Subclinical Hypothyroidism is Associated with Cognitive Impairment in Patients with Cerebral Small Vessel Disease

Objective: To investigate the association between subclinical hypothyroidism (SCH) and cognitive function in patients with cerebral small vessel disease (CSVD).Methods: We evaluated 528 patients with CSVD in this retrospective study. SCH was defined as elevated levels of thyroid stimulating hormone with normal concentrations of free thyroxine. Magnetic resonance imaging was performed to assess the total CSVD burden score and the Montreal Cognitive Assessment was used to measure the cognitive function. Participants were grouped based on cognitive function or total CSVD burden score. Multivariate logistic regression and mediation analysis models were used to estimate the association of SCH with cognitive function and CSVD burden.Results: SCH was an independent risk factor for cognitive impairment in patients with CSVD after adjustment for potential confounding factors (OR: 1.939; 95% CI: 1.170 to 3.213; P=0.010). Additionally, SCH was independently associated with severe CSVD burden after adjustment for potential confounding factors (OR: 1.668; 95% CI: 1.085 to 2.564; P=0.020). Mediation analysis found a significant moderating effect (P=0.021) of the severe CSVD burden on the relation between SCH and cognitive impairment after adjustment for potential confounding factors. A 30.1% of the total effect between this relation was attributable to the presence of severe CSVD burden. Conclusion: SCH was associated with an increased risk of cognitive impairment in patients with CSVD. The mediating role of severe CSVD burden suggests that SCH may lead to cognitive impairment through the presence of severe CSVD burden. These findings may suggest strategies for screening for SCH in the context of cognitive impairment in patients with severe CSVD.