Diabetes-Related Alzheimer's Set to Increase

Insulin also affects vascular function in the brain. “It's very well known that insulin resistance is accompanied by peripheral vascular dysfunction, but the understanding that this may also manifest in the brain is very new and potentially important.”

In insulin resistance, there is a down-regulation of the phosphoinositide-3 (PI3) kinase pathway, which mediates vascular relaxation. But the mitogen-activated protein (MAP) kinase pathway, which mediates vasoconstriction, is driven by high levels of insulin and does not downregulate with insulin resistance. “You get a reduction in vasodilation and hyperactivation of vasoconstriction,” Dr. Craft said. “This imbalance is thought to underlie many of the vascular dysfunctions associated with insulin resistance.”

She saw this in a recent study of 196 brains (71 with dementia). The brains were divided into four groups: normal, diabetic without dementia, diabetic with dementia, and dementia without diabetes (Arch. Neuro. 2009;66:315-22).

“We saw a surprising pattern when we looked at plaques and tangles: The brains of the patients with dementia but no diabetes had a high load, as anticipated, but the brains of diabetic patients with dementia had a plaque load that was similar to the normal controls.”

The patients with both dementia and diabetes did, however, show high levels of microvascular lesions, which were absent in the other groups. “The volume of the lesions is small, so they are almost certainly not directly responsible for the cognitive impairment, but this finding may point to some broader based vascular dysfunction,” Dr. Craft said.

Memory loss in Alzheimer's may be tied to loss of insulin receptors (red).

Source Courtesy Fernanda G. De Felice and William L. Klein, Ph.D. (appeared in Proc. Natl. Acad. Sci. U.S.A. 2009;106:1971-6)