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Subclinical hyperthyroidism and the risk of dementia. The Rotterdam study


: Dr M. M. B. Breteler, Department of Epidemiology & Biostatistics, Erasmus University Medical School, PO Box 1738, 3000 DR Rotterdam, the Netherlands. Fax: +31 10 4089382; E-mail:


We investigated the prospective relationship between thyroid status and the risk of dementia and Alzheimer's disease among a random sample of 1843 participants, aged 55 years and over, from the population-based prospective Rotterdam Study.

Thyroid status was measured at baseline (1990–93), through assessment of serum antibodies to thyroid peroxidase (TPO-Abs, positive: >10 IU/ml), serum TSH levels, and when TSH was abnormal (<0·4 or >4·0 mU/l), serum thyroxin levels (T4). At baseline and at follow up, after on average 2 years, participants were screened for dementia. Diagnoses were based on international criteria.

Persons with reduced TSH levels at baseline had a more than threefold increased risk of dementia (RR = 3·5, 95%CI: 1·2–10·0) and of Alzheimer's disease (RR = 3·5, 95%CI: 1·1–11·5), after adjustment for age and sex. Among persons with reduced TSH levels, T4 levels appeared to be positively related to the risk of dementia (RR per SD increase = 2·9, 95%CI: 0·7–12·2), although none of those who became demented had a T4 level above the normal range (>140 nmol/l). The risk of dementia was especially increased in subjects with low TSH who were positive for TPO-Abs (RR = 23·7, 95%CI: 4·0–140).

This is the first prospective study to suggest that subclinical hyperthyroidism in the elderly increases the risk of dementia and Alzheimer's disease.