Interactive Effects of Apolipoprotein E ε4 and Triiodothyronine on Memory Performance in Patients With Subjective Cognitive Decline

Abstract

Background: The aim of the present study was to investigate the associations between thyroid hormones, cognitive performance, and apolipoprotein E (APOE) genotype in euthyroid patients with subjective cognitive decline (SCD). Methods: We recruited 197 euthyroid patients that fulfilled the criteria for SCD. All participants were classified into APOE ε4 carriers and non-carriers based on the presence of the APOE ε4 allele. Patients with SCD who had the APOE ε2/ε4 genotype were excluded from the study. We then performed correlation and regression analyses to evaluate the associations between cognitive performance and thyroid hormones in APOE ε4 carriers and non-carriers. Results: We found no significant differences in cognitive function between APOE ε4 carriers and non-carriers. However, higher levels of triiodothyronine (T3) were associated with better verbal memory performance (immediate and delayed recall tasks) in APOE ε4 carriers, whereas a negative association was found in APOE ε4 non-carriers. Furthermore, there was a significant interactive effect of APOE ε4 status and T3 levels on verbal memory performance (immediate and delayed recall tasks). Conclusions: These findings suggest that in patients with SCD, T3 might have a protective effect on memory in those who are APOE ε4 carriers. The differential susceptibility hypothesis would thus support a gene-by-hormone crossover interaction between APOE ε4 allele and T3 in this study. Early identification and intervention of high-risk individuals for cognitive decline is important to establish new strategies for preventing dementia.

Keywords: Alzheimer's disease; apolipoprotein E; subjective cognitive decline; thyroid hormone; triiodothyronine.

Figure 1

Flow chart of the study participants. SCD, subjective cognitive decline; MRI, magnetic resonance imaging; APOE, apolipoprotein E.

Figure 2

Scatter plots investigating the relation between memory performance and serum T3 levels in patients with SCD according to APOE ε4 status showing interaction effects of APOE ε4 status and T3 level on the results of (A) the SVLT immediate recall (p = 0.032) and (B) the SVLT delayed recall (p = 0.004) task. T3, triiodothyronine; SCD, subjective cognitive decline; APOE, apolipoprotein E; SVLT, Seoul verbal learning test.