Cognition and Neuropsychological Testing In Multiple Sclerosis

Cognitive changes in multiple sclerosis (MS) are relatively common and can include difficulties with memory, focus, attention, multitasking, judgement, visuospatial function, and others.  Such symptoms can feel ‘invisible’ as they are not always obvious or noticeable to others but have a substantial impact on a person’s day-to-day function. Many notice that cognitive symptoms develop before their first ‘MS attack.’ A study from Norway showed that persons with MS (pwMS) had changes on cognitive testing a few years before the onset of more ‘typical’ MS symptoms (Cortese et al., 2016).  

The frequency of cognitive symptoms in pwMS varies. A review by Benedict tabulated estimates of cognitive impairment in different phenotypes of MS: 20–25% of persons with clinically isolated syndrome and radiologically isolated syndrome, 30–45% of persons with relapsing-remitting multiple sclerosis, and 50–75% of persons with secondary progressive multiple sclerosis (Benedict et al., 2020).  

Predictors of cognitive impairment in pwMS are not clear, though worse cognitive outcomes have been associated with older age, greater level of physical disability, male sex, lower education, higher lesion burden, more frequent relapses, longer duration, and a progressive course (Cavaco et al., 2022). Cognitive dysfunction can have a substantial impact on function in pwMS. For example, about a quarter of pwMS who fail driving assessments do so because of cognitive dysfunction (Krasniuk et al., 2017).  

Ways to Test Cognition

There are several options available to assess cognition. These can range from simple tests that can be done in clinic with your healthcare provider to more detailed assessments with a neuropsychologist. These tests attempt to quantify different cognitive domains such as memory, attention, visual function, and others. Test scores are usually calculated and compared to averages obtained from healthy people in a similar age group with similar levels of education. Different tests will focus on different areas of cognition. For example, visual spatial function can be assessed by gauging line angles. Different cognitive tasks can help examiners localize the areas of the brain that are impacted by MS or other conditions that impact the brain.  

The symbol digit modalities test (SDMT) is a 90-second test that can be done on a sheet of paper to try and identify cognitive deficits in pwMS(Parmenter et al., 2007). This is an example of a ‘screening test’ which tries to help identify who may need more advanced testing. The Processing Speed Test (PST) is a tablet-based test that mirrors the SDMT. Other, more general screening tests done for cognitive impairment that a health care provider may do include the Montral Cognitive Assessment (MoCA), Mini Mental Status Exam (MMSE), or the Kokmen Short Test of Mental Status (STMS). These tests can be repeated over time to try and quantify changes in cognition.  

Neuropsychological testing is a more comprehensive test typically done with a psychologist or neuropsychologist. A few different extended testing batteries have been developed for MS and include the Minimal Assessment of Cognitive Function In Multiple Sclerosis (MACFIMS) and Brief International Cognitive Assessment for Multiple Sclerosis (BICAMS). These may take 1-2 hours, depending on the tests, and require trained personnel to administer the tests. There is increasing interest in automated testing approaches, such as smartphone applications, which may make it easier to monitor cognitive changes.  

Recommendations

It is recommended to screen for cognitive symptoms in pwMS. This may start with a simple discussion with health care providers about cognitive symptoms.  Anyone with symptoms or concerns about their cognition warrant screening with tests such as the SDMT (Kalb et al., 2018). The SDMT can also be repeated to monitor for any changes in cognition.  

More comprehensive assessments, such as those with neuropsychology, are recommended for anyone who tests positive on initial cognitive screening.  Such detailed assessments are also warranted in those who notice a cognitive decline over time or individuals applying for disability. Testing can be repeated to again assess for any changes.  

For pwMS with cognitive symptoms or abnormalities on cognitive testing it is important to assess contributing causes. MS absolutely is a cause of cognitive changes but so can medication side effects, uncontrolled pain, poor sleep, and infections. These are potentially reversible contributors to cognitive symptoms and worth investigating as addressing them may lead to improvement. 

Future Directions

Remote testing through different personal device applications is a potentially easier way to monitor a person’s cognition. Several studies have looked at the application of PST(Foong et al., 2023). A recent observational study looked at the long-term trajectory of digital cognitive testing. Those who scored lower on the initial testing tended to have more decline over time (Foong et al., 2025). These kinds of monitoring are being used more and more in research to try and monitor treatment responses. In the clinic, these may be used as another way to monitor a person’s disease progression or stability. These types of tests do not replace more detailed cognitive assessments; however, but may help in risk stratification or identification of those that would benefit from more detailed assessments with neuropsychologists.  

Conclusions

Cognitive changes are frequently seen in MS. There are several ways to assess cognition. This may include short screening tests in the clinic or potentially at home, or assessments with psychologists or neuropsychologists. More comprehensive testing can help identify other causes or contributors to a person’s cognitive symptoms. Screening regularly for cognitive symptoms is increasingly recommended in routine practice.