High Thyroid Hormone Levels May Increase Dementia Risk

One hypothesis is that thyroid function affects dementia risk through nonvascular pathways.
One hypothesis is that thyroid function affects dementia risk through nonvascular pathways.

High and high-normal thyroid function is linked to greater risk of developing dementia, but not vascular brain disease, according to research published in Neurology.1

Previous research has outlined a definitive role for thyroid hormone in both brain and cardiovascular function, and dysfunction has been linked to cardiovascular disease.2,3 Given that cardiovascular risk factors are being investigated as possible modifiable risk factors for dementia, researchers led by Layal Chaker, MD, MSc, of Erasmus University Rotterdam, the Netherlands investigated the role of thyroid function in dementia, cognitive decline, and vascular brain disease.

The study examined a subgroup of 9446 participants (mean age 65) prospectively enrolled into the Rotterdam Study. Researchers used Cox models adjusted for age, sex, cardiovascular risk factors, and education to investigate the association between thyroid-stimulating hormone (TSH) and free thyroxine with incident dementia. Linear and logistic regression was used to evaluate the associations between thyroid function, cognitive scores, and subclinical vascular brain disease as seen on MRI.

Over the course of follow-up (mean 8 years), 601 patients developed dementia (Alzheimer's dementia n=487). Higher levels of TSH were found to be associated with lower dementia risk for both the full and normal ranges of thyroid function, independent of cardiovascular risk factors (hazard ratio [HR] 0.90, 95% confidence interval [CI] 0.83–0.98; and HR 0.76, 95% CI 0.64–0.91, respectively). Participants with higher levels of free thyroxine were found to have greater dementia risk (HR 1.04, 95% CI 1.01–1.07).

Higher levels of TSH were associated with better cognitive scores (P =.021), and in older women, a 5% decrease in absolute 10-year dementia risk. Notably, thyroid function was not found to be associated with subclinical vascular brain disease.

The results, the authors concluded, suggest that thyroid hormone impacts dementia risk through nonvascular pathways. Alternate hypotheses proposed by researchers include the possibility that excess free thyroxine may alter gene expression in critical neural pathways or that neurotoxicity secondary to oxidative stress may lead to premature neuronal death.

Additionally, participants with preclinical dementia may exhibit behavioral changes, including diet, which may alter thyroid function. “In other words, we may not be observing a true effect of thyroid hormone on dementia risk but rather the opposite,” the authors concluded.

Ultimately, further research is needed to better understand the pathways in which thyroid function affects dementia risk.

Disclosures: Oscar H. Franco, MD, PhD, works in ErasmusAGE, a center for aging research funded by Nestle' Nutrition (Nestec Ltd), Metagenics Inc, and AXA. Robin P Peeters, MD, PhD, has received lecture and consultancy fees from Genzyme.

References

  1. Chaker L, Wolters FJ, Bos D, et al. Thyroid function and the risk of dementia: The Rotterdam Study. Neurology. 2016 Sep 16. doi:10.1212/WNL.0000000000003227 [Epub ahead of print]
  2. Klein I, Danzi S. Thyroid disease and the heart. Circulation. 2007;116:1725–1735.
  3. Cappola AR, Ladenson PW. Hypothyroidism and atherosclerosis. J Clin Endocrinol Metab. 2003;88:2438–2444.
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