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Objective: Mean levels of cognitive functioning typically do not show an association with self-reported cognitive fatigue in persons with multiple sclerosis (PwMS), but some studies indicate that cognitive variability has an association with cognitive fatigue. Additionally, coping has been shown to be a powerful moderator of some outcomes in multiple sclerosis (MS). To date, however, coping has not been considered as a possible moderator of the relationship between cognitive fatigue and cognitive variability in MS. The current study examined this relationship., Method: We examined 52 PwMS. All participants were administered the Fatigue Impact Scale, the Coping Orientation to Problems Experienced Questionnaire, and cognitive tests. Indices of variability for memory and attention/executive functioning tests were used as outcome variables. Avoidant coping, active coping, and composite coping indices were used as moderators., Results: The interaction analyses for the avoidant coping and composite coping indices were significant and accounted for 8 and 11% of the attention/executive functioning variability outcome, respectively. The interactions revealed that at low levels of cognitive fatigue, attention/executive functioning variability was comparable between the low and high avoidant and composite coping groups. However, at high levels of cognitive fatigue, PwMS using lower levels of avoidant coping (less maladaptive coping) showed less variable attention/executive functioning scores compared with those using higher levels of avoidant coping. We found a similar pattern for the composite coping groups., Conclusion: At high levels of cognitive fatigue, PwMS using adaptive coping showed less attention/executive functioning variability. These findings should be considered in the context of treatment implications.

Objective: Little is known about the relationship between neuropsychological test performance, cognitive symptom reporting, and depressive symptoms after sport-related concussion. Accordingly, this cross-sectional study examined these relationships in collegiate athletes. It was hypothesized that depressive symptoms would moderate and mediate the relationship between performance-based and self-reported cognitive functioning after concussion., Methods: After sustaining a sport-related concussion, 110 collegiate athletes completed a neuropsychological battery, the Post-Concussion Symptoms Scale, and the Beck Depression Inventory-Fast Screen. Neuropsychological test performance, depressive symptoms, and their interactions were entered into distinct hierarchical linear regression analyses with self-reported cognition as the dependent variable to assess moderation. Mediation was analyzed using the PROCESS macro with 5000 bootstrap samples and a 95% confidence interval., Results: There was a significant interaction between the mean memory composite and depressive symptoms when predicting cognitive symptom reporting, p = 0.047. Simple effects tests revealed that for athletes who had a lower memory composite score, an increase in depressive symptoms led to an increase in self-reported cognitive dysfunction, p < 0.001, ηp2 = 0.11. Depressive symptoms partially mediated the relationship between the memory composite and cognitive symptom reporting, indirect effect = -0.26, 95%CI[-0.58,0.001], but this relationship was not found for any other neurocognitive domain., Conclusions: For tests of memory, depressive symptoms moderated and partially mediated the relationship between performance-based and self-reported cognitive functioning after sport-related concussion. Athletes reporting high depressive symptoms and cognitive dysfunction may need more comprehensive evaluations to inform return-to-play decisions, and depression could be a treatment target for athletes who report high levels of cognitive dysfunction after concussion., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

As the population ages, the prevalence of cognitive impairment due to neurodegenerative diseases such as Alzheimer disease (AD) is expected to double in the United States to nearly 14 million over the next 40 years. AD and related dementias (ADRD) are a leading cause of morbidity and mortality and among the costliest to society. Although emerging biomedical interventions for ADRD focus on early stages and are currently limited to AD, care management can benefit patients with ADRD across the disease course. Moreover, some causes of cognitive impairment are modifiable, and optimal overall management may slow or prevent additional decline. Nevertheless, a sizable proportion of cases of cognitive impairment among older adults remain undiagnosed. Primary care practitioners are often the first health care professionals to encounter cognitive concerns or to be able to observe changes in function resulting from cognitive impairment; hence, they have much to contribute to population health solutions for detecting cognitive impairment among older adults. In this report, we present key points and gaps in knowledge about methods for detecting cognitive impairment in primary care clinics. These were developed via an interdisciplinary Geriatrics Summit hosted by the National Academy of Neuropsychology in 2022, attended by representatives of national organizations engaged in work to improve care of older adults. We propose a novel workflow to facilitate detecting cognitive impairment during routine primary care, focusing on opportunities provided by the annual wellness visit, a preventive visit available to Medicare beneficiaries, along with additional recommendations and opportunities for clinical practice and research., (© 2024 Annals of Family Medicine, Inc.)

Background: There is limited research examining whether mental health problems increase the risk for future concussions, even though these problems are highly prevalent in college-aged populations-including student-athletes., Purpose/hypothesis: To examine whether affective disturbance (ie, depressive and anxiety symptoms) at baseline increases the risk for prospective concussion. It was hypothesized that athletes with co-occurring depressive/anxiety symptoms would incur the greatest risk for injury., Methods: A total of 878 collegiate athletes completed baseline neuropsychological testing. Athletes were separated into the following 4 groups based on self-reported anxiety and depressive symptoms at baseline: healthy controls; depressive symptoms alone; anxiety symptoms alone; and co-occurring depressive and anxiety symptoms. Of the 878 athletes, 88 sustained future concussions. Logistic regression was conducted with prospective concussion (yes/no) as the outcome and the affective group as the predictor. Sport was included as a covariate., Results: After controlling for sport, athletes in the co-occurring depressive/anxiety symptoms group were more than twice as likely to be diagnosed with a future concussion compared with healthy controls (odds ratio, 2.72 [95% CI, 1.33-5.57]; P = .01). The co-occurring depressive/anxiety symptoms group also showed an increased risk for prospective concussion compared with the depressive symptoms alone and anxiety symptoms alone groups, respectively. However, the results were not statistically significant. Athletes in the depressive symptoms alone and anxiety symptoms alone groups did not show a significantly increased risk for prospective concussion compared with healthy controls., Conclusion: Athletes with co-occurring depressive/anxiety symptoms at baseline showed a notably increased risk of being diagnosed with a future concussion, even after controlling for sport. This suggests that co-occurring depressive/anxiety symptoms infer a unique risk that is associated with a greater susceptibility to concussion diagnosis., Competing Interests: The authors have declared that there are no conflicts of interest in the authorship and publication of this contribution. AOSSM checks author disclosures against the Open Payments Database (OPD). AOSSM has not conducted an independent investigation on the OPD and disclaims any liability or responsibility relating thereto. Ethical approval of this study was obtained from The Pennsylvania State University (ref No. CR00020147)., (© The Author(s) 2024.)

Objective: The present study examined physical activity as a possible moderator in the relationship between pain and depressive symptoms among persons with multiple sclerosis (PwMS)., Method: Fifty-three PwMS completed a comprehensive neuropsychological test battery and psychosocial questionnaires. Pain was operationalized as a composite of measures from the Brief Pain Inventory. Metabolic equivalents (METs) of energy expended during self-reported vigorous activity (VA), moderate activity (MA), and walking, as well as global physical activity which combined the three, were derived from the International Physical Activity Questionnaire-Short Form. Self-reported physical activity was measured using the Cognitive Health Questionnaire Exercise Scale. Regressions on depressive symptoms (Beck Depression Inventory-Fast Screen) examining both conceptualizations of physical activity, pain, and their interactions were explored., Results: Regression analyses revealed that interactions between pain and each measure of global physical activity were significant (p = .01). Simple effects tests revealed that pain only influenced depressive symptoms in PwMS with low global physical activity METs (p < .001) and low overall self-reported physical activity (p < .001). The separate interactions between pain and METs during self-reported VA, MA, and walking on depressive symptoms were not significant., Conclusion: We found that global physical activity moderated the relationship between pain and depressive symptoms in MS. Specifically, pain influenced depressive symptoms in PwMS who engaged in less overall physical activity. These results highlight the importance of screening PwMS for pain and suggest that behavioral interventions aimed at increasing overall lifestyle physical activity may be useful in improving depressive outcomes in PwMS with pain., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

The purpose of this exploratory study was to examine interactive relationships between a common brain-derived neurotrophic factor (BDNF) polymorphism (Val66Met) and biological sex on cognitive functioning in a sample of healthy adolescent athletes. Participants included 82 student athletes (age: M  = 12.85 years, SD  = 1.13) who were involved in a clinically-based sports-concussion management program. Athletes completed the ImPACT computerized battery at baseline and provided buccal samples for determination of their BDNF genotype. Two-way ANOVAs were used to evaluate the effect of BDNF genotype (Met+ vs. Met-) and sex (male vs. female) on cognitive functioning (subgroup n 's: Female/Met+ = 12, Female/Met- = 26, Male/Met+ = 12, Male/Met- = 32). ANOVAs revealed non-significant main effects for both BDNF genotype and sex across all four cognitive composites. However, there was a significant BDNF genotype by sex interaction for the visual-motor speed composite ( p  = .015; η p 2  = .073), such that female Met carriers demonstrated better performance than male Met carriers. In contrast, no differences were found on visual-motor speed performance between females and males without a Met allele. Although these results will need to be replicated using larger samples, our preliminary findings lend support to the view that the Met allele may be somewhat neuroprotective in healthy adolescent females.

Objective: The primary aim of this paper is to review evidence and clinical implications related to lifestyle activities associated with promoting brain and cognitive health. Our review targets four key lifestyle factors: physical activity and exercise, social engagement, cognitively stimulating activity, and consuming Mediterranean-style diets., Method: We conducted a critical review of the lifestyle factor literature in the four domains listed earlier. We contextualize this literature review by translating findings, when possible, into evidence-based recommendations to consider when providing neuropsychological services., Results: There is significant current evidence supporting the role of physical activity and exercise, social engagement, cognitively stimulating activity, and consuming Mediterranean-style diets on positive brain and cognitive health outcomes. While some null findings are present in all four areas reviewed, the weight of the evidence supports the notion that engaging in these activities may promote brain and cognitive functioning., Conclusions: Clinical neuropsychologists can have confidence in recommending engagement in physical activity, social activity, and cognitively stimulating activity, and adhering to a Mediterranean-style diet to promote brain and cognitive health. We discuss limitations in existing lifestyle factor research and future directions to enhance the existing evidence base, including additional research with historically underrepresented groups and individuals with neurological conditions., (© The Author(s) 2023. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permission@oup.com.)

Objective: The primary aim of this paper is to accelerate the number of randomized experimental studies of the reliability and validity in-home tele-neuropsychological testing (tele-np-t)., Method: We conducted a critical review of the tele-neuropsychology literature. We discuss this research in the context of the United States' public and private healthcare payer systems, including the Centers for Medicare & Medicaid Services (CMS) and Current Procedural Terminology (CPT) coding system's telehealth lists, and existing disparities in healthcare access., Results: The number of tele-np publications has been stagnant since the onset of the COVID-19 pandemic. There are less published experimental studies of tele-neuropsychology (tele-np), and particularly in-home tele-np-t, than other tele-np publications. There is strong foundational evidence of the acceptability, feasibility, and reliability of tele-np-t, but relatively few studies of the reliability and validity of in-home tele-np-t using randomization methodology., Conclusions: More studies of the reliability and validity of in-home tele-np-t using randomization methodology are necessary to support inclusion of tele-np-t codes on the CMS and CPT telehealth lists, and subsequently, the integration and delivery of in-home tele-np-t services across providers and institutions. These actions are needed to maintain equitable reimbursement of in-home tele-np-t services and address the widespread disparities in healthcare access., (© The Author(s) 2023. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permission@oup.com.)

To investigate cognitive reserve as a possible moderator in the relationship between fatigue and depressive symptoms in persons with multiple sclerosis (PwMS). Fifty-three PwMS (37 female; mean age, 52.66; mean education, 14.81) completed comprehensive neuropsychological testing and psychosocial questionnaires assessing the perceived effects of fatigue (Fatigue Impact Scale) and depressive symptoms (Beck Depression Inventory-Fast Screen). Cognitive reserve (CR) was operationalized as Fixed CR and Malleable CR. Fixed CR was quantified as the standardized mean of years of education and a vocabulary-based estimate of premorbid intelligence. Malleable CR was quantified as the standardized mean of cognitive exertion, exercise, and socializing items from the Cognitive Health Questionnaire. Regressions on depressive symptoms examining fatigue, both conceptualizations of CR, and their interactions were explored. A Bonferroni correction was used; results were considered significant at an alpha level of p < .01. The interactions between fatigue and both conceptualizations of CR were significant, p = .005 (Fixed CR); p = .004 (Malleable CR). Simple effects tests revealed that fatigue only predicted depressive symptoms in PwMS with low Fixed CR or low Malleable CR (p's < .001), and not in those with high Fixed or high Malleable CR (p > .01). Cognitive reserve moderated the relationship between fatigue and depressive symptoms in PwMS. Specifically, fatigue does not appear to influence depression in PwMS with high cognitive reserve. Having higher cognitive reserve (either Fixed or Malleable) may reduce the likelihood that fatigue will lead to depressive symptoms in MS., (© The Author(s) 2023. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objective: Research on the neurocognitive effects of comorbid mood/anxiety disturbance in college athletes is limited. Previous research found that athletes with comorbid depression/anxiety performed worse on measures of attention/processing speed (A/PS) at baseline compared to healthy controls. However, this work solely examined mean performance. The current study expands upon this work by examining intraindividual variability (IIV) in relation to affective disturbance., Method: 835 (M = 624, F = 211) collegiate athletes completed baseline neuropsychological testing. Athletes were separated into four groups (Healthy Mood [n = 582], Depression Alone [n = 137], Anxiety Alone [n = 54], and Co-Occurring Depression/Anxiety [n = 62]) based on self-reported anxiety and depression. IIV was examined globally and within composites of A/PS and memory via intraindividual standard deviation, with higher scores indicating greater variability., Results: Linear regression results revealed that the Co-Occurring Depression/Anxiety group exhibited greater variability within the memory composite compared to the Healthy Mood group, as well as the Depression Alone and Anxiety Alone groups. The Depression Alone and Anxiety Alone groups did not differ from the Healthy Mood group on memory IIV. None of the groups differed on A/PS or global IIV., Conclusions: Athletes with co-occurring depression/anxiety demonstrated greater variability in performance on memory tasks. Greater dispersion is predictive of greater cognitive decline following concussion; therefore, it is important that neuropsychological performance is interpreted beyond measures of central tendency. These findings also highlight the importance of having baseline data available for athletes with affective disturbance, as these factors may influence performance, place athlete at risk for poorer outcomes, and skew future post-concussion comparisons., (© The Author(s) 2023. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permission@oup.com.)

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)., Competing Interests: Declaration of interests SMG reports honoraria from Hexal and research grants from Biogen, the German Ministry for Education and Research, the German Ministry of Health, Deutsche Forschungsgemeinschaft, and the National Multiple Sclerosis Society (NMSS). TF reports personnel fees for consultancies (including data monitoring committees and advisory boards) from Bayer, Bristol Myers Squibb, CSL Behring, Enanta Pharmaceuticals, Fresenius Kabi, Galapagos, Johnson & Johnson, Janssen Pharmaceuticals, LivaNova, Minoryx Therapeutics, Novartis, Roche, Vifor Pharma, Immunic Therapeutics, and Kyowa Kirin. BM is an employee of the GAIA Group, the owner and distributor of commercial digital health interventions including Deprexis and the multiple sclerosis-specific internet-delivered cognitive behavioural therapy Amiria. RM-M reports personal fees from training in cognitive behavioural therapy for irritable bowel syndrome for Central and North West London NHS Foundation Trust and University of Southampton, outside the submitted work. She receives payment for consultancy to Mahana Therapeutics, has share options in Mahana Therapeutics, and is a beneficiary of a licence agreement between Mahana Therapeutics and King's College London. SGL has participated in numerous clinical trials, receiving research support from Roche, Biogen, TG Therapeutics, Novartis, Bristol-Myers Squibb, Atara Biotherapeutics, Anokion, Immunic Therapeutics, Sanofi, and the Patient-Centered Outcomes Research Institute; has received support from NMSS-Investigator initiated studies on multiple sclerosis wellness and rehabilitation; and has unpaid board positions for the Friends of the Multiple Sclerosis Achievement Center and the Mid America Chapter of the NMSS. CR reports a stipend from Förderfond der Medizinischen Fakultät, Universitätsklinikum Hamburg Eppendorf. I-KP declares grants from Deutsche Multiple Sklerose Gesellschaft, Novartis, Teva Pharmaceuticals, and Roche; payment or honoraria from Almirall, Bayer Pharma, Biogen, BMS, Celgene, Genzyme, Janssen Pharmaceuticals, Merck, Novartis, Roche, and Teva Pharmaceuticals; and participation on data safety monitoring boards or advisory boards for Biogen, BMS, Janssen Pharmaceuticals, Merck, Novartis, and Roche. FP reports grants from the German Ministry for Education and Research, Deutsche Forschungsgemeinschaft, the Einstein Foundation, the Guthy Jackson Charitable Foundation, the EU FP7 Framework Program, Biogen, Genzyme, Merck Serono, Novartis, Bayer, Roche, Parexel, and Almirall; payment or honoraria from the Guthy Jackson Foundation, Bayer, Biogen, Merck Serono, Sanofi Genzyme, Novartis, Viela Bio, Roche, Union Chimique Belge (UCB), Mitsubishi Tanabe, and Celgene; support for attending meetings or travel from Guthy Jackson Foundation, Bayer, Biogen, Merck Serono, Sanofi Genzyme, Novartis, Alexion, Viela Bio, Roche, UCB, Mitsubishi Tanabe, and Celgene; participation on data safety monitoring boards or advisory boards for Celgene, Roche, UCB, and Merck; and unpaid editor positions for PLoS One and Neurology Neuroimmunology & Neuroinflammation. NLS receives research grants from the National Institutes of Health National Institute of Neurological Disorders and Stroke and a leadership role as Chair of the National Medical Advisory Committee of the NMSS. JMB has served on the Novartis unbranded speakers’ bureau and has received grant support from Genzyme. PAA has served on the EMD Serono speakers’ bureau and served as a consultant for Biogen and Roche Pharmaceuticals. CH reports payment or honoraria for presentations from Roche. All other authors declare no competing interests., (Copyright © 2023 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Objective: Depressive disorder occurs in up to 50% of persons with Multiple Sclerosis (PwMS). Accurate assessment of depression in MS is essential in clinical settings because depressive symptomatology can affect the clinical course of the disease., Methods: We translated, adapted, and tested the Spanish version of the Chicago Multiscale Depression Inventory (CMDI), a specific test to assess depression in neurological disorders. We compare our results with those obtained with previous versions of the questionnaire (English and Italian). Finally, we also analyze the relationship between the results obtained on the CMDI and demographic, clinical, and cognitive variables., Results: The results obtained with the Spanish version of the CMDI were similar to those observed in previous published versions. We also observed higher depression scores in PwMS (especially in progressive forms) compared with healthy controls. Moreover, depression symptomatology was related to higher disability and fatigue and worse cognitive performance in PwMS., Conclusions: The results support the validity of the CDMI in the Spanish population, as well as the association between depression and other characteristic symptoms of MS. These findings also emphasize the importance of good assessment and multidisciplinary treatment of depression in PwMS., (© The Author(s) 2022. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permission@oup.com.)

Although several single-nucleotide polymorphisms have been associated with cognitive functioning in a variety of healthy and clinical samples, the influence of gene × gene interactions on cognition is poorly understood. The purpose of this study was to examine interactive relationships between apolipoprotein E (APOE) and brain-derived neurotrophic factor (BDNF) polymorphisms on cognitive functioning in a sample of healthy adolescent athletes. Participants of this cross-sectional study included 78 student-athletes (52.6% male; age: M  = 13.31, SD  = 1.23). Athletes completed the Immediate Post-Concussion and Cognitive Testing (ImPACT) computerized battery at baseline. APOE and BDNF genotypes were determined with buccal samples (APOE ε4+: n  = 26; APOE ε4-: n  = 52; BDNF Met+: n  = 23; BDNF Met-: n  = 55). Two-way analyses of variance (ANOVAs) were used to evaluate the associations among APOE (ε4+ vs. ε4-) and BDNF (Met+ vs. Met-) genotypes and the ImPACT cognitive composites and two-factor model. No main effects were observed for either APOE or BDNF genotypes across the cognitive outcomes. However, there was a significant APOE × BDNF genotype interaction for the verbal ( p= .009, η p 2 =.091) and visual ( p  = .012, η p 2 =.082) memory composites and the memory factor ( p  = .001, η p 2 =.133), such that ε4+/Met+ carriers demonstrated poorer performance relative to other allele combinations. No significant interactions were observed for the visual motor speed ( p  = .263, η p 2 =.017) or reaction time ( p  = .825, η p 2 =.001) composites or the speed factor ( p  = .205, η p 2 =.022). Our findings suggest an important relationship between APOE and BDNF genotypes on verbal and visual memory performance in healthy adolescent athletes. Clinicians may use this information to offer individualized concussion management based on individual athlete characteristics related to genetics and cognition.

Context: Poor sleep is common in collegiate student-athletes and is associated with heterogeneous self-reported complaints at baseline. However, the long-term implications of poor sleep at baseline have been less well studied., Objective: To examine the implications of insufficient sleep at baseline, as well as factors such as symptom reporting and neurocognitive performance at baseline associated with insufficient sleep, for the risk of sport-related concussion (SRC)., Design: Cross-sectional study., Setting: Undergraduate institution., Patients or Other Participants: Student-athletes (N = 614) were divided into 2 groups based on the hours slept the night before baseline testing: sufficient (>7.07 hours) or insufficient (≤5.78 hours) sleepers. Athletes who went on to sustain an SRC during their athletic careers at our university were identified., Main Outcome Measure(s): Four symptom clusters (cognitive, physical, affective, and sleep) and headache were examined as self-reported outcomes. Four neurocognitive outcome measures were explored: mean composite of memory, mean composite of attention/processing speed, memory intraindividual variability (IIV), and attention/processing speed IIV., Results: Insufficient sleepers at baseline were nearly twice as likely (15.69%) as sufficient sleepers (8.79%) to go on to sustain an SRC. Insufficient sleepers at baseline, whether or not they went on to sustain an SRC, reported a higher number of baseline symptoms than did sufficient sleepers. When compared with either insufficient sleepers at baseline who did not go on to incur an SRC or with sufficient sleepers who did go on to sustain an SRC, the insufficient sleep group that went on to incur an SRC performed worse at baseline on mean attention/processing speed., Conclusions: The combination of insufficient sleep and worse attention/processing speed performance at baseline may increase the risk of sustaining a future SRC., (© by the National Athletic Trainers' Association, Inc.)

Objective: Persons with multiple sclerosis (PwMS) are at increased risk for cognitive dysfunction. Considering the impact and potential ramifications of cognitive dysfunction, it is important that cognition is routinely assessed in PwMS. Thus, it is also important to identify a screener that is accurate and sensitive to MS-related cognitive difficulties, which can inform decisions for more resource-intensive neuropsychological testing. However, research focused on available self-report screeners has been mixed, such as with the Multiple Sclerosis Neuropsychological Screening Questionnaire (MSNQ). This study aims to clarify the relationship between subjective and objective assessment of cognitive functioning in MS by examining domain-specific performance and intraindividual variability (IIV)., Methods: 87 PwMS (F = 65, M = 22) completed a comprehensive neuropsychological battery which included self- and informant-report measures of neurocognitive functioning. Scores were examined in relation to mean performance on five domains of cognitive functioning and two measures of IIV., Results: The MSNQ-Self was inversely associated with executive function, verbal memory, and visual memory; it was not associated with IIV. The MSNQ-Informant was inversely associated with executive function and verbal memory, and positively associated with one measure of IIV. The MSNQ-Self showed a correlation of moderate effect size with depression ( r = .39) while the MSNQ-Informant did not., Conclusions: Results suggest that the MSNQ-Self and MSNQ-Informant show similar utility. Our findings also suggest that domains of executive function and memory may be most salient, thus more reflected in subjective reports of cognitive functioning. Future work should further examine the impact of mood disturbance with cognitive performance and IIV.

Background: Self- and informant-report measures are often useful in predicting objective cognitive performance; however, the relationship between these reports and mood, anxiety, and fatigue requires further examination. Additionally, it remains unclear as to how these factors might be associated with objective neurocognitive performance., Methods: Eighty-six persons with multiple sclerosis (PwMS; F = 65, M = 21) completed a comprehensive neuropsychological battery that included objective neurocognitive measures, subjective reports of neurocognitive function with the Multiple Sclerosis Neuropsychological Screening Questionnaire (MSNQ) Self-Report (MSNQ-S) and Informant-Report (MSNQ-I), and self-report measures of anxiety, depression, and fatigue. Hierarchical linear regressions were conducted with depression, anxiety, the interaction between depression and anxiety, cognitive fatigue, and physical fatigue as predictors. Outcome variables included the MSNQ-S, MSNQ-I, each of five neurocognitive composites, and global intraindividual variability (IIV)., Results: Although greater cognitive fatigue was associated with greater reported cognitive dysfunction, it was not associated with objective neurocognitive impairment. Greater depression predicted poorer performance on measures of processing speed and verbal memory, though the effects became non-significant once accounting for anxiety. The interaction between depression and anxiety predicted greater neurocognitive IIV; those with high levels of depression and anxiety demonstrated greater dispersion of scores., Conclusions: Cognitive fatigue may skew one's perception of their cognition, though it is not associated with objective impairment. However, co-occurring depression and anxiety were associated with greater variability which is a marker of poorer neurocognitive integrity. Our findings highlight the importance of accounting for depression, anxiety, and cognitive fatigue in PwMS, given that they are all potentially modifiable factors., (© The Author(s) 2022. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objective: To examine the relationship between sleep disturbance and functional outcomes following a concussion. Also, to explore athlete and injury-related variables that may be related to risk factors for poor sleep following concussion., Method: 124 collegiate athletes completed a neuropsychological evaluation within 14 days of sustaining a sport-related concussion (SRC). Athletes were categorized as sleep disturbed (n = 52) or not sleep disturbed (n = 72). Outcome variables included symptom reports, cognitive performance (mean performance and variability), and mood (depression). Injury characteristics and athlete characteristics explored were loss of consciousness (LOC) associated with the injury, whether the athlete was immediately removed from play, and history of prior concussions., Results: Sleep disturbed athletes reported more symptoms, F(4, 119) = 7.82, p < 0.001, ƞ2 = 0.21, were more likely to be symptomatic at the time of testing, χ2(1, N = 124) = 19.79, p < 0.001, φ = 0.40, and were marginally more likely to experience clinically significant depression, χ2(1, N = 120) = 3.03, p = 0.08, φ = 0.16, than not sleep disturbed athletes. There were no cognitive differences between the groups, p > 0.05. A greater proportion of sleep disturbed athletes experienced LOC (30%) compared to not sleep disturbed athletes (13%), χ2(1, N = 118) = 4.99, p = 0.03, φ = -0.21., Conclusion: Sleep disturbances following SRC are associated with a broad range of self-reported symptoms. LOC may be associated with an increased risk of developing sleep disturbances; alternatively, sleep disturbances may increase the risk of LOC following concussion., (© The Author(s) 2022. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Persons with multiple sclerosis (PwMS) have been considered at high risk for vaccination and/or acquisition of COVID-19 related to their reduced immune systems and daily regimen of immune suppressing therapy. Substantiated and unsubstantiated reports on these unknown circumstances increased anxiety and depression. Low-dose naltrexone (LDN) is a potentially effective off-label therapy shown to be effective at controlling fatigue for several autoimmune disorders including MS. This study utilized a small population of PwMS from central Pennsylvania in order to determine whether LDN therapy altered their perceived anxiety or depression during the early months of COVID-19. Utilizing mailed surveys, self-reported anxiety and depression scores were found to be significantly lower for PwMS who were prescribed LDN either alone or as an adjuvant to a standard disease modifying therapy (DMT) in comparison to those on oral disease-modifying therapies (DMTs). The data suggest that the non-toxic, inexpensive biotherapeutic may be beneficial in lessening anxiety., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Objectives: The current study explored how affective disturbances, particularly concomitant anxiety and depressive symptoms, impact baseline symptom self-reporting on the Post-Concussion Symptoms Scale (PCSS) in college athletes., Methods: Athletes were separated into four groups (Healthy Control (HC) ( n = 581), Depression Only ( n = 136), Anxiety Only ( n = 54), Concomitant Depression/Anxiety ( n = 62)) based on their anxiety and depression scores. Groups were compared on Total PCSS Score as well as 5 PCSS Symptom Cluster scores (Cognitive, Physical, Affective, Sleep, and Headache)., Results: The three affective groups reported significantly greater symptomatology than HCs, with the Concomitant group showing the highest symptomatology scores across all clusters. The depressive symptoms only group also reported significantly elevated symptomatology, compared to HCs, on every symptom cluster except headache. The anxiety symptoms only group differed from HCs on only the cognitive symptoms cluster. Additionally, the Concomitant group reported significantly increased PCSS symptomatology, in terms of total scores and all 5 symptom clusters, compared to the depressive symptoms only and anxiety symptoms only groups., Conclusions: Our findings suggest that athletes experiencing concomitant depressive/anxiety symptoms report significantly greater levels of symptomatology across all 5 PCSS symptom clusters compared to HCs. Further, results suggest that athletes experiencing concomitant affective disturbance tend to report greater symptomatology than those with only one affective disturbance. These findings are important because, despite the absence of concussion, the concomitant group demonstrated significantly elevated symptomatology at baseline. Thus, future comparisons with post-concussion data should account for this increased symptomatology, as test results may be skewed by affective disturbances at baseline.

Objective: The present study examined coping style as a possible moderator in the relationship between pain and depression in persons with multiple sclerosis (PwMS)., Methods: Fifty-four PwMS completed a comprehensive neuropsychological test battery and psychosocial questionnaires that assessed physical, cognitive, and emotional functioning. Using four pain indices (i.e., average pain, current pain, pain intensity, and pain interference) from the Brief Pain Inventory (BPI), an overall pain index was created to capture a more comprehensive index of individuals' overall pain intensity and interference. The COPE questionnaire was used to derive three coping indices: active coping, avoidant coping, and a composite cope index that accounts for the relative contributions of both active and avoidant coping. The Beck Depression Inventory-Fast Screen (BDI-FS) was used to measure depressive symptomatology. A series of hierarchical linear regressions were conducted with depressive symptoms as the outcome variable., Results: Regression analyses revealed that the interactions between overall pain and each conceptualization of coping were significant (p = .001-.003). Simple effects tests revealed that overall pain only predicted depressive symptoms in PwMS with low active coping (p < .001), high avoidant coping (p < .001), and less adaptive coping via the composite coping index (p < .001)., Conclusion: We found that pain predicted depressive symptoms in PwMS who utilized more avoidant and less active coping strategies. Interventions aimed to improve coping style may be effective in enhancing the ability to manage pain and, subsequently, improve depression outcomes in MS., (© The Author(s) 2022. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objective: The goal of this study was to determine the impact of the relationship between cognitive reserve and coping strategy on quality of life (QoL) outcomes in persons with MS (PwMS) across multiple domains., Methods: We examined the effect of the interactions between coping style and cognitive reserve on QoL and disease burden in 97 persons with MS (PwMS). Coping strategy, either active or avoidant, was measured using the COPE inventory. We defined cognitive reserve as a composite measure of years of education and scores on the Shipley-2 Vocabulary subtest. QoL and disease burden were assessed using the Functional Assessment of MS (FAMS) scale and the Expanded Disability Status Scale, respectively. We examined both the FAMS individual subscales and the overall QoL score., Results: For those with higher cognitive reserve, greater avoidant coping was associated with lower QoL for the thinking and fatigue subscale (p < 0.001) and poorer overall QoL (p = 0.03); greater active coping was associated with poorer QoL for mobility (p = 0.001). However, these associations did not hold for those with lower cognitive reserve. Furthermore, there were no associations between coping strategy and cognitive reserve with disease burden., Conclusions: This study extends previous findings by demonstrating that avoidant coping, rather than active coping, is associated with poorer thinking and fatigue and overall QoL only for PwMS with greater cognitive reserve. Counseling PwMS on the impact of coping strategies on QoL outcomes, especially for those with greater cognitive reserve, may improve quality of life outcomes in this population., (© The Author(s) 2022. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objective: The present study aimed to explore the prevalence of subconcussive head trauma, traumatic brain injury (TBI), potential hypoxic events, and hypoxic brain injury (HBI) in victims of physical intimate partner violence (IPV). The study also aimed to characterize the injury presentation and mechanisms of injury in this population., Method: A group of 47 female participants with a history of at least one relationship that included physical violence completed a structured interview assessing for subconcussive hits, TBI, and HBI. Participants ranged in age from 19 to 55, and had an average of 15.3 years of education. Forty-four participants completed the structured interview in person and three participants completed the interview over the phone., Results: The majority of participants reported sustaining at least one impact to the head and approximately half of the participants sustained at least one impact that resulted in a mild TBI. Approximately half of the participants experienced at least one incident of having difficulty breathing due to a violent act from their partner, and approximately one-third of participants reported symptoms consistent with mild HBI. The most common mechanisms of injury were being hit with a closed fist and being strangled., Conclusions: The high levels of head trauma observed in this study highlight the need for clinical and community providers to screen victims of physical IPV for head trauma. The unique characteristics of this population (female sex, high frequency of injuries, and presence of HBIs) indicate that research evaluating the cognitive effects of injuries in this population is needed.

Objectives: The oral Symbol Digit Modalities Test (SDMT) has become the standard for the brief screening of cognitive impairment in persons with multiple sclerosis (PwMS). It has been shown to be sensitive to sensory-motor factors involving rudimentary oral motor speed and visual acuity, as well as multiple sclerosis (MS) affective-fatigue factors including depression, fatigue, and anxiety. The present study was designed to provide a greater understanding of these noncognitive factors that might contribute to the oral SDMT by examining all these variables in the same sample., Methods: We examined 50 PwMS and 49 healthy controls (HCs). All participants were administered the oral SDMT, two sensory-motor tasks (visual acuity and oral motor speed), and three affective-fatigue measures (depression, fatigue, and anxiety)., Results: Partially consistent with hypotheses, we found that sensory-motor skills, but not affective-fatigue factors, accounted for some of the group differences between the MS and HC groups on the oral SDMT, reducing the MS/HC group variance predicted from 10% to 4%. Also, PwMS with below average sensory-motor abilities had oral SDMT scores that were lower than PwMS with intact sensory-motor skills (p < .05). Finally, 71% of PwMS in the below-average sensory-motor group were impaired on the oral SDMT compared with 14% of the intact group (p = .006)., Conclusions: When the oral SDMT is used as the sole screening tool for cognitive impairment in MS, clinicians should know that limitations in visual acuity and rudimentary oral motor speed should be considered as possibly being associated with performance on it in MS.

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.

Examine the effect of subconcussive impact accumulation on cognitive/functional, imaging, and biomarker outcomes over the course of a single season, specifically in contact sport athletes at collegiate level or younger. Systematic review following PRISMA guidelines and using Oxford Center for Evidence-Based Medicine 2011 Levels of Evidence and Newcastle Ottawa Assessment Scale. PubMed MEDLINE, PsycInfo, SPORT-Discus, Web of Science. Original research in English that addressed the influence of subconcussive impacts on outcomes of interest with minimum preseason and postseason measurement in current youth, high school, or college-aged contact sport athletes. 796 articles were initially identified, and 48 articles were included in this review. The studies mostly involved male football athletes in high school or college and demonstrated an underrepresentation of female and youth studies. Additionally, operationalization of previous concussion history and concussion among studies was very inconsistent. Major methodological differences existed across studies, with ImPACT and diffusion tensor imaging being the most commonly used modalities. Biomarker studies generally showed negative effects, cognitive/functional studies mostly revealed no effects, and advanced imaging studies showed generally negative findings over the season; however, there was variability in the findings across all types of studies. This systematic review revealed growing literature on this topic, but inconsistent methodology and operationalization across studies makes it challenging to draw concrete conclusions. Overall, cognitive measures alone do not seem to detect changes across this timeframe while imaging and biomarker measures may be more sensitive to changes following subconcussive impacts., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objectives: The current study aims to examine the prevalence rates and the relationship of symptoms of depression, anxiety, and comorbid depression/anxiety with neurocognitive performance in college athletes at baseline. We hypothesized a priori that the mood disturbance groups would perform worse than healthy controls, with the comorbid group performing worst overall., Methods: Eight hundred and thirty-one (M = 620, F = 211) collegiate athletes completed a comprehensive neuropsychological test battery at baseline which included self-report measures of anxiety and depression. Athletes were separated into four groups [Healthy Control (HC) (n = 578), Depressive Symptoms Only (n = 137), Anxiety Symptoms Only (n = 54), and Comorbid Depressive/Anxiety Symptoms (n = 62)] based on their anxiety and depression scores. Athletes' neurocognitive functioning was analyzed via Z score composites of Attention/Processing Speed and Memory., Results: One-way analysis of variance revealed that, compared to HC athletes, the comorbid group performed significantly worse on measures of Attention/Processing Speed but not Memory. However, those in the depressive symptoms only and anxiety symptoms only groups were not significantly different from one another or the HC group on neurocognitive outcomes. Chi-square analyses revealed that a significantly greater proportion of athletes in all three affective groups were neurocognitively impaired compared to the HC group., Conclusions: These results demonstrate that collegiate athletes with comorbid depressive/anxiety symptoms should be identified, as their poorer cognitive performance at baseline could complicate post-concussion interpretation. Thus, assessing for mood disturbance at baseline is essential to obtain an accurate measurement of baseline functioning. Further, given the negative health outcomes associated with affective symptomatology, especially comorbidities, it is important to provide care as appropriate.

Background: The Symbol Digit Modalities Test (SDMT) has been recommended for use in clinical trials and outcome studies to monitor cognitive change. However, defining what is a meaningful change has been elusive for several years., Objective: The present investigation aimed to develop methods for assessing individual-level statistically significant change on the SDMT - reliable change indices (RCIs) and standardized regression-based (SRB) equations., Methods: A total of 219 healthy individuals completed the oral version SDMT at baseline, 6-month and 1-year follow-up., Results: The SDMT demonstrated high reliability across all time points (r's = 0.83 to 0.86). Reliable change scores of 7, 8, and 10 points for the 6-month intervals represented statistically meaningful change at the 0.70, 0.80, and 0.90 confidence intervals, respectively. Over 1-year, a difference of 8, 10, and 12 was statistically meaningful at the 0.70, 0.80, and 0.90 confidence intervals, respectively. SRB equations are also provided taking into account additional factors found to be predictive of SDMT scores over time., Conclusion: Clinicians frequently denote a decline of 4 points on the SDMT as meaningful. Results in this large normative sample show that higher cut-points are needed to demonstrate statistically significant decline at the individual level. RCIs are provided for 6 month and one year assessment, which is typical in clinical practice and trials. SRB equations are also provided for use when applicable and may provide a more precise assessment of meaningful change., (Copyright © 2021. Published by Elsevier B.V.)

Objective : Cognitive impairment affects as many as 65% of people with multiple sclerosis (PWMS), and memory impairment confers greater severity of disability and functional impairment. Depression is also common among PWMS, and lifetime prevalence rates are as high as 50%. Research has yet to clearly define the relationship between memory dysfunction and depression among PWMS, and may reflect incomplete assessment of depressive symptoms. The present study examined different aspects of depressive symptoms including anhedonia (i.e., diminished positive mood) and their relationships with verbal learning and memory among PWMS. Method : Participants were 48 healthy individuals and 96 PWMS. They were primarily Caucasian (90.3%) and female (75.0%). Participants completed the California Verbal Learning Test-2 (CVLT-2) to assess verbal learning and memory and the Chicago Multiscale Depression inventory to assess depressed mood (CMDI-Mood) and diminished positive mood (CMDI-DPM). Results : Linear regression revealed that the main effect of CMDI-DPM and the interaction of CMDI-DPM and CMDI-Mood significantly explained variance across learning, recall, and recognition CVLT-2 indices. Follow-up analyses indicated that CMDI-DPM was only significant in the absence of high CMDI-Mood scores. CMDI-Mood explained variance in only CVLT-2 Trial B. Conclusions : Depressed mood had little direct effect upon memory performance in PWMS. In the absence of severe depressed mood, higher levels of positive mood corresponded to better memory performance. However, the impact of diminished positive mood was rendered null among those endorsing high levels of depressed mood. These data may imply that anhedonia corresponds with poorer memory function among PWMS, and suggests that investigators and clinicians should assess multiple mood dimensions among PWMS.

Objective: The purpose of this study was to evaluate whether loss of consciousness (LOC), retrograde amnesia (RA), and anterograde amnesia (AA) independently influence a particular aspect of post-concussion cognitive functioning-across-test intra-individual variability (IIV), or cognitive dispersion., Method: Concussed athletes (N = 111) were evaluated, on average, 6.04 days post-injury (SD = 5.90; Mdn = 4 days; Range = 1-26 days) via clinical interview and neuropsychological assessment. Primary outcomes of interest included two measures of IIV-an intra-individual standard deviation (ISD) score and a maximum discrepancy (MD) score-computed from 18 norm-referenced variables., Results: Analyses of covariance (ANCOVAs) adjusting for time since injury and sex revealed a significant effect of LOC on the ISD (p = .018, ηp2 = .051) and MD (p = .034, ηp2 = .041) scores, such that athletes with LOC displayed significantly greater IIV than athletes without LOC. In contrast, measures of IIV did not significantly differ between athletes who did and did not experience RA or AA (all p > .05)., Conclusions: LOC, but not RA or AA, was associated with greater variability, or inconsistencies, in cognitive performance acutely following concussion. Though future studies are needed to verify the clinical significance of these findings, our results suggest that LOC may contribute to post-concussion cognitive dysfunction and may be a risk factor for less efficient cognitive functioning.

Objective: Sleep deprivation is common among both college students and athletes and has been correlated with negative health outcomes, including worse cognition. As such, the current study sought to examine the relationship between sleep difficulties and self-reported symptoms and objective neuropsychological performance at baseline and post-concussion in collegiate athletes., Method: Seven hundred seventy-two collegiate athletes completed a comprehensive neuropsychological test battery at baseline and/or post-concussion. Athletes were separated into two groups based on the amount of sleep the night prior to testing. The sleep duration cutoffs for these group were empirically determined by sample mean and standard deviation (M = 7.07, SD = 1.29)., Results: Compared with athletes getting sufficient sleep, those getting insufficient sleep the night prior to baseline reported significantly more overall symptoms and more symptoms from each of the five symptom clusters of the Post-Concussion Symptom Scale. However, there were no significant differences on objective performance indices. Secondly, there were no significant differences on any of the outcome measures, except for sleep symptoms and headache, between athletes getting insufficient sleep at baseline and those getting sufficient sleep post-concussion., Conclusion: Overall, the effect of insufficient sleep at baseline can make an athlete appear similar to a concussed athlete with sufficient sleep. As such, athletes completing a baseline assessment following insufficient sleep could be underperforming cognitively and reporting elevated symptoms that would skew post-concussion comparisons. Therefore, there may need to be consideration of prior night's sleep when determining whether a baseline can be used as a valid comparison.

Background: The Modified Fatigue Impact Scale (MFIS) is one of the most common self-report measures used to assess fatigue in multiple sclerosis (MS). Despite its widespread use, there are no existing normative data for the MFIS., Objective: The present investigation aimed to develop normative data for the MFIS in a large community sample, stratified by age, gender, and education and to compare the derived new cutoffs to an existing cutoff., Methods: A total of 675 healthy individuals, stratified by age, gender, and education completed the MFIS. After the removal of 19 outliers, the final sample consisted of 656 individuals. Archival data of 540 individuals with MS who completed the MFIS were also included to analyze the utility of the new cutoffs., Results: There were no main effects on the MFIS for gender. However, there were main effects for age and education. Specifically, younger cohorts (25-34 and 35-44) reported less physical fatigue compared to the two oldest cohorts (55-64 and 65-74). Similar effects were found for total MFIS fatigue with individuals aged 55-64 reporting greater overall fatigue than 35-44 year olds. Finally, 18-24 year olds reported significantly higher levels of cognitive fatigue compared to 35-44 and 65-74 aged cohorts. No other effects were observed for age. Individuals with higher education consistently reported less fatigue. Subsequent analyses also revealed an interaction effect for age x gender. When examining the age x gender interaction, women age 18-24 reported significantly greater levels of physical, cognitive, psychosocial, and total fatigue than their male counterparts. In contrast, men aged 65-74 reported greater physical, cognitive, and total fatigue than women their age. Comparisons of the existing cutoff of the MFIS to the new age, gender, and education specific cutoffs found either comparable or slightly higher rates of fatigue with the latter., Conclusion: Based on these findings, updated normative data and age, gender, and education specific cutoffs are provided. Utilization of these updated norms will result in a more accurate assessment of fatigue and will be valuable for those conducting research and/or clinical practice with individual with MS., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: The Symbol Digit Modalities Tests (SDMT) is the most sensitive measure to multiple sclerosis (MS)-related cognitive dysfunction. However, existing normative data has been under scrutiny. Specifically, they are outdated, do not take into account gender, and are poorly stratified by education. More importantly, there exists no oral only version norms, which is typical administration among individuals with MS., Objective: The present investigation aimed to develop updated normative data of the oral version SDMT in which age, gender, and education were taken into consideration., Methods: A total of 675 healthy individuals, stratified by age, gender, and education completed the oral version SDMT., Results: Significant effects were found for age, gender, and education, consistent with previous contentions. Specifically, performance on the SDMT tends to decline with age, with the most noticeable decline beginning in the third decade of life and continuing into the sixth decade. Women, in general perform better than men, with an average of 5.1 more points. Finally, education effects were apparent among those aged 25-54., Conclusion: Based on these findings, updated normative data are provided. Utilization of these updated norms will result in a much needed and more accurate assessment of processing speed for individuals with MS., Competing Interests: Declaration of Competing Interest The Author(s) declare(s) that there is no conflict of interest. This work was supported by the National Multiple Sclerosis Society., (Copyright © 2020 Kessler Foundation. Published by Elsevier B.V. All rights reserved.)

Objective: To examine neuropsychological test differences following concussion between collegiate athletes screening positive and negative for depression., Method: Participants included 113 (91 male) college athletes, who were assessed at baseline and following diagnosis of sport-related concussion (SRC). The Beck Depression Inventory-Fast Screen was used as a screener for depression. Athletes were categorized as either depressed (≥4) or nondepressed (<4) following injury and compared on composites for memory and attention-processing speed. Groups were also compared on reliable change index scores from baseline, as well as on proportion of impaired scores., Results: Depressed athletes performed significantly worse than did nondepressed athletes on the Memory Composite (p = .04, d = .51) but not on the Attention-Processing Speed Composite score (p = .15, d = .46). Chi-square tests indicated that, compared with nondepressed athletes, a significantly higher number of depressed athletes showed reliable decreases on the following test indices: Verbal Memory Composite of the Immediate Post-Concussion Assessment and Cognitive Testing (p = .03, φ = .21), Brief Visuospatial Memory Test-Revised Total (p = .02, φ = .22), and Hopkins Verbal Learning Test-Revised Total (p = .05, φ = .19). Chi-square test indicated that, compared with nondepressed athletes, a significantly higher proportion of depressed athletes met criteria for impairment (p = .02, φ = .23)., Conclusion: Whether examining the data at the intraindividual or group level, there are memory deficits associated with the combination of an SRC and depression. The results highlight the importance of screening for depression to provide a more complete picture of an individual's functioning postconcussion. (PsycINFO Database Record (c) 2020 APA, all rights reserved).

Objective: The purpose of this study was to examine sex differences in neuropsychological functioning after sports-related concussion using several approaches to assess cognition: mean performance, number of impaired scores, and intraindividual variability (IIV)., Method: In the study, 152 concussed college athletes were administered a battery of neuropsychological tests, on average, 10 days post-concussion (SD = 12.75; Mdn = 4 days; Range = 0-72 days). Mean performance was evaluated across 18 individual neuropsychological variables, and the total number of impaired test scores (>1.5 SD below the mean) was calculated for each athlete. Two measures of IIV were also computed: an intraindividual standard deviation (ISD) score and a maximum discrepancy (MD) score., Results: Analyses of covariance revealed that, compared with males, females had significantly more impaired scores and showed greater variability on both IIV indices (ISD and MD scores) after adjusting for time since injury and post-concussive symptoms. In contrast, no significant effects of sex were found when examining mean neuropsychological performance., Conclusion: Although females and males demonstrated similar mean performance following concussion, females exhibited a greater level of cognitive impairment and larger inconsistencies in cognitive performance than males. These results suggest that evaluating cognitive indices beyond mean neuropsychological scores may provide valuable information when determining the extent of post-concussion cognitive dysfunction.

Objective: The relationship between depression and sports-related concussion is complex and has implications both pre- and post-injury. The current study established the construct validity, convergent and discriminant, of the affective symptom cluster of The Immediate Post-Concussion Assessment and Cognitive Test (ImPACT) post-concussion symptom scale (PCSS) as a screening tool for depression., Method: Nine hundred and thirty (M = 695, F = 235) college athletes were assessed at baseline using the ImPACT PCSS and Beck-Depression Inventory-Fast Screen (BDI-FS). Previous factor analysis identified four symptom clusters on the PCSS: affective, physical, cognitive, and sleep. Clinically significant depression was operationalized as a BDI-FS score ≥4. Receiver Operating Characteristic curves (ROC) were used to determine the ideal cutoff, Chi-square tests of independence were calculated to establish convergent validity, and Fisher's r-to-z comparisons were used to establish discriminant validity of the affective symptom cluster., Results: The 90th percentile cutoff yielded the highest sensitivity and specificity on the affective symptom cluster for males (4) and females (6). The correlation between BDI-FS and the 90th percentile cutoff was statistically significantly higher in females (φ = .96) than males (φ = .83), Z = 9.49, p < .001. When correlating the BDI-FS with each PCSS symptom cluster, the correlation with the affective symptom cluster was stronger than its correlation with cognitive, sleep, and physical clusters across gender., Discussion: By utilizing a measure of depression within an existing and commonly used assessment, clinicians can easily screen for depression and identify athletes at risk for complicated recovery even in the absence of a supplemental depression assessment., (© The Author(s) 2018. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objective: The current study explored the moderating role of cognitive reserve on the relationship between disability and depression in a sample of individuals in which brain pathology is thought to contribute to depression (multiple sclerosis; MS)., Method: Fifty-four individuals with MS were examined. Depression was measured using the Beck Depression Inventory-Fast Screen (BDI-FS). In addition to collecting demographic (education) and disease burden (Expanded Disability Status Scale; EDSS) related variables, participants completed a neuropsychological test battery and psychosocial questionnaires. Cognitive reserve (CR) was conceptualized in two ways: Fixed CR and Malleable CR. Fixed CR was measured using years of education and crystallized intelligence (Shipley Vocabulary). Malleable CR was operationalized as a composite of measures from the Cognitive Heath Questionnaire (CHQ). Two regressions on depression (BDI-FS) examining either type of cognitive reserve, EDSS, and their interactions were explored. Results: The interaction between EDSS and both conceptualizations of cognitive reserve were significant, t(50) = -2.60, p = .013, PRE = .12 (Fixed CR); t(47) = -2.02, p = .049, PRE = .08 (Malleable CR). Simple effects testing revealed the same pattern regardless of the type of cognitive reserve examined; EDSS predicted depression only in those with low cognitive reserve., Conclusions: Cognitive reserve moderates the relationship between disability and depression in MS; disability does not appear to influence depression in those with high cognitive reserve., (© The Author(s) 2018. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Introduction: In people with multiple sclerosis (MS), depression symptoms could be a direct consequence of neuropathological processes or a secondary consequence of coping with debilitating illness. We investigated the interaction of white matter structure and patient coping style in predicting positive and negative emotion symptoms of depression., Method: Participants completed a neuropsychological battery, including the Chicago Multiscale Depression Inventory (CMDI) and a measure of coping strategies that has Active Coping (more adaptive) and Avoidant Coping (less adaptive) scales. Participants also completed a diffusion tensor imaging (DTI) scan, from which fractional anisotropy (FA) was calculated to assess integrity in tracts of interest, and the interaction of FA and coping style was analyzed to predict depression symptoms., Results: Significant FA and Active Coping interaction effects for predicting CMDI Negative Emotion scores were found for the anterior thalamic radiation and uncinate fasciculus white matter tracts. For people with MS who showed relatively reduced integrity of these tracts, use of more Active Coping moderated the relationship of microstructure and negative emotion symptoms of depression. This moderating relationship was not seen with other tracts of interest or with positive emotion., Conclusion: There was a protective effect of adaptive coping style against the experience of negative emotion among people with MS who showed compromised regional white matter integrity of certain tracts that connect temporal and thalamic regions to frontal cortex.

Introduction: Interpreting change in cognitive performance across baseline and post-concussion evaluations is complicated by poor understanding of how incentives, such as return-to-play, may impact performance. This study examines the influence of an anticipated financial incentive on two sets of outcomes from the ImPACT computerized battery: (a) cognitive composites, meant to serve as measures of cognitive function, and (b) validity indices, proposed as indicators of invalid performance., Method: 81 uninjured college students, randomized into two groups, completed a concussion assessment battery including ImPACT. The control group received standard administration instructions. The incentive group was told they would receive $20 if their scores ranked in the top third of students who completed testing. Test examiners were blinded to condition, and participants were debriefed upon study completion., Results: Given the non-normal distribution of the ImPACT cognitive composites and validity indices, non-parametric statistics were used to compare performance between incentive and control groups. Results of Mann-Whitney U tests revealed no significant differences between groups on the ImPACT cognitive composites (all p > .05, r = .04 to .19). In contrast, compared with the control group, the incentive group performed significantly better on all five validity indices: Impulse Control Composite (p = .036, r = .23); Xs and Os Total Incorrect (p = .035, r = .23); Word Memory Learning Percent Correct (p = .036, r = .23); Design Memory Learning Percent Correct (p = .018, r = .26); and Three Letters Total Letters Correct (p = .027, r = .25)., Conclusions: Expectation of financial incentive did not influence performance on the four cognitive composites-the ImPACT's standard metrics of cognitive function. However, the incentive group, relative to controls, exhibited better performance on each of the five validity indices. These results suggest that ImPACT validity indices are more sensitive to incentive-related changes in effort than the ImPACT cognitive composites, providing support for the validity indicator indices as measures of effort toward testing.

Rationale: People living with MS often report feeling stigmatized, but little research has examined the psychological impact of this, which is important considering the high prevalence of depression in this population., Objectives: The aim of this study was to assess, concurrently and prospectively, the association between stigma and depression in people living with MS., Methods: Data were available from 5369 participants enrolled in the semi-annual survey conducted by the North American Research Committee on Multiple Sclerosis (NARCOMS). Participants reported their MS stigma and depression in the spring 2013 update survey (T1) and their depression again one year later (T2). Demographic and health-related covariates were also assessed., Results: People experiencing higher levels of stigma reported more depression symptoms and were more likely to meet the threshold for clinical depression at both times, even controlling for covariates. Higher levels of stigma also predicted T2 depression, controlling for T1 depression (and covariates), suggesting a possible causal association. Greater psychosocial reserve, a composite of measures assessing participants' feelings of belonging, social support, and sense of control, attenuated the association between stigma and depression., Conclusions: Stigma is an important but understudied predictor of depression in people living with MS, but greater psychosocial reserve provides a buffer., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Recovery from traumatic brain injury (TBI) is heterogeneous, with injury characteristics and neuropathological findings accounting for a relatively modest proportion of the variance in clinical outcome. Furthermore, premorbid personality traits and psychological characteristics may moderate psychosocial recovery. Constructs from the field of positive psychology have been examined in multiple illness populations and are increasingly gaining attention as factors that may influence recovery from TBI. Positive affect, hope, optimism, adaptive coping style, and resilience have all been examined in the context of TBI. These phenomena are of particular interest because they may inform treatment, either by reducing psychological distress and promoting better adjustment, or by augmenting existing therapies to improve engagement. In general, research suggests that higher levels of these factors predict better psychosocial functioning after injury. However, brain injury itself is associated with reduced levels of many of these positive traits, either relative to uninjured control samples or preinjury functioning. There have been proposals for targeting these positive traits in the context of TBI rehabilitation. Although more research is needed, the few controlled trials aimed at improving adaptive coping skills have shown promising results. Other positive psychological phenomena, such as grit, optimism, and positive affect are deserving of further study as potential intervention targets.

Objective: The Immediate Post-Concussion Assessment and Cognitive Testing (ImPACT) is a commonly used tool in sports concussion assessment. While test-retest reliabilities have been established for the ImPACT cognitive composites, few studies have evaluated the psychometric properties of the ImPACT's Post-Concussion Symptom Scale (PCSS). The purpose of this study was to establish the test-retest reliability of symptom indices associated with the PCSS., Participants and Methods: Participants included 38 undergraduate students (50.0% male) who underwent neuropsychological testing as part of their participation in their psychology department's research subject pool. The majority of the participants were Caucasian (94.7%) and had no history of concussion (73.7%). All participants completed the ImPACT at two time points, approximately 6 weeks apart. The PCSS was the main outcome measure, and eight symptom indices were calculated (a total symptom score, three symptom summary indices, and four symptom clusters)., Results: Pearson correlations (r) and intraclass correlation coefficients (ICCs) were computed as measures of test-retest reliability. Overall, reliabilities ranged from low to high (r = .44 to .80; ICC = .44 to .77). The cognitive symptom cluster exhibited the highest test-retest reliability (r = .80, ICC = .77), followed by the positive symptom total (PST) index, an indicator of the total number of symptoms endorsed (r = .71, ICC = .69). In contrast, the commonly used total symptom score showed lower test-retest reliability (r = .67, ICC = .62). Paired-samples t tests revealed no significant differences between test and retest for any of the symptom variables (all p > .01). Finally, reliable change indices (RCI) were computed to determine whether differences observed between test and retest represented clinically significant change. RCI values were provided for each symptom index at the 80%, 90%, and 95% confidence intervals., Conclusion: These results suggest that evaluating additional symptom indices beyond the total symptom score from the PCSS is beneficial. Findings from this study can be applied to athlete samples to assess reliable change in symptoms following concussion.

Objective: The purpose of this study was to determine whether the ε4 allele of the APOE gene influences neurocognitive outcome following sports-related concussion. It was hypothesized that participants with an ε4 allele would show poorer neurocognitive performance and greater neurocognitive variability than those without an ε4 allele., Method: Participants included 57 concussed collegiate athletes (77.2% male) who participated in a concussion management program at a large university. All athletes underwent a comprehensive neuropsychological assessment and provided a DNA sample for determination of their APOE genotype. The test battery included measures sensitive to concussion, covering the broad domains of learning and memory, attention, processing speed, and executive functions., Results: The sample was divided into ε4 + (n = 20) and ε4 - (n = 37) groups. No significant differences were found between athletes with and without an ε4 allele when examining mean neurocognitive standardized scores (all p > .05; d = 0.16-0.18). However, athletes with an ε4 allele were more likely to show a greater number of impaired neurocognitive scores post-injury compared to athletes without an ε4 allele, χ2(1, N = 57) = 3.96, p = < .05, φ = 0.26. Additionally, athletes with an ε4 allele demonstrated greater neurocognitive variability than athletes without an ε4 allele, t(55) = -2.04, p < .05, d = 0.53., Conclusions: This research furthers our understanding of how genetic factors uniquely contribute to neurocognitive performance differences following concussion. Our findings suggest a possible relationship between the ε4 allele and post-concussion impairment, as well as between the ε4 allele and neurocognitive performance variability, suggesting that the ε4 genotype may be a risk factor for less efficient cognitive processing in concussed athletes., (© The Author 2017. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objective: The use of normative data is a hallmark of the neuropsychological assessment process. Within the context of sports-related concussion, utilizing normative data is especially essential when individualized baseline data are unavailable for comparison. The primary purpose of this study was to establish normative data for a comprehensive neuropsychological test battery used in the assessment of sports-related concussion. A secondary aim was to provide normative data for pertinent demographic variables relevant to the assessment of college athletes, including sex, previous head injuries (PHI), and history of attention deficit hyperactivity disorder (ADHD)/learning disability (LD)., Method: Participants included male and female college athletes (N = 794) who were involved in a concussion management program at an NCAA Division I university between 2002 and 2015. Athletes were administered a comprehensive neuropsychological test battery at baseline designed to assess the following cognitive domains: learning and memory, attention and concentration, processing speed, and executive functioning. The test battery primarily comprises paper-and-pencil measures., Results: Normative data are presented for the overall athlete sample. Additional sub-norms are then provided for specified demographic populations (i.e., sex, PHIs, and history of ADHD/LD). Findings indicate that there are mild cognitive differences between men and women, as well as between those athletes with and without a history of ADHD/LD. Given these findings, additional norms are provided for men and women with and without a history of ADHD/LD., Conclusions: In the absence of baseline testing, the normative data presented here can be used clinically to assess athletes' cognitive functioning post-concussion., (© The Author 2016. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objective: Depression has been traditionally explored in the context of multiple sclerosis (MS) as a binary construct (depressed, not depressed). However, given the 50% lifetime prevalence rate of depression in MS, it may be useful to consider not only currently depressed versus nondepressed patients, but to evaluate groups that better characterize the complexity of MS depression. The objective of the current study was to examine demographic, cognitive, illness, and psychosocial variables thought to associate with depression in MS across 3 groups: currently depressed, remitted depression, and never been depressed., Method: Fifty-four individuals with MS were examined. Current depression status was measured using the Beck Depression Inventory-Fast Screen (BDI-FS; Beck, Steer, & Brown, 2000). Past depression was evaluated using the Structured Clinical Interview for DSM-IV Disorders (SCID-IV; First, Spitzer, Gibbon, & Williams, 1998) and a semistructured psychosocial interview., Results: The results of the current study show that evaluating depression in 3 groups is useful for exploring risk, protective, and compensatory factors of depression in MS. A consistent grouping pattern (e.g., the remitted depression group always functioning the same as the never been depressed group) was not found among the variables examined; rather, several different patterns were observed. Several of these patterns revealed differences between the remitted depression and never been depressed groups; these differences would not have been observed had these 2 groups been combined into a "not currently depressed" group., Conclusions: These different patterns yield important information about the complex relationships of depression in MS that may be obscured when depression is viewed as a binary construct. (PsycINFO Database Record, ((c) 2017 APA, all rights reserved).)

Introduction: Headache is one of the most commonly reported and longest lasting symptoms that concussed athletes report, yet the etiology of headache symptoms following concussion is not entirely clear. The purpose of this study was to determine whether the e4 allele of the apolipoprotein E (APOE) gene influences the presence and severity of postconcussion headache., Method: Participants were composed of 45 concussed athletes and 43 healthy/nonconcussed athletes who were involved in a clinically based sports concussion management program. All athletes completed the Post-Concussion Symptom Scale (PCSS). The "headache" symptom from the PCSS was the primary outcome variable. Buccal samples were collected and analyzed to determine APOE genotype., Results: A significantly greater proportion of concussed e4+ athletes than e4- athletes endorsed headache. Furthermore, concussed e4+ athletes endorsed more severe headaches than e4- athletes. When examining the healthy/nonconcussed sample (i.e., athletes at baseline), results showed no differences between e4 allele groups with respect to the presence and severity of headache., Conclusions: These findings show that when compared to concussed e4- athletes, e4+ athletes are more likely to (a) endorse postconcussion headache and (b) report more severe headache symptoms following concussion. Conversely, it appears that the e4 allele does not influence baseline reports of headache. Thus, results suggest that those with the e4 genotype may be at a higher risk for experiencing headache-related difficulties only after a concussion is sustained.

Background: Baseline neuropsychological testing is commonly used in the management of sports-related concussion. However, underperformance due to poor effort could lead to invalid conclusions regarding postconcussion cognitive decline. We designed the Motivation Behaviors Checklist (MBC) as an observational rating scale to assess effort towards baseline neuropsychological testing. Here we present preliminary data in support of its reliability and validity., Method: MBC items were generated based on the consensus of a panel of graduate students, undergraduates, and a clinical neuropsychologist who conduct neuropsychological evaluations for a sports concussion management program. A total of 261 college athletes were administered a standard neuropsychological test battery in addition to the MBC. A subset of evaluations (n= 101) was videotape and viewed by a second rater. Exploratory factor analysis (EFA) was used to refine the scale, and reliability and validity were evaluated., Results: EFA revealed that the MBC items represent four latent factors-Complaints, Poor Focus, Psychomotor Agitation, and Impulsivity. Reliability analyses demonstrated that the MBC has good inter-rater reliability (intraclass correlation coefficient, ICC = .767) and internal consistency (α = .839). The construct validity of the MBC is supported by large correlations with examiners' ratings of effort (ρ = -.623) and medium-sized relationships with cognitive performance and self-ratings of effort (|ρ| between .263 and .345). Discriminant validity was supported by nonsignificant correlations with measures of depression and postconcussion symptoms (ρ = .056 and .082, respectively)., Conclusions: These findings provide preliminary evidence that the MBC could be a useful adjunct to baseline neuropsychological evaluations for sports-concussion management.

Unemployment is high among individuals with multiple sclerosis (MS). Certain disease variables and demographics have been found to distinguish employed and unemployed individuals. However, these variables only account for 14-20% of the variance. Other factors, such as coping, perceived stress and social support, in the workforce have been proposed, but not yet fully examined. The purpose of the present investigation was to examine the role of known factors associated with unemployment in MS, as well as coping and perceived work stress and social support. Sixty-eight women with MS were asked about their employment status and reasons for leaving. They completed a comprehensive assessment including measures of cognition, disease symptoms, psychological functioning, coping and stress. Consistent with previous findings, certain disease and demographic variables were associated with being unemployed. In particular, women who left work due to their MS were found to be older, had a longer disease duration and progressive course, reported greater disability and fatigue, and performed worse on a cognitive measure. However, we also found that coping style distinguished those who were employed from those who left work due to their MS. In particular, those who left work reported utilizing maladaptive coping mechanisms such as behavioral disengagement and substance use. With regard to perceived work stress and support, individuals who were employed reported that job security and fellow co-workers were more of an uplift than a hassle in their lives, suggesting some benefit in employment. These findings suggest that further consideration be given to role of coping and perception of the benefit of employment among individuals with MS when making recommendations regarding work decisions.