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From the Laboratory of Epidemiology, Demography, and Biometry (Drs. Volpato, Guralnik, and Launer), National Institute on Aging, Bethesda; Departments of Medicine and Epidemiology (Dr. Fried), The Johns Hopkins Medical Institutions, Baltimore; National Institutes of Health (Dr. Remaley), Clinical Center, Clinical Pathology Department, Bethesda; Division of Endocrinology, Diabetes, and Nutrition (Dr. Cappola), University of Maryland School of Medicine, Baltimore; and Department of Clinical and Experimental Medicine (Dr. Volpato), University of Ferrara, Italy.
Address correspondence and reprint requests to Dr. Stefano Volpato, National Institute on Aging, 7201 Wisconsin Avenue, Room 3C-309, Bethesda, MD 20892; e-mail: vlt{at}unife.it
Background: Clinical and subclinical hypothyroidism is associated with cognitive impairment.
Objective: This study investigated the association between thyroxine (T4) and thyroid-stimulating hormone (TSH) level and change over time in cognitive performance in a sample of older women with normal thyroid gland function.
Methods: T4 and TSH were measured at baseline in 628 women (
65 years) enrolled in the Women’s Health and Aging Study, a community-based study of physically impaired women. Cognitive function was assessed at baseline and after 1, 2, and 3 years, using the Mini-Mental State Examination (MMSE). Incident cognitive decline was defined as a decrease of more than one point/year in MMSE score between baseline and the end of the follow-up. The analysis included 464 subjects with normal thyroid gland function with a baseline and at least one follow-up MMSE.
Results: At baseline there was no association between T4 and TSH level and cognitive function. In longitudinal analysis, adjusting for age, race, level of education, and other covariates, compared with women in the highest T4 tertile (8.1 to 12.5 µg/dL), those in the lowest tertile (4.5 to 6.5 µg/dL) had a greater decline in MMSE score (-0.25 point/year vs -0.12 point/year; p = 0.04). A total of 95 women (20.5%) had cognitive decline during the study period (mean MMSE decline, 5.5 points). Compared with women in the highest T4 tertile, those in the lowest tertile had a twofold risk of cognitive decline (adjusted relative risk, 1.97; 95% CI, 1.10 to 3.50). The results were not modified by baseline cognitive and physical function. There was no association between baseline TSH level and change in cognitive function.
Conclusions: In older women, low T4 levels, within the normal range, were associated with a greater risk of cognitive decline over a 3-year period. Thyroid hormone levels may contribute to cognitive impairment in physically impaired women.
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