Multiple sclerosis: What is it and how can it affect cognitive functioning?

By Clara Stein

What is multiple sclerosis?

Multiple sclerosis (MS) is a neurodegenerative and chronic inflammatory disease of the central nervous system, affecting the brain and the spinal cord. A core feature of MS is demyelination, which disrupts the communication between nerve cells. Nerve cells or neurons communicate with one another by passing on electro-chemical signals. To speed up the transmission of signals from one neuron to the next, an insulating layer called myelin sheath (see image below) wraps around the axons of neurons in the central nervous system. As such, myelination plays a crucial role in enabling efficient communication between neurons.

Image credit: freely available under the Pixabay license, retrieved from https://pixabay.com/vectors/red-science-diagram-cell-neuron-41524/

In MS, the myelin sheath is damaged through a process known as demyelination. Whilst the exact cause of MS remains elusive, we do know that it is the body’s own immune system which breaks down the myelin. The immune system starts treating myelin as foreign, which is why MS is also referred to as an autoimmune disease. This causes inflammation and damages both the myelin sheath and the axon that it is wrapping around, resulting in lesions in the brain and spinal cord of people living with MS.

MS is the most common disabling neurological diseases amongst younger adults and is typically diagnosed between the ages of 20 and 40. An estimated 2.8 million people live with MS worldwide [1] and MS has a relatively high prevalent rate in Ireland, affecting 193 in 100,000 people (compared to 35.9 in 100,000 globally) [2]. 

People with MS may experience a range of different symptoms, depending on the location and load of their lesions. However, some symptoms are commonly experienced, and these include sensory impairments, such as visual impairments, fatigue, bladder or bowel dysfunction, tremor, lack of balance, disrupted coordination of voluntary muscle movements, and limb weakness [3]. In addition to physical symptoms, 40-60% of people with MS also experience cognitive impairment [4]. For most of the 20th century, cognitive impairment was ignored by MS researchers, who treated it as a purely physical disability. In recent decades, cognitive impairment has gained widespread recognition by the research community. This is important as cognitive impairment can strongly influence daily functioning, for example impacting people’s social relationships, employment status and outcomes, and quality of life [1].

How does MS affect cognitive functioning?

Cognitive impairment in MS can potentially affect various cognitive domains, once again depending on an individual’s lesion load and location [4]. However, the most affected cognitive domains include information processing speed, which describes the ability to rapidly identify and integrate information, episodic memory and learning, an example of which would be word list learning and recall, visuospatial abilities, working memory, and attention [4,5]. To test whether a person living with MS is indeed experiencing cognitive impairment, neuropsychological tests tapping into these cognitive domains have been developed. 

However, there is often a discrepancy between the level of cognitive impairment indicated by cognitive assessments and the level of cognitive difficulties self-reported by people living with MS [6,7]. Specifically, many people with MS report higher levels of cognitive difficulties in their everyday life than evident in their objective test scores [8]. For example, a person with MS may notice and report forgetting where they put a book (or their glasses) more frequently than before their diagnosis. However, this person may still perform well on cognitive tests. This discrepancy between self-reported and objectively assessed cognitive functioning appears to be associated with depression and fatigue [8,9]. Up to 90% of people with MS experience fatigue and up to a third of people with MS experience depression, making depression and fatigue two of the most common MS symptoms [8,10,11,12,13]. 

Specifically, depression and fatigue seem to contribute to contribute to the discrepancy in cognitive functioning by increasing people’s likelihood to report cognitive difficulties. That is, people with higher levels of depression and fatigue are more likely to experience cognitive difficulties in their everyday life. Some very interesting research by Kinsinger and colleagues [6] has demonstrated that a successful therapy intervention for depression and fatigue can reduce the discrepancy between self-reported and objective cognitive functioning. Participants in this study reported less cognitive difficulties post-treatment, whilst their objective cognitive performance remained stable, illustrating how depression and fatigue impact subjective reports of cognitive difficulties. 

Our research in the UCD Neuropsychology lab

It is crucial to understand the nature and predictors of cognitive impairment in order to provide tailored support for people living with MS. In particular, gaining a clearer understanding of risk factors contributing to the experience of higher levels of cognitive difficulties in daily life is crucial as these can strongly influence quality of life, independently of depression and disease severity [14]. 

Within the UCD Neuropsychology lab, Clara Stein’s master’s research investigates whether a person’s estimated general intellectual abilities prior to MS onset may contribute to the discrepancy between self-reported and objective cognitive functioning. Clara works in collaboration with St Vincent’s University Hospital, and under supervision of Prof Jessica Bramham and Dr Fiadhnait O’Keeffe to conduct this research.

It appears that higher levels of estimated general intellectual abilities prior to MS onset can protect against cognitive impairment, allowing people with MS to perform within the norm on objective cognitive assessments [15,16]. Leading on from this research, Clara tests the hypothesis that people with higher estimated general intellectual abilities prior to MS onset might notice declines in their everyday cognitive functioning, before these are evident in cognitive assessments. For example, a person living with MS may have really high baseline cognitive abilities. This person may still perform well on cognitive assessments after MS onset and thus might seem unimpaired. Yet, in comparison to their baseline abilities, this person could have actually declined. 

Our data collection is still ongoing! We are looking forward to analysing our data soon, so please watch this space for updates and results. 

To find out more about the lived experience of people with MS, as well as mood and cognition in MS, please feel free to check out the below resources:

The MS Society of Ireland https://www.ms-society.ie

Mood & Cognition in MS https://www.youtube.com/watch?v=9uKYOpN4pyA

References

1.     Walton, C., King, R., Rechtman, L., Kaye, W., Leray, E., Marrie, R. A., Robertson, N., La Rocca, N., Uitdehaag, B., van der Mei, I., Wallin, M., Helme, A., Angood Napier, C., Rijke, N., & Baneke, P. (2020). Rising prevalence of multiple sclerosis worldwide: Insights from the Atlas of MS (3rd edition). Multiple Sclerosis (Houndmills, Basingstoke, England), 26(14), 1816–1821. https://doi.org/10.1177/1352458520970841

2.     MS International Federation. (2020). Atlas of MS (3rd edition). https://www.atlasofms.org/fact-sheet/ireland

3.     Huang, W.-J., Chen, W.-W., & Zhang, X. (2017). Multiple sclerosis: Pathology, diagnosis and treatments. Experimental and Therapeutic Medicine, 13(6), 3163–3166. https://doi.org/10.3892/etm.2017.4410

4.     Macías Islas, M. Á., & Ciampi, E. (2019). Assessment and impact of cognitive impairment in multiple sclerosis: An overview. Biomedicines, 7(1), 22. https://doi.org/10.3390/biomedicines7010022

5.     Strober, L. B., Rao, S. M., Lee, J.-C., Fischer, E., & Rudick, R. (2014). Cognitive impairment in multiple sclerosis: An 18 year follow-up study. Multiple Sclerosis and Related Disorders, 3(4), 473–481. https://doi.org/10.1016/j.msard.2014.03.004

6.     Kinsinger, S. W., Lattie, E., & Mohr, D. C. (2010). Relationship between depression, fatigue, subjective cognitive impairment, and objective neuropsychological functioning in patients with multiple sclerosis. Neuropsychology,24(5), 573–580. http://dx.doi.org/10.1037/a0019222

7.     Middleton, L. S., Denney, D. R., Lynch, S. G., & Parmenter, B. (2006). The relationship between perceived and objective cognitive functioning in multiple sclerosis. Archives of Clinical Neuropsychology: The Official Journal of the National Academy of Neuropsychologists, 21(5), 487–494. https://doi.org/10.1016/j.acn.2006.06.008

8.     Hughes, A. J., Bhattarai, J. J., Paul, S., & Beier, M. (2019). Depressive symptoms and fatigue as predictors of objective-subjective discrepancies in cognitive function in multiple sclerosis. Multiple Sclerosis and Related Disorders, 30, 192–197. https://doi.org/10.1016/j.msard.2019.01.055

9.     Bol, Y., Duits, A. A., Hupperts, R. M., Verlinden, I., & Verhey, F. R. (2010). The impact of fatigue on cognitive functioning in patients with multiple sclerosis. Clinical Rehabilitation, 24(9), 854–862. http://dx.doi.org/10.1177/0269215510367540

10.  Boeschoten, R. E., Braamse, A. M. J., Beekman, A. T. F., Cuijpers, P., van Oppen, P., Dekker, J., & Uitdehaag, B. M. J. (2017). Prevalence of depression and anxiety in Multiple Sclerosis: A systematic review and meta-analysis. Journal of the Neurological Sciences, 372, 331–341. https://doi.org/10.1016/j.jns.2016.11.067

11.  Freal, J. E., Kraft, G. H., & Coryell, J. K. (1984). Symptomatic fatigue in multiple sclerosis. Archives of Physical Medicine and Rehabilitation, 65(3), 135–138.

12.  Marrie, R. A., Reingold, S., Cohen, J., Stuve, O., Trojano, M., Sorensen, P. S., Cutter, G., & Reider, N. (2015). The incidence and prevalence of psychiatric disorders in multiple sclerosis: A systematic review. Multiple Sclerosis Journal, 21(3), 305–317. https://doi.org/10.1177/1352458514564487

13.  Nagaraj, K., Taly, A. B., Gupta, A., Prasad, C., & Christopher, R. (2013). Prevalence of fatigue in patients with multiple sclerosis and its effect on the quality of life. Journal of Neurosciences in Rural Practice, 4(3), 278–282. https://doi.org/10.4103/0976-3147.118774

14.  Samartzis, L., Gavala, E., Zoukos, Y., Aspiotis, A., & Thomaides, T. (2014). Perceived cognitive decline in multiple sclerosis impacts quality of life independently of depression. Rehabilitation Research and Practice, 2014, Article e128751. https://doi.org/10.1155/2014/128751

15.  Amato, M. P., Prestipino, E., Bellinvia, A., Niccolai, C., Razzolini, L., Pastò, L., Fratangelo, R., Tudisco, L., Fonderico, M., Mattiolo, P. L., Goretti, B., Zimatore, G. B., Losignore, N. A., Portaccio, E., & Lolli, F. (2019). Cognitive impairment in multiple sclerosis: An exploratory analysis of environmental and lifestyle risk factors. PLOS ONE, 14(10), Article e0222929. https://doi.org/10.1371/journal.pone.0222929

16.  Sumowski, J. F., Chiaravalloti, N., & DeLuca, J. (2009). Cognitive reserve protects against cognitive dysfunction in multiple sclerosis. Journal of Clinical and Experimental Neuropsychology, 31(8), 913–926. https://doi.org/10.1080/13803390902740643