Relationship between gray matter volume and cognitive learning in CIS patients on disease-modifying treatment

J Neurol Sci. 2014 Dec 15;347(1-2):229-34. doi: 10.1016/j.jns.2014.10.002. Epub 2014 Oct 8.


Background: Repeated administration of Paced Auditory Serial Addition Test (PASAT) results in a considerable learning effect in short- or long-term follow-up studies. However, the relationship between PASAT learning and changes in magnetic resonance imaging (MRI) parameters is yet to be investigated.

Objectives: The aim of this study is to determine if change in brain MRI metrics predicts evolution of PASAT in high functioning clinically isolated syndrome (CIS) patients on disease-modifying treatment (DMT).

Methods: This prospective 48-month observational study examined 128 CIS patients treated with 30 μg of intramuscular interferon beta-1a once a week. The correlation between PASAT and MRI measures was assessed at baseline, at 6 months and then annually over the 48-month follow up. Linear mixed model analysis adjusted for age, gender, education and DMT was used to model the temporal association between MRI measures and PASAT performance.

Results: MRI revealed 2.5% gray matter (GM) volume loss and 4.3 point increase in PASAT score over 48 months. MS patients evidenced significantly greater PASAT score absolute change, had lower loss of GM volume (p=.008) but not significant change in cortical (p=.061), white matter (p=.086) or whole brain volumes (p=.879).

Conclusions: The present study reveals a significant relationship between higher PASAT learning effect and less GM atrophy in CIS patients on DMT. These findings suggest that change in PASAT associated more with GM than WM pathology, and that treatment strategies oriented toward GM volume preservation may play an important role in prevention of cognitive deterioration in CIS patients.

Keywords: Clinically isolated syndrom; Cognition; Gray matter; Learning effect; MRI; Multiple sclerosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Atrophy
  • Brain / pathology*
  • Cognition* / drug effects
  • Disease Progression
  • Female
  • Follow-Up Studies
  • Gray Matter / pathology
  • Humans
  • Interferon beta-1a
  • Interferon-beta / therapeutic use*
  • Magnetic Resonance Imaging*
  • Male
  • Middle Aged
  • Multiple Sclerosis / drug therapy
  • Multiple Sclerosis / pathology*
  • Neuropsychological Tests
  • Prospective Studies
  • Time Factors
  • Treatment Outcome


  • Interferon-beta
  • Interferon beta-1a