Increased Glucose Levels Are Associated With Episodic Memory in Nondiabetic Women Olov Rolandsson 1 , Anna Backeström 1 , Sture Eriksson 2 , Göran Hallmans 3 and Lars-Göran Nilsson 4 1 Department of Public Health and Clinical Medicine, Family Medicine, Umeå University, Umeå, Sweden 2 Department of Community Medicine and Rehabilitation, Geriatric Medicine, Umeå University, Umeå, Sweden 3 Department of Public Health and Clinical Medicine, Nutritional Research, Umeå University, Umeå, Sweden 4 Department of Psychology, Stockholm University, Stockholm, Sweden Address correspondence and reprint requests to Dr. Olov Rolandsson, Family Medicine, Department of Public Health and Clinical Medicine, NUS, S-901 85 Umeå, Sweden. E-mail: olov.rolandsson{at}fammed.umu.se Abstract OBJECTIVE —Patients with type 2 diabetes have an increased risk of a reduction in cognitive function. We investigated the hypothesis that plasma glucose is associated with a reduction in episodic and/or semantic memory already in nondiabetic subjects. RESEARCH DESIGN AND METHODS —We linked two large population-based datasets in Sweden: the Betula study, in which a random sample from the population aged 35–85 years was investigated for cognitive function, including episodic and semantic memory; and the Västerbotten Intervention Program, a health survey with subjects aged 40, 50, and 60 years, that includes measuring of fasting and 2-h plasma glucose, along with other risk factors for diabetes and cardiovascular disease. We identified 411 (179 men and 232 women, mean age 50.6 ± 8.0 years) nondiabetic subjects, free from dementia, who had participated in the two surveys within 6 months. RESULTS —Women had better episodic (score 7.37 ± 1.42) and semantic memory (score 16.05 ± 2.76) than men (score 6.59 ± 1.29 and 15.15 ± 2.92, respectively, P < 0.001 for both). In an adjusted multivariate model, fasting plasma glucose (fPG) and 2-h plasma glucose (2hPG) were significantly negatively associated with episodic memory (fPG: B −0.198, SE 0.068, β −0.209, P = 0.004; and 2hPG: B −0.061, SE 0.031, β −0.148, P = 0.048, respectively) in women but not in men. The association was not found in relation to semantic memory. CONCLUSIONS —We conclude that an increase in plasma glucose is associated with impairment in episodic memory in women. This could be explained by a negative effect on the hippocampus caused by raised plasma glucose levels. 2hPG, 2-hour plasma glucose CES-D, the Center for Epidemiologic Studies Depression Scale fPG, fasting plasma glucose IFG, impaired fasting glucose IGT, impaired glucose tolerance MMSE, Mini Mental State Examination OGTT, oral glucose tolerance test VIF, variance inflation factor VIP, Västerbotten Intervention Program Footnotes Published ahead of print at http://diabetes.diabetesjournals.org on 31 October 2007. DOI: 10.2337/db07-1215. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact. Accepted October 25, 2007. Received August 30, 2007. DIABETES