Abstract
The incidence of dementia is steadily increasing worldwide. The risk factors for dementia are diverse, and include genetic background, environmental factors, sex differences, and vascular abnormalities. Among the subtypes of dementia, diabetes-related dementia is emerging as a complex type of dementia related to metabolic imbalance, due to the increase in the number of patients with metabolic syndrome and dementia worldwide. Thyroid hormones are considered metabolic regulatory hormones and affect various diseases, such as liver failure, obesity, and dementia. Thyroid dysregulation affects various cellular mechanisms and is linked to multiple disease pathologies. In particular, hypothyroidism is considered a critical cause for various neurological problems—such as metabolic disease, depressive symptoms, and dementia—in the central nervous system. Recent studies have demonstrated the relationship between hypothyroidism and brain insulin resistance and dyslipidemia, leading to diabetes-related dementia. Therefore, we reviewed the relationship between hypothyroidism and diabetes-related dementia, with a focus on major features of diabetes-related dementia such as insulin resistance, neuronal dysfunction, and dyslipidemia.
Highlights
Thyroid hormones (THs) secreted from the thyroid gland are regulated by the thyrotropinreleasing hormone (TRH), which is released from the hypothalamus, and the thyroidstimulating hormone (TSH), which is released from the pituitary gland [1]
Thyroid dysregulation is an important issue both in metabolic syndromes and neurological disorders, because TH is involved in the regulation of cell death response, the modulation of neuronal function, the production of neurotransmitters, the regulation of glucose metabolism, and the regulation of lipid metabolism
We summarized the mechanisms of neuronal dysfunction, insulin resistance, and dyslipidemia in both hypothyroidism and diabetes-related dementia
Summary
Thyroid hormones (THs) secreted from the thyroid gland are regulated by the thyrotropinreleasing hormone (TRH), which is released from the hypothalamus, and the thyroidstimulating hormone (TSH), which is released from the pituitary gland [1]. Some clinical studies mention that hypothyroidism is not directly related to dementia neuropathology, and that levels of TSH are not directly related to cognitive impairment [18,19]. One functional MRI clinical study showed working memory loss in subclinical hypothyroidism patients, and subsequently, working memory loss was improved by thyroxine treatment [31]. Some epidemiological studies have mentioned that the risk of dementia and cognitive impairment is increased in patients with diabetes compared to subjects without [41,42]. Many researchers report that the relationship between diabetes and dementia are involved in vascular alteration [47,48] and impaired cerebral insulin signaling [49], leading to cognition [49,50]. A recent study mentioned the association between thyroid dysfunction and dementia and suggested related metabolic mechanisms [51]. Thyroid dysfunction is strongly related to dementia and diabetic pathologies, such as insulin resistance and impaired glucose metabolism. We review recent evidence on the relationship and related mechanisms between hypothyroidism and diabetes-related dementia
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