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Background: The impact of chronic moderate and profound hyponatremia on neurocognitive performance, motor skills, and mood stability has not been investigated systematically so far, and results regarding mild to moderate hyponatremia are inconsistent. Furthermore, it is not known whether treatment has an effect on outcome in these patients., Methods: A total of 130 hospitalized patients with confirmed euvolemic hyponatremia (<130 mEq/L) were subjected to a test battery (Mini-Mental State Examination, DemTect, Trail-Making Tests A and B, Beck Depression Inventory, Timed-up-and-go Test) before and after treatment; additionally, 50 normonatremic group-matched patients served as reference group., Results: The scores of all tested domains were significantly worse in the hyponatremia group (median serum sodium [Na + ] 122 (119-126) mEq/L) as compared to the reference group (P <0.001), and the odds of obtaining a pathological test result increased markedly with more profound hyponatremic states (odds ratios between 5.0 and 21.8 in the group with Na + <120 mEq/L compared to reference group). Inversely, treatment led to a significant amelioration of all test results with medium to large effect sizes. Linear regression models revealed the increment of Na + as an important predictor of test outcome., Conclusion: We demonstrate a clear association between lower levels of Na + beyond mild hyponatremia and impairment of neurocognitive and motor performance as well as mood disorders. Our analysis further suggests a causal role of hyponatremia in this context. However, there are apparent differences between the distinct tested domains warranting further investigations., (Copyright © 2020 Elsevier Inc. All rights reserved.)