Relationships Between Hyperglycemia and Cognitive Performance Among Adults

Cox DJ, Kovatchev BP, Gonder-Frederick LA, et al. Diabetes Care. 2005;28:71-77.

Cognitive difficulties associated with hyperglycemia occur frequently in persons with diabetes, but whether these difficulties affect quality of life and daily functioning is unclear. Several mechanisms have been proposed to explain this association between hyperglycemia and cognition, including dysfunction of the blood-brain barrier microvasculature; alteration of neurotransmitter synthesis and reuptake; and changes in insulin availability to the brain. The acute effect of hypoglycemia on decline of cognitive-motor function is well known, but the effect of hyperglycemia on cognitive-motor function is less clear. Therefore, the purpose of this prospective study was to objectively assess the acute effects of hyperglycemia on cognitive-motor dysfunction in persons with type 1 or type 2 diabetes.

Three separate double-blind studies were conducted for 1 month each. The studies comprised a total of 232 adults with either type 1 or type 2 diabetes. Participants were instructed to use a handheld computer that required them to complete various cognitive-motor tests 3 to 4 times daily throughout the study and then to measure their blood glucose levels; Blood glucose levels were categorized into 5 different ranges and then used to predict cognitive performance test results. Cognitive performance tests included mental subtraction problems, paced serial addition tests, reaction-time trials, and word recall tests. Test results were measured by speed to complete tests, number of errors made, and/or number of words recalled.

The findings showed that hyperglycemia was associated with a slower speed in completing all cognitive tests and a greater number of errors in mental subtraction. This association appears to be nonlinear; there may be a blood glucose threshold around 15 mmol/L beyond which cognitive function declines. The effects of hyperglycemia on cognition were highly individualized, affecting approximately 55% of all participants, and may be attributed to greater routine exposures to hyperglycemia. Of those participants affected, most showed either cognitive slowing or increased errors; only 25% showed both cognitive slowing and increased errors.

These results, along with similar results showing cognitive dysfunction with hypoglycemia, suggest that the optimal blood glucose range for cognitive-motor function is between 4 and 15 mmol/L. The clinical importance of these findings is that certain daily tasks of persons with diabetes may be negatively affected by extreme blood glucose levels—daily tasks such as balancing checkbooks, calculating insulin dosing, and other tasks requiring good cognitive function. Such negative consequences may motivate diabetes patients to achieve tighter blood glucose control.