Simplified Testing for Cognitive Function in Multiple Sclerosis

It should be no surprise that multiple sclerosis (MS)--a disease that involves neurological damage--is significantly associated with neuropsychological impairment.¹ Among patients with newly diagnosed disease and in those with a benign course, 20% and 40% show signs of cognitive impairment, as do at least half of patients with secondary progressive MS.

Assessing the degree of cognitive impairment can be a challenge for clinicians who treat patients with MS outside of a major medical center and who have little access to experts trained in administering cognitive tests.

Recently, a committee of 12 neurologists and neuropsychologists who have carried out considerable research into cognitive impairment of MS convened to create a brief cognitive assessment for MS that is designed for small treatment centers with few staff members and no trained neuropsychologists. The result was the Brief International Cognitive Assessment for MS (BICAMS).^2,3

A prominent authority in the field, and a member of the expert committee, Ralph Benedict, PhD, offers background information about BICAMS here. Dr Benedict is Professor of Neurology, Psychiatry, and Psychology, School of Medicine and Biomedical Sciences at the State University of New York at Buffalo.

Q. Why measure cognitive function in patients with MS?
A. Routine evaluation of cognition can help patients navigate problems related to their daily life and their work environment. When carried out reliably, such evaluation can detect cognitive decline and serve as a guide to disease progression and treatment failure.

Q. What need inspired the creation of BICAMS?
A. Valid strategies to assess cognitive function in MS patients currently require the expertise of psychologists or neuropsychologists, who may not be available in many centers. Also, the BICAMS narrows the scope from existing validated strategies to the core elements that are minimally necessary and most sensitive.

Q. How does BICAMS differ from previous tools to measure cognitive impairment in MS?
BICAMS includes just 3 tests from the more extensive Minimal Assessment of Cognitive Function in MS [MACFIMS].^4,5 These tests are the Symbol Digit Modalities Test [SDMT]⁶ and the initial learning component  of 2 memory tests: California Verbal Learning Test Second Edition [CVLT2]⁷ and Brief Visuospatial Memory Test-Revised [BVMT-R].^8,9

In the SDMT, patients are given a standard sheet of paper that shows a grid with a series of 9 symbols that are repeated in no obvious order. In a key at the top, each symbol is assigned a single digit. Patients are asked to read across the grid and say which digit is associated with each of the symbols, in order. The outcome measure is the number of correct answers in 90 seconds. The SDMT is a valid measure of mental processing speed.

The CVLT2, a test of auditory/verbal learning, is a list of 16 words. The examiner reads the list to the patient, who must repeat as many of the items as possible, in any order. The BICAMS committee recommended allowing the patient 5 attempts, or trials, at the learning challenge. The total number of items recalled over 5 trials has been found to be the most sensitive measure of learning.

In the BVMT-R, 6 abstract designs are presented for 10 seconds and then removed from view. The patient is asked to sketch the images from memory using pencil and paper. Learning trials are scored from 0 to 12, based on accuracy and location. The outcome measure is the total score over 3 trials.

Q. Is BICAMS intended for research, for clinical assessment-or both? How well does it work?
A. It is intended for both. All of the BICAMS tests differentiate MS patients from healthy controls; results correlate well with vocational outcomes. A specific decline of 4 to 5 points on the SDMT has been correlated with job loss. However, more research is needed to establish clear thresholds for clinically meaningful changes.

Q. How widely is BICAMS used in the US today?
A. It’s not clear how often BICAMS is used as a stand-alone set of tests. As part of the larger Minimal Assessment of Functional Impairment in Multiple Sclerosis battery used by neuropsychologists, the BICAMS tests are probably in use in about 20% of specialty MS centers in the United States. The SDMT is most popular, briefer, and most sensitive, and I suspect it is used in many MS centers.

Q. Where can the clinician find instructions to score results of the tests and norms to interpret them?
A. The SDMT, CVLT2, and BVMT-R are well established and easy to purchase from test publishers. Standardized instructions are available when the tests are purchased. Furthermore, the BICAMS team is developing Web-based data for centers and is interested in validating BICAMS in non-English–speaking countries.

Q. What are the prospects for treatment or rehabilitation of MS patients with cognitive impairment?
A. There is burgeoning research activity on the role of pharmacological and rehabilitative approaches to cognitive impairment in MS.¹⁰ At this time, there are no indicated treatments, but this is likely to change in the near future.

References:
1. Benedict RH, Zivadinov R. Risk factors for and management of cognitive dysfunction in multiple sclerosis. Nat Rev Neurol. 2011;10:332-342.
2. Langdon DW, Amato MP, Boringa J, et al. Recommendations for a Brief International Cognitive Assessment for Multiple Sclerosis (BICAMS). Mult Scler. 2012;18:891-898.
3. Benedict R, Amato MP, Boringa J, et al. Brief International Cognitive Assessment for MS (BICAMS): international standards for validation. BMC Neurol. 2012;12:55.
4. Benedict RH, Fischer JS, Archibald CJ, et al. Minimal neuropsychological assessment of MS patients: a consensus approach. Clinic Neuropsychol. 2002;16:381-397.
5. Benedict RH, Cookfair D, Gavett R, et al. Validity of the Minimal Assessment of Cognitive Function in Multiple Sclerosis (MACFIMS). J Intl Neuropsychol Soc. 2006;12:549-558.
6. Smith A. Symbol Digit Modalities Test (SDMT). Manual (revised). Los Angeles: Western Psychological Services; 1982.
7. Delis DC, Kramer JH, Kaplan E, Ober BA. Califorina Verbal Learning Test. 2nd ed. San Antonio: The Psychological Corporation; 2000.
8. Benedict RHB, Schretlen D, Groninger L, et al. Revision of the Brief Visuospatial Memory Test: studies of normal performance, reliability, and validity. Psychol Assess. 1996;8:145-153.
9. Benedict RHB. Brief Visuospatial Memory Test - Revised: Professional Manual. Odessa, FL: Psychological Assessment Resources, Inc; 1997.
10. Benedict RH, Walton MK. Evaluating cognitive outcome measures for MS clinical trials: what is a clinically meaningful change? Mult Scler. 2012 Jul 24; [Epub ahead of print].