An investigation of auditory processing in relapsing-remitting multiple sclerosis.

Multiple sclerosis (MS) is one of the most common neurological diseases in North America and it is frequently associated with sensory processing difficulties, cognitive deficits, and psychiatric illness. While many studies have examined cognitive deficits in MS measured by behavioural responses and neuroimaging techniques, only a few studies have examined neurophysiological measures of auditory functioning in MS, such as the mismatch negativity (MMN). The MMN is an event-related potential that indicates automatic auditory change detection. This study examined whether MMN endpoints measured by electroencephalography (EEG) differ in individuals with relapsing-remitting MS compared to healthy controls and whether the symptomatology of MS, including symptoms of depression and fatigue, are related to MMN measures. A multi-feature MMN paradigm, which includes five distinct deviant tones, was used to assess auditory cortex function in MS. There were no significant differences in MMN amplitudes or latencies between the MS and control group (p < 0.05) and corresponding effect sizes were small. However, there was a correlation between reduced MMN amplitudes in response to an intensity deviant and physician-reported disability. The intensity MMN may be more sensitive to deterioration in this population. Ultimately, this study provides a comprehensive profile of early auditory processing abilities in MS and suggests that a reduction in the MMN response may be representative of disease severity in MS.

Usability, Acceptability, and Impact of a Pediatric Teledermatology Mobile Health Application.

OBJECTIVE: Pediatric dermatology appointment wait times often exceed several months. We evaluated the usability, acceptability, and clinical impact of a store-and-forward teledermatology mobile application (app) linking families with pediatric dermatologists. METHODS: Parents of children age 6 weeks to 17 years or individuals 18-21 years old were invited (by e-mail or referral) to participate in this single group, prospective study. Within the app, users photographed the skin condition, answered questions, and submitted their case for review. One pediatric dermatologist viewed cases, diagnosed conditions, and provided instructions and prescriptions. User surveys immediately following app use and 1 week later, supplemented by electronic logs, assessed usability, acceptability, and impact. RESULTS: One hundred ninety-seven parents and one adolescent submitted cases within 39 days of invitation. App users were more likely to be white than those in the population invited (67% vs. 34%, p < 0.001) and their children were slightly younger (mean 7.3 vs. 9.0 years, p < 0.001). A majority, 83% found the app easy to use, 97% felt that submitting a case took "the right amount of time," 87% were satisfied, and 93% would use the app again. Prescription receipt was associated with increased app satisfaction (p = 0.008). The median user received a response in 2.8 h (interquartile range 1.1-6.4). Had the app been unavailable, 44% reported that they would have waited for primary care, 32% for a dermatology appointment, and 7% would have gone to an urgent care clinic. CONCLUSIONS: A mobile health app allowing families to directly consult a pediatric dermatologist was usable, acceptable, and expedited care.

Adverse health behaviours are associated with depression and anxiety in multiple sclerosis: A prospective multisite study.

BACKGROUND: Depression and anxiety are common among people with multiple sclerosis (MS), as are adverse health behaviours, but the associations between these factors are unclear. OBJECTIVE: To evaluate the associations between cigarette smoking, alcohol use, and depression and anxiety in MS in a cross-Canada prospective study. METHODS: From July 2010 to March 2011 we recruited consecutive MS patients from four MS clinics. At three visits over two years, clinical and demographic information was collected, and participants completed questionnaires regarding health behaviours and mental health. RESULTS: Of 949 participants, 75.2% were women, with a mean age of 48.6 years; most had a relapsing-remitting course (72.4%). Alcohol dependence was associated with increased odds of anxiety (OR: 1.84; 95% CI: 1.32-2.58) and depression (OR: 1.53; 95% CI: 1.05-2.23) adjusting for age, sex, Expanded Disability Status Scale (EDSS), and smoking status. Smoking was associated with increased odds of anxiety (OR: 1.29; 95% CI: 1.02-1.63) and depression (OR: 1.37; 95% CI: 1.04-1.78) adjusting for age, sex, EDSS, and alcohol dependence. Alcohol dependence was associated with an increased incidence of depression but not anxiety. Depression was associated with an increased incidence of alcohol dependence. CONCLUSION: Alcohol dependence and smoking were associated with anxiety and depression. Awareness of the effects of adverse health behaviours on mental health in MS might help target counselling and support for those 'at risk'.

Updated clinical practice guidelines for concussion/mild traumatic brain injury and persistent symptoms.

OBJECTIVE: To introduce a set of revised guidelines for the management of mild traumatic brain injury (mTBI) and persistent symptoms following concussive injuries. QUALITY OF EVIDENCE: The Guidelines for Mild Traumatic Brain Injury and Persistent Symptoms were made available in March 2011 based on literature and information up to 2008. A search for new clinical practice guidelines addressing mTBI and a systematic review of the literature evaluating treatment of persistent symptoms was conducted. Healthcare professionals representing a range of disciplines from Canada and abroad attended a consensus conference to revise the original guidelines in light of new evidence. MAIN MESSAGE: A modified Delphi process was used to create 96 recommendations addressing the diagnosis and management of mTBI and persistent symptoms, including post-traumatic headache, sleep disturbances, mental health disorders, cognitive difficulties, vestibular and vision dysfunction, fatigue and return to activity/work/school. Numerous resources, tools and treatment algorithms were also included to aid implementation of the recommendations. CONCLUSION: The revised clinical practice guideline reflects the most current evidence and is recommended for use by clinicians who provide care to people who experience PPCS following mTBI.

Cognition in early relapsing-remitting multiple sclerosis: consequences may be relative to working memory.

The Relative Consequence Model proposes multiple sclerosis (MS) patients have a fundamental deficit in processing speed that compromises other cognitive functions. The present study examined the mediating role of processing speed,as well as working memory, in the MS-related effects on other cognitive functions for early relapsing-remitting patients. Seventy relapsing-remitting MS patients with disease duration not greater than 10 years and 72 controls completed tasks assessing processing speed, working memory, learning, and executive functioning. The possible mediating roles of speed and working memory in the MS-related effects on other cognitive functions were evaluated using structural equation modeling. Processing speed was not significantly related to group membership and could not have a mediating role. Working memory was related to group membership and functioned as a mediating/intervening factor. The results do not support the Relative Consequence Model in this sample and they challenge the notion that working memory impairment only emerges at later disease stages. The results do support a mediating/intervening role of working memory. These results were obtained for early relapsing-remitting MS patients and should not be generalized to the broader MS population. Instead, future research should examine the relations that exist at other disease stages.

The role of executive attention in the acquisition of mathematical skills for children in Grades 2 through 4.

We examined the role of executive attention, which encompasses the common aspects of executive function and executive working memory, in children's acquisition of two aspects of mathematical skill: (a) knowledge of the number system (e.g., place value) and of arithmetic procedures (e.g., multi-digit addition) and (b) arithmetic fluency (i.e., speed of solutions to simple equations such as 3+4 and 8-5). Children in Grades 2 and 3 (N=157) completed executive attention and mathematical tasks. They repeated the mathematical tasks 1 year later. We used structural equation modeling to examine the relations between executive attention and (a) concurrent measures of mathematical knowledge and arithmetic fluency and (b) growth in performance on these measures 1 year later. Executive attention was concurrently predictive of both knowledge and fluency but predicted growth in performance only for fluency. A composite language measure predicted growth in knowledge from Grade 2 to Grade 3. The results support an important role for executive attention in children's acquisition of novel procedures and the development of automatic access to arithmetic facts.

Recognition of masked and unmasked facial expressions in males and females and relations with mental wellness.

Background: While the effects of mask wearing/facial occlusion are known to impair facial expression recognition, little is known about the role of mental wellness on facial expression recognition, as well as the influence of sex on misattribution errors (i.e., confusions between emotions). In this large study, we aimed to address the relation between facial expression recognition and loneliness, perceived stress, anxiety, and depression symptoms in male and female adults. Methods: We assessed the influence of mask-wearing on facial expression recognition [i.e., accuracy and response time (RT)] via an online study in N = 469 adult males and females across Canada. Results: Expectedly, recognition was impaired under masked conditions (i.e., lower accuracy, longer RTs, more misattribution errors). Females were faster and more accurate than males, with less misattribution errors. A novel finding was that people with higher perceived stress were less accurate at identifying masked fearful faces. Perceived stress influenced the relation between sex and RT to masked happy faces; males with high stress scores were slower to recognize masked happy faces, the opposite was true for females. Finally, this study was among the first to show that higher loneliness predicted shorter RT to unmasked faces. Impact: Our results show that facial expression recognition is impaired by mask-wearing, and that sex and mental health features are important predictors of performance. Such insight could be detrimental in certain sectors of the population (e.g., health care or education), and inform policies being adopted in future pandemics.

Measuring the attention networks and quantitative-electroencephalography correlates of attention in depression.

Given the association between major depressive disorder (MDD) and cortical inefficiency related to executive control, specifically in the sense that individuals with MDD may recruit more cognitive resources to complete tasks at the same capacity as those without MDD, the current study was interested in examining the attention networks and executive functioning of those with MDD. Past research has used the Attention Network Test (ANT) to measure changes of attention in clinical vs. healthy populations; however, theoretical concerns have been raised regarding the task. The Combined Attention Systems Task (CAST) was developed to address these concerns and was used in our study in combination with quantitative-electroencephalography (QEEG) to assess both behavioural and neurophysiological changes in participants with MDD (n = 18) compared to healthy controls (HCs; n = 22). We found no behavioural differences between MDD and HC groups suggesting individuals with MDD in our sample were not experiencing the executive functioning deficits previously reported in the literature. Neurophysiological measures of attention revealed that MDD participants had greater theta and alpha1 activity relative to HCs, suggesting that although individuals with MDD do not show deficits in behavioural attention, they exhibit altered neural processing which underlies cognitive function.

A pilot study of electrocortical activity in dysfunctional anger: decreased frontocortical activation, impaired attention control, and diminished behavioral inhibition.

Dysfunctional anger, though not a primary clinical diagnosis per se, does present clinically as a pathological mood for which treatment is sought. Few studies have probed the neurocortical correlates of dysfunctional anger or assessed if cognitive processes, such as attention, are altered in dysfunctional anger. Though dysfunctional and high trait anger appears to be associated with biased processing of anger-eliciting information, few studies have examined if dysfunctional anger modulates attention more generally. This is a notable gap as volitional attention control is associated with effective emotive regulation, which is impaired in dysfunctional anger and in associated acts of aggression. In this pilot study, we examined performance and electroencephalographic (EEG) profiles during a 12-min continuous performance task (CPT) of sustained attention in 15 adults with dysfunctional anger (Anger group) and 14 controls (control group). The Anger group had fewer hits at the end of the CPT, which correlated with decreased frontocortical activation, suggesting decreased engagement of frontal circuits when attention is taxed. The Anger group had more false alarms overall indicating impaired response inhibition. Increased right cortical activation during the initial portion of CPT existed in the Anger group, perhaps reflecting greater engagement of frontal circuits (i.e. effort) during initial stages of the task compared to controls. Finally, increased overall beta1 power, suggesting increased cortical activation, was noted in the Anger group. These EEG patterns suggest a hypervigilant state in dysfunctional anger, which may interfere with effective attention control and decrease inhibition. Such impairments likely extend beyond the laboratory setting, and may associate with aggressive acts in real life.

Clinical practice guidelines for mild traumatic brain injury and persistent symptoms.

OBJECTIVE: To outline new guidelines for the management of mild traumatic brain injury (MTBI) and persistent postconcussive symptoms (PPCS) in order to provide information and direction to physicians managing patients' recovery from MTBI. QUALITY OF EVIDENCE: A search for existing clinical practice guidelines addressing MTBI and a systematic review of the literature evaluating treatment of PPCS were conducted. Because little guidance on the management of PPCS was found within the traumatic brain injury field, a second search was completed for clinical practice guidelines and systematic reviews that addressed management of these common symptoms in the general population. Health care professionals representing a range of disciplines from across Canada and abroad were brought together at an expert consensus conference to review the existing guidelines and evidence and to attempt to develop a comprehensive guideline for the management of MTBI and PPCS. MAIN MESSAGE: A modified Delphi process was used to create 71 recommendations that address the diagnosis and management of MTBI and PPCS. In addition, numerous resources and tools were included in the guideline to aid in the implementation of the recommendations. CONCLUSION: A clinical practice guideline was developed to aid health care professionals in implementing evidencebased, best-practice care for the challenging population of individuals who experience PPCS following MTBI.

Cortical thickness abnormalities in attention deficit hyperactivity disorder revealed by structural magnetic resonance imaging: Newborns to young adults.

Attention deficit hyperactivity disorder (ADHD) is a neurodevelopmental condition for which we have an incomplete understanding, and so brain imaging methods, such as magnetic resonance imaging (MRI), may be able to assist in characterising and understanding the presentation of the brain in an ADHD population. Statistical and computational methods were used to compare participants with ADHD and neurotypical controls at a variety of developmental stages to assess detectable abnormal neurodevelopment potentially associated with ADHD and to assess our ability to diagnose and characterise the condition from real-world clinical MRI examinations. T1-weighted structural MRI examinations (n = 993; 0-31 years old [YO]) were obtained from neurotypical controls, and 637 examinations were obtained from patients with ADHD (0-26 YO). Measures of average (mean) regional cortical thickness were acquired, alongside the first reporting of regional cortical thickness variability (as assessed with the standard deviation [SD]) in ADHD. A comparison between the inattentive and combined (inattentive and hyperactive) subtypes of ADHD is also provided. A preliminary independent validation was also performed on the publicly available ADHD200 dataset. Relative to controls, subjects with ADHD had, on average, lowered SD of cortical thicknesses and increased mean thicknesses across several key regions potentially linked with known symptoms of ADHD, including the precuneus and supramarginal gyrus.

The symbol digit modalities test and the paced auditory serial addition test involve more than processing speed.

BACKGROUND: Slowed processing speed is the most frequently reported cognitive deficit for people with multiple sclerosis (MS). However, measures used to assess processing speed may also recruit other cognitive abilities. The present objective was to determine the contributions of different cognitive functions to performance on two commonly used processing speed measures: the Symbol Digit Modalities Test (SDMT) and the Paced Auditory Serial Addition Test (PASAT). METHODS: Adults with relapsing-remitting MS (n = 70) and controls (n = 72) completed the SDMT, PASAT, and multiple measures assessing processing speed, working memory, and learning. Hierarchical regression analyses were used to examine the contributions of MS, processing speed, working memory, learning, and all possible interactions among factors to SDMT and PASAT scores. RESULTS: Processing speed and working memory generally contributed to performance on the SDMT and PASAT, with learning additionally contributing to SDMT performance. However, significant interactions revealed processing speed did not influence PASAT performance for individuals with high working memory ability whereas processing speed became increasingly more important as working memory declined to average and low levels. Further, processing speed was associated with SDMT performance for patients with MS but not controls. CONCLUSIONS: These findings support a multifactorial interpretation of the SDMT and PASAT, which facilitates their usefulness as screening measures for cognitive decline but prevents them from identifying which specific cognitive functions are affected.

Text Message Reminders for the Second Dose of Influenza Vaccine for Children: An RCT.

BACKGROUND AND OBJECTIVES: Among children requiring 2 influenza doses in a given season, second dose receipt nearly halves the odds of influenza. Nationally, many children do not receive both needed doses. This study sought to compare the effectiveness of text message reminders with embedded interactive educational information versus usual care on receipt and timeliness of the second dose of influenza vaccine. METHODS: This trial took place over the 2017 to 2018 and 2018 to 2019 influenza seasons among 50 pediatric primary care offices across 24 states primarily from the American Academy of Pediatrics' Pediatric Research in Office Settings practice-based research network. Caregiver-child dyads of children 6 months to 8 years in need of a second influenza vaccination that season were individually randomized 1:1 into intervention versus usual care, stratified by age and language within each practice. Intervention caregivers received automated, personalized text messages, including educational information. Second dose receipt by April 30 (season end) and by day 42 (2 weeks after second dose due date) were assessed using Mantel Haenszel methods by practice and language. Analyses were intention to treat. RESULTS: Among 2086 dyads enrolled, most children were 6 to 23 months and half publicly insured. Intervention children were more likely to receive a second dose by season end (83.8% versus 80.9%; adjusted risk difference (ARD) 3.8%; 95% confidence interval [0.1 to 7.5]) and day 42 (62.4% versus 55.7%; ARD 8.3% [3.6 to 13.0]). CONCLUSIONS: In this large-scale trial of primary care pediatric practices across the United States, text message reminders were effective in promoting increased and timelier second dose influenza vaccine receipt.

Quality of clinical practice guidelines for persons who have sustained mild traumatic brain injury.

BACKGROUND: Mild TBI is one of the most common neurological disorders occurring today. For individuals who experience persistent symptoms following mild TBI, consequences can include functional disability, stress and time away from one's occupation. The objective of the study was to evaluate the quality of clinical practice guidelines (CPGs) that include recommendations on the care of persons who have sustained mild TBI and associated persistent symptoms. METHODS: A minimum of four appraisers used the Appraisal of Guidelines for Research and Evaluation (AGREE) instrument to evaluate seven CPGs found via a systematic search of bibliographic databases and internet resources. RESULTS: High AGREE scores were obtained for the domains Scope and Purpose and Clarity and Presentation. The CPGs fared less well on Rigour of Development, Stakeholder Involvement, Editorial Independence and Applicability. The number of recommendations addressing the care of persistent symptoms following mild TBI was meager, with the exception of military guidelines. CONCLUSIONS: There is considerable variability in the quality of guidelines addressing mild TBI and, overall, the CPGs reviewed score lower on Rigour of Development than CPGs for other medical conditions. There is a clear need for clinical guidance on the management of individuals who experience persistent symptoms following mild TBI.

Clinically detectable structural abnormalities in pediatric-onset multiple sclerosis: A large-scale magnetic resonance imaging analysis.

BACKGROUND: Multiple Sclerosis is characterized by neural demyelination. Structural magnetic resonance imaging (MRI) provides soft tissue contrast, which forms the basis of techniques for extracting regional biomarkers across a participant's brain. OBJECTIVES: To investigate the clinical presentation of multiple sclerosis in a large-scale MRI analysis that includes thorough consideration of extractable structural measurements (average and variability of regional cortical thicknesses, cortical surface measurements, and volumes). METHODS: We performed a large-scale retrospective analysis of 370 T1 structural volumetric MRIs from 64 participants with multiple sclerosis and compared them with a large cohort of neurotypical participants, consisting of 993 MRIs from 988 participants. Regionally distributed measurements of cortical thickness (average and standard deviation) were extracted along with surface area, surface curvature, and volumetric measurements. RESULTS: The largest observed finding involved regionally distributed reductions in average cortical thickness, with the parahippocampal region exhibiting the largest effect size, a finding that may be linked with known hippocampal atrophy in multiple sclerosis. Group-wise differences were also observed in terms of distributed volume, surface area, and surface curvature measurements. CONCLUSIONS: Participants with pediatric-onset multiple sclerosis present clinically with a variety of structural abnormalities, including perirhinal cortex thickness abnormalities not previously reported in the literature.

The Computerized Test of Information Processing (CTIP) offers an alternative to the PASAT for assessing cognitive processing speed in individuals with multiple sclerosis.

OBJECTIVE: To compare the ability of the Computerized Test of Information Processing (CTIP) to detect impaired cognitive processing speed in patients with multiple sclerosis (MS) with a traditional 3.0 second Paced Auditory Serial Addition Test (PASAT) and the Adjusting-PASAT which allows for calculation of a speed score. BACKGROUND: A primary cognitive deficit in MS is an impaired ability to process information quickly. Unfortunately, relatively few clinical tests effectively measure information processing speed. Of these, the PASAT is generally acknowledged to be the most sensitive, but use of this test is constrained by several factors. METHODS: All tests were administered to 30 adults with relapsing-remitting MS and 30 control participants. RESULTS: A series of analysis of variances revealed MS participants performed significantly worse than controls on the CTIP and the 3.0 second PASAT, whereas no significant difference was observed for the Adjusting-PASAT. CONCLUSIONS: The results suggest the CTIP can detect deficits in the speed at which people with MS process information. Thus, the CTIP offers an alternative means to the 3.0 second PASAT included in the Multiple Sclerosis Functional Composite for assessing such impairment.

MMN-Indexed Auditory Change Detection in Major Depressive Disorder.

In major depressive disorder (MDD), event-related potentials that are involved in auditory cortex function (i.e. N100 and P300) often have greater latencies and decreased amplitudes. The auditory mismatch negativity (MMN) is thought to be produced by generators in the auditory cortex, as well as the frontal lobes. Reports on differences in MMN in those with MDD have been varied. It was hypothesized that the wide range of results in the literature may be due to the use of different deviant types in eliciting the MMN. To attempt and explain these inconsistencies, the current study employed a multifeature MMN paradigm with 5 deviant tone types in community-dwelling participants with a diagnosis of MDD. We found those with MDD had higher MMN amplitudes following tones that deviated in intensity and location, but no difference in MMNs elicted by the other deivants (relative to unaffected controls). Location MMN deviants were negatively correlated with depression severity scores (i.e. larger MMN with greater severity). We also found longer MMN latencies following the pitch deviant. These results suggest the early auditory change detection process is altered in MDD, but only following certain types of auditory stimuli. Potential explanations for these findings, including high levels of anxiety and the influence of tryptophan are explored. Equally, the current report highlights the importance of using various deviant types when examining the MMN in clinical populations.

Vaccine hesitancy and influenza beliefs among parents of children requiring a second dose of influenza vaccine in a season: An American Academy of Pediatrics (AAP) Pediatric Research in Office Settings (PROS) study.

To receive adequate protection against influenza, some children 6 months through 8 y old need two doses of influenza vaccine in a given season. Currently, only half of those receiving the first dose receive a second. Our objective was to assess vaccine hesitancy and influenza disease and vaccine knowledge, attitudes, and beliefs among caregivers of children who received the first of their two needed doses. As part of a national-randomized control trial of second dose text-message influenza vaccine reminders (2017-2018 season), a telephone survey collected caregiver and index child demographic information. Each child had received the first of two needed influenza vaccine doses. Caregivers completed a measure of general vaccine hesitancy - the five-question Parent Attitudes About Childhood Vaccines Survey Tool (PACV-5) - and questions about influenza infection and vaccine. We assessed associations between participant demographic characteristics, vaccine hesitancy, and influenza beliefs and calculated the standardized proportion of caregivers endorsing each outcome using logistic regression. Analyses included responses from 256 participants from 36 primary care practices in 24 states. Some caregivers (11.7%) reported moderate/high vaccine hesitancy and many had misperceptions about influenza disease and vaccine. In multivariable models, no single variable was consistently associated with inaccurate knowledge, attitudes, and beliefs. These results demonstrate that caregivers whose children received the first dose of influenza vaccine may still be vaccine hesitant and have inaccurate influenza beliefs. Pediatricians should consider broadly addressing inaccurate beliefs and promoting vaccination even after caregivers agree to the first dose.

Long-term Cognitive Outcomes in Patients With Pediatric-Onset vs Adult-Onset Multiple Sclerosis.

IMPORTANCE: Cognitive impairment in multiple sclerosis (MS) can lead to reduced quality of life, social functioning, and employment. Few studies have investigated cognitive outcomes among patients with pediatric-onset MS (POMS) over the long term. OBJECTIVE: To compare long-term information-processing efficiency between patients with POMS and adult-onset MS (AOMS). DESIGN, SETTING, AND PARTICIPANTS: This population-based longitudinal cohort study accessed the Swedish MS Registry (SMSreg), which collates information from all 64 neurology clinics in Sweden. Registered cases with definite MS in the SMSreg with an onset before April 15, 2018, and at least 2 Symbol Digit Modalities Test (SDMT) scores recorded were included. Only persons aged 18 to 55 years and with duration of disease of less than 30 years at the time of SDMT administration were included, to ensure comparable ranges between patients with POMS and AOMS. Of 8247 persons with an SDMT recorded in the SMSreg, 5704 met inclusion criteria, 300 (5.3%) of whom had POMS. Data were collected from April 1, 2006, through April 15, 2018 and analyzed from April through August 2018. EXPOSURES: Pediatric-onset MS (onset <18 years of age) vs AOMS (onset ≥18 years of age). MAIN OUTCOMES AND MEASURES: Information-processing efficiency measured every 6 or 12 months by the SDMT. Linear mixed-effects models were used to compare all available SDMT scores between patients with POMS and those with AOMS. Persons with cognitive impairment (ever vs never) were identified using regression-based norms and compared between POMS and AOMS groups using logistic regression. RESULTS: Of the 5704 participants, 4015 were female (70.4%), and 5569 had a relapsing-onset disease course (97.6%). Most participants were exposed to a disease-modifying therapy (DMT) during follow-up (98.8%). Median age at baseline for the POMS group was 25.6 years (interquartile range, 21.0-31.7 years) and for the AOMS group, 38.3 years (interquartile range, 31.4-45.2 years). A total of 46 429 unique SDMT scores were analyzed. After adjustment for sex, age, disease duration, disease course, total number of SDMTs completed, oral or visual SDMT form, and DMT exposure, the SDMT score for patients with POMS was significantly lower than that of patients with AOMS (ß coefficient, -3.59 [95% CI, -5.56 to -1.54]). The SDMT score for patients with POMS declined faster than that of patients with AOMS (ß coefficient, -0.30 [95% CI, -0.42 tp -0.17]). The odds of cognitive impairment were also significantly elevated in the POMS group (odds ratio, 1.44; 95% CI, 1.06-1.98). CONCLUSIONS AND RELEVANCE: In adulthood, patients with POMS demonstrated a more rapid reduction in information-processing efficiency over time and were more likely to experience cognitive impairment than patients with AOMS, independent of age or disease duration. Further investigation is required to understand the mechanisms by which early MS onset influences cognitive outcomes.

Comorbid anxiety, depression, and cognition in MS and other immune-mediated disorders.

OBJECTIVE: To 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. METHODS: Participants (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. RESULTS: All 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. CONCLUSION: Anxiety 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.