Cognitive Functioning

Early research in cognitive functioning focused on type 2 diabetes as a theoretical model of accelerated aging [e.g., Kent (101)] but, more recently, there has been interest in potential changes in cognition that might make patient adherence to treatment more difficult (102). Both chronically elevated high blood sugars and recurrent low blood sugar levels have the potential to independently contribute to cognitive dysfunction, for example through changes to the blood - brain barrier transport of glucose. Verbal learning and memory skills may be especially disrupted in type 2 diabetes, but mainly for patients older than 60 years of age (103 - 105).

Other cognitive skills, such as attention, executive function, and psychomotor efficiency, were less affected. Although most research on cognition in diabetes has been conducted with type 1 patients, studies show that middle-aged type 2 individuals are apparently protected, insofar as researchers have only infrequently reported learning and memory impairments in that age group. It is likely that older adults have an increased risk of diabetes-associated memory dysfunction as a consequence of a synergistic interaction between diabetes-related blood glucose changes and the structural and functional changes occurring in the central nervous system that are part of the normal aging process (106,107).

Multiple diabetes-related comorbid conditions (i.e., hyperinsulinaemia, hypertension, hypercholesterolaemia) may individually and synergistically impact learning and memory skills [see review by Ryan and Geckle (104)]. For example, hyperinsulinaemia may independently affect the central nervous system.

Insulin levels usually rise with age, and are strong predictors of cognitive impairment in adults without diabetes. Data from the Framingham study showed that both hypertension and diabetes independently affect cognition generally, and memory skills in particular. Given their high rates in type 2 diabetes, it is notable that hypertension and hypercholesterolaemia interacts with hyperinsulinemia to disrupt memory. Generally, there is evidence to support the view that verbal learning and memory skills are particularly vulnerable to disruption in type 2 diabetes compared with other cognitive skills as a result of diabetes and its comorbidities. Recent data has indicated a link between insulin resistance and Alzheimer's disease (AD). Although the mechanism linking these conditions is unclear, the predominate hypothesis is that insulin resistance, accompanied by hyperinsulinemia and subsequent glucose metabolism disturbances, leads to neurodegen-eration, and ultimately, AD (108 - 110). This association suggests that future AD treatments should focus on reversing or preventing insulin abnormalities (111,112).