Association Between Subclinical Thyroid Dysfunction and Cognitive Decline: Findings From the ELSA-Brasil Study

Thyroid dysfunction has been associated with cognitive decline and dementia. However, the role of subtle thyroid hormone alterations in cognitive function is still debatable.

Participants without overt thyroid dysfunction aged 35-74 years at baseline were evaluated in 3 study waves (2008-2010, 2012-2014, and 2017-2019). We assessed baseline thyroid-stimulating hormone (TSH), free thyroxine (FT4), and free triiodothyronine (FT3). Cognitive performance was evaluated every 4 years in each wave using 10-word immediate and late recall, word recognition, semantic (animals category) and phonemic (letter f) verbal fluency, and the trail-making B-version tests. A global composite z-score was derived from these tests. The associations of TSH, FT4, and FT3 levels with cognitive decline over time were evaluated using linear mixed-effect models adjusted for sociodemographic, clinical, and lifestyle variables.

In 9 524 participants (mean age 51.2 ± 8.9 years old, 51% women, 52% White), there was no association between baseline TSH, FT4, and FT3 levels and cognitive decline during the follow-up. However, increase in FT4 levels over time was associated with faster memory (β = -0.004, 95% CI = -0.007; -0.001, p = .014), verbal fluency (β = -0.003, 95% CI = -0.007; -0.0005, p = .021), executive function (β = -0.004, 95% CI = -0.011; -0.003, p < .001), and global cognition decline (β = -0.003, 95% CI = -0.006; -0.001, p = .001). Decrease in FT4 levels over time was associated with faster verbal fluency (β = -0.003, 95% CI = -0.007; -0.0004, p = .025) and executive function (β = -0.004, 95% CI = -0.007; -0.0003, p = .031) decline.

An increase or decrease in FT4 levels over time was associated with faster cognitive decline in middle-aged and older adults without overt thyroid dysfunction during 8 years of follow-up.