Subclinical thyroid dysfunction and the risk of cognitive decline: a meta-analysis of prospective cohort studies

Context: Although 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: This study sought to determine the risk of dementia and cognitive decline associated with subclinical thyroid dysfunction among prospective cohorts. Data Sources: We searched in MEDLINE and EMBASE from inception until November 2014. Study Selection: Two physicians identified prospective cohorts that assessed thyroid function 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. The primary outcome was dementia and decline in cognitive function was the secondary outcome. Data Synthesis: Eleven prospective cohorts followed 16,805 participants during a median followup of 44.4 months. Five studies analyzed the risk of dementia in subclinical hyperthyroidism (SHyper) (n 6410), six in subclinical hypothyroidism (SHypo) (n 7401). Five studies analyzedMMSE decline in SHyper (n 7895), seven in SHypo (n 8960). In random-effects models, the pooled adjusted risk ratio for dementia in SHyper was 1.67 (95% confidence interval, 1.04; 2.69) and 1.14 (95% confidence interval, 0.84; 1.55) in SHypo vs euthyroidism, both without evidence of significant heterogeneity (I2 0.0%). The pooled mean MMSE decline from baseline to followup (mean 32 mo) did not significantly differ between SHyper or SHypo vs euthyroidism. Conclusions: SHyper might be associated with an elevated risk for dementia, whereas SHypo 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.