Thyroid dysfunction and the risk of dementia and cognitive decline: Systematic review, meta-analysis and clinical implications

Context: While both overt hyper- and hypothyroidism are known to lead to cognitive impairment, data on the association between subclinical thyroid dysfunction and cognitive function are conflicting. Objective: To determine the risk of dementia and cognitive decline associated with subclinical thyroid dysfunction among prospective cohort studies. Data Sources: Search in MEDLINE and EMBASE (inception until November 2014) and reference lists of key articles without language restrictions. Study Selection: Two physicians identified prospective cohorts that assessed thyroid function at baseline and cognitive outcomes (dementia; Mini-Mental State Examination, MMSE). Data Extraction: Data were extracted by one reviewer following standardized protocols and verified by a second reviewer. Both reviewers independently assessed study quality. The primary outcomes were dementia and decline in cognitive function measured by MMSE. We calculated risk ratios and 95% confidence intervals using random-effects models. Data Synthesis: Eleven prospective cohorts followed 16,805 participants during a median follow-up of 44.4 months. Five studies analyzed the risk of dementia in subclinical hyperthyroidism (n=6410), six in subclinical hypothyroidism (n=7401). Five studies analyzed MMSE decline in subclinical hyperthyroidism (n=7895), seven in subclinical hypothyroidism (n=8960). In random-effects models, the pooled adjusted RR for dementia in subclinical hyperthyroidism was 1.67 (95% confidence interval [CI] 1.04-2.69) and 1.14 (95%CI 0.84-1.55) in subclinical hypothyroidism versus euthyroidism, both without evidence of significant heterogeneity (I2=0.0%). Sensitivity analyses pooling only studies with formal outcome adjudication or population-based studies yielded similar results. The pooled mean MMSE decline from baseline to follow-up (mean 32 months) did not significantly differ between subclinical hyper- or hypothyroidism versus euthyroidism. Conclusions: Subclinical hyperthyroidism might be associated with an elevated risk for dementia, while subclinical hypothyroidism is not, and both conditions are not associated with faster decline in MMSE over time. Available data are limited, and additional large, high-quality studies are needed