Low vitamin D levels are associated with cognitive impairment in patients with Hashimoto thyroiditis

Of 212 patients diagnosed as HT were consecutively recruited from the First Affiliated Hospital of Jiaxing University between 16 March 2014 and 24 February 2017. Diagnosis of HT was based on positive anti-thyroid peroxidase antibodies (TPOAbs) and/or anti-thyroglobulin antibodies (TgAbs), associated with a ultrasound patterns suggestive of HT. Eligibility criteria included: (1) Chinese ethnicity; (2) age from 18 to 60 years; (3) stable L-thyroxine treatment; (4) harboring the willingness to give informed consent. Exclusion criteria were: (1) patients with a history of other endocrine diseases; (2) patients with a history of cognitive or psychiatric disorders; (3) patients with a history of osteoporosis; (4) patients receiving vitamin D replacement therapy. Meanwhile, 200 healthy volunteers without any euthyroid, neurological or psychiatric diseases, were recruited from a health survey of the same regions.

Demographic and clinical variables were obtained from participant report and electronic medical records. Demographic inclued age, sex, body mass index (BMI) and education. BMI was calculated as weight (kg)/squared height (m²). A fasting morning venous blood sample was obtained from each participant. Levels of serum thyroid-stimulating hormone (TSH), free-triiodothyronine (FT3), free thyroxine (FT4), TgAbs, and TPOAbs were determined with automated immuno chemiluminescent assay (ICMA) kits (Abbott Laboratories, IL, USA). Levels of serum 25-hydroxyvitamin D (25(OH)D) were determined using a competitive protein-binding assay (Roche Diagnostics, Mannheim, Germany). The inter-assay variation coefficient for 25(OH)D measurement was 8.5%. Serum 25(OH)D levels in HT patients were divided into four quartiles (≤ 34.0, 34.1–40.0, 40.1–47.0 and ≥ 47.1 nmol/L), as the raw data of 25(OH)D were skewed. The median 25-hydroxyvitamin D values for all quartiles were 30.8, 36.6, 43.7 and 53.1 nmol/L, respectively.

Cognitive funtion was assessed using Montreal Cognitive Assessment score (MoCA), a simple cognitive screening tool with superior sensitivity [18]. The MoCA is a one-page 30-point test that can be administered in 10 min. It covers important cognitive domains, including short-term memory, visuospatial abilities, executive functions, attention, concentration, working memory, and language, together with orientation to time and place. Based on the MoCA scoring system, patients were divided into two groups: the patients who had MoCA scores < 26 were selected as mild cognitive impairment (MCI) group, and the other patients who had MoCA scores of 26 or greater were selected as the group without MCI. These evaluations were administered by the same experienced psychologist who was blind to the laboratory results of HT patients.

Data were presented as number (percentage) for categorical variables, mean ± standard deviation (SD) for normally distributed variables, and medians (25th, 75th percentiles) for non-normally distributed variables. Comparisons between the groups were conducted using the χ² test, Fisher’s exact test, Student t test, and Mann–Whitney U test, as appropriate. Binary logistic regression including age, sex, and the factors with P < 0.10 in the univariate analysis, was performed to examine significant risk factors for cognitive impairment in HT patients. The abnormally distributed parameters were log-transformed for satisfying the log-linearity assumption. The results were presented as odds ratios (OR) with corresponding 95% confidence intervals (CI). All Statistical analysis were performed by using SPSS 22.0 (Chicago, IL). Significance level was defined as P < 0.05.

Of 212 patients with HT, 18 were excluded from this analysis: 2 with a history of dementia, 6 taking vitamin D replacement therapy, and 10 who refused to participate in this study. There were no significant differences in age and sex between our study cohort (N = 194) and those excluded. Of 194 participants, 158 were male (81.4%) and their mean (SD) age was 49.4 (9.8) years. The patients in this study did not differ from the controls in terms of age, sex, BMI, education, as well as levels of TSH, FT3, and FT4 (all P > 0.05) (Table 1).

Of the 194 patients who formed the study sample, 55 (28.4%, 42 female, 13 male) were diagnosed with MCI. Serum levels of 25(OH)D were markedly lower in patients with HT than in healthy controls (40.4 (34.3–46.9) vs. 58.3 (52.1–64.8) nmol/L, P < 0.001). There was a postive correlation between 25(OH)D levels and MoCA scores (r = 0.828, P < 0.001; Fig. 1a). Compared with patients without MCI, patients with MCI had significantly lower 25(OH)D levels (33.9 ± 6.2 vs. 44.3 ± 9.6 nmol/L, P < 0. 001), while serum TSH, FT3, FT4, and antibodies levels were not different. 25(OH)D levels were inversely correlated with TPOAbs levels (r = − 0.316, P < 0.001; Fig. 1b). No correlation was observed between 25(OH)D levels and age, sex, BMI, education, as well as levels of TSH, FT3, FT4, and TgAbs (all P > 0.05). Significant differences in 25(OH)D quartiles of HT patients were detected between the patients with MCI and the patients without MCI (P < 0.001) (Table 2).

With all HT patients taken as a whole, quartile 2 and quartile 3 taken as the references used for serum 25(OH)D levels, and cognitive impairment taken as a dependent variable in the logistic analysis, serum 25(OH)D levels (≤ 34.0 and ≥ 47.1 nmol/L) were significantly associated with cognitive impairment in patients with HT (OR 6.279, 95% CI 2.673–14.834, P < 0.001; OR 0.061, 95% CI 0.008–0.491, P = 0.009, respectively) (Table 3).