Investigating the Impact of Polypharmacy and Anticholinergic Medication Burden on Objective Cognitive Performance in Adults With Multiple Sclerosis.

BACKGROUND: Polypharmacy, or the use of 5 or more daily medications, is common in adults with multiple sclerosis (MS), and is often due to various physical, cognitive, and emotional symptoms. However, research regarding the association between polypharmacy and cognitive outcomes in MS is sparse. Furthermore, individuals with MS often use medications with anticholinergic properties, which are commonly associated with cognitive impairment and other central nervous system adverse effects. Currently, the utility of scales measuring anticholinergic burden in MS is unknown. This study aims to investigate the relationship between polypharmacy, anticholinergic burden, and objective cognitive performance in MS. METHODS: We recruited 90 individuals with MS during routine visits at an MS specialty clinic in Kansas City. Participants completed a brief, virtual cognitive assessment and answered questions about their health. Participants provided their medication lists from which we determined polypharmacy and scores on several anticholinergic burden scales. Statistical analyses included Spearman correlations and linear regression models. RESULTS: Approximately 44% of the individuals surveyed met the criteria for polypharmacy. The number of daily medications was negatively correlated with cognitive performance (rs = -0.45, P < .001). Further, the Drug Burden Index accounted for additional variance in cognitive performance beyond that explained by age, education, MS disease duration, and comorbidities [ΔR2 = .12, F(5, 84) = 7.84, P < .001.]. CONCLUSIONS: Clinicians should consider the possible negative consequences of polypharmacy when addressing cognitive concerns in MS. Anticholinergic burden scales may be valuable in this regard. Future investigations could explore behavioral and pharmacological interventions aimed at reducing polypharmacy in MS.

Association between frailty and sleep quality in people living with multiple sclerosis and obesity: An observational cross-sectional study.

BACKGROUND: A majority of the people with multiple sclerosis (pwMS) experience sleep disturbances. Frailty is also common in pwMS. The geriatric literature strongly suggests that frailty is associated with worse sleep outcomes in community-dwelling older adults, but this association has yet to be explored among pwMS. This study focused on examining the association between frailty and sleep quality in pwMS. METHODS: Seventy-six people with both MS and obesity (mean age: 47.6 ± 10.9 years, 81.6 % female, mean body mass index (BMI): 37.10 ± 5.5 kg/m2, mean Patient Determined Disease Steps (PDDS): 0.82 ± 1.20) were included in this cross-sectional secondary analysis. A comprehensive frailty index (FI) based on 41 health deficits from various health domains was calculated based on standardized procedures. Sleep quality was determined by the Pittsburgh Sleep Quality Index questionnaire (PSQI). RESULTS: Overall, 67.1 % of the participants were identified as non-frail (FI ≤ 0.25), and 32.9 % were identified as frail (FI > 0.25). A significant correlation was observed between FI scores and global PSQI scores (ρ = 0.43, p < 0.05). Cross-tabulation analyses revealed that frail participants had worse subjective sleep quality, sleep latency, habitual sleep efficiency, sleep disturbances, daytime dysfunction, and higher use of sleep medications compared to non-frail participants (p < 0.05). CONCLUSIONS: The current study identified a significant association between frailty and sleep quality in people with both MS and obesity with minimal disability. These findings underscore the importance of untangling the relationship between frailty and sleep quality in pwMS. These results could lead to a more targeted approach for rehabilitation interventions aiming to improve frailty in MS.

Modifying diet and exercise in multiple sclerosis (MoDEMS): A randomized controlled trial for behavioral weight loss in adults with multiple sclerosis and obesity.

BACKGROUND: Obesity is a risk factor for developing multiple sclerosis (MS) and MS-related disability. The efficacy of behavioral weight loss interventions among people with MS (pwMS) remains largely unknown. OBJECTIVE: Examine whether a group-based telehealth weight loss intervention produces clinically significant weight loss in pwMS and obesity. METHODS: Seventy-one pwMS were randomized to the weight loss intervention or treatment-as-usual (TAU). The 6-month program promoted established guidelines for calorie reduction and increased physical activity. Anthropometric measurements, mobility tasks, self-report questionnaires, and accelerometry were used to assess changes at follow-up. RESULTS: Mean percent weight loss in the treatment group was 8.6% compared to 0.7% in the TAU group (p < .001). Sixty-five percent of participants in the intervention achieved clinically meaningful weight loss (⩾ 5%). Participants in the treatment group engaged in 46.2 minutes/week more moderate-to-vigorous physical activity than TAU participants (p = .017) and showed improvements in quality of life (p = .012). Weight loss was associated with improved mobility (p = .003) and reduced fatiguability (p = .008). CONCLUSION: Findings demonstrate the efficacy of a behavioral intervention for pwMS and obesity, with clinically significant weight loss for two-thirds of participants in the treatment condition. Weight loss may also lead to improved mobility and quality of life.

Concussion Characteristics in the National Hockey League Before and After the Introduction of Rule 48.

Importance: A rule prohibiting a direct hit to the lateral side of the head (ie, Rule 48-Illegal Check to the Head) was introduced in the National Hockey League (NHL) in the 2010-2011 season and refined in the 2011-2012 season to widen the application to include direct contact to all areas of the head. Objective: To compare the incidence and proportion of concussions that occurred following hits to the head before and after the implementation of Rule 48. Design, Setting, and Participants: This retrospective cohort study used a before and after design to evaluate concussions among NHL players in regular season games. Data from the 4 seasons preceding the implementation of Rule 48 (2006-2007 to 2009-2010) were compared with data from 5 seasons following its implementation (2014-2015 to 2018-2019). Data were analyzed from October 31, 2021, to November 30, 2022. Main Outcomes and Measures: The incidence and relative proportion of concussion characteristics and mechanisms before and after the introduction of Rule 48. Results: In the analysis of 688 concussions for NHL seasons spanning 2006 to 2010 (n = 231) and 2014 to 2019 (n = 457), there was an overall increase in the incidence of concussion between the 2 time frames, although the incidence of concussions due to hits to the lateral aspect of the head decreased from 1.6/100 games to 1.0/100 games (estimated difference, 0.6/100 games [90% credible interval (CrI), 0.30/100 games to 0.90/100 games). There was also a reduction of 18.8 (90% CrI, 13.0-23.7) percentage points in the proportion of concussions due to hits to the lateral aspect of the head from 80 of 231 concussions (34.6%) to 61 of 457 concussions (13.3%). The incidence of concussions following hits to the head from body checks using the shoulder, arm, and glove was similar before and following the implementation of Rule 48. However, the proportion was reduced 14.7 percentage points from 113 of 231 concussions (48.9%) before to 149 of 457 concussions (32.6%) after implementation of Rule 48 (90% CrI of the difference, 8.9-20.7 percentage points). Conclusions and Relevance: The findings of this cohort study of NHL players suggest that after the introduction of Rule 48, the incidence rate and proportion of concussions from contact to the lateral aspect of the head decreased, as did the proportion of concussions following direct hits to the head.

A pilot study evaluating the prefeasibility of a behavioral weight loss program in people with multiple sclerosis.

Weight loss interventions seldom include individuals with neurologic disease. The aims of the present study were to: 1) develop and assess the prefeasibility of a 6-month telehealth behavioral weight loss program for people with multiple sclerosis (MS) and obesity and 2) examine changes in weight loss (primary outcome), physical activity, and fruit/vegetable consumption at follow-up. Participants with obesity and MS engaged in a 24-week weight loss program. Participants followed established diet, exercise, and self-monitoring guidelines and attended weekly online group meetings. Median percentage weight loss was 10.54 % (SD = 7.19). Participants who adhered more closely to the self-monitoring guidelines (r = 0.81, p =.02), and who averaged higher weekly active minutes (r = 0.91, p =.002) achieved greater percentage weight loss. Six of the eight pilot participants achieved clinically meaningful weight loss (>5%) after 6-months.

Internet-delivered cognitive behavioural therapy programme to reduce depressive symptoms in patients with multiple sclerosis: a multicentre, randomised, controlled, phase 3 trial.

BACKGROUND: Depression is three to four times more prevalent in patients with neurological and inflammatory disorders than in the general population. For example, in patients with multiple sclerosis, the 12-month prevalence of major depressive disorder is around 25% and it is associated with a lower quality of life, faster disease progression, and higher morbidity and mortality. Despite its clinical relevance, there are few treatment options for depression associated with multiple sclerosis and confirmatory trials are scarce. We aimed to evaluate the safety and efficacy of a multiple sclerosis-specific, internet-based cognitive behavioural therapy (iCBT) programme for the treatment of depressive symptoms associated with the disease. METHODS: This parallel-group, randomised, controlled, phase 3 trial of an iCBT programme to reduce depressive symptoms in patients with multiple sclerosis was carried out at five academic centres with large outpatient care units in Germany and the USA. Patients with a neurologist-confirmed diagnosis of multiple sclerosis and depressive symptoms were randomly assigned (1:1:1; automated assignment, concealed allocation, no stratification, no blocking) to receive treatment as usual plus one of two versions of the iCBT programme Amiria (stand-alone or therapist-guided) or to a control condition, in which participants received treatment as usual and were offered access to the iCBT programme after 6 months. Masking of participants to group assignment between active treatment and control was not possible, although raters were masked to group assignment. The predefined primary endpoint, which was analysed in the intention-to-treat population, was severity of depressive symptoms as measured by the Beck Depression Inventory-II (BDI-II) at week 12 after randomisation. This trial is registered at ClinicalTrials.gov, NCT02740361, and is complete. FINDINGS: Between May 3, 2017, and Nov 4, 2020, we screened 485 patients for eligibility. 279 participants were enrolled, of whom 101 were allocated to receive stand-alone iCBT, 85 to receive guided iCBT, and 93 to the control condition. The dropout rate at week 12 was 18% (50 participants). Both versions of the iCBT programme significantly reduced depressive symptoms compared with the control group (BDI-II between-group mean differences: control vs stand-alone iCBT 6·32 points [95% CI 3·37-9·27], p<0·0001, effect size d=0·97 [95% CI 0·64-1·30]; control vs guided iCBT 5·80 points [2·71-8·88], p<0·0001, effect size d=0·96 [0·62-1·30]). Clinically relevant worsening of depressive symptoms was observed in three participants in the control group, one in the stand-alone iCBT group, and none in the guided iCBT group. No occurrences of suicidality were observed during the trial and there were no deaths. INTERPRETATION: This trial provides evidence for the safety and efficacy of a multiple sclerosis-specific iCBT tool to reduce depressive symptoms in patients with the disease. This remote-access, scalable intervention increases the therapeutic options in this patient group and could help to overcome treatment barriers. FUNDING: National Multiple Sclerosis Society (USA).

Acute evaluation of sport-related concussion and implications for the Sport Concussion Assessment Tool (SCAT6) for adults, adolescents and children: a systematic review.

OBJECTIVES: To systematically review the scientific literature regarding the acute assessment of sport-related concussion (SRC) and provide recommendations for improving the Sport Concussion Assessment Tool (SCAT6). DATA SOURCES: Systematic searches of seven databases from 2001 to 2022 using key words and controlled vocabulary relevant to concussion, sports, SCAT, and acute evaluation. ELIGIBILITY CRITERIA: (1) Original research articles, cohort studies, case-control studies, and case series with a sample of >10; (2) ≥80% SRC; and (3) studies using a screening tool/technology to assess SRC acutely (<7 days), and/or studies containing psychometric/normative data for common tools used to assess SRC. DATA EXTRACTION: Separate reviews were conducted involving six subdomains: Cognition, Balance/Postural Stability, Oculomotor/Cervical/Vestibular, Emerging Technologies, and Neurological Examination/Autonomic Dysfunction. Paediatric/Child studies were included in each subdomain. Risk of Bias and study quality were rated by coauthors using a modified SIGN (Scottish Intercollegiate Guidelines Network) tool. RESULTS: Out of 12 192 articles screened, 612 were included (189 normative data and 423 SRC assessment studies). Of these, 183 focused on cognition, 126 balance/postural stability, 76 oculomotor/cervical/vestibular, 142 emerging technologies, 13 neurological examination/autonomic dysfunction, and 23 paediatric/child SCAT. The SCAT discriminates between concussed and non-concussed athletes within 72 hours of injury with diminishing utility up to 7 days post injury. Ceiling effects were apparent on the 5-word list learning and concentration subtests. More challenging tests, including the 10-word list, were recommended. Test-retest data revealed limitations in temporal stability. Studies primarily originated in North America with scant data on children. CONCLUSION: Support exists for using the SCAT within the acute phase of injury. Maximal utility occurs within the first 72 hours and then diminishes up to 7 days after injury. The SCAT has limited utility as a return to play tool beyond 7 days. Empirical data are limited in pre-adolescents, women, sport type, geographical and culturally diverse populations and para athletes. PROSPERO REGISTRATION NUMBER: CRD42020154787.

Reinforcer pathology, probabilistic choice, and medication adherence in patients with multiple sclerosis.

The reinforcer pathology model posits that core behavioral economic mechanisms, including delay discounting and behavioral economic demand, underlie adverse health decisions and related clinical disorders. Extensions beyond substance use disorder and obesity, however, are limited. Using a reinforcer pathology framework, this study evaluates medical adherence decisions in patients with multiple sclerosis. Participants completed behavioral economic measures, including delay discounting, probability discounting, and a medication purchase task. A medical decision-making task was also used to evaluate how sensitivity to mild side effect risk and efficacy contributed to the likelihood of taking a hypothetical disease-modifying therapy. Less steep delay discounting and more intense (greater) medication demand were independently associated with greater adherence to the medication decision-making procedure. More generally, the pattern of interrelations between the medication-specific and general behavioral economic metrics was consistent with and contributes to the reinforcer pathology model. Additional research is warranted to expand these models to different populations and health behaviors, including those of a positive health orientation (i.e., medication adherence).

Characterizing Symptoms Before and Following Concussion in Professional Hockey.

OBJECTIVE: Examine SCAT5 baseline and acute symptom subscales in professional hockey players. DESIGN: Longitudinal case-control. SETTING: Preseason medical evaluations and suspected concussion evaluations. PARTICIPANTS: NHL/AHL players were given the NHL-modified SCAT5 before the 2018-2019 season (n = 1924). During the season, English-speaking players evaluated within 1 day of injury and diagnosed with concussion (n = 140) were compared with players evaluated for possible concussion, but not given a concussion diagnosis (n = 174). INDEPENDENT VARIABLES: Concussion diagnosis and demographic characteristics. MAIN OUTCOME MEASURES: Postconcussion Symptoms Scale (PCSS) items were subdivided into affective/emotional, cognitive, somatic/physical, sleep, and headache subscales. RESULTS: Cognitive (13%), somatic/physical (10%), sleep (26%), affective (18%), and headache (6%) symptoms were reported by players at baseline. Concussed players reported more acute symptoms than active controls on each of the subscales (all P's < 0.001). Players who underwent a suspected concussion evaluation were more likely to be diagnosed with concussion if they reported affective/emotional symptoms at baseline (P < 0.001). Postinjury cognitive (P < 0.001), somatic/physical (P < 0.001), and headache (P < 0.001) symptoms best differentiated concussed players and active controls. CONCLUSIONS: Player reports of increased cognitive difficulties, somatic/physical difficulties, and headache were most associated with concussion diagnosis at the acute evaluation. An abbreviated "acute" PCSS that includes only headache, cognitive, and/or physical symptoms may be useful for diagnostic purposes when evaluation time is limited. Approximately 2% of players reported significantly elevated affective/emotional symptoms at baseline and report of affective/emotional symptoms at baseline was associated with an increased likelihood of concussion diagnosis among players referred for a suspected concussion evaluation.

Determining Sport Concussion Assessment Tool fifth Edition (SCAT5) reliable change in male professional hockey players.

OBJECTIVES: The purpose of this paper is to provide reliable change metrics and assess the test-retest psychometrics of the Sport Concussion Assessment Tool fifth Edition (SCAT5) in a multilingual sample of professional ice hockey players. METHODS: The SCAT5 was administered to National Hockey League and American Hockey League male professional ice hockey players as part of the 2018 and 2019 season medical evaluations. We extracted data from an existing clinical database of players who were administered two consecutive baseline evaluations and had no intervening concussions to assess psychometric properties (eg, test-retest reliability) and develop reliable change metrics. RESULTS: Overall, 1007 players met inclusion criteria. Players were reassessed on average 344.52 (±62.52) days following their first baseline. Test-retest reliability ranged from r=0.3 to r=0.5. Reliable change metrics for Immediate Memory varied considerably dependent on form order. Significant differences were found between English versus non-English language preference on Immediate Memory and Concentration but not Delayed Memory or the modified Balance Error Scoring System (mBESS). Reliable change indices at the 90% CI were: Symptom Severity (5), Total Symptoms (3), Immediate Memory (3-8), Concentration (2), mBESS (5) and Delayed Memory (2-4). CONCLUSIONS: Our findings highlight the importance of considering form differences and language preference when determining reliable change from baseline on the SCAT5 in male professional hockey players. The relatively modest test-retest reliability of the measures leaves room for improved psychometric properties and increased sensitivity to concussion in future iterations of the SCAT.

The Utility of the King-Devick Test in Evaluating Professional Ice Hockey Players With Suspected Concussion.

OBJECTIVE: The purpose of this study was to (1) examine the diagnostic utility of the King-Devick (KD) in professional ice hockey players and (2) determine whether the KD provides unique variance in predicting a diagnosis of concussion when given in combination with the SCAT-5. STUDY DESIGN: Cohort Study. SETTING: Primary care. PATIENTS/PARTICIPANTS: Professional ice hockey players. INDEPENDENT VARIABLES: Diagnosis versus no diagnosis of concussion. MAIN OUTCOME MEASURES: King-Devick and SCAT-5 component scores. METHODS: In part 1, players suspected of having a concussion were evaluated at baseline and acutely with the KD and either the SCAT-3 or the SCAT-5. Players evaluated and not diagnosed with concussion served as active controls. In part 2, a separate group of players suspected of having a concussion was evaluated acutely with both the KD and SCAT-5. RESULTS: In part 1 of this study, 53 concussed players declined in performance on the KD from baseline to acute evaluation, whereas the performance of 76 active controls improved significantly. In part 2 of the study, 75 players were diagnosed with concussion and compared with 80 active controls who were evaluated and not diagnosed with concussion. Concussed players revealed a decline in KD performance from baseline to acute evaluation when compared with controls. However, the KD did not account for significant unique variance in predicting a diagnosis of concussion after accounting for SCAT-5 data. CONCLUSIONS: The KD is useful in differentiating concussed and not concussed athletes acutely, but the KD does not seem to add additional diagnostic value over and above the SCAT-5.

Perceived Fatigue Impact and Cognitive Variability in Multiple Sclerosis.

OBJECTIVE: People with Multiple Sclerosis (PwMS) and healthy controls (HCs) were evaluated on cognitive variability indices and we examined the relationship between fatigue and cognitive variability between these groups. Intraindividual variability (IIV) on a neuropsychological test battery was hypothesized to mediate the group differences expected in fatigue. METHOD: Fifty-nine PwMS and 51 HCs completed a psychosocial interview and battery of neuropsychological tests and questionnaires during a 1-day visit. Fatigue in this study was measured with the Fatigue Impact Scale (FIS), a self-report multidimensional measure of fatigue. IIV was operationalized using two different measures, a maximum discrepancy score (MDS) and intraindividual standard deviation (ISD), in two cognitive domains, memory and attention/processing speed. Two mediation analyses with group (PwMS or HCs) as the independent variable, variability composite (memory or attention/processing speed) measures as the mediators, total residual fatigue (after accounting for age) as the outcome, and depression as a covariate were conducted. The Baron and Kenny approach to testing mediation and the PROCESS macro for testing the strength of the indirect effect were used. RESULTS: Results of a mediation analysis using 5000 bootstrap samples indicated that IIV in domains of both attention/processing speed and memory significantly mediated the effect of patient status on total residual fatigue. CONCLUSION: IIV is an objective performance measure that is related to differences in fatigue impact between PwMS and HCs. PwMS experience more variability across tests of attention/processing speed and memory and this experience of variable performance may increase the impact of fatigue.

A Cross-Sectional Decision-Making Approach to Inform Neuropsychological Battery Development in Professional Hockey.

OBJECTIVE: Neuropsychologists commonly use a large battery of tests to inform clinical decisions. Decision analysis can be used to determine which individual tests play a role in the decision-making process. The objective of this project was to conduct quantitative and qualitative decision analysis of decisions by team neuropsychologists with professional hockey players being evaluated as part of the National Hockey League (NHL)/NHL Players Association Concussion Protocol. METHOD: We extracted neuropsychological data from an NHL clinical program database. Team neuropsychologists evaluated concussed players using a hybrid neuropsychological test battery. The neuropsychologists then determined whether players were experiencing concussion-related cognitive difficulties. Logistic regression was used to examine which tests accounted for unique variance in the decision-making process. We also conducted a survey of NHL neuropsychologists, asking them to rate the usefulness of each test in the battery. RESULTS: Five of the fifteen measures accounted for unique variance in team neuropsychologists' decisions, including the ImPACT Verbal Memory Composite, Visual Motor Composite, Reaction Time Composite, Symptom Score, and Brief Visuospatial Memory Test-Revised Delayed Recall. Notable discrepancies were uncovered between quantitative indications of usefulness and self-reported qualitative perceptions of test usefulness when making decisions. Qualitatively, clinicians reported that the Hopkins Verbal Learning Test-Revised, Symbol Digit Modalities Test, ImPACT Reaction Time, and Color Trails 2 were the most useful tests when making decisions. CONCLUSIONS: Along with validation studies, decision analysis can be used as part of a comprehensive evaluation process to inform the development of best-practice batteries for use among athletes with sports concussion.

Modifying Diet and Exercise in MS (MoDEMS): Study design and protocol for a telehealth weight loss intervention for adults with obesity & Multiple Sclerosis.

Weight loss improves overall health, and reduces inflammation, risk of stroke, heart attack, diabetes, certain cancers, and death among individuals with obesity. Weight loss also improves mobility, increases stamina, and elevates mood. Between 25 and 33% of people with Multiple Sclerosis (pwMS) have obesity. Multiple Sclerosis (MS) and obesity are independently associated with reduced mobility, increased fatigue, and depression. Most behavioral weight loss trials exclude individuals with neurologic disease. Consequently, few studies have examined the effects of weight loss on symptom presentation and health outcomes among pwMS and obesity. This is the first study examining the efficacy of a comprehensive behavioral weight loss intervention designed specifically for pwMS. The purpose of this study is to develop and assess the efficacy of a telehealth administered weight loss intervention tailored for pwMS. Additionally, we aim to determine if weight loss reduces physical and emotional symptoms in individuals with obesity and MS. We will enroll 70 pwMS in a wait-list crossover trial to examine the efficacy of our intervention. If successful, findings will help determine whether we can help participants lose clinically significant weight - and whether weight loss among pwMS and overweight/obesity reduces fatigue, and improves mobility, mood, and quality of life.