title: Thyroid function and the risk of dementia: The Rotterdam Study.
abstract: OBJECTIVE
  To study the role of thyroid function in dementia, cognitive function, and subclinical vascular brain disease with MRI.
  
  
  METHODS
  Analyses were performed within the Rotterdam Study (baseline 1997), a prospective, population-based cohort. We evaluated the association of thyroid-stimulating hormone (TSH) and free thyroxine with incident dementia using Cox models adjusted for age, sex, cardiovascular risk factors, and education. Absolute risks were calculated accounting for death as a competing risk factor. Associations of thyroid function with cognitive test scores and subclinical vascular brain disease (white matter lesions, lacunes, and microbleeds) were assessed with linear or logistic regression. Additionally, we stratified by sex and restricted analyses to normal thyroid function.
  
  
  RESULTS
  We included 9,446 participants with a mean age of 65 years. During follow-up (mean 8.0 years), 601 participants had developed dementia. Higher TSH was associated with lower dementia risk in both the full and normal ranges of thyroid function (hazard ratio [HR] 0.90, 95% confidence interval [CI] 0.83-0.98; and HR 0.76, 95% CI 0.64-0.91, respectively). This association was independent of cardiovascular risk factors. Dementia risk was higher in individuals with higher free thyroxine (HR 1.04, 95% CI 1.01-1.07). Absolute 10-year dementia risk decreased from 15% to 10% with higher TSH in older women. Higher TSH was associated with better global cognitive scores (p = 0.021). Thyroid function was not related to subclinical vascular brain disease as indicated by MRI.
  
  
  CONCLUSIONS
  High and high-normal thyroid function is associated with increased dementia risk. Thyroid function is not related to vascular brain disease as assessed by MRI, suggesting a role for thyroid hormone in nonvascular pathways leading to dementia.
authors.affiliation: From the Rotterdam Thyroid Center (L.C., T.I.M.K., R.P.P.) and Departments of Internal Medicine (L.C., T.I.M.K., R.P.P.), Epidemiology (L.C., F.J.W., D.B., T.I.M.K., A.H., O.H.F., A.D., M.W.V., R.P.P., M.A.I.), Neurology (F.J.W., P.J.K., M.A.I.), and Radiology (D.B., A.v.d.L., M.W.V., M.A.I.), Erasmus University Medical Center, Rotterdam, the Netherlands; and Department of Epidemiology (A.H.), Harvard T.H. Chan School of Public Health, Boston, MA.
authors.forename: Layal
authors.initials: L
authors.lastname: Chaker
authors.affiliation: From the Rotterdam Thyroid Center (L.C., T.I.M.K., R.P.P.) and Departments of Internal Medicine (L.C., T.I.M.K., R.P.P.), Epidemiology (L.C., F.J.W., D.B., T.I.M.K., A.H., O.H.F., A.D., M.W.V., R.P.P., M.A.I.), Neurology (F.J.W., P.J.K., M.A.I.), and Radiology (D.B., A.v.d.L., M.W.V., M.A.I.), Erasmus University Medical Center, Rotterdam, the Netherlands; and Department of Epidemiology (A.H.), Harvard T.H. Chan School of Public Health, Boston, MA.
authors.forename: Frank J
authors.initials: FJ
authors.lastname: Wolters
authors.affiliation: From the Rotterdam Thyroid Center (L.C., T.I.M.K., R.P.P.) and Departments of Internal Medicine (L.C., T.I.M.K., R.P.P.), Epidemiology (L.C., F.J.W., D.B., T.I.M.K., A.H., O.H.F., A.D., M.W.V., R.P.P., M.A.I.), Neurology (F.J.W., P.J.K., M.A.I.), and Radiology (D.B., A.v.d.L., M.W.V., M.A.I.), Erasmus University Medical Center, Rotterdam, the Netherlands; and Department of Epidemiology (A.H.), Harvard T.H. Chan School of Public Health, Boston, MA.
authors.forename: Daniel
authors.initials: D
authors.lastname: Bos
authors.affiliation: From the Rotterdam Thyroid Center (L.C., T.I.M.K., R.P.P.) and Departments of Internal Medicine (L.C., T.I.M.K., R.P.P.), Epidemiology (L.C., F.J.W., D.B., T.I.M.K., A.H., O.H.F., A.D., M.W.V., R.P.P., M.A.I.), Neurology (F.J.W., P.J.K., M.A.I.), and Radiology (D.B., A.v.d.L., M.W.V., M.A.I.), Erasmus University Medical Center, Rotterdam, the Netherlands; and Department of Epidemiology (A.H.), Harvard T.H. Chan School of Public Health, Boston, MA.
authors.forename: Tim I M
authors.initials: TI
authors.lastname: Korevaar
authors.affiliation: From the Rotterdam Thyroid Center (L.C., T.I.M.K., R.P.P.) and Departments of Internal Medicine (L.C., T.I.M.K., R.P.P.), Epidemiology (L.C., F.J.W., D.B., T.I.M.K., A.H., O.H.F., A.D., M.W.V., R.P.P., M.A.I.), Neurology (F.J.W., P.J.K., M.A.I.), and Radiology (D.B., A.v.d.L., M.W.V., M.A.I.), Erasmus University Medical Center, Rotterdam, the Netherlands; and Department of Epidemiology (A.H.), Harvard T.H. Chan School of Public Health, Boston, MA.
authors.forename: Albert
authors.initials: A
authors.lastname: Hofman
authors.affiliation: From the Rotterdam Thyroid Center (L.C., T.I.M.K., R.P.P.) and Departments of Internal Medicine (L.C., T.I.M.K., R.P.P.), Epidemiology (L.C., F.J.W., D.B., T.I.M.K., A.H., O.H.F., A.D., M.W.V., R.P.P., M.A.I.), Neurology (F.J.W., P.J.K., M.A.I.), and Radiology (D.B., A.v.d.L., M.W.V., M.A.I.), Erasmus University Medical Center, Rotterdam, the Netherlands; and Department of Epidemiology (A.H.), Harvard T.H. Chan School of Public Health, Boston, MA.
authors.forename: Aad
authors.initials: A
authors.lastname: van der Lugt
authors.affiliation: From the Rotterdam Thyroid Center (L.C., T.I.M.K., R.P.P.) and Departments of Internal Medicine (L.C., T.I.M.K., R.P.P.), Epidemiology (L.C., F.J.W., D.B., T.I.M.K., A.H., O.H.F., A.D., M.W.V., R.P.P., M.A.I.), Neurology (F.J.W., P.J.K., M.A.I.), and Radiology (D.B., A.v.d.L., M.W.V., M.A.I.), Erasmus University Medical Center, Rotterdam, the Netherlands; and Department of Epidemiology (A.H.), Harvard T.H. Chan School of Public Health, Boston, MA.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Koudstaal
authors.affiliation: From the Rotterdam Thyroid Center (L.C., T.I.M.K., R.P.P.) and Departments of Internal Medicine (L.C., T.I.M.K., R.P.P.), Epidemiology (L.C., F.J.W., D.B., T.I.M.K., A.H., O.H.F., A.D., M.W.V., R.P.P., M.A.I.), Neurology (F.J.W., P.J.K., M.A.I.), and Radiology (D.B., A.v.d.L., M.W.V., M.A.I.), Erasmus University Medical Center, Rotterdam, the Netherlands; and Department of Epidemiology (A.H.), Harvard T.H. Chan School of Public Health, Boston, MA.
authors.forename: Oscar H
authors.initials: OH
authors.lastname: Franco
authors.affiliation: From the Rotterdam Thyroid Center (L.C., T.I.M.K., R.P.P.) and Departments of Internal Medicine (L.C., T.I.M.K., R.P.P.), Epidemiology (L.C., F.J.W., D.B., T.I.M.K., A.H., O.H.F., A.D., M.W.V., R.P.P., M.A.I.), Neurology (F.J.W., P.J.K., M.A.I.), and Radiology (D.B., A.v.d.L., M.W.V., M.A.I.), Erasmus University Medical Center, Rotterdam, the Netherlands; and Department of Epidemiology (A.H.), Harvard T.H. Chan School of Public Health, Boston, MA.
authors.forename: Abbas
authors.initials: A
authors.lastname: Dehghan
authors.affiliation: From the Rotterdam Thyroid Center (L.C., T.I.M.K., R.P.P.) and Departments of Internal Medicine (L.C., T.I.M.K., R.P.P.), Epidemiology (L.C., F.J.W., D.B., T.I.M.K., A.H., O.H.F., A.D., M.W.V., R.P.P., M.A.I.), Neurology (F.J.W., P.J.K., M.A.I.), and Radiology (D.B., A.v.d.L., M.W.V., M.A.I.), Erasmus University Medical Center, Rotterdam, the Netherlands; and Department of Epidemiology (A.H.), Harvard T.H. Chan School of Public Health, Boston, MA.
authors.forename: Meike W
authors.initials: MW
authors.lastname: Vernooij
authors.affiliation: From the Rotterdam Thyroid Center (L.C., T.I.M.K., R.P.P.) and Departments of Internal Medicine (L.C., T.I.M.K., R.P.P.), Epidemiology (L.C., F.J.W., D.B., T.I.M.K., A.H., O.H.F., A.D., M.W.V., R.P.P., M.A.I.), Neurology (F.J.W., P.J.K., M.A.I.), and Radiology (D.B., A.v.d.L., M.W.V., M.A.I.), Erasmus University Medical Center, Rotterdam, the Netherlands; and Department of Epidemiology (A.H.), Harvard T.H. Chan School of Public Health, Boston, MA. r.peeters@erasmusmc.nl.
authors.forename: Robin P
authors.initials: RP
authors.lastname: Peeters
authors.affiliation: From the Rotterdam Thyroid Center (L.C., T.I.M.K., R.P.P.) and Departments of Internal Medicine (L.C., T.I.M.K., R.P.P.), Epidemiology (L.C., F.J.W., D.B., T.I.M.K., A.H., O.H.F., A.D., M.W.V., R.P.P., M.A.I.), Neurology (F.J.W., P.J.K., M.A.I.), and Radiology (D.B., A.v.d.L., M.W.V., M.A.I.), Erasmus University Medical Center, Rotterdam, the Netherlands; and Department of Epidemiology (A.H.), Harvard T.H. Chan School of Public Health, Boston, MA.
authors.forename: M Arfan
authors.initials: MA
authors.lastname: Ikram
mesh_terms: D000368:Aged; D001921:Brain / Q000000981:diagnostic imaging*; D002318:Cardiovascular Diseases / Q000097:blood / Q000000981:diagnostic imaging / Q000453:epidemiology; D003430:Cross-Sectional Studies; D003704:Dementia / Q000097:blood* / Q000000981:diagnostic imaging* / Q000453:epidemiology; D005500:Follow-Up Studies; D006801:Humans; D015994:Incidence; D008279:Magnetic Resonance Imaging; D008875:Middle Aged; D011446:Prospective Studies; D012307:Risk Factors; D012680:Sensitivity and Specificity; D013961:Thyroid Gland / Q000378:metabolism; D013972:Thyrotropin / Q000097:blood*; D013974:Thyroxine / Q000097:blood*
chemical_list: D013972:Thyrotropin; D013974:Thyroxine