Cognitive impairment has been documented in uremia with partial improvement after dialysis. Nocturnal daily hemodialysis (NHD) is a novel dialysis modality with multiple benefits. Previous reports have shown marked improvements in quality of life, cardiac function, resolution of peripheral vascular disease, and reversal of central sleep apnea. We hypothesized that patients maintained on NHD would have better cognitive functioning than those receiving conventional therapy. Using a longitudinal study design, patients were tested at baseline and again after >or=6 months NHD. At each of the two time points, a battery of 10 neuropsychological tests were used to evaluate three domains of cognitive functioning--attention and working memory skills, psychomotor efficiency and processing speed, and learning efficiency. Clinical subjective symptoms for cognitive functioning and depression were measured using the Patients Assessment of Own Functioning inventory and the Beck Depression Index. Twelve patients (six males, six females) were recruited. Patients were aged 39.6+/-3.3 years at the time of first testing. Thirty-three percent were diabetic, with a mean Charlson comorbidity score of 3.5+/-2.0. Depression (defined as >16 on the Beck Depression Index score) was not seen in any patient. Over the 6-month period, a 22% reduction in cognitive symptoms (P=0.01), 7% improvement in psychomotor efficiency and processing speed (P=0.02), and 32% improvement in attention and working memory (P=0.04) was seen. Learning efficiency scores were unchanged. NHD may be associated with improved general cognitive efficiency as measured by psychomotor efficiency and attention and working memory.