Diabetes and Alzheimer's Disease: Mechanisms and Nutritional Aspects

Abstract

Blood glucose homeostasis is well maintained by coordinated control of various hormones including insulin and glucagon as well as cytokines under normal conditions. However, chronic exposure to diabetic environment with high fat/high sugar diets and physical/mental stress can cause hyperglycemia, one of main characteristics of insulin resistance, metabolic syndrome, and diabetes. Hyperglycemia impairs organogenesis and induces organ abnormalities such as cardiac defect in utero. It is a risk factor for the development of metabolic diseases in adults. Resulting glucotoxicity affects peripheral tissues and vessels, causing pathological complications including diabetic neuropathy, nephropathy, vessel damage, and cardiovascular diseases. Moreover, chronic exposure to hyperglycemia can deteriorate cognitive function and other aspects of mental health. Recent reports have demonstrated that hyperglycemia is closely related to the development of cognitive impairment and dementia, suggesting that there may be a cause-effect relationship between hyperglycemia and dementia. With increasing interests in aging-related diseases and mental health, diabetes-related cognitive impairment is attracting great attention. It has been speculated that glucotoxicity can result in structural damage and functional impairment of brain cells and nerves, hemorrhage of cerebral blood vessel, and increased accumulation of amyloid beta. These are potential mechanisms underlying diabetes-related dementia. Nutrients and natural food components have been investigated as preventive and/or intervention strategy. Among candidate components, resveratrol, curcumin, and their analogues might be beneficial for the prevention of diabetes-related cognitive impairment. The purposes of this review are to discuss recent experimental evidence regarding diabetes and cognitive impairment and to suggest potential nutritional intervention strategies for the prevention and/or treatment of diabetes-related dementia.

Keywords: Cognitive function; Dementia; Diabetes Mellitus; Hyperglycemia; Resveratrol.

Figure 1. Suggested mechanisms underlying hyperglycemia-induced impairment of cognitive function. Brain insulin resistance and amyloidogenesis are considered as main factors for hyperglycemia-induced impairment of cognitive function, and affected by neuroinflammation, oxidative stress, and mitochondrial dysfunction. Chronic progression of these two main factors causes neuropathological changes disrupting neuronal integrity and function (neurodegeneration), which eventually leads to cognitive disability and dementia.

Figure 2. Acute/chronic hyperglycemia and cognitive function. Acute hyperglycemia facilitates insulin transport into brain resulting in acute hyperinsulinemia. Presence of high levels of insulin for a short time improves spatial and verbal memory. On the other hand, chronic exposure to high blood glucose in brain induces chronic brain insulin resistance. Uncontrolled brain insulin resistance accompanied with impaired brain insulin signaling and limited availability of insulin may cause poor cognitive function.

BBB, blood-brain barrier.