Five cognitive phenotypes in multiple sclerosis

A new classification for cognitive deficits in MS could complement the EDSS score to aid assessment of clinical impairment and therapeutic decisions.

The Neurology Blog
by Dr. Sophie Christoph

A new classification for cognitive deficits in MS could complement the EDSS score to aid assessment of clinical impairment and therapeutic decisions.

In addition to the loss of function at the physical level, it is often the less visible, emotional and mental symptoms of MS that carry a significant disease burden. Approximately 43% - 70%1 of people with MS are affected by cognitive impairment. These start early2 but often go undiagnosed for a long time.3

It is therefore important to give adequate importance to screening for cognitive impairment in routine care and to incorporate the findings into treatment. Cognitive deficits can be a prognostic sign and an indicator of early damage.2

Subdivision into subtypes with characteristic clinical and radiological features

A recent study published in JAMA Neurology, which examined 1,212 MS patients (mean age 41 years, 65% women) from eight centres in Italy, suggests a categorisation into five cognitive phenotypes that could add just this level to the EDSS.4,5

Only clinically stable patients with MS and healthy controls who were not taking psychoactive medications and who had no other neurological or other disorder, learning disability, severe head trauma or alcohol/drug abuse were included.

Using the statistical technique of latent class analysis (LCA), they identified the following subtypes:

  1. Preserved cognition:
    235 patients (19.4%), who showed no significant difference from participants in the control group.
  2. Mild impairment of verbal memory/semantic fluency:
    362 patients (29.9%) who showed mild impairment in Selective Reminding Test (SRT) and word list generation. Compared to participants with preserved cognition, reduced hippocampal volume was evident on MRI.
  3. Mild impairment of multiple domains:
    236 patients (19.5%) who showed mild impairment in SRT (Selective Reminding Test), SDMT (Symbol Digit Modalities Test), SCWT (Stroop Color and Word Test) and PASAT (Paced Auditory Serial Addition Test), as well as a decrease in cortical grey matter on MRI.
  4. Severe impairment of executive function/attention:
    167 patients (13.8%) who had severely decreased performance on SCWT (Stroop Colour and Word Test) and PASAT (Paced Auditory Serial Addition Test) and increased T2 lesion volume on MRI.
  5. Severe impairment of multiple domains:
    212 patients (17.5%) with severely reduced performance in all of the aforementioned tests. MRI showed volume loss in almost all brain regions measured (with the exception of the globus pallidus, amygdala and caudate nucleus).

Patients with preserved cognition (1) and mild impairment of verbal memory/semantic fluency (2) were on average significantly younger and had a shorter duration of disease than more cognitively impaired participants.
The relative frequencies of the two most severe categories (4 and 5) increased steadily from early relapsing-remitting MS to late relapsing-remitting MS to secondary progressive MS. Severely impaired cognitive phenotypes predominated in patients with progressive MS (here 19% were classified as grade 4 and 36% as grade 5).

Conclusion

Given the heterogeneity of cognitive impairment in patients with MS, further studies would be desirable for verification, as only a proportion of subjects received MRI here and this was a purely cross-sectional study. Neurology Advisor also notes that the data are based on a clinical sample that may not be representative of the general MS population.5

The nevertheless valuable paper concludes by saying:
"...by defining homogeneous and clinically significant phenotypes, the limitations of traditional dichotomous classification in MS can be overcome. These phenotypes may provide a more meaningful measure of the cognitive status of MS patients and help to more accurately label clinical disability, assist clinicians in making treatment decisions, and determine individualised cognitive rehabilitation strategies."

References:
1. Grzegorski, T. & Losy, J. Cognitive impairment in multiple sclerosis - a review of current knowledge and recent research. Rev Neurosci 28, 845-860 (2017).
2. Grey Matters, Too | The Role Of Grey Matter In Managing Multiple Sclerosis And Related Brain Atrophy. https://www.msgreymatters.com/.
3. Prof. Giovannoni. Cognitive Testing In MS. https://soundcloud.com/gavin-giovannoni/cognitive-testing-in-ms.
4. Meo, E. D. et al. Identifying the Distinct Cognitive Phenotypes in Multiple Sclerosis. JAMA Neurol 78, 414-425 (2021).
5. New Classification of Cognitive Phenotypes for Patients With MS. Neurology Advisor https://www.neurologyadvisor.com/topics/multiple-sclerosis/new-classification-of-cognitive-phenotypes-for-patients-with-ms/ (2021).