A Prospective Analysis of Elevated Fasting Glucose Levels and Cognitive Function in Older People: Results From PROSPER and the Rotterdam Study

OBJECTIVE: To investigate the relationship between fasting glucose levels, insulin resistance, and cognitive impairment in old age. Diabetes is associated with cognitive impairment in older people. However, the link between elevated fasting glucose levels and insulin resistance in nondiabetic individuals, and the risk of cognitive impairment is unclear. RESEARCH DESIGN AND METHODS: We analyzed data from, in total, 8,447 participants in two independent prospective studies: the PROspective Study of Pravastatin in the Elderly at Risk (PROSPER), 5,019 participants, aged 69–84 years, and the Rotterdam Study, 3,428 participants, aged 61–97 years. Fasting glucose levels were assessed at baseline in both studies; fasting insulin levels were assessed in the Rotterdam Study only. Cognitive function was assessed in both studies at baseline and during follow-up. RESULTS: Subjects with diabetes had impaired cognitive function at baseline. In contrast, in people without a history of diabetes, there was no clear association between baseline fasting glucose levels and executive function and memory, nor was there a consistent relationship between elevated baseline fasting glucose levels and the rate of cognitive decline in either cohort. Insulin resistance (homeostasis model assessment index) was also unrelated to cognitive function and decline. CONCLUSIONS: Elevated fasting glucose levels and insulin resistance are not associated with worse cognitive function in older people without a history of diabetes. These data suggest either that there is a threshold for effects of dysglycemia on cognitive function or that factors other than hyperglycemia contribute to cognitive impairment in individuals with frank diabetes.