Disparities in DMT treatment: Demographic and neurocognitive differences between MS patients currently treated versus not treated with disease-modifying therapies.

BACKGROUND: Current treatment guidelines recommend consideration of disease-modifying therapy (DMT) for all multiple sclerosis (MS) patients, but barriers to access have begun to be identified. In particular, prior studies have found that people with higher education have better access to DMTs, perhaps explained by the association of higher education with higher income. And while the majority of people with MS are women, being male is also associated with higher income. These factors argue for the need to better understand whether there are differences in DMT uptake based on sex and education. Finally, in addition to well-documented benefits of DMTs for slowing disease progression, there is growing evidence to suggest benefits of DMTs for cognitive functioning. OBJECTIVE: Determine whether rates of DMT treatment differ based on education and sex. Secondarily, we investigate whether neurocognitive test performance differs in treated versus not treated groups. METHODS: In cross-sectional data, mixed effects linear regression evaluated differences in education and sex of those treated versus not treated with DMTs. Models included the following predictors: age, disease duration, MS subtype, sex/education, disability, atrophy, and T2 lesion volume. Propensity score weights were extracted to obtain unbiased estimates of the relationship between DMT status and each outcome of interest. The same models evaluated performance differences between groups on an iPad-based processing speed test (PST) and manual dexterity test (MDT). RESULTS: Controlling for covariates, individuals with less education (OR=1.09, 95 % CI=[1.03, 1.14], p = 0.003) and women (OR=0.80, 95 % CI=[0.72, 0.90], p < 0.001) were less likely to be currently treated with DMTs. Small effect size association was shown for DMT treatment with better performance on PST (beta=0.09, CI=[0.06, 0.13], p < 0.001) and MDT (beta=0.05, CI=[0.01,0.08], p = 0.011). CONCLUSIONS: Women and people with lower education had a lower likelihood of being currently treated with DMTs. After controlling for all relevant variables, an independent (small) association of DMT treatment to better performance on tests of processing speed and fine motor dexterity was found. Reasons for disparities remain to be investigated in future work, and may include employment status, health insurance coverage, or sex differences in risk tolerance.

Longitudinal Disability, Cognitive Impairment, and Mood Symptoms in Patients With Anti-NMDA Receptor Encephalitis.

BACKGROUND AND OBJECTIVES: Longitudinal outcomes in anti-NMDA receptor encephalitis (anti-NMDARe) are still not fully understood and may not be adequately captured with the modified Rankin Scale (mRS), often the sole reported outcome. We aim to characterize longitudinal outcomes in anti-NMDARe using multiple outcome measures. METHODS: This single-center, retrospective, observational study examined outcome measures (mRS and Clinical Assessment Scale in Autoimmune Encephalitis [CASE]) in adults with NMDA receptor-IgG in CSF at short- and long-term follow-ups using linear and logistic regression modeling. Patients with evaluations for cognitive impairment (Montreal Cognitive Assessment/Mini-Mental State Examination), depression (Patient Health Questionnaire-9), and anxiety (General Anxiety Disorder-7) >6 months from symptom onset were correlated with final CASE scores. RESULTS: Thirty-eight patients (76% female, median disease onset age = 28 years, range = 1-75 years) were included. The majority received first-line immunosuppressants (97%) at a median of 3.9 weeks (interquartile range [IQR] = 2.1-9.7) from symptom onset and 68% received second-line therapies. At baseline, median/mean mRS and CASE were 4 (IQR = 3-5) and 12.9 (SD = 7.2), respectively. At short-term follow-up (median = 10 weeks, IQR = 6-17), factors associated with higher CASE and mRS included dysautonomia, coma/lethargy, seizures/status epilepticus, and intensive care unit admission (p < 0.05). At long-term follow-up (median = 70 weeks, IQR = 51-174), median/mean mRS and CASE were 2 (IQR = 1-3) and 4.4 (SD = 4.2), respectively. Only weakness at symptom onset predicted higher mRS scores (odds ratio = 5.6, 95% confidence interval 1.02-30.9, p = 0.047). Despite both mRS and CASE improving from baseline (p < 0.001), only 9 patients (31%) returned to their premorbid function. Among patients with cognitive and mood evaluations >6 months from onset, moderate-severe cognitive impairment (42%), depression (28%), and anxiety (30%) were frequent. Cognitive and depression measures were associated with final CASE subscores (including memory, language, weakness, and psychiatric). DISCUSSION: Multiple clinical factors influenced short-term outcomes, but only onset weakness influenced long-term mRS, highlighting that mRS is predominantly affected by global motor function. Although mRS and CASE improved over time for most patients, these outcome measures did not capture the full extent of long-term functional impairment in terms of mood, cognition, and the ability to return to premorbid function. This emphasizes the need for increased utilization of more nuanced cognitive and mood outcome measures.

Utility of the Brief Assessment of Cognitive Health (BACH) computerized screening tool in identifying MS-related cognitive impairment.

BACKGROUND: Current guidelines recommend that individuals with MS are screened annually for processing speed deficits, often using the Symbol Digit Modalities Test (SDMT). However, given the heterogeneity of cognitive deficits in individuals with MS, other screening measures that assess a range of cognitive domains are necessary. The current cross-sectional study aimed to examine the ability of the computerized, self-administered Brief Assessment of Cognitive Health (BACH) screening measure to detect the presence of cognitive impairment in adults with MS as determined by performance on a standard neuropsychological test battery. METHODS: Seventy-two individuals with MS completed the BACH and a comprehensive neuropsychological test battery. Receiver operating characteristic (ROC) analyses were conducted to investigate the ability of the BACH to identify cognitively impaired and cognitively intact individuals. ROC analyses were also conducted to compare the ability of the SDMT to discriminate between cognitively intact and cognitively impaired groups as a comparison with the BACH. RESULTS: Cognitive impairment was observed in 56 % of the sample. The BACH showed acceptable ability to discriminate between cognitively intact and cognitively impaired groups (AUC = 0.78). Additionally, the BACH was able to adequately predict cognitive impairment in domains other than processing speed (AUC = 0.71). The SDMT also demonstrated adequate utility in identifying individuals with cognitive impairment (AUC = 0.73); however, the SDMT was not able to adequately predict cognitive impairment in domains other than processing speed (AUC = 0.56). CONCLUSION: The BACH showed adequate ability to detect cognitive impairment in individuals with MS. The BACH was able to identify impairments across various assessed cognitive domains, including individuals with and without processing speed deficits.

Standalone Performance Validity Tests May Be Differentially Related to Measures of Working Memory, Processing Speed, and Verbal Memory in Patients With Multiple Sclerosis.

Cognitive functioning may account for minimal levels (i.e., 5%-14%) of variance of performance validity test (PVT) scores in clinical examinees. The present study extended this research twofold: (a) by determining the variance cognitive functioning explains within three distinct PVTs (b) in a sample of patients with multiple sclerosis (pwMS). Seventy-five pwMS (Mage = 48.50, 70.6% female, 80.9% White) completed the Victoria Symptom Validity Test (VSVT), Word Choice Test (WCT), Dot Counting Test (DCT), and three objective measures of working memory, processing speed, and verbal memory as part of clinical neuropsychological assessment. Regression analyses in credible groups (ns ranged from 54 to 63) indicated that cognitive functioning explained 24% to 38% of the variance in logarithmically transformed PVT variables. Variance from cognitive testing differed across PVTs: verbal memory significantly influenced both VSVT and WCT scores; working memory influenced VSVT and DCT scores; and processing speed influenced DCT scores. The WCT appeared least related to cognitive functioning of the included PVTs. Alternative plausible explanations, including the apparent domain/modality specificity hypothesis of PVTs versus the potential sensitivity of these PVTs to neurocognitive dysfunction in pwMS were discussed. Continued psychometric investigations into factors affecting performance validity, especially in multiple sclerosis, are warranted.

Associations Between Cognitive Impairment and Neuroimaging in Patients with Multiple Sclerosis.

OBJECTIVE: Multiple sclerosis (MS) is a debilitating inflammatory and neurodegenerative disease which commonly involves cognitive dysfunction. Magnetic resonance imaging (MRI) studies have shown that patients with MS (pwMS) have diffuse patterns of brain atrophy, however, the relationship between the presentation of cognitive dysfunction and brain tissue loss remains understudied. Given the integral function of thalamus as a central nervous system relay center and its involvement in various brain circuits, thalamic atrophy may play a key role in the development and progression of cognitive dysfunction. The purpose of this study is to examine the relationship between cognitive impairment in pwMS and thalamic atrophy. METHODS: A total of 121 pwMS who had neuropsychological testing and quantitative MRI within 1 year of each were retrospectively identified. Grouped LASSO linear regression with 10-fold cross validation was used to estimate each neuropsychological test score with thalamic volume as the focal predictor and all other demographic and MRI metrics as covariates. RESULTS: Rates of impairment ranged from 19% to 44%. Results showed notable associations between thalamic volume and Symbol Digit Modalities Test (ß = 0.11), Brief Visuospatial Memory Test, delayed (ß = 0.12), California Verbal Learning Test, delayed and total (ß = 0.24 and ß = 0.15 respectively), and Trail Making Test Part A (ß = -0.01), after adjusting for covariates. CONCLUSIONS: These findings demonstrate an independent association between thalamic volumes and processing speed and memory performance, after accounting for demographic, clinical, and other MRI variables, among pwMS.

Neuropsychological Testing in Autoimmune Encephalitis: A Scoping Review.

BACKGROUND AND OBJECTIVES: Identifying optimal methods for evaluation and monitoring of cognitive outcomes in AE is important for clinical care and research. This scoping review aimed to evaluate neuropsychological tests (NPT) that are most frequently impaired in AE cohorts to provide recommendations for a standardized NPT battery for AE outcome. METHODS: PubMed search for studies examining NPT in patients with AE was conducted on June 9, 2023. Studies were screened for inclusion/exclusion criteria as follows: at least 1 NPT, individual NPT test scores with comparison with healthy controls or normative data and neural-IgG status, total sample size ≥5, and English manuscript available. RESULTS: The search yielded 5,393 studies, of which 3,359 were screened, 107 were full text reviewed, and 32 met inclusion/exclusion criteria, anti-NMDA-R (k = 18), anti-LGI1 (k = 10), anti-GABAB-R (k = 2), anti-GAD-65 (k = 4), and anti-CASPR2 (k = 3). The cognitive domains most frequently impaired were visual and verbal episodic memory, attention/working memory, processing speed, and aspects of executive functions. DISCUSSION: Given the dearth of literature examining NPT in AE in combination with small sample sizes and methodological differences, more research in this area is needed. However, we provide recommendations for a test battery to be used in future studies, with the aim of standardizing research in this area. Based on the available literature, we recommend the use of comprehensive NPT batteries, spanning all cognitive domains. The highest yield measures may include the tests of (1) visual and verbal learning/memory, (2) basic and sustained attention, (3) processing speed, and (4) executive functions.

Aerobic cycling reduces fatigue and improves pain in persons with multiple sclerosis: A preliminary study.

Fatigue and pain are prevalent in persons with multiple sclerosis (PwMS), negatively impacting quality of life (QoL). Clinical management is challenging due to their multiple underlying causes. Aerobic exercise elicits central and peripheral effects, which may effectively manage MS-related symptoms. Our aim was to determine the effects of an aerobic cycling intervention on symptoms impacting QoL. Eighteen participants completed a 12-week moderate- to high-intensity aerobic cycling intervention. Participants reported significant improvements in physical fatigue, overall fatigue, pain intensity, and pain interference. Aerobic exercise should be considered as part of a multi-faceted approach to improve fatigue and pain in PwMS.

"It's on the tip of my tongue!" exploring confrontation naming difficulties in patients with multiple sclerosis.

BACKGROUND: Naming difficulty is commonly reported by patients with multiple sclerosis (pwMS). Though many cognitive batteries recommended for pwMS include fluency tasks, they do not include naming tasks. The aim of this study was to examine the prevalence of naming impairment in pwMS by using a measure of confrontation naming and to identify correlates with neuroimaging. METHODS: One-hundred-eighty-five pwMS (Mage = 48.75 ± 11.23) completed neuropsychological testing and fifty had brain MRI scans within one year of neuropsychological testing. Controlling for demographic variables, partial correlations and hierarchical regressions with language tests as the outcome variables and neuroimaging variables as predictors were performed. RESULTS: Performance on language tasks ranged within low average to average, with impairment most frequently found on a measure of confrontation naming (Boston Naming Test [BNT];27.6%), followed by a measure of phonemic fluency (Controlled Oral Word Association Test [COWAT]; 24.3%) and semantic fluency (animals [AF]; 18.3%). In the subset of patients with neuroimaging, thalamic volume had the strongest relationship with language variables, followed by white matter volume and T2 lesion volume. Language variables had no association with fractional gray matter volume. Of the language measures, BNT demonstrated the strongest relationship with MRI variables, followed by AF. There were no significant associations between neuroimaging variables and COWAT. Regression results revealed that fractional thalamic volume significantly contributed to BNT scores after adjusting for demographics, while T2 lesion volume predicted AF and no neuroimaging variables emerged as predictors for COWAT after controlling for demographics. CONCLUSIONS: Objective naming impairment is common in pwMS and are more strongly associated with neuroimaging of MS brain pathology than verbal fluency tasks that are commonly used in cognitive batteries for pwMS. Continued research on language (especially naming) deficits and neuroimaging correlates (particularly thalamic involvement) in pwMS is needed.

Cleveland Clinic Cognitive Battery (C3B): Normative, Reliability, and Validation Studies of a Self-Administered Computerized Tool for Screening Cognitive Dysfunction in Primary Care.

BACKGROUND: The self-administered iPad-based Cleveland Clinic Cognitive Battery (C3B) was designed specifically for the efficient screening of cognitive functioning of older adults in a primary care setting. OBJECTIVE: 1) Generate regression-based norms from healthy participants to enable demographic corrections to facilitate clinical interpretation; 2) estimate test-retest reliability and practice effects; 3) examine ability to discriminate mild cognitive impairment (MCI) from healthy aging; 4) d etermine validity of screening in a distracting clinical environment; and 5) determine completion rates and patient satisfaction in a primary care setting. METHODS: Study 1 (S1) recruited a stratified sample of 428 healthy adults, ages 18-89, to generate regression-based equations. S2 assessed 2-week test-retest reliability and practice effects in 30 healthy elders. S3 recruited 30 MCI patients and 30 demographically-matched healthy controls. In S4, 30 healthy elders self-administered the C3B in a distracting environment and in a quiet private room in counterbalanced order. In a demonstration project, 470 consecutive primary care patients were administered the C3B as part of routine clinical care (S5). RESULTS: C3B performance was primarily influenced by age, education, and race (S1), had acceptably high test-retest reliability and minimal practice effects (S2), discriminated MCI from healthy controls (S3), was not negatively impacted by a distracting clinical environment (S4), had high completion rates (>92%) and positive ratings from primary care patients (S5). CONCLUSION: The C3B is a computerized cognitive screening tool that is reliable, validated, self-administered, and is conducive to integration into a busy primary care clinical workflow for detecting MCI, early Alzheimer's disease, and other related dementias.

Considerations regarding noncredible performance in the neuropsychological assessment of patients with multiple sclerosis: A case series.

Determining the validity of data during clinical neuropsychological assessment is crucial for proper interpretation, and extensive literature has emphasized myriad methods of doing so in diverse samples. However, little research has considered noncredible presentation in persons with multiple sclerosis (pwMS). PwMS often experience one or more factors known to impact validity of data, including major neurocognitive impairment, psychological distress/psychogenic interference, and secondary gain. This case series aimed to illustrate the potential relationships between these factors and performance validity testing in pwMS. Six cases from an IRB-approved database containing pwMS referred for neuropsychological assessment at a large, academic medical center involving at least one of the above-stated factors were identified. Backgrounds, neuropsychological test data, and clinical considerations for each were reviewed. Interestingly, no pwMS diagnosed with major neurocognitive impairment was found to have noncredible performance, nor was any patient with noncredible performance in the absence of notable psychological distress. Given the variability of noncredible performance and multiplicity of factors affecting performance validity in pwMS, clinicians are strongly encouraged to consider psychometrically appropriate methods for evaluating validity of cognitive data in pwMS. Additional research aiming to elucidate base rates of, mechanisms begetting, and methods for assessing noncredible performance in pwMS is imperative.

A proposed new taxonomy of cognitive phenotypes in multiple sclerosis: The International Classification of Cognitive Disorders in MS (IC-CoDiMS).

BACKGROUND: Characterization of cognitive impairment (CI) in multiple sclerosis into distinct phenotypes holds promise for individualized treatments and biomarker exploration. OBJECTIVE: Apply a previously validated, neuropsychologically driven diagnostic algorithm to identify a taxonomy of the type of cognitive phenotypes in multiple sclerosis. METHODS: An algorithm developed and validated in other neurological diseases was applied to a cohort of 1281 people with multiple sclerosis who underwent clinical neuropsychological evaluation across three multiple sclerosis centers. A domain was marked impaired if scores on two tests within the domain fell below one of the two thresholds of interest (compared to controls; -1.0 SD and -1.5 SD below the mean). Results were then tabulated for each participant to determine the type of impairments across the sample. RESULTS: At -1 SD threshold, 48.7% were intact, 21.6% had single-domain, 14.3% bi-domain, and 15.4% multi-domain impairment. At -1.5 SD threshold, 72.9% were intact, 14.0% had single-domain, 8.2% bi-domain, and 5.0% multi-domain impairment. Processing speed was the most frequent single-domain impairment, followed by executive function and memory. CONCLUSIONS: These findings advance the taxonomy of cognitive phenotypes in multiple sclerosis and clarify the type and distribution of possible cognitive diagnoses, pave the way for further investigation of associated biomarkers, and provide clinically meaningful information to guide individualized treatment and rehabilitation.

Cognitive outcomes in anti-LGI-1 encephalitis.

OBJECTIVE: Cognitive impairment is one of the most common symptoms of anti-leucine rich glioma inactivated 1 (anti-LGI-1) encephalitis, but little is known about the cognitive profile of these patients. This study characterized the cognitive profile of patients with anti-LGI-1 encephalitis and compared patterns of impairment to healthy controls and other patient groups with known temporal lobe/limbic involvement. METHODS: A retrospective analysis of adult patients with anti-LGI-1 encephalitis who underwent neuropsychological assessment was conducted. Performance patterns of anti-LGI-1 patients were compared to patients deemed cognitively healthy (HC), as well as patients with amnestic mild cognitive impairment (aMCI) and temporal lobe epilepsy (TLE). RESULTS: Among 10 anti-LGI encephalitis patients (60% male, median age 67.5 years) who underwent neuropsychological testing (median = 38.5 months from symptom onset), cognitive deficits were common, with 100% of patients showing impairment (≤1.5 SD below mean) on 1+ measures and 80% on 2+ measures. Patients with anti-LGI-1 encephalitis performed worse than controls on measures of basic attention, vigilance, psychomotor speed, complex figure copy, and aspects of learning/memory. Of measures which differed from controls, there were no differences between the anti-LGI-1 and TLE patients, while the anti-LGI-1 patients exhibited higher rates of impairment in basic attention and lower rates of delayed verbal memory impairment compared to the aMCI patients. CONCLUSIONS: Long-term cognitive deficits are common in patients with anti-LGI-1 encephalitis and involve multiple domains. Future research in larger samples is needed to confirm these findings.

Nonmemory Composite Embedded Performance Validity Formulas in Patients with Multiple Sclerosis.

OBJECTIVE: Research regarding performance validity tests (PVTs) in patients with multiple sclerosis (MS) is scant, with recommended batteries for neuropsychological evaluations in this population lacking suggestions to include PVTs. Moreover, limited work has examined embedded PVTs in this population. As previous investigations indicated that nonmemory-based embedded PVTs provide clinical utility in other populations, this study sought to determine if a logistic regression-derived PVT formula can be identified from selected nonmemory variables in a sample of patients with MS. METHOD: A total of 184 patients (M age = 48.45; 76.6% female) with MS were referred for neuropsychological assessment at a large, Midwestern academic medical center. Patients were placed into "credible" (n = 146) or "noncredible" (n = 38) groups according to performance on standalone PVT. Missing data were imputed with HOTDECK. RESULTS: Classification statistics for a variety of embedded PVTs were examined, with none appearing psychometrically appropriate in isolation (areas under the curve [AUCs] = .48-.64). Four exponentiated equations were created via logistic regression. Six, five, and three predictor equations yielded acceptable discriminability (AUC = .71-.74) with modest sensitivity (.34-.39) while maintaining good specificity (≥.90). The two predictor equation appeared unacceptable (AUC = .67). CONCLUSIONS: Results suggest that multivariate combinations of embedded PVTs may provide some clinical utility while minimizing test burden in determining performance validity in patients with MS. Nonetheless, the authors recommend routine inclusion of several PVTs and utilization of comprehensive clinical judgment to maximize signal detection of noncredible performance and avoid incorrect conclusions. Clinical implications, limitations, and avenues for future research are discussed.

Examining the Clinical Utility of Selected Memory-Based Embedded Performance Validity Tests in Neuropsychological Assessment of Patients with Multiple Sclerosis.

Within the neuropsychological assessment, clinicians are responsible for ensuring the validity of obtained cognitive data. As such, increased attention is being paid to performance validity in patients with multiple sclerosis (pwMS). Experts have proposed batteries of neuropsychological tests for use in this population, though none contain recommendations for standalone performance validity tests (PVTs). The California Verbal Learning Test, Second Edition (CVLT-II) and Brief Visuospatial Memory Test, Revised (BVMT-R)-both of which are included in the aforementioned recommended neuropsychological batteries-include previously validated embedded PVTs (which offer some advantages, including expedience and reduced costs), with no prior work exploring their utility in pwMS. The purpose of the present study was to determine the potential clinical utility of embedded PVTs to detect the signal of non-credibility as operationally defined by below criterion standalone PVT performance. One hundred thirty-three (133) patients (M age = 48.28; 76.7% women; 85.0% White) with MS were referred for neuropsychological assessment at a large, Midwestern academic medical center. Patients were placed into "credible" (n = 100) or "noncredible" (n = 33) groups based on a standalone PVT criterion. Classification statistics for four CVLT-II and BVMT-R PVTs of interest in isolation were poor (AUCs = 0.58-0.62). Several arithmetic and logistic regression-derived multivariate formulas were calculated, all of which similarly demonstrated poor discriminability (AUCs = 0.61-0.64). Although embedded PVTs may arguably maximize efficiency and minimize test burden in pwMS, common ones in the CVLT-II and BVMT-R may not be psychometrically appropriate, sufficiently sensitive, nor substitutable for standalone PVTs in this population. Clinical neuropsychologists who evaluate such patients are encouraged to include standalone PVTs in their assessment batteries to ensure that clinical care conclusions drawn from neuropsychological data are valid.

Is computerized screening for processing speed impairment sufficient for identifying MS-related cognitive impairment in a clinical setting?

BACKGROUND: Annual screening for processing speed impairment (PSI) is recommended for patients with multiple sclerosis (pwMS). However, cognitive deficits in pwMS are heterogeneous, and whether PSI screening identifies patients with impairment in other cognitive domains is unclear. The objective of this study was to examine sensitivity and specificity of the self-administered, computerized Processing Speed Test (PST) in identifying cognitive impairment defined by a comprehensive neuropsychological battery (NPT). METHODS: Ninety-one pwMS completed PST and NPT, with raw scores demographically adjusted. Cognitive impairment on NPT was defined as performance <5th percentile in at least one domain. Receiver operating characteristic (ROC) analyses were performed to determine the ability of the PST to discriminate between cognitively normal (CN) and cognitively impaired with PSI (CI-PSI) and cognitively impaired with normal processing speed (CI-PSN) groups. RESULTS: Cognitive impairment was observed in 23.1% of pwMS on PST and in 42.9% on NPT. PST demonstrated excellent ability to discriminate between CN (57.1%) and CI-PSI (20.9%) groups (Area Under the Curve [AUC] = 0.86, p < 0.001). In contrast, PST was unable to discriminate CN and CI-PSN (22.0%) groups (AUC = 0.42, p = 0.32). CONCLUSION: The PST demonstrates excellent ability to detect PSI in pwMS but is unable to identify cognitively impaired pwMS without PSI, highlighting the importance of developing additional screening measures.

Does obesity exacerbate brain lesion volume and atrophy in patients with multiple sclerosis?

BACKGROUND: Obesity is common among patients with multiple sclerosis (pwMS) and has been shown to exacerbate central inflammation, a key factor in disease progression. The purpose of this cross-sectional study is to examine the possible relationships between obesity, as measured by body mass index (BMI), and MS-related brain changes in atrophy and lesion volume, as measured from MRI, in a large, representative sample of pwMS. METHODS: BMI and MRI data, along with demographic and disease variables, were acquired from the Multiple Sclerosis Partners Advancing Technology and Health Solutions (MS PATHS) registry. Unadjusted and adjusted partial correlations, controlling for gender, race, age, education level, MS phenotype, disability and disease duration, examined the associations between BMI and MRI outcomes, which included brain parenchymal fraction, white matter fraction, gray matter fraction, thalamic volume, and T2 lesion volume. RESULTS: The sample consisted of 3,046 pwMS. Unadjusted and adjusted BMI-MRI correlations accounted for between 0.4% and 2.0% of shared variance (R2). When considering the relationship between MRI outcomes and BMI category (normal weight, overweight, obese), multiple regression analyses continued to show minimal association, with BMI category accounting for no more than 1.5% of shared variance. CONCLUSIONS: No clinically meaningful associations were found between BMI and MRI outcomes in this large, representative sample of MS patients, regardless of demographics and disease variables. These unexpected negative results will require replication with a longitudinal design using more precise measures of obesity.

Is Obesity Related to Processing Speed Impairment in Patients with Multiple Sclerosis: Results of a Large-Scale, Multicenter Study.

BACKGROUND: Obesity is linked to greater physical disability and increased comorbidities among patients with multiple sclerosis (MS). Its contribution to cognition in this group is unclear. This observational study examines the link between obesity and processing speed in a large sample of patients with MS (PwMS). METHODS: As part of routine clinical care at our center, PwMS completed the Processing Speed Test (PST), an electronic implementation of the Symbol Digit Modalities Test (SDMT). Height and weight were used to calculate body mass index (BMI). Bivariate correlations were conducted to examine the association between PST and BMI in the group overall and in subgroups based on demographic and clinical variables. A one-way ANOVA examined differences in PST by BMI categories (normal weight, overweight, obese). RESULTS: The sample included 8,713 patients. No association between PST and BMI was found in the entire sample (r = .01), nor within subgroups based on demographic and disease variables. No difference in PST score was found between BMI categories. CONCLUSIONS: No association between BMI and processing speed was found among PwMS regardless of demographic or disease-specific patient characteristics.

Performance Validity Testing in Multiple Sclerosis.

OBJECTIVE: Performance validity tests (PVTs) are designed to detect nonvalid responding on neuropsychological testing, but their associations with disease-specific and other factors are not well understood in multiple sclerosis (MS). We examined PVT performance among MS patients and associations with clinical characteristics, cognition, mood, and disability status. METHOD: Retrospective data analysis was conducted on a sample of patients with definite MS (n = 102) who were seen for a clinical neuropsychological evaluation. Comparison samples included patients with intractable epilepsy seen for presurgical workup (n = 102) and patients with nonacute mild traumatic brain injury (mTBI; n = 50). Patients completed the Victoria Symptom Validity Test (VSVT) and validity cutoffs were defined as <16/24 and <18/24 on the hard items. RESULTS: In this MS cohort, 14.4% of patients scored <16 on the VSVT hard items and 21.2% scored <18. VSVT hard item scores were associated with disability status and depression, but not with neuropsychological scores, T2 lesion burden, atrophy, disease duration, or MS subtype. Patients applying for disability benefits were 6.75 times more likely to score <18 relative to those who were not seeking disability. Rates of nonvalid scores were similar to the mTBI group and greater than the epilepsy group. CONCLUSIONS: This study demonstrates that nonvalid VSVT scores are relatively common among MS patients seen for clinical neuropsychological evaluation. VSVT performance in this group relates primarily to disability status and psychological symptoms and does not reflect factors specific to MS (i.e., cognitive impairment, disease severity). Recommendations for future clinical and research practices are provided.

Fatigue in primary genetic mitochondrial disease: No rest for the weary.

Rates of perceived fatigue, anxiety, depression, sleepiness and mitochondrial disease severity were assessed prospectively in 2017-2018 using established validated questionnaires in 48 adult patients with genetically confirmed primary mitochondrial disease. Fatigue was found to be very common among patients with primary mitochondrial disease, with 34 to 48 (71-100%) patients reporting fatigue depending on the measure used, and the severity of fatigue correlating with the severity of disease. Moderate-to-severe depression (10/48; 20.8%) anxiety (28/48; 58.3%) and sleep problems (16/48; 33.3%) were frequent in our patients with fatigue and these conditions were even more prevalent in those with severe fatigue. In conclusion, perceived fatigue was common in patients with primary mitochondrial disease and appeared to correlate with disease severity. Depression, anxiety and sleep disorders were more common in the cohort than those with other chronic diseases but with rates similar to that seen in multiple sclerosis. The severity of perceived fatigue correlated with an increased risk of these comorbid conditions. The Fatigue Severity Scale may more selectively measure non-anxiety/sleep-related fatigue in primary mitochondrial disease and additional testing is planned.