Thyroid status and brain circulation: The Rotterdam Study.

Context Whether thyroid dysfunction is related to altered brain circulation in the general population remains unknown. Objective We determined the association of thyroid hormones with different markers of brain circulation within community-dwelling elderly. Design Three subcohorts of the Rotterdam Study, starting in 1989, 2000 and 2006 respectively. Setting Population-based. Patients or other participants A total of 5,142 participants (mean age, 63.8 years; 55.4% women), underwent venapuncture to measure serum thyroid-stimulating hormone (TSH), free thyroxine (FT4). Main outcome measures Between 2005 and 2015, all participants underwent phase-contrast brain magnetic resonance imaging to assess global brain perfusion (mL of blood flow/100 mL of brain/min). Arteriolar retinal calibers were assessed using digitized images of stereoscopic fundus color transparencies in 3,105 participants as markers of microcirculation. We investigated associations of TSH, FT4 with brain circulation measures using (non-)linear regression models. Results. FT4 (in pmol/L) levels had an inverse u-shaped association with global brain perfusion, such that high and low levels of FT4 were associated with lower global brain perfusion compared to middle levels of FT4. The difference in global brain perfusion between high FT4 levels (25 pmol/L) and middle FT4 levels (FT4 = 15 pmol/L; P non-linearity = 0.002) was up to -2.44 mL (95% confidence interval (95%CI)= -4.31; -0.56). Similarly, higher and lower levels of FT4, compared with middle FT4 levels, were associated with arteriolar retinal vessels (mean difference up to -2.46 µm, 95%CI -4.98; 0.05 for lower FT4). Conclusions These results suggest that thyroid dysfunction could lead to brain diseases such as stroke or dementia through a suboptimal brain circulation that is potentially modifiable.