Quinlan, P., Horvath, A., Wallin, A., & Svensson, J. (2019). Low serum concentration of free triiodothyronine (FT3) is associated with increased risk of Alzheimer’s disease. Psychoneuroendocrinology, 99, 112–119. https://doi.org/10.1016/j.psyneuen.2018.09.002
JAN 2019: Study reports increased risk of Alzheimer’s disease with low-normal Free T3 thyroid hormone.
“Patients in the lowest FT3 quartile had a more than twofold increased risk of progressing to AD compared to those in the highest quartile (HR=2.63; 95% CI=1.06–6.47).”
For every 1 pmol/L rise in FT3, Alzheimer’s progression risk decreased by approximately half (HR=0.54; 95% CI=0.32–0.92), even after correcting for age and gender.
Quinlan et al reported a study of patients who sought help from a memory clinic in Sweden. Their study took place over 6 years, during which time 55 of the 302 participants converted to Alzheimer’s disease (18.2%). The mean follow-up time from testing to disease progression was 2.6 years.
TSH and Free T4 levels were not associated with Alzheimer’s disease progression.
All of their FT3 levels were in the reference range, and all were considered “clinically euthyroid.”
None of the participants were taking thyroid hormones.
None of the participants were ill in any way that could have caused cognitive difficulty.
Reference ranges: TSH: 0.3–4.2 mlU/l • FT4: 12–22 pmol/L • FT3: 3.1–6.8 pmol/L
Averages across all 302 participants:
- TSH 2.1 (46% of range)
- FT4 15.6 (36% of range)
- FT3 4.8 (46% of range)
The highest risk existed in the lowest quartile:
- FT3 3.5–4.5 pmol/L (10% – 38% of range)
- average FT3 4.3 (32% of range)
- average FT4 of 14.9 (29% of range) and TSH of 2.1.
- 71% in this quartile were women
Patients in the highest quartile had least risk:
- FT3 5.3–6.7 pmol/L (59% – 97% of range)
- Average FT3 5.56 (66% of range)
- Average FT4 of 16.6 (46% of range) and TSH of 2.3.
- 39% in this quartile were women
The researchers reasoned that “when the brain is already suffering from on-going AD neuropathology, a lack of T3 could contribute to further disease progression.”
“The results or our study endorses 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 [Alzheimer’s].”
“Moreover, our findings may suggest that supplementation with THs [thyroid hormones] could be of use in patients with prodromal AD.”
“Further studies are therefore needed to investigate if supplementation with thyroxine (T4) or liothyronine (T3) may contribute to the maintenance of cognitive function, thereby delaying the onset of dementia in patients with SCI or MCI.”
We applaud this study for including Free T3 and subjecting this measurement to such careful analysis.
A key strength of this study’s methodology was the way it divided patients by FT3 quartiles. We encourage future studies of FT3 and health to use this method.
The patients’ thyroid hormone levels on average across the entire cohort were unremarkable, so the study would not have discovered anything of significance if they had not divided patients into quartiles (4 categories) across their TSH, Free T4 and Free T3 levels.
This is one of only a handful of studies that has examined Free T3 levels in relation to cognitive decline. Two previous studies found similar results, but in older and more frail populations. This article discussed a prior study (Gusselkoo et al, 2004) that discovered low FT3 associated with “faster cognitive decline” in patients over 85 years of age, and another recent study (Pasqualetti et al, 2018) that associated low FT3/FT4 ratio with reduced cognition in an acutely ill geriatric ward (again, over 85 years old).
A major limitation of this study was that it did not measure FT3 levels over time, only at baseline. In this study, we don’t know how much an individual patient’s FT3 levels varied, but the strong pattern in the data suggests that they likely had chronically low levels over time.
In addition, like most studies that correlate FT3 levels and health outcomes, this one excluded treated thyroid patients from study.
- On one hand, excluding thyroid patients was wise because thyroid hormone medication would have distorted the results considerably. For example, levothyroxine monotherapy inflates FT4 and lowers FT3 at the same TSH as healthy controls.
- On the other hand, thyroid patients’ exclusion is a weakness from the perspective of thyroid patients on standard T4 monotherapy who struggle with lower FT3 levels.
We can only hope that future studies at this same clinic will focus on treated thyroid patients as a cohort and compare our results with those of this untreated population.
In general, researchers’ neglect of T3, the most important and essential thyroid hormone must come to an end.
This study should give impetus for FT3 to be included in more and more studies as a variable.