Diabetes, Alzheimer's disease and apolipoprotein genotype

Non-insulin dependent diabetes mellitus (NIDDM) has been associated with a number of physiological consequences including neuropathy, retinopathy and incidence of vascular disease. Recently, several authors reviewed studies that suggested that NIDDM is associated with cognitive impairments leading to a higher incidence of dementia and Alzheimer's disease. The current diagnostic practices that typically exclude from an AD diagnostic any patients with suspected vascular dementia, makes it very hard to resolve this issue and likely result in an underestimation of the number of people with Alzheimer's disease and diabetes. When people with cerebrovascular disease are included, diabetes is associated with an increased risk for Alzheimer's disease. Studies that have examined peripheral glucoregulation in Alzheimer's disease are not consistent but some show small to moderate impairments in insulin sensitivity. One recent study suggest that in people that have both diabetes and an ApoE4 allele, the risk of developing Alzheimer's disease is more than double the risk of people with an ApoE4 allele without diabetes. Although diabetes does not produce any of the usual brain pathology associated with Alzheimer's disease, one study has shown that diabetes dramatically increases the amyloid deposition and neurofibrillary tangles in people with the ApoE4 genotype. Taken together, the data available suggest that diabetes is probably a risk factor for Alzheimer's disease mainly through the cerebrovascular disease diabetes causes. In people with other risk factors such as ApoE4 allele, diabetes appears to lead to a more dramatic increase in Alzheimer's disease pathology. (C) 2003 Elsevier Inc. All rights reserved.