Neurometabolite and cognitive changes in hypothyroid patients in response to treatment: In-vivo ¹H MRS study

The disturbances in thyroid hormones lead to altered brain metabolism, function, and cognition. Neuroimaging studies have shown structural and functional changes in hypothyroidism. Present study investigates the neuro-metabolite changes in dorsolateral prefrontal cortex (DLPFC) and posterior parietal cortex (PPC) and associated decline cognitive function in hypothyroid patients before and after thyroxine treatment. We performed neuropsychological test and ¹H MRS in hypothyroid patients (n = 25) and controls (n = 30). In addition, follow-up data was also collected from 19 patients treated with levo-thyroxine for 32 weeks. The concentration of the neurometabolites were calculated using LCModel. MRS data were analyzed using analysis of covariance (ANCOVA), with age and gender as covariates. A paired t-test was conducted to compare the baseline hypothyroid with the follow-up. Partial correlations were utilised to assess possible associations between neuropsychological scores and neurometabolites with age and gender as covariates. Spearman correlation was performed between thyroid hormone levels and neurometabolites. Hypothyroid patients showed an impairment in delayed recall, immediate recall of semantic, visual retention, recognition of objects memory, attention, and motor function at baseline, which improved significantly after thyroxine therapy. At baseline, patients with hypothyroidism exhibited significantly higher levels of choline compounds (GPC + PCh) [Cho]. No significant normalization of Cho levels was observed, despite achieving euthyroidism with thyroxine treatment. Cho levels showed a positive correlation with TSH in PPC and a negative correlation with T4 in DLPFC and PCC. Cho levels also showed negative correlations with delayed recall, immediate recall of semantic, visual retention memory and MMSE scores. The MRS findings show increased levels of Cho in hypothyroid patients compared to healthy controls. These Cho levels are not reversible within 32 weeks of treatment, suggesting that a longer follow-up may be needed to see if levels can be normalized.