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. 2021 Jan 6;16(1):10.
doi: 10.1186/s13023-020-01661-9.

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

Lucas Mix  1 , Olivia Schreiber-Katz  2 , Claudia D Wurster  1 , Zeljko Uzelac  1 , Sophia Platen  1 , Christina Gipperich  1 , Gresa Ranxha  2 , Gary Wieselmann  2 , Alma Osmanovic  2 , Albert C Ludolph  3   4 , Susanne Petri  2 , Dorothée Lulé  1
Affiliations

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

Lucas Mix et al. Orphanet J Rare Dis. .

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.

Keywords: Cognition; Cognitive adaptation; Edinburgh cognitive and behavioural ALS screen (ECAS); Executive function; Hammersmith functional motor scale expanded (HFMSE); Reading the mind in the eyes test; SMA; Social cognition; Spinal muscular atrophy.

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Conflict of interest statement

The authors declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: LM reports no conflict of interests. OSK has received honoraria as a speaker/consultant and/or funding for travel expenses from the German Neuromuscular Society [Deutsche Gesellschaft fuer Muskelkranke (DGM e.V.)], Novartis, Biogen GmbH, the Jain Foundation and Biermann Verlag GmbH. She has received academic research support by the Ludwig-Maximilians-University of Munich, FoeFoLe program, Reg.-No. 747, 11/11-05/13, and the Hannover Medical School Young Faculty Program, 2018-2020. She has received research support from the Friedrich-Baur-GmbH, Burgkunstadt 12/13-12/15 and the German Neuromuscular Society “Deutsche Gesellschaft fuer Muskelkranke (DGM e.V.), 2019-2021. CDW received honoraria from Biogen (as an Advisory board member and for lectures) and from Hoffmann-La Roche (as a consultant and Advisory board member). She also received travel expenses from Biogen. ZU received honoraria from Biogen for lectures and consultation. SP reports no conflict of interests. CG reports no conflict of interests. GR received travel funding from Biogen GmbH. GW reports no conflicts of interest. AO has received honoraria as a speaker/consultant from the German Neuromuscular Society “Deutsche Gesellschaft fuer Muskelkranke (DGM e.V.)” and Biogen GmbH. She has received academic research support by PRACTIS—Clinician Scientist Program of Hannover Medical School, funded by the German Research Foundation (DFG, ME 3696/3-1). ACL received honoraria from AB Science, Biogen, Cytokinetics, GSK, Orion Pharma, Novartis, Tau Rx Therapeutics Ltd., TEVA Pharmaceuticals, Mitsubishi and Hoffmann-La Roche. SPe has received grants by the German Neuromuscular Society [Deutsche Gesellschaft fuer Muskelkranke (DGM e.V.)], the Federal Ministry of Education and Research (BMBF), the German Israeli Foundation (GIF) for Scientific Research and Development and the EU Joint Programme for Neurodegenerative Disease Research (JPND). She has received speaking honoraria from Desitin Pharma, Biogen GmbH, Novartis and TEVA as well as fees for consulting from Biogen GmbH, Roche Pharma, Cytokinetics Inc., DL reports no disclosures.

Figures

Fig. 1
Fig. 1
Association between general cognition (ECAS total score) and age in adult patients with SMA (N = 29). Dark blue = SMA type II, light blue = SMA type III; ECAS = Edinburgh Cognitive and Behavioural ALS (amyotrophic lateral sclerosis) Screen, total score (score 0 to 136); the data show a significant correlation between general cognitive skills (measured with ECAS total score) and age (τ = 0.30, p = 0.023)
Fig. 2
Fig. 2
Association between executive function (ECAS domain) and motor function (HFMSE) in adult patients with SMA (N = 25). Dark blue = SMA type II, light blue = SMA type III ECAS = Edinburgh Cognitive and Behavioural ALS (amyotrophic lateral sclerosis) Screen, domain for “executive function” (score 0–48); HFMSE = Hammersmith Functional Motor Scale Expanded measures physical function on a scale from 0 to 66; the data point labelled “2”, represents two patients, the one labelled “4”, represents four patients; the data show a significant inverse correlation of executive and physical function (τ = − 0.36, p = 0.018)
Fig. 3
Fig. 3
Association between disease onset and motor function (HFMSE) in adult patients with SMA (N = 27). Dark blue = SMA type II, light blue = SMA type III; HFMSE = Hammersmith Functional Motor Scale Expanded measures physical function on a scale from 0 to 66; the data points labelled “4” and “6”, four and six patients respectively; the data show a significant correlation of age at disease onset and physical function (τ = 0.69, p < 0.001)
Fig. 4
Fig. 4
Scores of adult patients with SMA (N = 29) and controls (N = 19) in the cognitive domains of ECAS. ECAS = Edinburgh Cognitive and Behavioural ALS (amyotrophic lateral sclerosis) Screen with the following domains (maximum scores are indicated in brackets): ME = memory (max. 24); VS = visuospatial abilities (max. 12); LA = language (max. 28); VF = verbal fluency (max. 24); EF = executive function (max. 48); the ECAS total score has a maximum of 136 points
Fig. 5
Fig. 5
Association between executive function (ECAS domain) and theory of mind (RMET; as a measure of social cognition) in adult patients with SMA (N = 29). Dark blue = SMA type II, light blue = SMA type III; ECAS = Edinburgh Cognitive and Behavioural ALS (amyotrophic lateral sclerosis) Screen, domain for “executive function” (score 0 to 48); RMET = Reading the Mind in the Eyes Test, a test for theory of mind with scores between 0 and 24; the data point labelled “2”, represents two patients; the data show a significant correlation of executive function in ECAS and theory of mind as a measure of social cognition in RMET (τ = 0.30, p = 0.034)
Fig. 6
Fig. 6
Scores of adult patients with SMA (N = 31) and controls (N = 19) in the RMET for theory of mind as a measure of social cognition. RMET = Reading the Mind in the Eyes Test, a test for theory of mind with scores between 0 and 24; patient group and control group do not differ significantly in their expertise in theory of mind
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References

    1. Verhaart IEC, Robertson A, Leary R, et al. A multi-source approach to determine SMA incidence and research ready population. J Neurol. 2017;264(7):1465–1473. doi: 10.1007/s00415-017-8549-1. - DOI - PMC - PubMed
    1. Verhaart IEC, Robertson A, Wilson IJ, et al. Prevalence, incidence and carrier frequency of 5q-linked spinal muscular atrophy—a literature review. Orphanet J Rare Dis. 2017;12(1):124. doi: 10.1186/s13023-017-0671-8. - DOI - PMC - PubMed
    1. Kolb SJ, Kissel JT. Spinal muscular atrophy. Neurol Clin. 2015;33(4):831–846. doi: 10.1016/j.ncl.2015.07.004. - DOI - PMC - PubMed
    1. Zerres K, Rudnik-Schöneborn S, Forrest E, Lusakowska A, Borkowska J, Hausmanowa-Petrusewicz I. A collaborative study on the natural history of childhood and juvenile onset proximal spinal muscular atrophy (type II and III SMA): 569 patients. J Neurol Sci. 1997;146(1):67–72. doi: 10.1016/s0022-510x(96)00284-5. - DOI - PubMed
    1. Dangouloff T, Servais L. Clinical evidence supporting early treatment of patients with spinal muscular atrophy: current perspectives. Ther Clin Risk Manag. 2019;15:1153–1161. doi: 10.2147/TCRM.S172291. - DOI - PMC - PubMed

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