Cognitive impairment in Chinese adult patients with type III spinal muscular atrophy without disease-modifying treatment

OBJECTIVE: Spinal muscular atrophy (SMA) is a neurodegenerative disorder characterized by the degeneration of motor neurons in the spinal cord. It remains uncertain whether the cognitive performance of adult patients with SMA is impaired. The objective of this study was to assess the cognitive profile of adult Chinese patients with SMA and the association between clinical features and cognitive ability, particularly executive function. METHODS: This cross-sectional study included 22 untreated adult patients with type III SMA and 20 healthy subjects. The following variables were assessed: general intelligence, memory, attention, language, executive function, depression, anxiety, and other demographic and clinical parameters. In addition, physical function was evaluated using the Hammersmith Functional Motor Scale Expanded (HFMSE), the Revised Upper Limb Module (RULM), and the 6-Minute Walk Test (6MWT). RESULTS: SMA patients had lower scores than healthy subjects in the Verbal Fluency Test, Stroop effect, Total Errors, Perseverative Responses, Perseverative Errors, and Non-perseverative Errors in the Wisconsin Card Sorting Test, showing impaired abilities of SMA patients in executive function. In the Attention Network Test (ANT), the results indicated that the SMA patients also had selective deficits in their executive control networks. Ambulant patients had better executive function test performance than non-ambulant ones. Compromised executive abilities in patients with SMA were correlated with a younger age at onset, poorer motor function, and higher levels of anxiety and depression. CONCLUSION: Our study presented the distribution of cognitive impairment in a Chinese cohort with SMA. Patients with type III SMA showed selective deficits in executive function, which may be associated with disease severity, physical impairment, depression and anxiety. Future cognitive studies, accounting for motor and emotional impairment, are needed to evaluate if executive impairment is driven by specific brain changes or by those confounding factors.