Monitoring cognitive functioning in MS will trigger anxiety in patients: Yes

In theory, routine monitoring of cognitive function in multiple sclerosis (MS) could be useful. ¹ In practice, routine cognitive screening is complicated by multiple challenges related to flaws in administration, inaccurate test interpretation, and adverse effects on the patient’s experience including creating unnecessary anxiety and stress. Alternative strategies for addressing cognitive concerns are available. Clinicians need to listen carefully to the patient and family, ask targeted questions, apply clinical observation and judgment, and incorporate quantitative neuroimaging methods to identify high-risk patients. Most critical is to know when and for whom clinical neuropsychological referral is needed.

Cognitive impairment is common in MS. ² Up to 65% of MS patients will show relative deficits on neuropsychological testing compared to age-matched controls with slowed cognitive processing as an early and among the most common findings. ² Subtle cognitive effects can even occur as early as radiologically isolated syndrome. ³ Fortunately, dementia is less common but still occurs more frequently in individuals with MS than among the general population; among US Veterans with MS who were 55 years old or more, dementia was present in 12%. ⁴

MS patients themselves are often poor reporters of subtle cognitive changes and neurologists are not much better. A much more reliable indicator of clinically significant cognitive change is family members. ⁵ When family members or the patients themselves are concerned about cognitive problems, neuropsychological testing is appropriate and referral for cognitive testing and potentially for cognitive rehabilitation should be considered. ⁶ Additional considerations to improve cognitive performance include training programs such as BrainHQ, ⁷ healthy diet, and physical exercise.

While appropriate neuropsychological referral can be extremely useful, routine cognitive screening within the neurologist’s office can be misguided and lead to confusion. First, the most widely used screening measure, the Symbol Digit Modality Test (SDMT) ⁸ does not purely assess cognition. The oral version of the SDMT is sensitive to the effects of multiple neurologic functions beyond pure information processing. The SDMT requires good vision, normal extraocular function and tracking, and the ability to verbally articulate answers. ⁸ However, MS can be associated with visual impairment, poor extraocular motor function, dysarthria, and slowed verbal output. In fact, this is one reason why the SDMT is so well correlated with subregional brain volumes. ² These non-cognitive neurologic factors such as vision and speech can also fluctuate according to time of day, body temperature, and preceding activity level. Unfortunately, most neurologists fail to consider these influences when analyzing test scores.

A second challenge with implementing cognitive screening within a neurology practice is that typically the cognitive tests are not administered by trained psychometricians as would be the case if referred for formal neuropsychological testing. There is tremendous variability in a patient’s ability to fully engage and focus on performing a cognitive test, which can be exacerbated by time of day, level of anxiety, temperature, among other factors. When patients first hear the instructions, they often become uncomfortable and anxious. On one hand, they want to please their provider and perform well. However, they may be afraid that they will be perceived as unintelligent. With repeat testing, many MS patients become even more anxious. Many younger individuals with MS (particularly those in the pediatric age group) will openly share their animosity regarding SDMT testing. Unfortunately, within a neurology practice, those administering the tests often have insufficient training or experience to effectively reassure patients and place them at ease or encourage full participation. Tests are typically administered by a research assistant or nurse, rarely the neurologist, none of whom have the training or experience of a clinical neuropsychologist or a supervised psychometrician. As a result, patient performance can show wild fluctuations from one administration to another varying 10% to 20% in our experience and certainly beyond the 4–8 points recommended as being clinically significant. These test fluctuations can occur in otherwise stable individuals on high-efficacy disease-modifying therapies and do not correspond to any clinically meaningful change in other aspects of daily living, family report, neurologic function, or neuroimaging findings.

A third challenge with routine cognitive screening is that the neurologists interpreting the screening measures lack the training and expertise of an experienced clinical neuropsychologist. When a neuropsychologist is asked to evaluate the cognitive ability of an MS patient, they take a careful and detailed clinical history to estimate premorbid function. In addition, neuropsychologists include measures within their neuropsychological batteries which provide estimates of premorbid function, for example, vocabulary or fund of knowledge measures. In contrast, neurologists often fail to take into consideration whether a patient had a learning disability, attentional deficits, or required special intervention during early schooling. As a result, deviations from normal cognitive performance are attributed to MS when, in fact, MS may have had little to no bearing on the test performance. Standardized neuropsychological test batteries have established normative databases which can be used to interpret an individual’s performance within a specific clinical context. Many screening procedures lack extensive normative databases.

Another approach for monitoring patients other than cognitive screening that can provide quantitative and more reliable data of potentially prognostic value is to utilize neuroimaging. Incorporating quantitative neuroimaging into clinical assessment circumvents the problems associated with cognitive screening. As patients with MS are routinely imaged with brain magnetic resonance imagings (MRIs) annually or every other year, adding brain volume assessments provides sensitive biomarkers which can predict current and subsequent cognitive function. ⁹ Clinically available brain volume assessment has emerged as a much more reliable, objective, and non-stressful approach for monitoring clinical status. ¹⁰ There are now regulatory agency approved software programs that can be incorporated into clinically acquired neuroimaging exams. Brain volume measurement is a standardized reliable and powerful predictor of subsequent cognitive status and neurologic disability. ⁹ While there are limitations in obtaining and interpreting MRI volume studies, these software packages provide powerful tools that can be used to monitor our patients. Furthermore, these methods are becoming more widely available and their reliability and sensitivity to change will only improve with time. Incorporation of brain volume measurement in routine practice is a much more powerful method for monitoring patient function and predicting future capabilities.

In summary, cognitive testing should be performed by clinical neuropsychologists where individuals administering the tests have the training and experience to put patients at ease, acquire meaningful and reliable data, and have the knowledge appropriate for correct interpretation of results. In contrast to the variable and subjective performance on screening measures administered by inadequately trained personnel, neuroimaging is objective, does not induce additional stress, does not depend on patient engagement, and provides a powerful indicator of future cognitive performance.