Background: Exact mechanisms underlying cognitive dysfunction in diabetes mellitus (DM) remain unclear. Imaging studies of the brain could help to identify possible structural brain lesions underlying cognitive dysfunction. Objective: To describe a detailed neuropsychological profile in patients functioning independently with type 2 DM. Secondly, correlations were studied between cognitive impairment and brain lesions on magnetic resonance imaging (MRI), i.e. periventricular hyperintensities (PVH), deep white matter lesions (DWML), medial temporal lobe atrophy (MTA), cerebral atrophy and lacunar infarcts. In addition, the influence of relevant disease variables of DM was studied. Methods: 92 patients withtype 2 DM (mean age 73.2±5.7 years, mean duration 13.8±10.8 years) and 44 control subjects (mean age 72.9±5.3 years) were included and underwent an extensive neuropsychological test battery and an MRI of the brain. Results: Neuropsychological scores were worse for each cognitive domain except for memory functions after adjustment for hypertension in a group of elderly patients with type 2 DM compared to healthy control subjects. Only PVH were independently associated with motor speed, whereas all other MRI measures were not independently associated with cognitive impairment. Interactions between the different MRI measures were not present. Glycosylated haemoglobin (HbA1c) and duration of DM were significantly associated with cognitive dysfunction. Conclusions: The data of this cross-sectional study show that type 2 DM is associated with diminished cognitive function in different cognitive domains, while memory is less affected after adjustment for hypertension. The association of cognitive impairment with MRI measures is equivocal, whereas HbA 1 c and duration of DM were significantly associated with cognitive dysfunction.