BRAIN IN DIABETES: RESPONSE TO INCREASED METABOLIC DEMAND

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The hippocampus, a brain structure located deep in the temporal lobe, is key for learning and memory. The investigators and several other groups have shown that among normal elderly the MRI-determined volume of the hippocampus is directly related to recent memory performance. The study hypothesizes that there is a specific association between abnormalities in peripheral glucose metabolism and reductions in MRI-derived hippocampal volumes and recent memory performance and that, relative to controls, individuals with type-2 diabetes will have greater hippocampal and memory reductions than those with pre-diabetes. In addition, these relationships will be anatomically and neuropsychologically specific and will remain after accounting for overall brain atrophy. It also postulates that cerebral perfusion reactivity will predict memory performance and hippocampal volumes. Diabetics, who have been shown to have a blunted cerebral vascular response to acetazolamide, will have the largest memory impairments and hippocampal volume reductions. These relationships will be anatomically and neuropsychologically specific and will remain after accounting for brain atrophy. The objectives of the study are as follows: 1) To ascertain for the first time whether there are specific associations between recent memory deficits in diabetes and volume reductions of the hippocampus using validated, reliable, and standardized methods. The investigators will assess whether relative to matched normal controls, individuals with type-2 diabetes as well as non diabetic subjects with insulin resistance syndrome, who are now referred to by the American Diabetes Association (ADA) as having pre-diabetes, have learning and memory impairments that are specifically associated with hippocampal volume reductions measured with MRI. In addition, the investigators will ascertain whether individuals with type-2 diabetes have greater deficits in learning and memory, as well as larger reductions in hippocampal volumes, than prediabetic individuals. 2) To ascertain whether relative to matched normal controls, mid-life individuals with type-2 diabetes show less vasomotor reactivity in response to the cerebral vasodilating stimulus of acetazolamide (Diamox) than those with pre-diabetes. The investigators will also assess whether this diminished vasomotor reactivity is specifically related to memory impairments and hippocampal volume reductions.