Abstract
Background: Cognitive impairment is common in multiple sclerosis (MS). Interpretation of neuropsychological tests requires the use of normative data. Traditionally, normative data have been reported for discrete categories such as age. More recently continuous norms have been developed using multivariable regression equations that account for multiple demographic factors. Regression-based norms have been developed for use in the Canadian population for tests included in the MACFIMS and BICAMS test batteries. Establishing the generalizability of these norms is essential for application in clinical and research settings.Objectives: We aimed to (i) test the performance of previously published Canadian regression-based norms in an independently collected sample of Canadian healthy controls; (ii) compare the ability of Canadian and non-Canadian regression-based norms to discriminate between healthy controls and persons with MS; and (iii) develop regression-based norms for several cognitive tests drawn from batteries commonly used in MS that incorporated race/ethnicity in addition to age, education, and sex.Methods: We included 93 adults with MS and 96 healthy adults in this study, with a replication sample of 104 (MS) and 39 (healthy adults). Participants reported their sociodemographic characteristics, and each was administered the oral Symbol Digit Modalities Test (SDMT), the California Verbal Learning Test (CVLT-II), and the Brief Visuospatial Memory Test-Revised (BVMT-R). From the healthy control data, we developed regression-based norms incorporating race, age, education and sex. We then applied existing discrete norms and regression-based norms for the cognitive tests to the healthy controls, and generated z-scores which were compared using Spearman rank and concordance coefficients. We also used receiver operating characteristic (ROC) curves to compare the ability of each set of norms to discriminate between participants with and without MS. Within the MS samples we compared the ability of each set of norms to discriminate between differing levels of disability and employment status using relative efficiency.Results: When we applied the published regression norms to our healthy sample, impairment classification rates often differed substantially from expectations (7%), even when the norms were derived from a Canadian (Ontario) population. Most, but not all of the Spearman correlations between z-scores based on different existing published norms for the same cognitive test exceeded 0.90. However, concordance coefficients were often lower. All of the norms for the SDMT reliably discriminated between the MS and healthy control groups. In contrast, none of the norms for the CVLT-II or BVMT-R discriminated between the MS and healthy control groups. Within the MS population, the norms varied in their ability to discriminate between disability levels or employment status; locally developed norms for the SDMT and CVLT-II had the highest relative efficiency.Conclusion: Our findings emphasize the value of local norms when interpreting the results of cognitive tests and demonstrate the need to consider and assess the performance of regression-based norms developed in other populations when applying them to local populations, even when they are from the same country. Our findings also strongly suggest that the development of regression-based norms should involve larger, more diverse samples to ensure broad generalizability.
Highlights
Over 40% of persons with multiple sclerosis (MS) are thought to experience cognitive impairment which adversely affects social participation, independence, and employment [1, 2]
The neuropsychological tests conducted examined cognitive domains most often affected in MS, and the comorbidities of interest [17, 18] and included tests of information processing speed, verbal learning and memory, and visual learning and memory. From these tests we examined the test scores comprising the Brief International Cognitive Assessment for Multiple Sclerosis (BICAMS), i.e., the oral Symbol Digit Modalities Test (SDMT) [19], the California Verbal Learning Test (CVLT-II; Trial 1–5 total recall score) [20], and the Brief Visuospatial Memory Test-Revised (BVMT-R; summed recall score for all three learning trials) [21]
We examined the ability of the norms to discriminate between employed and unemployed persons with MS, where employment status was determined based on the Work Productivity and Impairment Scale [32]
Summary
Over 40% of persons with multiple sclerosis (MS) are thought to experience cognitive impairment which adversely affects social participation, independence, and employment [1, 2]. Given that access to comprehensive neuropsychological assessments is often limited, several abbreviated test batteries have been recommended for use in persons with MS, including the Brief International Cognitive Assessment for Multiple Sclerosis (BICAMS) [4]. Intelligence Quotient scores have risen over time [8], and use of outdated norms may lead to misclassification of cognitive status by underestimating the normal range of performance [9]. In consideration of these issues, recommendations for international validation of the BICAMS were made to encourage its adoption [10]. Establishing the generalizability of these norms is essential for application in clinical and research settings
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