Increased risk of dementia in hypothyroidism: A Danish nationwide register-based study

Clin Endocrinol (Oxf). 2021 Jun;94(6):1017-1024. doi: 10.1111/cen.14424. Epub 2021 Jan 31.

Abstract

Objective: Globally, the prevalence of individuals with dementia is increasing, and identification of risk factors is of paramount interest. Using population-based registers, we evaluated whether hypothyroidism is a risk factor for dementia.

Design: Register-based cohort study.

Patients and methods: Risk of dementia was evaluated in two cohorts. The DNPR cohort comprises 111,565 hypothyroid patients, diagnosed between 1995 and 2012, and 446,260 euthyroid age- and sex-matched individuals (median follow-up 6.2 years). The OPENTHYRO cohort comprises 233,844 individuals with at least one measurement of serum thyrotropin (TSH) between 1995 and 2011, of whom 2,894 had hypothyroidism (median follow-up 7.2 years). Primary outcome was dementia defined as an International Classification of Diseases 10 code, or prescription of medicine for dementia.

Results: In the DNPR cohort, risk of dementia was significantly increased in subjects with hypothyroidism (HR 1.22; 95% CI: 1.17-1.27), which attenuated after adjusting for pre-existing comorbidity (HR 0.82; 95% CI: 0.79-0.86). Stratification of age into ≤56 and >56 years showed an inverse relationship between age and risk of dementia (HR≤56 years. 2.03; 95% CI: 1.62-2.53 and HR>56 years . 1.00; 95% CI: 0.96-1.05). In the OPENTHYRO cohort, the risk of dementia was significantly increased for each 6 months of elevated TSH (HR 1.12; 95% CI: 1.07-1.16).

Conclusions: Hypothyroidism is associated with increased risk of dementia. The association is influenced by comorbidity and age. Every 6 months of elevated TSH increased the risk of dementia by 12%, suggesting that also the length of hypothyroidism influences the risk of dementia.

Keywords: Alzheimer's disease; Hashimoto's disease; Hypothyroidism; autoimmunity; register study; vascular dementia.

MeSH terms

  • Cohort Studies
  • Dementia* / epidemiology
  • Dementia* / etiology
  • Denmark / epidemiology
  • Humans
  • Hyperthyroidism*
  • Hypothyroidism* / complications
  • Hypothyroidism* / epidemiology
  • Middle Aged
  • Risk Factors
  • Thyrotropin

Substances

  • Thyrotropin