The relationship of glucose-stimulated insulin secretion to cerebral glucose metabolism and cognition in healthy middle-aged and older adults

Abstract Insulin resistance (IR) has been related to reduced cerebral glucose metabolism in regions identified as hypometabolic in Alzheimer's clinical syndrome. Insulin secretion (IS) has been less studied than IR despite findings that decreased IS is an early indicator of future type 2 diabetes and a potential predictor of Alzheimer's clinical syndrome. We investigated whether higher IR and lower IS would be associated with greater age-related reductions in regional cerebral glucose metabolism and worse cognitive performance. Two-hour oral glucose tolerance testing (OGTT) and 18F-fluorodeoxyglucose (FDG) positron emission tomography were performed on 1-2 occasions on a sample of healthy middle-aged and older adults from the Wisconsin Alzheimer's Disease Research Center (ADRC). Neuropsychological tests were completed during ADRC Clinical Core visits. Pattern of findings suggested that lower (not higher) IS was related to higher regional cerebral glucose metabolism in middle aged but not older adults, and lower (not higher) IS was also related to better immediate recall. In the context of healthy insulin sensitivity, lower IS may be beneficial to brain health.