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J Clin Endocrinol Metab. 2016 Dec;101(12):4945-4954. Epub 2016 Sep 30.

Subclinical Thyroid Dysfunction and the Risk of Cognitive Decline: a Meta-Analysis of Prospective Cohort Studies.

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Department of General Internal Medicine (C.R., D.S., C.E.A., C.B., D.A., N.R.), Inselspital, Bern University Hospital, University of Bern, 3010 Bern, Switzerland; Institute of Primary Health Care (BIHAM), Faculty of Medicine (B.R.d.C., N.R.), University of Bern, 3012 Bern, Switzerland; Service of Endocrinology, Diabetes and Metabolism (T.-H.C.), University Hospital of Lausanne, 1011 Lausanne, Switzerland; University of Cambridge Metabolic Research Laboratories (T.-H.C.), Wellcome Trust-MRC Institute of Metabolic Science, Addenbrooke's Hospital, Cambridge CB2 0QQ, United Kingdom; Department of Epidemiology (L.C., R.P.P.), Rotterdam Thyroid Center, 3015 GE Rotterdam, The Netherlands; School of Psychiatry and Clinical Neurosciences (O.P.A.), University of Western Australia, Perth 6009, Australia; School of Sport, Exercise and Health Sciences (E.H.), Loughborough University, Loughborough LE11 3TU, United Kingdom; Department of Cardiology (S.T.), Leiden University Medical Center, 2333 ZA Leiden, The Netherlands; Kuakini Medical Center and the Department of Geriatric Medicine (K.M.), John A. Burns School of Medicine, University of Hawaii, Honolulu, Hawaii 96817; Department of Gerontology and Geriatrics (S.P.M.), Leiden University Medical Center, Leiden and Institute for Evidence-based Medicine in Old Age (IEMO), 2333 ZA Leiden, The Netherlands; Department of Public Health and Primary Care (J.G.), Leiden University Medical Center, 2333 ZA Leiden, The Netherlands; and Department of Medicine (D.C.B.), University of California-San Francisco, San Francisco California 94143.



Although both overt hyper- and hypothyroidism are known to lead to cognitive impairment, data on the association between subclinical thyroid dysfunction and cognitive function are conflicting.


This study sought to determine the risk of dementia and cognitive decline associated with subclinical thyroid dysfunction among prospective cohorts.


We searched in MEDLINE and EMBASE from inception until November 2014.


Two physicians identified prospective cohorts that assessed thyroid function and cognitive outcomes (dementia; Mini-Mental State Examination [MMSE]).


Data were extracted by one reviewer following standardized protocols and verified by a second reviewer. The primary outcome was dementia and decline in cognitive function was the secondary outcome.


Eleven prospective cohorts followed 16,805 participants during a median followup of 44.4 months. Five studies analyzed the risk of dementia in subclinical hyperthyroidism (SHyper) (n = 6410), six in subclinical hypothyroidism (SHypo) (n = 7401). Five studies analyzed MMSE decline in SHyper (n = 7895), seven in SHypo (n = 8960). In random-effects models, the pooled adjusted risk ratio for dementia in SHyper was 1.67 (95% confidence interval, 1.04; 2.69) and 1.14 (95% confidence interval, 0.84; 1.55) in SHypo vs euthyroidism, both without evidence of significant heterogeneity (I2 = 0.0%). The pooled mean MMSE decline from baseline to followup (mean 32 mo) did not significantly differ between SHyper or SHypo vs euthyroidism.


SHyper might be associated with an elevated risk for dementia, whereas SHypo is not, and both conditions are not associated with faster decline in MMSE over time. Available data are limited, and additional large, high-quality studies are needed.

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