Subclinical Hypothyroidism and Cognitive Impairment: Systematic Review and Meta-Analysis

J Clin Endocrinol Metab. 2015 Nov;100(11):4240-8. doi: 10.1210/jc.2015-2046. Epub 2015 Aug 25.


Background: The association between subclinical hypothyroidism (sHT) and cognitive impairment or risk of dementia is not well-defined, especially in the elderly, where the assessment of central nervous system function is challenging. The aim of this systematic review and meta-analysis was to evaluate the possible effect of sHT on cognitive decline and the risk of dementia.

Methods: Cognitive function was the primary outcome, evaluated as composite endpoint of incidence or prevalence of dementia or difference of Mini Mental State Examination, Wechsler Adult Intelligence Scale, and Wechsler Memory Scale-Revised scores.

Results: Thirteen studies were included in the meta-analysis. A significant risk of cognitive alteration was observed only in sHT individuals younger than age 75 years: composite endpoint odds ratio (OR) 1.56 (95% confidence interval [CI] 1.07-2.27, P = .02, I(2) = 82.5%), risk of dementia OR 1.81 (95% CI 1.43-2.28, P < .01, I(2) = 35%). Mean serum thyroid-stimulating hormone (TSH) levels and the OR of composite endpoint were positively correlated. No significant effect of sHT was found when considering all the studies as a whole: composite endpoint OR 1.26 (95% CI 0.96-1.66, P = .09, I(2) = 87.2%), risk of dementia OR 1.42 (95% CI, 0.97-2.07, P = .07, I(2) = 66.8%), Mini Mental State Examination mean difference -0.059 (95% CI -0.464 to 0.346 P = .78, I(2) = 51.8%).

Conclusions: This meta-analysis demonstrates a relationship between sHT and cognitive impairment only in individuals younger than 75 years of age and those with higher TSH concentrations. No correlation was found while considering all the studies as a whole. The lack of utilization of age-related serum TSH reference ranges and consequent potential misdiagnosis of sHT in older people may account for this.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't
  • Review
  • Systematic Review

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Cognition Disorders / etiology*
  • Cognition Disorders / psychology*
  • Female
  • Humans
  • Hypothyroidism / complications*
  • Hypothyroidism / drug therapy
  • Hypothyroidism / psychology*
  • Male
  • Middle Aged
  • Neuropsychological Tests
  • Thyroid Function Tests
  • Treatment Outcome