[Dementia and diabetes mellitus].
Dementia and Diabetes mellitus (DM) are major health problems nowadays. DM leads to a significant cognitive decline and increases the risk of dementia, mostly Alzheimer's Disease (AD) and vascular dementia (VaD) by 50-100% and 100-150%, respectively. Amyloid beta (Abeta), the main pathogenic factor in AD development, is eliminated by advanced glycation end products (AGEs) and degraded by insulin degrading enzyme (IDE) for which it competes with insulin. Insulin stimulates secretion of Abeta and promotes brain inflammation. DM I and II cause slowing down of mental speed, lowering of mental flexibility and DM II learning and memory disturbances. DM acts both directly by hyperglycaemia and hyperinsulinaemia and by the blood vessel changes. Hyperglycaemia changes synapse plasticity and leads to cognitive decline. AGEs disrupt the neuron function and bonding to Abeta increases its aggregability. Glycation of tau protein promotes production of neurofibrillary tangles (NFT), the main intracellular pathogenic factor in AD. AGE 2 in DM causes pathological angiogenesis and apoptosis of neurons. AGE receptor (RAGE) is also the specific Abeta receptor with which it produces reactive oxygen species that has, as a result, disruption of mitochondrial function and reduction of neuronal energy resources. Insulinoresistance is linked with the dysexecutive syndrome, and hyperinsulinaemia increases the risk of AD especially by enhancing phosphorylation oftau protein and formation of NFT. Application of insulin showed improvement of memory, behaviour and affect in AD patients. Good glycoregulation emerged as an important factor in dementia prevention, and a better insight in relations of DM and brain function will lead to new potential dementia therapies.
Pavlović
Dragan M
DM
Pavlović
Aleksandra M
AM
D000544:Alzheimer Disease / Q000209:etiology* / Q000503:physiopathology; D016229:Amyloid beta-Peptides / Q000378:metabolism; D001921:Brain / Q000378:metabolism; D048909:Diabetes Complications; D003920:Diabetes Mellitus / Q000378:metabolism / Q000523:psychology; D005947:Glucose / Q000378:metabolism; D017127:Glycation End Products, Advanced / Q000378:metabolism; D006801:Humans; D006943:Hyperglycemia / Q000378:metabolism
D016229:Amyloid beta-Peptides; D017127:Glycation End Products, Advanced; D005947:Glucose