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Objective To determine whether comorbid diabetes and hypertension are associated with cognition in multiple sclerosis (MS) after accounting for psychiatric comorbidities. Methods Participants completed a structured psychiatric interview, the Hospital Anxiety and Depression Scale (HADS), a comorbidity questionnaire, and cognitive testing including the Symbol Digit Modalities Test (SDMT), California Verbal Learning Test (CVLT-II), Brief Visuospatial Memory Test-Revised (BVMT-R), and verbal fluency. Test scores were converted to age-, sex- and education-adjusted z-scores. We evaluated associations between diabetes and hypertension and the four cognitive z-scores using a multivariate linear model, adjusting for comorbid depression and anxiety disorders, psychotropic medications, disease-modifying therapies, smoking status and body mass index. Results Of 111 participants, most were women (82.9%) with relapsing remitting MS (83.5%), of mean (SD) age 49.6 (12.7) years. Comorbidity was common; 22.7% participants had hypertension, 10.8% had diabetes, 9.9% had current major depression, and 9.9% had current anxiety disorders. Mean (SD) z-scores were: SDMT −0.66 (1.15), CVLT-II −0.43 (1.32), BVMT-R −0.49 (1.07) and fluency −0.59 (0.86). Diabetes (p = 0.02) and anxiety disorder (p = 0.02) were associated with cognitive function overall. Diabetes was associated with lower BVMT-R (β = −1.18, p = 0.0015) and fluency (β = −0.63, p = 0.037) z-scores. Anxiety was associated with lower SDMT (β = -1.07, p = 0.0074) z-scores. Elevated anxiety symptoms (HADS-A ≥ 11) were associated with lower z-scores on the SDMT and CVLT-II. Conclusion Comorbidities, including diabetes and anxiety, are associated with cognitive dysfunction in MS. Their presence may contribute to the heterogeneous pattern of impairments seen across individuals and they may represent targets for improved management of cognitive symptoms.

Background Few studies have evaluated the association between comorbidities associated with increased vascular risk and brain volume changes in multiple sclerosis (MS). To date, findings have not been consistent with respect to which comorbidities are associated with lower brain volumes or whether comorbidities associated with increased vascular risk are associated with greater brain volume loss over time. Objectives We aimed to evaluate the association between the Framingham Risk Score (FRS) which evaluates vascular risk and normalized whole brain volume in MS. Methods We included 98 participants with MS who underwent two brain MRIs two years apart, from which whole brain volumes were calculated. Each participant reported their comorbidities and medications taken. Blood pressure, height and weight were recorded and we calculated the FRS. We tested the association between the FRS at baseline and brain volume at the second time point using quantile regression adjusting for baseline normalized brain volume, age, gender and use of disease-modifying therapy. Results As the FRS increased, brain volume was lower, both at enrollment (β= -0.24; 95%CI: -0.42, -0.04) and at follow-up (-0.27; 95%CI: -0.45, -0.08). After further adjustment for age, gender, and use of disease modifying therapy, higher FRS remained associated with lower brain volume at follow-up at the 90th percentile of brain volume (β= -2.22; 95%CI: -3.40, -1.04) but not at the 10th or 50th percentiles. Conclusion Higher FRS were associated with lower brain volumes in persons with MS at baseline, and with brain volume loss over time. This effect was most pronounced for persons with higher brain volumes at baseline, which suggests that prevention, detection and effective management of comorbidities associated with vascular risk in people with MS is particularly important early in the disease course.

Background Within the multiple sclerosis (MS) population, depression and anxiety are highly prevalent comorbidities that are associated with adverse outcomes such as diminished quality of life and disability progression. In the general population, many people who do not meet formal diagnostic criteria for depression or anxiety disorders still identify a need for mental health care. Limited data are available regarding the perceived need for mental health care among persons with MS. Objective We aimed to determine factors associated with a perceived need for mental health care in the MS population. Methods Participants with MS completed the Hospital Anxiety and Depression Scale (HADS) to assess severity of depression and anxiety symptoms, and reported whether they perceived a need for mental health care, in the context of a larger study examining the burden of psychiatric disorders in immune-mediated inflammatory disease. Participants were also evaluated using the Structured Clinical Interview for DSM-IV-TR (SCID) to diagnose depression or anxiety disorders. Participants reported their sociodemographic characteristics, and underwent physical assessments to determine their disability status. Descriptive analyses and binary logistic regression models were used to determine sociodemographic and clinical factors associated with perceived need for mental health care. Results Of 255 participants enrolled, 251 were included in this analysis. Most participants were women, Caucasian, with post-secondary education, with a mean (SD) age at enrollment of 50.9 (12.9) years. They predominantly had a relapsing-remitting MS course. Nearly one-quarter of participants had a current SCID diagnosis of depression or anxiety (n = 57, 22.7%). Overall, 31.8% (n = 80) of participants reported a need for mental health care. These individuals were slightly younger at enrollment (p = 0.037), but otherwise did not differ with respect to sociodemographic characteristics, compared to participants not reporting this need. Those identifying need for mental health care also had an earlier age of MS symptom onset (p = 0.011). After adjusting for sociodemographic and clinical factors, elevated symptoms of depression (odds ratio [OR] 2.36; 95%CI: 1.06, 5.25) and anxiety (OR 6.08; 95%CI: 2.78, 13.3) were associated with an increased likelihood of reporting a need for mental health care. Any current SCID diagnosis of depression or anxiety was not associated with perceived need for mental health care after accounting for symptoms of depression and anxiety. Conclusions One-third of people with MS identified a need for mental health care. Symptoms of anxiety and depression, but not current diagnosed mental health disorders, were the predominant factors associated with a perceived need for care.

Background Psychiatric comorbidity is prevalent in persons with multiple sclerosis (MS). Few studies have assessed whether second-generation disease-modifying therapies (DMT) are associated with adverse psychiatric effects. Objective We aimed to systematically review the literature regarding the APEs associated with natalizumab, fingolimod, dimethyl fumarate, teriflunomide and alemtuzumab in MS. As a secondary objective, we evaluated changes in anxiety or depression scores following treatment with the aforementioned DMTs. Methods We searched MEDLINE, EMBASE, International Pharmaceutical Abstracts, PsychINFO, Central Register of Controlled Trials & Cochrane database of systematic reviews for published studies, and clinicaltrials.gov and regulatory documents from the US and Canada for unpublished studies. Data sources were searched from inception to September 2017. Studies reporting adverse psychiatric effects involving any DMT of interest were included. We report the incidence proportions of the adverse psychiatric effects and, where applicable, risk differences between DMT-exposed and unexposed individuals along with the corresponding 95% confidence intervals. We calculated the standardized mean differences (SMD) of changes in anxiety and depression scores if reported as study outcomes, and pooled the data using random effects meta-analysis. Results Of 4389 abstracts screened, 78 met the inclusion criteria, including 48 clinical trials, 28 observational studies and 2 case reports. Depression was the most commonly reported adverse psychiatric effect. Incidence proportions for all adverse psychiatric effects ranged from 0 to 24.7%. None of the DMT studied were associated with a statistically significant increased risk of any adverse psychiatric effect (range of risk difference: -7.69% [95%CI: -16.06%, 5.56%] to 6.67 [-8.56, 15.59]). Eighteen studies examined changes in depression or anxiety following fingolimod, natalizumab or dimethyl fumarate treatment; depression symptoms improved in fingolimod-treated groups (SMD [95%CI]: 1.18 [0.17, 2.19]). We did not identify studies examining changes in these outcomes following treatment with any of the other DMTs. Conclusion The DMTs reviewed were not associated with an increased risk of adverse psychiatric effect in MS, and some may reduce the incidence of depressive symptoms. This may reflect either a positive direct effect (e.g. immune modulation) or an indirect effect arising due to a positive impact on disease activity or course.

Objective We aimed to evaluate the validity and reliability of multiple screening measures for depression and anxiety for use in the clinical care of people with multiple sclerosis (MS). Methods Participants with MS completed the Patient Health Questionnaire (PHQ-9), Hospital Anxiety and Depression Scale (HADS), Kessler-6 Distress Scale, PROMIS Emotional Distress Depression Short-Form 8a (PROMIS Depression) and Anxiety Short-Form 8a (PROMIS Anxiety), Generalized Anxiety Disorder 7-item Scale (GAD-7), and the Overall Anxiety and Severity Impairment Scale (OASIS). A subgroup repeated the screening measures two weeks later. All participants also completed a Structured Clinical Interview for DSM-IV-TR Axis I Disorders (SCID). For the screening measures we computed sensitivity, specificity, positive predictive and negative predictive value with SCID diagnoses as the reference standard and conducted receiver operating curve (ROC) analyses; we also assessed internal consistency and test-retest reliability. Results Of 253 participants, the SCID classified 10.3% with major depression and 14.6% with generalized anxiety disorder. Among the depression measures, the PHQ-9 had the highest sensitivity (84%). Specificity was generally higher than sensitivity, and was highest for the HADS-D with a cut-point of 11 (95%). In ROC analyses the area under the curve (AUC) did not differ between depression measures. Among the anxiety measures, sensitivity was highest for the HADS-A with a cut-point of 8 (82%). Specificity ranged from 83% to 86% for all measures except the HADS-A with a cut-point of 8 (68%). The AUC did not differ between anxiety measures. Conclusion Overall, performance of the depression and anxiety screening measures was very similar, with reasonable psychometric properties for the MS population, suggesting that other factors such as accessibility and ease of use could guide the choice of measure in clinical practice.