Cognitive function and quantitative electroencephalogram analysis in subjects recovered from COVID-19 infection.

BACKGROUND & OBJECTIVES: Objective assessment of post-COVID-19 cognitive dysfunction is highly warranted. This study aimed to evaluate the cognitive dysfunction of COVID-19 survivors with cognitive complaints, both clinically and neurophysiologically, using Quantitative Electroencephalogram (QEEG). METHODS: This case-control study was conducted on 50 recovered subjects from COVID-19 infection with cognitive complaints and 50 age, sex, and educational-matched healthy controls. Both groups were subjected to the following neurocognitive tests: Paired associate learning Test (PALT) and Paced Auditory Serial Addition Test (PASAT). The neurophysiological assessment was also done for both groups using QEEG. RESULTS: COVID-19 survivors had significantly lower PALT scores than controls (P < 0.001). QEEG analysis found significantly higher levels of Theta / Beta ratio in both central and parietal areas in patients than in the controls (P < 0.001 for each). The interhemispheric coherence for the frontal, central, and parietal regions was also significantly lower in patients than in the control group regarding alpha and beta bands. There were statistically significant lower scores of PALT and PASAT among cases with severe COVID-19 infection (P = 0.011, 0.005, respectively) and those who needed oxygen support (P = 0.04, 0.01, respectively). On the other hand, a statistically significantly lower mean of frontal alpha inter-hemispheric coherence among patients with severe COVID-19 infection (P = 0.01) and those needing mechanical ventilation support (P = 0.04). CONCLUSION: Episodic memory deficit is evident in COVID-19 survivors with subjective cognitive complaints accompanied by lower inter-hemispheric coherence in frontal regions. These clinical and neurophysiological changes are associated with hypoxia and COVID-19 severity.

Slowing processing speed is associated with cognitive fatigue in newly diagnosed multiple sclerosis patients.

OBJECTIVE: To further investigate objective measures of cognitive fatigue (CF), defined as the inability to sustain performance over time, in newly diagnosed multiple sclerosis (MS) patients, by conducting a performance analysis on the Paced Auditory Serial Addition Test (PASAT) based on the type of errors (omissions vs. incorrect responses) committed. METHOD: Sixty-two newly diagnosed patients with MS (pwMS) and 41 healthy controls (HC) completed the PASAT. Analysis of the change in performance during the test was performed by comparing the number of correct responses, incorrect responses, and omissions in the 1st versus the 3rd tertile of the PASAT. RESULTS: A significant decline in accuracy over time was observed to be related to an increment in the number of omissions, significantly more pronounced in pwMS than in HC. No change in the number of incorrect responses throughout the PASAT was observed for either group. CONCLUSIONS: CF can be detected even in newly diagnosed pwMS and might objectively manifest as a progressive increase in omissions during a sustained highly demanding task (i.e., PASAT). This pattern may reflect slowed processing speed and increased fatigue in pwMS. Focusing on omissions on the PASAT instead of correct responses only may improve its specificity as an objective measure of CF.

Cognition and Cognitive Fatigability: Association with Employment Status in Multiple Sclerosis.

BACKGROUND: Slowed processing speed impacts employment status in people with multiple sclerosis (PwMS). Studies on the Multiple Sclerosis Functional Composite (MSFC), which includes the Paced Auditory Serial Addition Test (PASAT), have demonstrated that the combined score predicts employment status. Whether PASAT performance alone is associated with employment status is less clear. In addition, no studies have yet evaluated whether cognitive fatigability (CF), as measured with the PASAT, is associated with employment status. The aim of the current study was to examine the association between PASAT performance, CF, and employment status in PwMS. METHODS: Hundred and eighty-six PwMS completed the PASAT as part of a larger neuropsychological battery. ANOVAs and chi-squares analyzed group differences between employed and unemployed participants with respect to demographics, PASAT performance scores, and CF. Linear regression determined whether PASAT performance and/or CF scores were associated with employment status. RESULTS: After controlling for demographic influences, group differences were noted between employed vs. unemployed individuals on PASAT performance scores only. Employment status was associated with PASAT performance scores but not CF. CONCLUSIONS: The current study confirmed that PASAT performance is associated with employment status in MS. Given that CF was not associated, it seems difficulties with information processing speed (IPS) and working memory have more impact on a PwMS's ability to remain employed rather than within-task performance decline.

Investigating mechanisms of cognitive control training: neural signatures of PASAT performance in depressed patients.

Major depression disorder (MDD) is characterized by cognitive control (CC) dysfunctions associated with increased attention toward negative information. The paced auditory serial addition task (PASAT) has been used as a targeted training of CC and studies show promising effects on depressive symptoms. However, neural mechanisms underlying its efficacy are still unclear. Based on previous findings of feedback-locked event-related potentials in healthy subjects, we investigated neural signatures during PASAT performance in 46 depressed patients. We found significantly larger amplitudes after negative than positive feedback for the P300 and late positive potential (LPP). However, this difference was not significant for the feedback-related negativity (FRN). Moreover, no associations of valence-specific ERPs and PASAT performance nor depressive symptoms were found. This indicates that depressed patients seem unable to use neural activation in late feedback processing stages (P300, LPP) to adapt accordingly. Moreover, lack of valence-specific neural reaction in early feedback processing stages (FRN) might point toward emotional indifference in depressed patients.Trial registration number: NCT03518749 Date of registration: May 8, 2018.

NIRS Studies Show Reduced Interhemispheric Functional Connectivity in Individuals with Multiple Sclerosis That Exhibit Cortical Hypoxia.

Many with multiple sclerosis (MS) have low cortical microvascular oxygen levels (hypoxia), which have been previously proposed to exacerbate inflammation in MS. We do not know if hypoxia impacts or relates to brain function. We hypothesise that within the MS population, those who have hypoxia may show reduced brain functional connectivity (FC). We recruited 20 MS participants and grouped them into normoxic and hypoxic groups (n = 10 in each group) using frequency-domain near-infrared spectroscopy (fdNIRS). Functional coherence of the haemodynamic signal, quantified with functional near-infrared spectroscopy (fNIRS) was used as a marker of brain function and was carried out during resting-state, finger-tapping, and while completing two neurocognitive tasks. Reduced FC was detected in the hypoxic MS group. fNIRS measures of haemodynamic coherence in MS could be a biomarker of functional impairment and/or disease progression.

Baseline characteristics and effects of fingolimod on cognitive performance in patients with relapsing-remitting multiple sclerosis.

BACKGROUND AND PURPOSE: Studies reporting the baseline determinants of cognitive performance and treatment effect on cognition in patients with multiple sclerosis (MS) are limited. We investigated the baseline correlates of cognition and the long-term treatment effects of fingolimod 0.5 mg once daily on cognitive processing speed and attention in patients with relapsing-remitting MS. METHODS: This post hoc analysis pooled data from the phase 3 FREEDOMS and FREEDOMS II trials (N = 1556). We assessed the correlation between baseline patient demographic and disease characteristics and baseline 3-second Paced Auditory Serial Addition Test (PASAT-3) scores (Spearman's rank test) and the changes from baseline in PASAT-3 (mixed model repeated measures model) in the fingolimod and placebo (up to 24 months) or placebo-fingolimod switched (from Month 24 up to 120 months) groups. Additionally, the predictive value of PASAT-3 score for future disease outcomes was assessed (Cox or logistic regression models). RESULTS: Among the variables assessed, lower PASAT-3 score at baseline correlated with higher disease burden (total brain volume, T2 lesion volume, and Expanded Disability Status Scale score), longer disease duration and older age (p < 0.0001 for all). Fingolimod significantly improved PASAT-3 scores from baseline versus placebo at 6 (1.3; p = 0.0007), 12 (1.1; p = 0.0044) and 24 months (1.1; p = 0.0028), with a sustained effect (overall treatment effect p = 0.0012) up to 120 months. Improvements were seen regardless of baseline cognitive status (PASAT quartile). Baseline PASAT-3 score was predictive of both clinical and magnetic resonance imaging measures of disease activity at Month 24 (p < 0.001 for all). CONCLUSION: Early fingolimod treatment may offer long-term cognitive benefit in patients with relapsing-remitting MS.

Prospective memory and working memory in comparison. New experimental paradigms.

Aim of the study: Prospective memory (PM) is a cognitive high load activity. Two main models showed the relation between working memory (WM) and PM. The preparatory attentional and memory processes model (PAM) posits an interdependence between WM and PM; while, the multiprocess framework assumes independence between these two functions.Materials and methods: With the aim to investigate this relation, two tasks were administered to a sample of 21 healthy participants. The first task (arithmetic) required low cognitive and WM load together with a prospective task, the second (PASAT) required high cognitive and WM load together with a prospective switching task. The prospective task included two modalities of administration: based on a sound cue (event-based) or at a given moment (time-based).Results: PM accuracy was influenced by WM only when paired to complex tasks that require high cognitive load on WM and active PM self-retrieval processes (time-PASAT).Conclusions: These results support partial independence between these two mechanisms.

Learning ability correlates with brain atrophy and disability progression in RRMS.

OBJECTIVE: To assess the prognostic value of practice effect on Paced Auditory Serial Addition Test (PASAT) in multiple sclerosis. METHODS: We compared screening (day -14) and baseline (day 0) PASAT scores of 1009 patients from the FTY720 Research Evaluating Effects of Daily Oral therapy in Multiple Sclerosis (FREEDOMS) trial. We grouped patients into high and low learners if their PASAT score change was above or below the median change in their screening PASAT quartile group. We used Wilcoxon test to compare baseline disease characteristics between high and low learners, and multiple regression models to assess the respective impact of learning ability, baseline normalised brain volume and treatment on brain volume loss and 6-month confirmed disability progression over 2 years. RESULTS: The mean PASAT score at screening was 45.38, increasing on average by 3.18 from day -14 to day 0. High learners were younger (p=0.003), had lower Expanded Disability Status Scale score (p=0.031), higher brain volume (p<0.001) and lower T2 lesion volume (p=0.009) at baseline. Learning status was not significantly associated with disability progression (HR=0.953, p=0.779), when adjusting for baseline normalised brain volume, screening PASAT score and treatment arm. However, the effect of fingolimod on disability progression was more pronounced in high learners (HR=0.396, p<0.001) than in low learners (HR=0.798, p=0.351; p for interaction=0.05). Brain volume loss at month 24 tended to be higher in low learners (0.17%, p=0.058), after adjusting for the same covariates. CONCLUSIONS: Short-term practice effects on PASAT are related to brain volume, disease severity and age and have clinically meaningful prognostic implications. High learners benefited more from fingolimod treatment.

Symbol Digit Modalities Test: A valid clinical trial endpoint for measuring cognition in multiple sclerosis.

BACKGROUND: The need for more robust outcomes in multiple sclerosis (MS) clinical trials has been a main priority of the field for decades. Dissatisfaction with existing measures has led to several consensus meetings and initiatives over the past few decades in hopes of defining and gaining acceptance of measures that are valid, reliable, sensitive to change and progression, and most importantly, relevant to those living with MS. The Multiple Sclerosis Outcome Assessments Consortium (MSOAC) was formed for this purpose. OBJECTIVE: The objective of this paper is to describe the results of the MSOAC plan to obtain qualification for a cognitive performance measure that meets these requirements. METHODS: Using data from 14 MS disease-modifying registration trials, we completed a comprehensive examination of the psychometric qualities of the Symbol Digit Modalities Test (SDMT) and the Paced Auditory Serial Addition Test (PASAT) with the goal of compiling evidence to support the utilization of one of these measures in future clinical trials. RESULTS AND CONCLUSION: Consistent with the published literature, the SDMT proved superior to the PASAT. The SDMT should be considered the measure of choice for MS trials in assessing cognitive processing speed.

Pelvic floor muscle activation in stress urinary incontinent women: Impact of a distraction task.

AIMS: Our purpose was to explore the involvement of cognition in voluntary and involuntary pelvic floor muscle (PFM) contraction in stress urinary incontinent women. METHODS: PFM contraction monitored by surface electromyography (EMG) was measured without a mental distraction task (DT), and with a DT called "paced auditory serial additional test" (PASAT). Forty stress incontinent women performed voluntary contractions of the external anal sphincter (EAS), and reflex EAS contractions induced by means of coughing were studied using the external intercostal muscle (EIC) EMG pattern. RESULTS: A DT altered PFM pre-activation when coughing: the reaction time between EIC muscle contraction and EAS contraction (called RT3) was respectively -54.94 ms (IQR -87.12; 3.12) without the PASAT and -3.99 ms (IQR: -47.92; 18.69) with a DT (P = 0.02, Wilcoxon's test). Concerning voluntary contraction, women activated their PFM sooner without than with a DT. CONCLUSION: The PASAT altered voluntary and reflex contractions of the PFM in stress urinary incontinent women. Our study suggests that cognition plays a role in urinary pathophysiology. Future studies should investigate rehabilitation programs that consider the role of cognition in stress urinary incontinent women.

Structural MRI correlates of PASAT performance in multiple sclerosis.

BACKGROUND: The Paced Auditory Serial Addition Test (PASAT) is a useful cognitive test in patients with multiple sclerosis (MS), assessing sustained attention and information processing speed. However, the neural underpinnings of performance in the test are controversial. We aimed to study the neural basis of PASAT performance by using structural magnetic resonance imaging (MRI) in a series of 242 patients with MS. METHODS: PASAT (3-s) was administered together with a comprehensive neuropsychological battery. Global brain volumes and total T2-weighted lesion volumes were estimated. Voxel-based morphometry and lesion symptom mapping analyses were performed. RESULTS: Mean PASAT score was 42.98 ± 10.44; results indicated impairment in 75 cases (31.0%). PASAT score was correlated with several clusters involving the following regions: bilateral precuneus and posterior cingulate, bilateral caudate and putamen, and bilateral cerebellum. Voxel-based lesion symptom mapping showed no significant clusters. Region of interest-based analysis restricted to white matter regions revealed a correlation with the left cingulum, corpus callosum, bilateral corticospinal tracts, and right arcuate fasciculus. Correlations between PASAT scores and global volumes were weak. CONCLUSION: PASAT score was associated with regional volumes of the posterior cingulate/precuneus and several subcortical structures, specifically the caudate, putamen, and cerebellum. This emphasises the role of both cortical and subcortical structures in cognitive functioning and information processing speed in patients with MS.

Behavioral evidence of emotion dysregulation in binge eaters.

Binge eating is the most common disordered eating symptom and can lead to the development of obesity. Previous self-report research has supported the hypothesis that individuals who binge eat report greater levels of general emotion dysregulation, which may facilitate binge-eating behavior. However, to date, no study has experimentally tested the relation between binge eating history and in-vivo emotion dysregulation. To do this, a sample of female college students who either endorsed binge eating (n = 40) or denied the presence of any eating pathology (n = 47) completed the Difficulties with Emotion Regulation Scale (DERS) and a behavioral distress tolerance task (the Paced Auditory Serial Addition Task-Computer: PASAT-C) known to induce negative affect and distress. The binge eating group was 2.96 times more likely to quit the PASAT-C early (χ2 = 5.04, p = 0.025) and reported greater irritability (F(1,84) = 7.09 p = 0.009) and frustration (F(1,84) = 5.00, p = 0.028) after completing the PASAT-C than controls, controlling for initial levels of these emotions. Furthermore, across the entire sample, quitting early was associated with greater emotion dysregulation on the DERS (rpb = 0.342, p < 0.01). This study is the first to demonstrate that individuals who binge eat show in-vivo emotional dysregulation on a laboratory task. Future studies should examine the PASAT-C to determine its potential clinical utility for individuals with or at risk of developing binge eating.

General Mathematical Ability Predicts PASAT Performance in MS Patients: Implications for Clinical Interpretation and Cognitive Reserve.

OBJECTIVES: The Paced Auditory Serial Addition Test (PASAT) is used to assess cognitive status in multiple sclerosis (MS). Although the mathematical demands of the PASAT seem minor (single-digit arithmetic), cognitive psychology research links greater mathematical ability (e.g., algebra, calculus) to more rapid retrieval of single-digit math facts (e.g., 5+6=11). The present study evaluated the hypotheses that (a) mathematical ability is related to PASAT performance and (b) both the relationship between intelligence and PASAT performance as well as the relationship between education and PASAT performance are both mediated by mathematical ability. METHODS: Forty-five MS patients were assessed using the Wechsler Test of Adult Reading, PASAT and Calculation Subtest of the Woodcock-Johnson-III. Regression based path analysis and bootstrapping were used to compute 95% confidence intervals and test for mediation. RESULTS: Mathematical ability (a) was related to PASAT (ß=.61; p<.001) and (b) fully mediated the relationship between Intelligence and PASAT (ß=.76; 95% confidence interval (CI95)=.28, 1.45; direct effect of Intelligence, ß=.42; CI95=-.39, 1.23) as well as the relationship between Education and PASAT (ß=2.43, CI95=.81, 5.16, direct effect of Education, ß=.83, CI95=-1.95, 3.61). DISCUSSION: Mathematical ability represents a source of error in the clinical interpretation of cognitive decline using the PASAT. Domain-specific cognitive reserve is discussed.

Influence of a distraction task on pelvic floor muscle contraction.

AIMS: Attention may play a key role in the contraction of pelvic floor muscles in stressful situations, meaning that mental distraction may be involved in urinary incontinence. METHODS: Informed consent was obtained from 20 healthy volunteers. The electromyographic (EMG) activity of the external anal sphincter (EAS) was recorded during voluntary contraction elicited by local stimulation. The trials were carried out twice: combined (or not) with a mental distraction task (PASAT), Paced auditory serial additional test. Reaction time, latency between the stimulus and maximum EAS EMG activity, duration of the contraction, maximum EAS EMG activity, and the area under the EAS EMG activity curve were measured. RESULTS: The mental distraction task led to a 3.98 times greater reaction time (RT), (P = 0.00001 Wilcoxon's test). The RT increased from 217 (IQR: 170-270) to 779 msec (IQR: 550-1,025, P < 0.0001) when the EAS contraction was combined with PASAT. However, the maximum EAS EMG activity was weaker during PASAT than in the absence of a mental distraction task: 0.0850 mv versus 0.0701 mv, that is, 1.21 times weaker (P = 0.00077, Wilcoxon's test). Finally, when the two conditions (respectively with and without the mental distraction task) were compared, no significant difference was found in the area under the EAS EMG activity curve (0.0157 mv sec vs. 0.0162 mv sec, ratio 1.01, P = 0.52). CONCLUSIONS: The mental distraction task altered voluntary contraction of the pelvic floor muscles.

Impaired practice effects following mild traumatic brain injury: an event-related potential investigation.

BACKGROUND: The negative effects of mild traumatic brain injury (mTBI) on attention are well established. Effects of practice on neuropsychological test performance have also been long recognized and more recently linked to electrophysiological indices of information processing. OBJECTIVE: The current study examined the behavioural and electrophysiological impact of mTBI on consistent practice of a neuropsychological test of attention. RESEARCH DESIGN: Prospective cohort study. METHODS: Adult participants with a history of mild TBI (n = 10; time since injury > 2 months, mean = 15.2 months) and healthy matched controls (n = 10) completed the Paced Auditory Serial Addition Task (PASAT) at four separate sessions. Event-related potentials (ERPs) were simultaneously recorded. RESULTS: Accuracy of PASAT performance in both groups improved significantly with practice. In healthy controls behavioural improvements were associated with significant attenuation of a frontally distributed ERP component marker of executive attention. These executive attention demands did not appear to ease with consistent practice in the mTBI group, who also endorsed more concussion-related symptoms. CONCLUSIONS: These preliminary results suggest sustained mental effort is required to achieve 'normal' performance levels following mTBI and support the use of practice-related, ERP indices of recovery from mTBI as a sensitive correlate of persistent post-concussion symptoms.

Gray matter atrophy is associated with functional connectivity reorganization during the Paced Auditory Serial Addition Test (PASAT) execution in Multiple Sclerosis (MS).

BACKGROUND AND PURPOSE: We explored the relationship between gray matter atrophy and reorganization of functional connectivity in multiple sclerosis patients during execution of the Paced Auditory Serial Addition Test (PASAT). MATERIALS AND METHODS: Seventeen patients and 15 healthy controls were selected for the study. Atrophy was determined using voxel-based morphometry, and atrophy-related connectivity changes were assessed using psychophysiological interaction analysis. Group differences, and correlations with PASAT performance and radiological variables were also examined. RESULTS: Gray matter atrophy in MS patients was circumscribed to the bilateral posterior cingulate gyrus/precuneus. Compared with controls, patients showed stronger connectivity between the left posterior cingulate gyrus/precuneus, and the left middle temporal gyrus and left cerebellum. A regression analysis in controls showed a negative correlation between PASAT scores and functional connectivity between: (1) the left posterior cingulate gyrus/precuneus, and left pre/postcentral gyri and left occipital gyrus, and (2) the right posterior cingulate gyrus/precuneus, and bilateral cerebellum and left pre/postcentral gyri. Patients showed a negative correlation between brain parenchymal fraction and functional connectivity between the left posterior cingulate gyrus/precuneus and left cerebellum. CONCLUSION: Patients with early MS and little brain damage presented more connectivity during PASAT execution, which may be interpreted as compensatory processes that help preserve cognitive functions.

Comparing long-term results of PASAT and SDMT scores in relation to neuropsychological testing in multiple sclerosis.

BACKGROUND AND OBJECTIVES: The Symbol Digit Modalities Test (SDMT) shows advantages over the Paced Auditory Serial Addition Test (PASAT) as a cognitive test in patients with multiple sclerosis (MS). To determine which of these tests is most valid and reliable over time as an indicator of the cognitive state of MS patients, long-term test results of both tests were compared in relation to scores of the Brief Repeatable Battery of Neuropsychological tests (BRBN). METHODS: For 485 MS patients visiting the VU University Medical Center Amsterdam for different research projects, a total number of 1078 visits with BRBN (including PASAT and SDMT) was planned. Observed and model-based correlations were used to calculate the construct validity of the SDMT and PASAT 3 seconds test (PASAT3) by comparing correlations with the BRBN-sumscore. The test-retest reliability of each test was also computed. RESULTS: For the construct validity, higher correlations were found between SDMT and BRBN compared to PASAT3 and BRBN, especially for the model-based correlations at baseline. The reliability of the measurements was good for all instruments, with the highest coefficients for the SDMT. CONCLUSION: As a single assessment tool for cognition in MS, the SDMT is more valid and reliable compared to PASAT3.

Active inhibition of task-irrelevant sounds and its neural basis in patients with attention deficits after traumatic brain injury.

PRIMARY OBJECTIVE: To examine active inhibition of irrelevant stimuli and evaluate its neural basis using functional near infrared spectroscopy in patients with attention deficits after traumatic brain injury (TBI). RESEARCH DESIGN: Case control study. METHODS AND PROCEDURES: Ten patients with TBI and 10 healthy control subjects participated in this study. The Paced Auditory Serial Addition Test (PASAT) was performed with (distracting PASAT) and without (PASAT) distracting Japanese kana phonetic characters presented between each number. A block design was used. Subjects alternately performed each task three times. MAIN OUTCOMES AND RESULTS: Healthy controls performed better than patients with TBI on both the tasks. When performing the PASAT, healthy controls showed significant activity in every region of interest except the right lateral prefrontal cortex (PFC), but patients with TBI showed significant activity only in the left anterior PFC and left lateral PFC. When performing the distracting PASAT, the right lateral PFC was active in healthy controls, but not in patients with TBI. CONCLUSION: These results confirm that patients with moderate-to-severe TBI were affected by distractors that influenced order processing. It is suggested that the working memory of patients with TBI was affected by distracting stimuli, whereas that of healthy individuals was not.

Resection of a pure androgen secreting adrenal adenoma in a postmenopausal woman: a case report.

Pure androgen secreting adrenal tumors are exceedingly rare, presenting in higher numbers in women compared with men, and are particularly rare in women of postmenopausal age. Postmenopausal hyperandrogenism is usually ovarian or adrenal in origin, with tumors representing an uncommon cause, which are more frequently ovarian but could also be adrenal. Herein we present a case of a 61-year-old postmenopausal woman, who had suffered multiple reproductive disturbances, presenting with a 10-year history of virilizing symptoms, most bothersome of which was generalized hirsutism, alongside clitoromegaly, irritability, and voice deepening. Work-up of the patient revealed a 1.5 cm left adrenal mass, which was removed through laparoscopic total adrenalectomy. Postoperatively, the patient's androgen levels dropped significantly. An adrenal androgen secreting tumor is a can't miss diagnosis that should always be considered in the evaluation of postmenopausal women with hyperandrogenism, alongside the more common etiologies. Regular hormonal follow-up is essential.

Cognitive processing speed is related to fall frequency in older adults with multiple sclerosis.

OBJECTIVE: To examine mobility, balance, fall risk, and cognition in older adults with multiple sclerosis (MS) as a function of fall frequency. DESIGN: Retrospective, cross-sectional design. SETTING: University research laboratory. PARTICIPANTS: Community-dwelling persons with MS (N=27) aged between 50 and 75 years were divided into 2 groups-single-time (n=11) and recurrent (n=16; >2 falls/12 mo) fallers-on the basis of fall history. INTERVENTION: Not applicable. MAIN OUTCOME MEASURES: Mobility was assessed using a variety of measures including Multiple Sclerosis Walking Scale-12, walking speed (Timed 25-Foot Walk test), endurance (6-Minute Walk test), and functional mobility (Timed Up and Go test). Balance was assessed with the Berg Balance Scale, posturography, and self-reported balance confidence. Fall risk was assessed with the Physiological Profile Assessment. Cognitive processing speed was quantified with the Symbol Digit Modalities Test and the Paced Auditory Serial Addition Test. RESULTS: Recurrent fallers had slower cognitive processing speed than single-time fallers (P ≤.01). There was no difference in mobility, balance, or fall risk between recurrent and single-time fallers (P>.05). CONCLUSIONS: Results indicated that cognitive processing speed is associated with fall frequency and may have implications for fall prevention strategies targeting recurrent fallers with MS.