Subclinical hyperthyroidism and the risk of dementia. The Rotterdam study

Clin Endocrinol (Oxf). 2000 Dec;53(6):733-7. doi: 10.1046/j.1365-2265.2000.01146.x.


AIMS AND SUBJECTS: 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.

Methods: 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.

Results: 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).

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

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Alzheimer Disease / blood
  • Alzheimer Disease / complications
  • Autoantibodies / blood
  • Dementia / blood
  • Dementia / complications*
  • Female
  • Follow-Up Studies
  • Humans
  • Hyperthyroidism / blood
  • Hyperthyroidism / complications*
  • Iodide Peroxidase / immunology
  • Logistic Models
  • Male
  • Middle Aged
  • Netherlands
  • Prospective Studies
  • Risk Factors
  • Thyrotropin / blood
  • Thyroxine / blood


  • Autoantibodies
  • Thyrotropin
  • Iodide Peroxidase
  • Thyroxine