Executive function is inversely correlated with physical function: the cognitive profile of adult Spinal Muscular Atrophy (SMA)

Abstract

Background Spinal muscular atrophy (SMA) issues from mutations in the survival of motor neuron (SMN) 1 gene. Loss or reduction of the SMN protein results in progressive muscle weakness. Whether this protein deficiency also affects cortical function remains unclear. While no data on adult patients exists so far, prior studies in children with SMA indicate cognitive abilities equal or even superior to healthy controls. This may suggest a possible compensatory—neuropsychological and interactional—process. The goal of this study was to assess the cognitive profile of adult patients with SMA, with a special focus on social cognition as a potential candidate for enhanced cognitive function through compensatory processes. Methods In a cross-sectional design, N = 31 adult SMA patients (types II and III) were assessed for language, verbal fluency, memory, visuospatial abilities and executive function with the Edinburgh Cognitive and Behavioural ALS Screen and for social cognition with the Reading the Mind in the Eyes Test. Physical function was evaluated using the Hammersmith Functional Motor Scale Expanded. N = 19 neurologically healthy controls were matched with patients for age, sex and years of education. Results In none of the abovementioned cognitive domains significant differences between SMA patients and controls were found. Among patients, no differences between type II SMA and type III SMA were detected for any domain. However, a trend towards better social cognition in patients with type II SMA, compared to those with type III SMA was observed. Furthermore, a significant inverse correlation of physical function and executive function was detected: lower motor function was associated with a better executive function. Conclusions This study shows cognitive abilities in adult SMA in the normal range for all assessed domains. Thus, reduction of SMN protein has no obvious negative impact on cognitive function. Executive functions are identified as the only cognitive domain correlated with disease severity. Therefore, executive functions may play a role in the adaptation to physical restrictions in SMA, making them a promising target for future research.

Cognitive Performance of Patients with Adult 5q-Spinal Muscular Atrophy and with Amyotrophic Lateral Sclerosis

“…However, the WST as a vocabulary test alone is not sufficient to fully assess general intelligence in its entirety; in the future, rather an entire test battery should be used. Surprisingly, the level of functional motor impairment measured by ALSFRS-R showed no association with the cognitive profile of patients, neither in SMA nor in ALS patients, which is in contrast to data by Mix et al (in press) [25]. A likely explanation may be that not the current motor handicap but the level of impairment during childhood and adolescence-the time when the compensational process might have taken place-affects the cognitive profile in a patient's adult life.…”

“…On the other hand, no difference in the remaining ECAS domains could be seen. Mix et al showed that the cognitive function in SMA is no worse than in healthy subjects (in press) [25]. Therefore, differences in cognitive performance between both groups may not only be explained by ALS-related cognitive impairment but may additionally be attributed to the above-mentioned compensatory developments in childhood in the SMA group.…”

“…In a previous study of this working group, no significant difference in cognitive function between SMA patients and healthy controls, but an influence of physical function on executive functions was observed (in press) [25]. Therefore, in this study, we aimed to further investigate the hypothesis that onset of motor deficits in early childhood results in higher education and better cognitive performance in comparison to equally physically impaired patients with later age at onset of a comparatively disabling disease, here ALS.…”

Frontotemporal Pathology in Motor Neuron Disease Phenotypes: Insights From Neuroimaging

“…Similar radiological findings have been described in type I SMA (115). For the most part, neuropsychological studies demonstrate preserved cognition (116)(117)(118)(119). This is with the caveat that these studies are mostly limited to children and omit the more severe clinical phenotypes (120).…”

“…The only neuropsychological study of adults with type II or type III SMA described normal rather than superior cognitive abilities. This study reported a possible adaptive mechanism of an inverse correlation between executive function and physical ability, but the level of executive function did not exceed healthy controls (116). In contrast, there are indications of attention and executive function deficits in children with type I SMA (120,126).…”