High Levels of Free Triiodothyronine Associated with Reduced Alzheimer’s Risk in Patients with Cognitive Impairment

High levels of free triiodothyronine — a type of thyroid hormone — are associated with a lower rate of Alzheimer’s disease risk in patients who have subjective or objective mild cognitive impairment, a new study shows.

The study, “Low serum concentration of free triiodothyronine (FT3) is associated with increased risk of Alzheimer’s disease,” was published in the journal Psychoneuroendocrinology.

Thyroid hormone (TH) receptors are widely expressed throughout the brain. They are essential for the developing central nervous system (CNS) in a fetus and can influence the adult CNS by promoting nerve development and cellular repair.

The thyroid gland is responsible for the production of two main hormones — thyroxine (T4) and triiodothyronine (T3) — upon stimulation by the thyroid stimulating hormone (TSH).

While very high or very low levels of thyroid hormones can cause different types of disease, studies have shown that variations within the normal range have also been associated with increased risk of age-associated impairments and mortality.

Epidemiological studies have shown that high thyroid hormone levels are associated with increased risk of dementia. However, specific studies conducted in Alzheimer’s disease patients suggest that thyroid hormone concentrations may actually be lower compared to those of healthy individuals. But little is known about the predictive role of these hormones during early disease stages, when patients show signs of cognitive dysfunction but do not have clinically detectable dementia.

Now, researchers conducted a study in patients with subjective cognitive impairment (SCI) or objective mild cognitive impairment (MCI) to determine whether serum thyroid hormone concentrations were associated with a risk of conversion to Alzheimer’s disease or vascular dementia.

Subjective cognitive impairment occurs when a patient reports a worsening of thinking abilities, including memory, but the decline cannot be verified by standard tests. Objective mild cognitive impairment is a syndrome of cognitive decline beyond that expected for an individual’s age and education level, but does not notably interfere with activities of daily living.

In this single-center study, researchers assessed the levels of TSH, free thyroxine (FT4), and free triiodothyronine (FT3) across 302 patients. None of the patients had received prior treatment with thyroid hormones.

During follow-up (mean 2.8 years), 82 patients (28%) progressed to dementia, among which 55 (18%) developed Alzheimer’s disease and 17 (6%) developed vascular dementia.

Statistical analysis revealed that levels of TSH, FT4, and FT3 were not associated with all-cause dementia or vascular dementia.

However, higher levels of FT3 were associated with a lower risk of developing Alzheimer’s: patients in the lowest quartile of FT3 levels had a twofold increase in the risk of developing Alzheimer’s compared to those in the highest quartile.

These associations remained significant even after adjusting for multiple confounding variables.

“In a memory clinic population, there was an inverse linear association between serum FT3 and risk of AD [Alzheimer’s disease] whereas THs [thyroid hormones] did not associate with all-cause dementia or VaD [vascular dementia],” researchers said.

“The results of our study endorse that monitoring of serum FT3 could be of additional value to the standard blood screening tests in patients who seek help for cognitive complaints, to assist in the prediction of the risk of AD,” they added.

The authors also suggested that supplementation with thyroid hormones could be of use in patients who are likely to develop Alzheimer’s disease but have not yet presented symptoms.