherlands.
  24. Atalmedial Diagnostics Centre, Amsterdam, the Netherlands.
  25. Department of Clinical Chemistry, Amsterdam UMC, Amsterdam, the Netherlands.
  26. Longitudinal Studies Section, Translational Gerontology Branch, Harbor Hospital, Baltimore, Maryland.
  27. National Institute on Aging NIA-ASTRA Unit, Baltimore, Maryland.
  28. Geriatric Research Education and Clinical Center, VA Healthcare System, Minneapolis, Minnesota.
  29. Department of Medicine, University of Minnesota, Minneapolis.
  30. Department of Psychiatry and Psychotherapy, University Medicine Greifswald, Greifswald, Germany.
  31. German Center for Neurodegenerative Diseases (DZNE), Site Rostock/Greifswald, Germany.
  32. Department of Epidemiology and Biostatistics, Amsterdam Public Health Research Institute, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands.
  33. Department of Sociology, VU University Amsterdam, Amsterdam, the Netherlands.
  34. Department of Epidemiology, Erasmus MC, Rotterdam, the Netherlands.
  35. Department of Clinical Studies, Radiation Effects Research Foundation, Hiroshima and Nagasaki, Japan.
  36. Department of Internal Medicine and Endocrinology, Amsterdam UMC, Amsterdam, the Netherlands.
  37. Department of Cardiology, Leiden University Medical Center, Leiden, the Netherlands.
  38. Netherlands Heart Institute, Utrecht, the Netherlands.
  39. Department of Brain and Cognitive Science, Seoul National University College of Natural Sciences, Seoul, South Korea.
  40. Department of Psychiatry, Seoul National University, College of Medicine, Seoul, South Korea.
  41. Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania.
  42. Department of Neurology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania.
  43. Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, South Korea.
  44. Institute of Clinical Chemistry and Laboratory Medicine, University Medicine Greifswald, Greifswald, Germany.
  45. DZHK (German Centre for Cardiovascular Research), partner site, Greifswald, Germany.
  46. Institute of Clinical Sciences, University of Birmingham, Birmingham, United Kingdom.
  47. Department of Internal Medicine, Erasmus MC, Rotterdam, the Netherlands.
  48. Academic Center for Thyroid Diseases, Erasmus MC, Rotterdam, the Netherlands.
  49. Division of Endocrinology, Diabetes and Clinical Nutrition, Department of Medicine, Oregon Health & Science University, Portland.
  50. Department of Radiology, University Medicine Greifswald, Greifswald, Germany.
  51. Department of Neurology, University Medicine Greifswald, Greifswald, Germany.
  52. Department of Biomedical Data Sciences, Section of Molecular Epidemiology, Leiden University Medical Center, Leiden, the Netherlands.
  53. Max Planck Institute for Biology of Ageing, Cologne, Germany.
  54. Namsos Hospital, Nord-Trøndelag Hospital Trust, Namsos, Norway.
  55. Department of Mental Health, NTNU, Norwegian University of Science and Technology, Trondheim, Norway.
  56. Institute for Community Medicine, University Medicine Greifswald, Greifswald, Germany.
  57. Department of Public Health, Section of Epidemiology, Center for Healthy Aging, University of Copenhagen, Copenhagen, Denmark.
  58. Department of Endocrinology and Diabetes, Fiona Stanley Hospital, Western Australia, Australia.
  59. Department of Public Health and Primary Care, Leiden University Medical Center, Leiden, the Netherlands.

PMID: 34491268 PMCID: PMC8424529 DOI: 10.1001/jamainternmed.2021.5078

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.

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