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

Research output: Contribution to journalArticle

Abstract

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
Volume9
Issue number4
DOIs
StatePublished - Aug 2019

Fingerprint

Dementia
Atherosclerosis
Thyroid Gland
Thyroid Diseases
Hyperthyroidism
Hypothyroidism
Autoimmune Diseases
Confidence Intervals
Social Adjustment
Iodide Peroxidase
Death Certificates
Neuropsychological Tests
Thyrotropin
Serum
Autoimmunity
Thyroxine
Thyroid Hormones
Artifacts
Interviews
Antibodies

Keywords

  • Cohort
  • Dementia
  • Epidemiology
  • Thyroid

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism

Cite this

Association between thyroid dysfunction and incident dementia in the atherosclerosis risk in communities neurocognitive study. / George, Kristen M.; Lutsey, Pamela L.; Selvin, Elizabeth; Palta, Priya; Windham, Beverly Gwen; Folsom, Aaron R.

In: Journal of Endocrinology and Metabolism, Vol. 9, No. 4, 08.2019, p. 82-89.

Research output: Contribution to journalArticle

George, Kristen M. ; Lutsey, Pamela L. ; Selvin, Elizabeth ; Palta, Priya ; Windham, Beverly Gwen ; Folsom, Aaron R. / Association between thyroid dysfunction and incident dementia in the atherosclerosis risk in communities neurocognitive study. In: Journal of Endocrinology and Metabolism. 2019 ; Vol. 9, No. 4. pp. 82-89.
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abstract = "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.",
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AU - George, Kristen M.

AU - Lutsey, Pamela L.

AU - Selvin, Elizabeth

AU - Palta, Priya

AU - Windham, Beverly Gwen

AU - Folsom, Aaron R.

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N2 - 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.

AB - 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.

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