Selected randomized controlled trials have usually had cognitive function improvement or decline, or AD or AD progression, as an outcome. The purpose of this review is to discuss the common molecular and cellular mechanisms between AD and T2DM, as well as the case of AD as type 3 diabetes.Įmphasis was placed on randomized controlled trials, while systematic reviews and meta-analyses related to the subject were also included. Studies have shown that AD and T2DM share many common pathophysiological mechanisms associated with insulin resistance, such as oxidative stress, insulin signaling disorder, mitochondrial dysfunction, neuroinflammation, advanced glycosylation end products (AGEs) and metabolic syndrome. In recent years, with the accumulation of findings suggesting that AD may represent a brain-specific form of DM (type 3 diabetes), there has been a growing interest in the role of β-amyloid and tau protein in the peripheral nervous system and its organs, as well as in inducing insulin resistance. Insulin resistance affects the way insulin works in target tissues and cells, leading to the well-known phenomenon of hyperglycemia, a condition in which too much glucose circulates in the blood plasma and characterizes T2DM T2DM has also been associated with an increased risk of dementia and of AD by 45–90% as well as an increased risk of AD in patients with T2DM. This dysfunction means that the secretion of insulin by the β-cells of the pancreatic islets (β-cell dysfunction) as well as the action of insulin on insulin-sensitive tissues such as the liver, adipose tissue and muscle do not function normally for the body (insulin resistance). Type 2 diabetes mellitus (T2DM) is always characterized by abnormal blood glucose levels, a phenomenon caused by the general dysfunction between the action and secretion of insulin. It is estimated that the global diabetes mellitus (DM) prevalence will rise from 9.3% (463 million people) in 2019 to 10.2% (578 million) by 2030 and 10.9% (700 million) by 2045. APOE is a lipid-binding protein with a key role in cholesterol homeostasis. The strongest genetic risk factor for AD is the e4 allele of apolipoprotein E (APOE4) relative to the e3 allele and the protective e2 allele. The exact cause of AD is not fully understood there is therefore currently no effective treatment despite the large number of clinical studies that have been performed. īrain lesions that occur in AD are accompanied by synaptic dysfunction, neurodegeneration and neuronal disorders, while the disease is characterized by extracellular plaques of insoluble β-amyloid protein and intracellular neurofibrillary tangles (NFTs) of hyperphosphorylated tau protein. According to recent reports, 5.8 million Americans aged 65 and older currently suffer from AD, a number which is projected to rise to 13.8 million by mid-century in the US alone. Studies suggesting AD as a metabolic disease caused by insulin resistance in the brain also offer strong support for the hypothesis that AD is a type 3 diabetes.Īlzheimer’s disease (AD) is a chronic neurodegenerative disease that is the most common type of dementia and is characterized by impaired memory and cognitive ability, as well as changes in behavior and personality. Similarly, AD patients are not routinely evaluated for high levels of insulin or for T2DM. Given that the T2DM patients are not routinely evaluated in terms of their cognitive status, they are rarely treated for cognitive impairment. Beta-amyloid, tau protein and amylin can accumulate in T2DM and AD brains. AD and T2DM are interlinked with insulin resistance, neuroinflammation, oxidative stress, advanced glycosylation end products (AGEs), mitochondrial dysfunction and metabolic syndrome. The findings of this review indicate the existence of a mechanistic interplay between AD pathogenesis with T2DM and, especially, disrupted insulin signaling. Research findings are presented to underline the vital role that insulin plays in the brain’s neurotransmitters, homeostasis of energy, as well as memory capacity. The purpose of the current review article is to discuss the shared pathophysiological connections between AD and T2DM.
Globally, the incidence of type 2 diabetes mellitus (T2DM) and Alzheimer’s disease (AD) epidemics is increasing rapidly and has huge financial and emotional costs.