New Study Clarifies Cognitive Function in Adults With SMA vs Healthy Adults

Physical disability is ubiquitous among patients with spinal muscular atrophy (SMA), a neurodegenerative disease that affects motor neurons and leads to progressively weaker muscles. Although intelligence quotient (IQ) has been studied in children, evidence is lacking when it comes to adult patients. A recent study published in Brain Sciences aimed to provide a better understanding of the cognitive function of adults with the condition.

SMA is stratified into 5 subtypes. Type 0 is the most severe (prenatal onset, restricted intrauterine movement), and is followed by type 1 (infants and children are never able to sit independently and require ventilatory support for respiratory failure). Patients with SMA type 2 can typically sit unassisted but not walk, those with type 3 may walk independently but eventually rely on a wheelchair, and type 4 SMA is adult-onset.

Aside from the physical disabilities, fatigue and depression are common occurrences for patients with SMA. For the current study, the researchers compared the IQ index scores of patients with SMA versus healthy adults in Germany.

IQ was measured using the Wechsler Adult Intelligence Scale (WAIS), the most widely used IQ measure in adults aged 16 to 89. The fourth edition of the German version of the WAIS (WAIS-IV) was used to calculate full-scale IQs, which include 2 index scores with 10 subtests:

• Verbal IQ
  • Verbal Comprehension Index (VCI)
    • Similarities
    • Vocabulary
    • Information
  • Working Memory Index (WMI)
    • Digit span
    • Arithmetic
• Performance IQ
  • Perceptual Reasoning Index (PRI)
    • Block Design
    • Matrix Reasoning
    • Visual Puzzles
  • Processing Speed Index (PSI)
    • Symbol search
    • Coding

PSI was excluded from the study due to time-dependent motor demands that would make the measurements invalid, given the various motor abilities of SMA patients. Instead, the study focused on VCI, WMI, and PRI. The Block Design test was also skipped due motor skill needs and replaced by a supplemental subtest called Picture Completion. The IQ test has a standardized score, with a mean of 100 and standard deviation of 15.

Thirty-three patients with a mean age of 35 (range, 18-58) years were included in the study. One patient had type 1 SMA and was only included in calculations for the total cohort, 15 had type 2 SMA, and 17 had type 3 SMA. In the overall type 2 and 3 cohorts, 69% (n = 21) of patients graduated high school and were accepted to a university vs 34.6% of healthy young adults. Of those patients who qualified, 53% (n = 17) currently studied or had studied at a university at some point prior to the study.

All of the patients involved in the study had received nusinersen, and patients were excluded if they had a traumatic brain injury, inflammatory brain disease, mood disorder, psychiatric disease (active or in the past), a medication other than nusinersen affecting the central nervous system, and other confounding factors that could be related to mental impairment.

The general population’s mean IQ is 100. In overall cohort of patients with type 2 or type 3 SMA, the mean (SD) IQ on the VCI was 96.21 (12.43), the mean PRI IQ was 95.61 (14.76), and the mean WMI IQ was 95.82 (15.72).

The IQ index scores for WMI and PRI were lower in the patients with SMA type 2 than the normal population. Patients with type 2 SMA had a mean PRI IQ of 90.73 (12.58) and a WMI IQ of 90.33 (12.95). Type 3 patients, however, had higher mean scores for VCI IQ, PRI IQ, and WMI IQ, at 95.47 (13.67), 99.53 (16.00), and 97.94 (13.45), respectively.

However, there was a trend toward lower cognitive performance. “IQ scores in patients with SMA type 3 were lower compared to normal population data, but those differences were not statistically significant,” the authors concluded.

“This study provided further evidence that SMA is a multisystemic disease and may refute the widespread hypothesis that SMA patients might improve their cognitive skills to compensate for their physical impairment,” they wrote.

Reference

Kizina K, Akkaya Y, Jokisch D, et al. Cognitive impairment in adult patients with 5q-associated spinal muscular atrophy. Brain Sci. Published online September 9, 2021. doi:10.3390/brainsci11091184