No effect of thyroid hormones on 5‐year mortality in patients with subjective cognitive decline, mild cognitive disorder, and Alzheimer’s disease

The present study aimed to investigate differences in circulating thyroid hormone levels, gender, education, depressive symptoms, and cognitive performance among patients with cognitive impairment, and also to examine their associations, as well as that of cognitive decline, with 5-year mortality. Between 1998 and 2017, a hospital-based, single-centre (Neurology Department of the General Hospital in Vienna, Austria), retrospective follow-up study enrolled 2102 patients with mild to severe cognitive impairment (grouped into subjective cognitive decline, mild cognitive impairment, and Alzheimer's disease). Cox proportional hazards models were used to calculate hazard ratios (HRs), with 95% confidence intervals (CIs), as well as to calculate stepwise adjustments for demographic variables (age, gender, and education), depressive symptoms (Geriatric Depression Scale, GDS-15), and neuropsychological abilities (four domains of a neuropsychological test battery of Vienna, NTVB). In univariate analyses, total triiodothyronine (TT3) levels differed significantly between Alzheimer's disease and mild cognitive impairment patients (p(diff) = .001). No other differences in cognitive impairment subgroups with any of the measured thyroid hormones were observed. Furthermore, in multivariate models, circulating TT3 was not associated with mortality (multivariable-adjusted HR per unit increase in TT3 = 0.56; 95% CI = 0.29-1.07). In multivariate models, we observed significantly lower 5-year mortality among women (HR = 0.56; 95% CI = 0.43-0.73) and those who scored higher on any of the four domains of the NBTV (e.g., attention and perceptual speed, HR = 0.63; 95% CI = 0.54-0.72); we also observed significantly higher 5-year mortality among patients with depressive symptoms (HR per one point score increase in GDS-15 = 1.06; 95% CI = 1.02-1.10), regardless of cognitive impairment subgroup. Among patients with various degrees of cognitive impairment, we found no associations of thyroid hormone levels with 5-year mortality. Gender, neuropsychological abilities, and depressive symptoms were each significant predictors of 5-year mortality. These results suggest that a neurocognitive test performance could serve as an important predictor of 5-year mortality among patients with cognitive impairment, although further studies with a more complete adjustment for comorbidities are needed to confirm these findings.