Cognitive Dysfunction and Diabetes Mellitus

Abstract

The deleterious effects of diabetes mellitus on the retinal, renal, cardiovascular, and peripheral nervous systems are widely acknowledged.Less attention has been given to the effect of diabetes on cognitive function.Both type 1 and type 2 diabetes mellitus have been associated with reduced performance on numerous domains of cognitive function.The exact pathophysiology of cognitive dysfunction in diabetes is not completely understood, but it is likely that hyperglycemia, vascular disease, hypoglycemia, and insulin resistance play significant roles.Modalities to study the effect of diabetes on the brain have evolved over the years, including neurocognitive testing, evoked response potentials, and magnetic resonance imaging.Although much insightful research has examined cognitive dysfunction in patients with diabetes, more needs to be understood about the mechanisms and natural history of this complication in order to develop strategies for prevention and treatment.(Endocrine Reviews 29: 494 -511, 2008) I. Introduction II.Cognitive Dysfunction in Patients with Diabetes A. Type 1 diabetes B. Type 2 diabetes C. Hypoglycemia and cognitive dysfunction D. Section summary III.Pathophysiology of Cognitive Dysfunction in Diabetes A. The role of hyperglycemia B. The role of vascular disease C. The role of hypoglycemia D. The role of insulin resistance and amyloid IV.Modalities for Assessment of Cognitive Dysfunction in Patients with Diabetes V. Future Directions VI.Conclusion I. Introduction D IABETES MELLITUS IS a complex metabolic diseasethat can have devastating effects on multiple organs in the body.Diabetes is the leading cause of end stage renal disease in the United States (1) and is also a common cause of vision loss, neuropathy, and cardiovascular disease.A less addressed and not as well recognized complication of diabetes is cognitive dysfunction.Patients with type 1 and type 2 diabetes mellitus have been found to have cognitive deficits that can be attributed to their disease.Both hypoglycemia and hyperglycemia have been implicated as causes of cog-nitive dysfunction, and many patients fear that recurrent hypoglycemia will impair their memory over time.Although much research has been done, the pathophysiology underlying this complication is not well understood, and the most appropriate methods to diagnose, treat, and prevent cognitive dysfunction in diabetes have not yet been defined.In this article, we will review the nature of cognitive dysfunction in type 1 and type 2 diabetes mellitus, the pathophysiology of cognitive dysfunction secondary to diabetes, methodologies used to assess cognitive deficits in patients with diabetes, and potential future directions of research that are needed to advance our understanding of this often overlooked complication of diabetes.The purpose of this article is to present a comprehensive review of the literature regarding the subject of cognitive dysfunction in diabetes mellitus.To do this, we performed MEDLINE searches for such key words and terms as "diabetes mellitus," "cognitive function," "cognition," "hypoglycemia," "insulin resistance," and "Alzheimer's disease," among others.We then pursued articles referenced in these sources.Although this is a comprehensive review, it is not exhaustive.In addition, it should be noted that the field of cognitive dysfunction in diabetes is still in its early stages.It must be remembered that although there have been many significant contributions regarding the association of diabetes and cognitive dysfunction and many hypotheses based on this association, the causative mechanisms of diabetes on cognitive dysfunction are still undergoing development. II. Cognitive Dysfunction in Patients with Diabetes A. Type 1 diabetesCognitive dysfunction in patients with diabetes mellitus was first noted in 1922, when patients with diabetes, who were "free from acidosis but usually not sugar free," were noted to have impaired memory and attention on cognitive testing compared with controls (2).Since then, there have been many studies designed to better delineate the scope and First Published Online April 24,