Association between thyroid dysfunction and incident dementia in the atherosclerosis risk in communities neurocognitive study

Kristen M. George, Pamela L. Lutsey, Elizabeth Selvin, Priya Palta, Beverly Gwen Windham, Aaron R. Folsom

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15 Scopus citations


Background: Abnormal thyroid hormone levels (high or low) and autoimmunity from autoimmune thyroid disease (AITD) may increase dementia risk. Methods: We examined the associations of thyroid dysfunction or possible AITD in 1990-1992 with dementia through 2017 in the Atherosclerosis Risk in Communities (ARIC) Neurocognitive Study. Thyroid dysfunction (subclinical and overt hypo- or hyperthyroidism and euthyroidism) was categorized from serum thyroid-stimulating hormone (TSH) and free thyroxine (FT4) cut-points and AITD from anti-thyroid peroxidase (anti-TPO) antibody positivity. Dementia was identified primarily based on cognitive test performance, neuropsychological examinations and clinician review of suspected cases. Additional cases of dementia were ascertained through telephone interviews or relevant hospital and death certificate codes. Cox regression with multivariable adjustment was used for analysis. Results: After exclusions for missing data, 12,481 participants were included in the analysis (mean index exam age 57 ± 5.7 (44% male, 25% black)), and 2,235 incident dementia cases were identified. AITD was not significantly associated with dementia. Subclinical hypothyroidism was associated with a lower risk of dementia (hazard ratio (HR) (95% confidence interval (CI)): 0.74 (0.60-0.92)), while overt hyperthyroidism was associated with a higher risk of dementia (HR (95% CI): 1.40 (1.02-1.92)) compared to euthyroid participants. Participants with serum FT4 concentrations above the 95th percentile were at an increased risk of dementia compared to those in the middle 90% of FT4 (HR (95% CI): 1.23 (1.02-1.48)). Conclusions: Subclinical hypothyroidism was associated with reduced risk of dementia, whereas overt hyperthyroidism, particularly very elevated FT4, was associated with increased risk of dementia. The association between subclinical hypothyroidism and reduced risk of dementia cannot be explained, but may have been an artifact due to change. By extrapolation, effective treatment of overt hyperthyroidism may modestly reduce dementia risk in older adults.

Original languageEnglish (US)
Pages (from-to)82-89
Number of pages8
JournalJournal of Endocrinology and Metabolism
Issue number4
StatePublished - Aug 2019

Bibliographical note

Funding Information:
We would like to thank the staff and participants of the ARIC study for their important contributions. We would also like to thank Dr. Lisa S. Chow at the University of Minnesota Department of Medicine, Division of Diabetes, Endocrinology, and Metabolism for technical support.

Funding Information:
Dr. George was supported by National Heart, Lung, and Blood Institute (NHLBI) Training Grant T32HL007779. Dr. Selvin was supported by NIH/NIDDK grants K24DK106414 and R01DK089174. Dr. Palta was supported by NIH/NIA grant K99AG052830. The Atherosclerosis Risk in Communities Study is carried out as a collaborative study supported by National Heart, Lung, and Blood Institute contracts (HHSN268201700001I, HHSN268201700002I, HHSN268201700003I, HHSN268201 700004I, HHSN268201700005I). Neurocognitive data were collected by U01 2U01HL096812, 2U01HL096814, 2U01HL 096899, 2U01HL096902, 2U01HL096917 from the NIH (NHLBI, NINDS, NIA and NIDCD), and with previous brain MRI examinations funded by R01-HL70825 from the NHLBI. Reagents for the thyroid function tests were donated by Roche Diagnostics.

Publisher Copyright:
© 2019 The authors.


  • Cohort
  • Dementia
  • Epidemiology
  • Thyroid


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