ObjectiveTo determine whether anxiety and depression are associated with cognition in multiple sclerosis (MS), and whether these associations are similar in other immune-mediated inflammatory diseases (IMID; including inflammatory bowel disease [IBD] and rheumatoid arthritis [RA]) and in anxious/depressed individuals (ANX/DEP) without an IMID.MethodsParticipants (MS: n = 255; IBD: n = 247; RA: n = 154; ANX/DEP: n = 308) completed a structured psychiatric interview, the Hospital Anxiety and Depression Scale, and cognitive testing, including the Symbol Digit Modalities Test, the California Verbal Learning Test, and Letter Number Sequencing test. Test scores were converted to age-, sex-, and education-adjusted z scores. We evaluated associations of anxiety and depression with the cognitive z scores using multivariate linear models, adjusting for disease cohort.ResultsAll cohorts exhibited higher rates of impairment (i.e., z less than or equal to −1.5) in the domains of processing speed, verbal learning, and delayed recall memory relative to general population norms. Higher levels of anxiety symptoms were associated with slower processing speed, lower verbal learning, and lower working memory performance (all p < 0.001); higher levels of depression symptoms were associated with slower processing speed. These associations did not differ across cohorts.ConclusionAnxiety and depression are associated with lower cognitive function in MS, with a similar pattern observed in persons with other IMID, including IBD and RA, and persons without an IMID. Managing symptoms of anxiety and of depression in MS, as well as other IMIDs, is important to mitigate their effect on cognition.

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.