Abstract

Objective: Uric acid as an antioxidant plays an important role in neurodegenerative disease. Our objective is to investigate the relationship between plasma uric acid and cognitive impairment in patients with amyotrophic lateral sclerosis (ALS).Methods: In this cross-sectional study, 124 ALS patients were screened by the Edinburgh Cognitive and Behavioral Screen (ECAS) and classified according to the revised Strong's criteria. Additionally, based on total ECAS cut-off score patients were categorized into those with cognitive impairment (ALS-cie) and those without cognitive impairment (ALS-ncie), and clinical data and uric acid level were compared between the two groups. Parameters with significant differences were further included in a multivariate linear regression analysis with ECAS score as a dependent variable. Hold-out validation was performed to evaluate the fitness of regression model.Results: Up to 60% of ALS patients showed cognitive or/and behavioral impairment. The ALS-cie group had lower education level (p < 0.001), older age at symptom onset (p = 0.001), older age at testing (p = 0.001), and lower plasma uric acid (p = 0.01). Multivariate analysis showed increased uric acid (β = 0.214, p = 0.01), lower age at testing (β = −0.378, p < 0.001), and higher education level (β = 0.424, p < 0.001) could predict higher ECAS score (F = 19.104, R2 = 0.381, p < 0.0001). Validation analysis showed that predicted ECAS score was significantly correlated with raw ECAS score in both the training set (rs = 0.621, p < 0.001) and the testing set (rs = 0.666, p < 0.001).Conclusions: Cognitive impairment was a common feature in our Chinese ALS patients. Plasma uric acid might help evaluate the risk of cognitive impairment in ALS patients when combined with education level and age at testing.

Highlights

  • Amyotrophic lateral sclerosis (ALS) is a fatal motor neuron disorder characterized by progressive loss of upper and lower motor neurons

  • We aimed to identify whether plasma uric acid could help evaluate cognitive impairment in Chinese ALS patients

  • One hundred and ninety ALS patients [20] who were admitted to Department of Neurology, Tongji Hospital in Wuhan between August 2017 and October 2020 were screened for this cross-sectional study

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Summary

Introduction

Amyotrophic lateral sclerosis (ALS) is a fatal motor neuron disorder characterized by progressive loss of upper and lower motor neurons. Diagnosis of cognitive impairment has been largely based on comprehensive neuropsychological tests [9], which could be limited by resource and time. Completion of those tests might be restricted by the physical disabilities of ALS patients. One study on hormonal peptides showed that plasma neuropeptide Y and leptin levels might be markers of cognitive changes measured by Addenbrooke’s Cognitive Examination-Revised in ALS patients [10]. Another study found significant differences in the plasma levels of 20 proteins by mass spectrometry analysis in 36 ALS patients with or without cognitive impairment using Addenbrooke’s Cognitive Examination-III [11]

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