Cognition and Brain Imaging in Type 1 Diabetes Gail Musen, PhD Corresponding author Gail Musen, PhD Joslin Diabetes Center, 1 Joslin Place, Boston, MA 02215, USA. E-mail: gail.musen@joslin.harvard.edu Current Diabetes Reports 2008, 8: 132–137 Current Medicine Group LLC ISSN 1534-4827 Copyright © 2008 by Current Medicine Group LLC Type 1 diabetes has mild effects on cognition that are influenced by age of onset, hyperglycemia, and hypo- glycemic episodes. Some of these changes occur quite early in the disease course. Studies using relatively new brain imaging techniques have also shown brain changes in adults and children that appear to be influ- enced by metabolic abnormalities present in diabetes. Early detections of brain changes may be early indica- tors of subsequent cognitive abnormalities. Introduction Interest in the effects of type 1 diabetes on the central nervous system (CNS) is growing. Historically, the best way to ascertain whether the CNS was impacted by dia- betes was to test cognitive performance. Although this method led to informative results [1••,2] suggesting modest detriments in cognitive function compared with nondiabetic individuals, the fndings were not easy to summarize because the impact on cognition was infu- enced by a myriad of variables, including age at diabetes onset [3], experience with severe hypoglycemic episodes [4], duration of diabetes [5], and extent of diabetes complications [5,6]. During the past decade, the use of MRI has become much more commonplace, allowing for a more direct measure of the impact of diabetes on the brain. This article provides a brief review of the impact of diabetes on cognitive functioning in type 1 diabetes. It also gives a broad overview of more recent efforts to investigate the subtler effects of diabetes on the CNS using electrophysiologic, structural, and functional MRI (fMRI). These techniques afford a more direct window to the underlying physical changes in the CNS that serve as the roots of cognitive performance. Cognition Effects of diabetes on long-term cognitive function Research on the cognitive effects of diabetes suggests that some patients with type 1 diabetes may have increased risk for cognitive dysfunction problems [7]. Typically, the changes are subtle and expressed as decreased recent memory and psychomotor slowing [7,8]. The clearest evi- dence of cognitive dif fculties is in children with onset of type 1 diabetes before age 6 [9,10]. Young type 1 diabetic patients have shown worse performance than controls on tests of psychomotor speed, learning, vocabulary, and block design [11]. Results from research on adults with type 1 diabetes with onset later than age 6 are less clear. The largest prospective clinical trials, the DCCT (Diabetes Control and Complications Trial) and the SDIS (Stockholm Diabetes Intervention Study), suggest that recurrent hypoglycemia is not a risk factor for subsequent cognitive abnormalities [12,13]. Deary and Frier [14] sug- gested that if patients with recurrent hypoglycemia were observed for a longer period of time, there may be evi- dence of cognitive impairment. However, a more recent follow-up of the DCCT cohort 12 years after the trial ended still showed no effects of severe hypoglycemia on long-term cognitive function [15]. Higher hemoglobin A 1c (HbA 1c ) levels were associated with declines in psychomo- tor ef fciency and motor speed. Whether hypoglycemic events occurring in the context of chronic hyperglycemia may make the CNS more vulnerable to the impact of diabetes and its associated metabolic abnormalities is not well understood [16]. Duration of diabetes, presence of complications, and aging can also take their toll on cognitive function- ing. To date, no longitudinal studies have compared cognitive decline in long-duration type 1 patients with nondiabetic control subjects; therefore, whether the effect of aging interacts with diabetes in a predictable way is not known. Ryan [17] investigated a related issue using a cross-sectional design comparing type 1 diabetic patients and nondiabetic adults. He noted that among many cognitive skills assessed (including learning and memory, problem solving, and psychomotor speed,) only the latter progressed more rapidly in diabetic patients.