OBJECTIVE: To examine the association of glycemic status to magnetic resonance imaging indicators of brain pathological changes. RESEARCH DESIGN AND METHODS: This was a cross-sectional, population-based study of 4,415 men and women without dementia (mean age 76 years) participating in the Age Gene/Environment Susceptibility-Reykjavik Study. Glycemic status groups included the following: type 2 diabetes (self-report of diabetes, use of diabetes medications, or fasting blood glucose > or =7.0 mmol/l [11.1%]); impaired fasting glucose (IFG) (fasting blood glucose 5.6-6.9 mmol/l [36.2%]); and normoglycemic (52.7%). Outcomes were total brain volume, white and gray matter volume, white matter lesion (WML) volume, and presence of cerebral infarcts. RESULTS: After adjustment for demographic and cardiovascular risk factors, participants with type 2 diabetes had significantly lower total brain volume (72.2 vs. 71.5%; P < 0.001) and lower gray and white matter volumes (45.1 vs. 44.9%, P < 0.01 and 25.7 vs. 25.3%, P < 0.001, respectively) and were more likely to have single (odds ratio 1.45 [95% CI 1.14-1.85]) or multiple (2.27 [1.60-3.23]) cerebral infarcts compared with normoglycemic participants. Longer duration of type 2 diabetes was associated with lower total brain volume and gray and white matter volume, higher WML volume (all P(trend) < 0.05), and a greater likelihood of single and multiple cerebral infarcts (all P(trend) < 0.01). CONCLUSIONS: Type 2 diabetic participants have more pronounced brain atrophy and are more likely to have cerebral infarcts. Duration of type 2 diabetes is associated with brain changes, suggesting that type 2 diabetes has a cumulative effect on the brain.

Persons with type 2 diabetes are at increased risk of cognitive dysfunction. Less is known about which cognitive abilities are affected and how undiagnosed diabetes and impaired fasting glucose relate to cognitive performance. The authors explored this question using data from 1,917 nondemented men and women (average age = 76 years) in the population-based Age, Gene/Environment Susceptibility-Reykjavik Study (2002-2006). Glycemic status groups included diagnosed diabetes (self-reported diabetes or diabetic medication use; n = 163 (8.5%)), undiagnosed diabetes (fasting blood glucose >or=7.0 mmol/L without diagnosed diabetes; n = 55 (2.9%)), and impaired fasting glucose (fasting blood glucose 5.6-6.9 mmol/L; n = 744 (38.8%)). Composites of memory, processing speed (PS), and executive function were constructed from a neuropsychological battery. Linear regression was used to investigate cross-sectional differences in cognitive performance between glycemic groups, adjusted for demographic and health factors. Persons with diagnosed diabetes had slower PS than normoglycemics (beta = -0.12; P < 0.05); diabetes duration of >or=15 years was associated with significantly poorer PS and executive function. Undiagnosed diabetics had slower PS (beta = -0.22; P < 0.01) and poorer memory performance (beta = -0.22; P < 0.05). Persons with type 2 diabetes have poorer cognitive performance than normoglycemics, particularly in PS. Those with undiagnosed diabetes have the lowest cognitive performance.