Cognition in Patients With Spinal Muscular Atrophy Tied to Disease Severity

Neurological adaptations may allow patients with spinal muscular atrophy (SMA) to enhance their cognitive abilities. Although patients with SMA performed worse on cognitive function tests compared with healthy control individuals, disease severity and motor function correlated with higher cognitive test scores in some domains. These are the findings of a study published in in Neuromuscular Disorders.

Patients with SMA experience functional decline and eventually die from respiratory failure. Typically, in patients with type 3 SMA, major motor milestones are reached but proximal muscular weakness develops during childhood. It’s not known if cognitive deficits occur in individuals with type 3 SMA, and if they do, whether they’re tied to clinical factors.

The objective of the current study was examine the relationship between cognitive and clinical factors in adult patients with type 3 SMA via a comprehensive neuropsychological battery, including tests in memory, executive function, language, visuospatial, and global cognitive functioning.

Researchers in Italy conducted a preliminary study of 22 patients with type 3 SMA compared with 22 age- and sex-matched healthy control individuals. Patients required screening scores of 24 or greater on the Mini Mental State Examination (MMSE) for inclusion in this study.

Following genetic testing, 13 patients (59.1%) in the SMA group had 4 SMN2 copies, 8 (36.4%) had 3 SMN2 copies, and 1 (4.5%) had 1 SMN2 copy. Increased number of copies equates to increased disease severity.

The researchers assessed motor function using the Hammersmith Functional Motor Scale for SMA (HFMSE), the Revised Upper Limb Module (RULM), and the 6-Minute Walk Test (6MWT).

A battery of 13 tests assessed cognitive function covering multiple domains. The Raven Progressive Matrices (RPM), Phonetic Fluency, Digit Span backward, Stroop Color-Word Test, and Trail Making Tests A (TMT-A) and B (TMT-B) assessed executive function. The Boston Naming Test (BNT) and Semantic Fluency measured language abilities, while the Rey-Osterrieth Complex Figure Test (ROCFT) assessed visuospatial abilities and the Digit Spin Forward and Rey Auditory Verbal Learning Test (RAVLT) assessed memory.

When adjusted for age and education levels, patients with SMA demonstrated significantly lower cognitive scores on tests assessing executive function, RPM (B=2.10; 95% CI, 0.74-3.46; P =.003), language, BNT (B=1.75; 95% CI, 0.13-3.37; P =.034), and visuospatial abilities, ROCFT copy (B=2.35; 95% CI, 0.82-3.8; P =.003) compared with control individuals.

Additionally, the researchers found these cognitive deficits across multiple domains correlated with motor functioning and disease severity. Patients with SMA with decreased motor function scored lower on attention tests, but higher on language, verbal fluency, and memory tests. Similarly, patients with increased SMA severity showed decreased attention and working memory capacity, but higher language and verbal fluency tests.

Patients with SMA may compensate for their physical disabilities through neuroplasticity which allows for reorganization of motor regions in the brain to enhance cognitive abilities.

Study limitations included small sample size, lack of adjustment for fatigue in the analysis, and educational differences in the SMA patients compared with control individuals, all of which might have impacted results.

“This study describes cognitive functioning in SMA type III that may reflect brain involvement in pathological mechanisms underlying SMA and the presence of domain-specific cognitive reallocation processes,” the authors concluded. “Moreover, it offers new perspectives for understanding how motor dysfunction can affect cognition and promote adaptive compensatory processes.”

Reference

Lenzoni S, Semenza C, Calligaro D, et al. Cognitive profiles and clinical factors in type III Spinal Muscular Atrophy: a preliminary study. Neuromuscular Disorders. Published May 11, 2022. doi:10.1016/j.nmd.2022.05.005