OBJECTIVE: Thyroid hormones play an essential role in metabolism regulation and circadian rhythm control. Recent studies approved their role in normal development and healthy function of central nervous system (CNS). The thyroid gland is a component of the hypothalamic-pituitary-thyroid axis disrupted during thyrotoxicosis and hypothyroidism, two main clinical conditions that induce more liability against dementia-related disease. METHOD: In the first step, this study evaluated the circular level of neuropeptide Y (NPY), leptin, oxytocin, and vasopressin in hyperthyroidism and hypothyroidism patients. In the second step, we investigated neurological and cognitive abnormalities by assessment of the hallmark proteins and peptides such as amyloid β (Aβ) variants, glycogen synthase kinase 3β (GSK-3β), and tau protein in thyroid-deficient samples. RESULTS: The results show increased content of leptin hormone in patients with hypothyroidism who also manifested high levels of vasopressin. Underactivation and overactivation of the thyroid gland are accompanied by reduced circular oxytocin. We may conclude that thyroid deficiency is associated with neurohormone dysregulation. Interestingly, both patient groups exhibited significant increases in Aβ40 and Aβ42 levels relative to the control group, which was also accompanied by the rise in GSK-3β; this might be interpreted as cholinergic system dysfunction and cognitive impairment. The results revealed tau content increased considerably in thyrotoxicosis but did not change significantly in hypothyroidism compared to the control group. CONCLUSION: Therefore, our results have shown that thyroid gland dysfunction is a risk factor for cognitive impairment, mainly through neuroendocrine dysregulation. This study provides a relationship between hyperthyroidism/hypothyroidism and biomarkers of neurological abnormalities in blood serum.