A decline in cognitive function has been reported in type 1 diabetes, but its relation to different disease factors such as hypoglycemic events and peripheral neuropathy is controversial. The objective of the present study was to identify factors that are important for cognitive impairment in type 1 diabetes. A cross-sectional study was performed in adult patients (N=150) with type 1 diabetes (duration 26.6+/-11.4 years). Function in different cognitive domains was evaluated by the same trained examiner, in order to eliminate inter-rater variability. Peripheral nerve function was tested quantitatively. Predictors of cognitive impairment were identified using multiple regression analysis. The major finding was that long diabetes duration and young age of diabetes onset were the strongest predictors of low scores in psychomotor speed, memory, processing speed, attention, working memory, verbal ability, general intelligence, executive functions and a low global score. The number of previous hypoglycemic events had no defined effect upon cognitive functioning. Other significant predictors were low compound muscle action potential (CMAP) (for visual perception-organization), old age (for visual-spatial ability), short stature, high BMI and hypertension. Presence of retinopathy and long-term metabolic control correlated with nerve conduction defects, but not with cognitive impairment. Although a history of hypoglycemic events was not a predictor of cognitive impairment, we cannot exclude the possibility that the influence of young age of diabetes onset depends on the effect of hypoglycemic events early in life. The clinical relationships of cognitive impairment differ from those of peripheral neuropathy, indicating a different pathogenesis. The influence of diabetes duration, BMI, height, age and CMAP may suggest that loss of the neuroprotective effects of insulin or insulin-like growth factors plays a role.