Faculty Bibliography

Introduction: MS is a neurodegenerative, autoimmune disease associated with significant symptom burden such as fatigue, cognitive impairment, motor dysfunction, and depression. Thus, there is a need for therapeutic options for accessible symptom management. tDCS is an emerging neuromodulation treatment that delivers low amperage direct current (=2 mA) to targeted brain regions through scalp electrodes. tDCS is thought to lower the neuronal threshold required for action potentials and is often used to augment the benefit achieved through repetitive stimulation. Recent studies have demonstrated that at-home, remotely supervised tDCS (RS-tDCS) sessions can are successful in reducing fatigue in MS, studies have yet to elucidate the longevity of symptom benefit. Method(s): Participants with MS (N = 26) were recruited to complete a 20 sessions of RS-tDCS over a four-week period (5 sessions per week). We utilized a left anodal dorsolateral prefrontal cortex (DLPFC) montage as the target point for the treatment. The tDCS stimulation was at 2.0 mA. Surveys were completed at least one month following completion of the last RS-tDCS session asking whether any treatment benefit was achieved and whether it was sustained. Half the participants (N =13) received a sham/placebo stimulation, while the other half of the participants (N = 13) received the active stimulation. Both lab technicians and participants were blinded to the participant's conditions. Result(s): 65% of all participants reported treatment benefit. 92% (N =12) among the active participants and 38% (N = 5) among sham participants experienced benefit. The active group experienced a greater rate of benefit compared to the sham group (p<0.001). Furthermore, half of the participants assigned to the active condition that reported experiencing benefit also indicated that the benefit persisted (50%) and only a single participant who experienced benefit in the sham condition indicated that benefit persisted (20%). Conclusion(s): RS-tDCS results in symptom improvement in an MS cohort both immediately after the treatment finishes as well as, for many participants, after one month after treatment finishes. More clinical research should be done to elucidate the mechanism of long-lasting neural change due to tDCS that may help to improve MS symptoms. Longer studies should be done to examine whether self-reported benefit increases with number of sessions.

Introduction: Transcranial direct current stimulation (tDCS) is a safe and well-tolerated form of noninvasive brain stimulation that delivers a low amplitude (1 - 4 mA) direct current through scalp electrodes. Cognitive impairment is a common and often disabling symptom of multiple sclerosis (MS) which has been shown to improve with cognitive training paired with tDCS. Here we compared the benefits of tDCS paired with either adaptive cognitive training (aCT) or non-adaptive cognitive training (nCT). To provide the extended treatment sessions needed for cognitive training, we administered tDCS to patients in their homes using our remotely supervised or RS-tDCS protocol. Method(s): MS participants were recruited for a double- blind, randomized, sham-controlled clinical trial with three arms: 1) active 2.5 mA tDCS paired with aCT, 2) sham 2.5 mA tDCS paired with aCT, and 3) active 2.5 mA tDCS paired with non-adaptive computer games (i.e. crossword puzzles, board games). Cognitive functioning and self-report outcomes were assessed during baseline and study visits via the Cogstate Brief Battery tests and Beck Depression Inventory (BDI) and Patient-Reported Outcomes Measurement Information System (PROMIS) questionnaires. Result(s): n=19 participants were recruited, of which 6 were randomized to the active condition, 7 to the sham condition, and 6 to the non-adaptive games condition. Comparing change from baseline to treatment end, the active tDCS/aCT group experienced the greatest cognitive improvement (mean z score change = 0.71), followed by sham tDCS/aCT: mean z score change = 0.26 and active tDCS/non-adaptive CT, mean z score change = 0.59). In addition, the active tDCS/aCT group had a greater improvement in the Beck Depression Inventory and PROMIS outcomes on fatigue and sleep. Conclusion(s): Extended treatment with tDCS paired with adaptive cognitive remediation leads to a greater benefit than either therapy alone. 2 Introduction: The symptom burden of multiple sclerosis (MS) often leads to disability and reduced quality of life. Cognitive impairment as well as symptoms such as fatigue and depression are common but remain without reliable treatment options. Cognitive training has shown to be efficacious in enhancing cognitive abilities for patients with neurological disorders. Our group has shown in the past that 60 sessions of adaptive cognitive training (aCT), completed at home via laptop computers and remotely supervised, can improve cognitive functioning in MS. aCT present advantages over traditional one-on-one cognitive rehabilitation such as the ability to complete training remotely in a user's home and reduced clinician burden. Beyond feasibility, aCT maintains the difficulty of its cognitive tasks by adapting in real time (i.e. through reduced stimuli presentation durations or reduced decision making time) to maintain arousal and engagement of the patient. tDCS is a form of noninvasive brain stimulation where a low amperage direct current is passed through scalp electrodes placed to target cortical regions for therapeutic benefit. Previously, we have shown that tDCS improves cognitive outcomes for patients with MS as well as clinical fatigue. This first goal of this study was to demonstrate the feasibility of extending tDCS therapy to 40 sessions in order to optimize therapeutic benefit when pairing with cognitive training. Our second goal was to compare tDCS with an active (adaptive) to placebo (nonadaptive) CT. We hypothesized that the synergistic use of both aCT and tDCS will lead to the greatest benefit to manage the symptoms of MS patients. Using our remotely supervised or RS-tDCS protocol to deliver monitored treatment at home, we compared the combined and relative contribution of each therapy in a long-term study. 3 Methods: Participants with MS were recruited for a double-blind, randomized, sham-controlled clinical trial with three arms. The trial's three arms consisted of: 1) active 2.5 mA tDCS paired with aCT, 2) sham 2.5 mA tDCS paired with aCT, and 3) active 2.5 mA tDCS paired with non-adaptive computer games (i.e. crossword puzzles, board games). Participants completed 40 sessions of their assigned condition from their home following the rigorous standards of RS-tDCS. Each session consisted of twenty minutes of electrical stimulation and cognitive training. All cognitive training, both adaptive and non-adaptive, was delivered through Posit Science's BrainHQ research platform. Participants were administered cognitive and self-report assessments at baseline study visit as well as study end visit to measure any change that occurred over the course of the study. Cognitive outcomes were assessed via the Cogstate Brief Battery and mood and fatigue outcomes were assessed via self-report assessments such as the Beck Depression Inventory (BDI) and Patient-Reported Outcomes Measurement Information System (PROMIS) questionnaires. 4 Results: n=19 participants have completed the 40 session study. n=7 were randomized to the aCT/Sham condition, n=6 were randomized to the nCT/Active condition, and n=6 were randomized to the aCT/Active condition. Preliminary efficacy results were calculated based on chance from baseline to treatment end on cognitive measures (Cogstate Brief Battery) and self-reported inventories (BDI and PROMIS). Assessing cognitive composite z-score changes, results indicate that aCT/Active participants demonstrated the greatest cognitive improvement (mean z score change = 0.71), followed by sham tDCS/aCT: mean z score change = 0.26 and active tDCS/non-adaptive CT, mean z score change = 0.59). In addition, the aCT/Active group had a larger improvement in the BDI and PROMIS outcomes on fatigue, mood, and sleep. Preliminary efficacy results for both cognitive assessments and self-report outcomes can be seen below in Figures 1 and 2. [Figure presented] [Figure presented] 3 Discussion and Conclusion(s): In this study we have demonstrated that extended tDCS treatment protocols are well-tolerated and feasible for study. Initial efficacy results suggest a clear advantage for adaptive cognitive training paired with RS-tDCS. As expected, the results from Figure 1 illustrate the greatest composite z-score change, which is indicative of cognitive improvement, were seen in patients under the aCT/Active condition. Figure B demonstrates a clear preliminary mood, fatigue and sleep improvement through the BDI and PROMIS outcomes. For positive affect, the aCT/Active condition shows a strong positive result compared to other conditions, which indicates a strong effect on the mood of MS participants. This same trend is seen in negative affect, fatigue and sleep, where all three variables have a negative change indicating a strong improvement in all three categories. Figure B displays the most favorable outcomes for mood, fatigue, and sleep are seen in participants under the aCT/Active conditions. In sum, extended RS-tDCS paired with adaptive cognitive training leads to greater improvements in cognition and affect, fatigue, and sleep than either therapy alone. While the study is in its preliminary stages, results support the synergistic benefit of tDCS plus an active therapy to lead to earlier and greater therapeutic benefits. References: Bikson, M., et al., Safety of Transcranial Direct Current Stimulation: Evidence Based Update 2016. Brain Stimul, 2016. Charvet, L., et al., Remotely-delivered cognitive remediation in multiple sclerosis (MS): protocol and results from a pilot study. Multiple Sclerosis Journal - Experimental, Translational and Clinical, 2015. Jensen RE, Moinpour CM, Potosky AL, et al. Responsiveness of 8 Patient-Reported Outcomes Measurement information System (PROMIS) measures in a large, community-based cancer study cohort. Cancer 2016. CogState. CogState 2015. February 10, 2015; Available from: https://urldefense.proofpoint.com/v2/url?u=http- 3A__cogstate.com_&d=DwIBAg&c=j5oPpO0eBH1iio48DtsedeElZfc04rx3ExJHeIIZuCs&r=Vk3H8b3- Ln6FkaEcmPdAL_q5c3LYlceRekv38KQMQsQ&m=Ude_SVbAVWih8UQQ6zoyI8ZGwjva7r8hMLvwlTWqC- I&s=z_LlsVJpt6mPZiI8AD251tPSHVibR3hsMD-JBv8vXK4&e=.

Chronic neurological disease often presents with comorbidities such as mood disorders, fatigue, and cognitive impairment. Noninvasive brain stimulation is a potential non- pharmacologic treatment option. Transcranial direct current stimulation (tDCS) delivers a low amplitude (1 - 4 mA) direct current through scalp electrodes and has been shown to be safe and well tolerated. Though various non-invasive neuromodulation technologies are available (e.g., transcranial magnetic stimulation), tDCS has many advantages compared to other stimulation methods including ease of use, lower cost, and better tolerability. tDCS has been shown to enhance mood, decrease fatigue, and improved rehabilitative outcomes in patients with neurological disorders. Currently, tDCS has not been approved for clinical implementation, often preventing those who can most benefit from this treatment with no access or left to attempt consumer self-treatment. As its benefit is cumulative, extended treatment schedules are needed in order to enhance the outcome and efficacy of cognitive or physical training reducing the feasibility of daily visits to the clinic. To overcome both the feasibility obstacle of consecutive, daily, in-clinic tDCS sessions and to serve populations that would most benefit from this treatment, we have studied long term treatment schedules (up to 60 sessions) in people with neurological disorders. Here we present four cases of extended tDCS treatments paired with cognitive training. 2 Methods: Adult patients with any neurological disorder referred for cognitive rehabilitation with tDCS were eligible for this study. Participants with an estimated premorbid level of cognitive functioning in the below average range (estimated by reading recognition on the Wide Range Achievement Test-4th Edition and a Symbol Digit Modalities Test >=3.0 SD published age- referenced normative means) were excluded to ensure basic cognitive capacity to participate. Eligible participants were enrolled in an open-label trial administering up to 60 RS-tDCS (up to 2.5 mA depending on the participant's tolerability of the stimulation for 20 minutes). Following our remotely supervised or RS-tDCS protocol [3], all tDCS was paired with cognitive training targeting cognitive processing speed and working memory (online research portals from Lumos Labs or Posit Science). Montage was dependent on the specific area of deficit. Sessions were administered daily for 5 days per week. At the baseline visit, participants were administered measures of cognitive and motor functioning and self-report symptom inventories. Participants were instructed on how to self- administer tDCS from home with live remote supervision via HIPAA compliant videoconferencing. If a participant did not meet the criteria for at-home treatment, they had the option to have sessions in clinic. Treatment was then delivered at home using the RS-tDCS telerehabilitation protocol [3]. Participants returned to clinic after treatment for follow up assessments. 3 Results: Case 1: A 19-year old woman with a seven year history of MS presented with moderate recurrent episodes of major depression. She received 40 sessions of cognitive training plus RS-tDCS sessions with dorsolateral prefrontal cortex (DLPFC) montage, left anodal (1.5mA x 20 minutes). After the initial 20 session treatment period, her depression resolved (BDI score decreased from 12 to 0) with improved cognitive processing speed (SDMT score improved from58 to 69). Her depression gradually returned and she completed a second set of 20 treatments, again responding with resolution of depressive symptoms. Case 2: A 35-year-old man with idiopathic hypersomnia received 40 sessions with DLPFC montage, left anodal (2.0 x 20 minutes). He had participated in multiple medication trials and had experienced minimal benefit with stimulants. Symptoms at baseline included mental fogginess, reduced attention, overall cognitive difficulties, constant daytime sleepiness, and low quality of life. Despite published reports of tDCS benefitting hypersomnia [2], no change was found on any self-report or cognitive measures. PROMIS scales (fatigue, positive affect, sleep related impairment, and pain) changed following completion of sessions from 37 to 38, 27 to 28, 56 to 55, and 3 to 3, respectively. Case 3: A 65-year-old woman with frontotemporal dementia received 60 sessions with DLPFC montage, left anodal (2.5 mA x 20 minutes). Cognitive testing, mood, and symptom inventories (Wechsler Adult Intelligence Scale, selected subtests, Delis-Kaplan Executive Function System, selected subtests, Symbol Digit Modalities Test, Brief Visual Memory Test-Revised, Beck Depression Inventory, PROMIS scales: fatigue, positive affect, sleep impairment, and depression, and the Fatigue Severity Scale) were administered at baseline and follow-up. Following completion of all sessions, there was a significant improvements in processing speed (SDMT score of 34 to 50), working memory (WAIS digit span scaled score of 11 to 12), verbal fluency (D-KEFS scaled scores of 11 to 17), delayed visual memory (BVMT-R z score of -1.08 to -0.17), Hamilton Depression Rating Scale score dropped from 15 to 11 and mood improved across sessions as shown by linear increases in positive affect. Case 4: A 71-year-old woman with progressive cerebellar ataxia received 60 sessions with a cerebellar montage (2.5 mA x 20 minutes). Symptoms at baseline included unsteady gait, difficulty ambulating in a straight line, and fine motor impairment. Shehad underwent numerous medication trials with no lasting benefit. The Lafayette grooved pegboard scores were significantly different for both hands from the baseline assessment. The patient performed 18% faster with the dominant hand, and 19% with the non-dominant hand, with a reduction amount to 2.07 and 1.92 in the z-score for the dominant and non-dominant hand respectively. Before the intervention, the Time Up and Go Test (TUG) score was 11.90s using a cane. At follow up, TUG score was 9.88s without any walking-aid. Following treatment, a mild improvement was observed in the 25 foot walking test (25-FWT), the patient completed the test 7% faster and without walking-aid compared to the baseline assessment. 4 Discussion and Conclusion(s): RS-tDCS is a safe, well-tolerated non-pharmacological option for the management of common neurologic disorder comorbidities. Continued research is needed in order to determine who best will respond to the treatment and optimal dosing parameters including potential taper schedules in order to achieve and maintain clinical benefit. References: 1. Brunoni, A.R., et al., Cognitive effects of transcranial direct current stimulation in depression: Results from the SELECT-TDCS trial and insights for further clinical trials. J Affect Disord, 2016. 202: p. 46-52. 2. Galbiati, A., et al. (2016). "The effects of Transcranial Direct Current Stimulation (tDCS) on Idiopathic Hypersomnia: a pilot study." Arch Ital Biol 154(1): 1-5 3. Charvet L, Shaw M, Dobbs B, Frontario A, Sherman K, Bikson M, et al. Remotely Supervised Transcranial Direct Current Stimulation Increases the Benefit of At-Home Cognitive Training in Multiple Sclerosis. Neuromodulation. 2017.

Introduction: VR immersion therapy is a practical, noninvasive and riskless technique with promising applications for rehabilitation. Preliminary studies have demonstrated its feasibility and effectiveness for various therapies targeting depression, anxiety disorders, and PTSD using exposure, relaxation, and mindfulness techniques. VR has also been shown to be an effective pain management tool for acute and chronic pain relief. These techniques tend to focus on distraction and redirecting cognitive resources from pain attention towards the VR stimuli. Patients with neurological disorders have high comorbidity rates for emotional disorders and disease-related pain. As the theorized mechanisms for VR therapy benefit are not disease-specific, we expect neurological patients to have generalized benefit. We propose VR for use in therapeutic paradigms to manage symptom burden in those with neurological disorders. Method(s): We recruited patients previously diagnosed with a neurological disorder. Participants completed a baseline assessment, multiple 1-hour virtual reality immersion sessions, and one follow-up assessment. Each participant completed self-report measures including the Patient Reported Outcomes Measurement Information System (PROMIS) along with side effect visual analog scales (i.e. fatigue and nausea), and the Positive and Negative Affect Schedule (PANAS) before and after each session to assess any symptom severity changes. VR sessions include structured schedules of virtual pain management, cyber painting, walking through vivid and calming settings, solving puzzles, among other therapeutic and immersive activities. Each session is constructed beforehand with different immersion activities by study personnel in order to provide interactive diversity to maintain participant engagement and immersion necessary for efficacious treatment. Result(s): The trial is currently underway. Results regarding compliance, feasibility, and efficacy will be presented. Conclusion(s): Virtual Reality therapy is a feasible treatment modality that can benefit participants diagnosed with neurological disorders by reducing symptom burden and other reported neurological complaints.

Introduction: Fatigue is one of the most prevalent and largely under-assessed non-motor symptoms in PD. Current potential therapies have limited effectiveness. Presently, tDCS has shown potential to improve certain symptoms of PD. We designed an RS-tDCS protocol to allow study participation from a patient's home while maintaining clinical trial standards. We utilized a live video-conferencing platform and specially designed equipment that 'unlocks' one session at a time.Study objective: to assess feasibility and explore the therapeutic potential of remotely supervised tDCS (RS-tDCS) paired with cognitive training (CT) for Parkinson's disease (PD) related fatigue: preliminary results. Method(s): Preliminary analysis of eighteen PD patients, age 35-89 that participated in a double-blind, randomized, sham controlled study with RS-tDCS paired with CT. Each participant completed 10 tDCS sessions (20-minute, 2.0-mA, bi-frontal DLPFC montage, left anodal), over a span of two weeks. After completion, 10 additional open label sessions were offered. Tolerability, safety and compliance were evaluated. Preliminary clinical effects were measured with the fatigue severity scale (FSS). Result(s): A total of 18 participants completed 330 RS-tDCS sessions (Table1); one subject did not complete 10 optional sessions and one withdrew consent. Tolerability of 2.0 mA stimulation with <=6 on visual analog scale for pain (VAS-Pain) was 100%. Systematically recorded side effects were: tingling 22.4%, itching 8.2%, burning sensation 11.5%, dizziness 0.3%, headache 3.3%, sleepiness 0.3%, and nausea 0.9% (Figure1). No serious AEs were reported. Compliance was 100% as subjects completed all required visits with no attrition or interruptions. Preliminary fatigue clinical effects of 10 sessions showed a significant decrease of FSS (p < 0.05) only in the real RS-tDCS group (Figure2). Further analysis of 20 real RS-tDCS sessions (10 Rand_real +10 Open_label) showed a greater significant decrease in FSS (p < 0.05) (Figure2). Responders (>30% FSS improvement) were 44% after 10 RS-tDCS sessions and 62% after 20 sessions. Conclusion(s): At-home RS-tDCS therapy paired with CT is safe and well-tolerated by PD patients, with the advantages of ease of recruitment and subject compliance. Acceptability was achieved by easy setup and intuitive design of the device. At-home RS-tDCS therapy paired with CT shows potential to remediate fatigue symptoms in PD but the small sample size limits efficacy conclusions. Our paradigm may be influential in designing future studies that will facilitate clinical trials with a larger subject population and extended trial duration. Supported by Grant No. PDF-TRG-1722 from the Parkinson's Foundation.

BACKGROUND AND PURPOSE/OBJECTIVE:Pediatric-onset multiple sclerosis (POMS) is a demyelinating disorder with unique clinical challenges. A brief computer-administered cognitive screening battery measuring processing speed (Cogstate) and the Brief International Cognitive Assessment in MS (BICAMS) detect cognitive impairment in POMS. The neuroanatomic correlates of these deficits are incompletely understood. The purpose of this study is to define the neuroanatomic underpinnings of deficits identified with cognitive screening batteries in POMS. METHODS:Participants with POMS and age-matched healthy controls (HCs) were screened with Cogstate and BICAMS. Diffusion tensor imaging assessed region-wise and tractography-based fractional anisotropy (FA). RESULTS:The POMS (n = 15) and HC (n = 21) groups were matched on age (mean ages 17.9 ± 3.2 vs. 17.8 ± 3.3 years, respectively) and on an estimate of general intellectual functioning. The Cogstate composite revealed significant slowing in POMS relative to HCs (P = .004), but the BICAMS composite did not significantly distinguish the groups (P = .10). The Cogstate composite showed moderate-to-strong correlations with regional FA (r = -.67 to -.82) and significantly associated with uncinate fasciculus FA following multiple comparisons correction (P = .002) in POMS. However, the BICAMS composite measure showed only weak-to-moderate correlations with FA in POMS (r = -.19 to -.57), with none surviving multiple comparisons correction. CONCLUSIONS:Computer-administered measures of cognitive processing are particularly sensitive in POMS and are closely linked to white matter FA.

Objective/UNASSIGNED:Assessment of performance validity is a necessary component of any neuropsychological evaluation. Prior research has shown that cutoff scores of ≤6 or ≤7 on Reliable Digit Span (RDS) can detect suboptimal effort across numerous adult clinical populations; however, these scores have not been validated for that purpose in an adult epilepsy population. This investigation aims to determine whether these previously established RDS cutoff scores could detect suboptimal effort in adults with epilepsy. Method/UNASSIGNED:Sixty-three clinically referred adults with a diagnosis of epilepsy or suspected seizures were administered the Digit Span subtest of the Wechsler Adult Intelligence Scale (WAIS-III or WAIS-IV). Most participants (98%) passed Trial 2 of the Test of Memory Malingering (TOMM), achieving a score of ≥45. Results/UNASSIGNED:Previously established cutoff scores of ≤6 and ≤7 on RDS yielded a specificity rate of 85% and 77% respectively. Findings also revealed that RDS scores were positively related to attention and intellectual functioning. Given the less than ideal specificity rate associated with each of these cutoff scores, together with their strong association to cognitive factors, secondary analyses were conducted to identify more optimal cutoff scores. Preliminary results suggest that an RDS cutoff score of ≤4 may be more appropriate in a clinically referred adult epilepsy population with a low average IQ or lower. Conclusions/UNASSIGNED:Preliminary findings indicate that cutoff scores of ≤6 and ≤7 on RDS are not appropriate in adults with epilepsy, especially in individuals with low average IQ or below.

Background: Clinical observations and emerging studies suggest that African American (AA) people with multiple sclerosis (MS) tend to fare worse than their Caucasian American (CA) counterparts. Existing studies are limited by few AA participants and could often not evaluate other potential contributing factors.
Objective(s): To compare socio-economic and clinical characteristics of a large population of AA and CA people with MS.
Method(s): MS PATHS is a network of 10 large MS centers located in the United States (7) and Europe (3); standardized collection of socio-demographic characteristics, including self-reported racial identity, as well as clinical and disease information are acquired at least annually during routine clinic visits. We included US-based MS PATHS participants with self-reported AA and CA racial identities who provided socio-economic and MS characteristics. We compared AA vs. CA with respect to socio-economic and MS metrics including disability (via Patient Determined Disease Steps [PDDS]) and objective neurological outcomes (via walking speed, manual dexterity and processing speed) using generalized linear models, as appropriate. Models for PDDS and neurologic outcomes were adjusted for age, sex, disease subtype and duration, employment, insurance status.
Result(s): Of US-based eligible participants in MS PATHS, 909 (14%) identify as AAs while 5842 (86%) identify as CAs and were included in the analyses. Relative to CAs, AAs tended to be younger (Mean 49.7y [standard deviation; SD: 12.3y] vs. 45.6y [12.5]; p< 0.0001), have fewer years of education (14.8y [2.6] vs. 14.1y [2.8]; p< 0.0001), have Medicaid insurance (48% vs. 30%; P< 0.0001) and be currently on disability or not working (29% vs. 39%; p< 0.0001). AAs had a 58% multivariable-adjusted higher odds of severe vs. mild disability relative to CAs (OR: 1.56; 95% CI: 1.21-2.02). They also had significantly slower walking and manual dexterity speeds (multivariable-adjusted mean %difference [95% CI]: 25-foot walking speed: 10% slower [7%-13%]; manual dexterity: 7% slower [5%-9%]) and significantly lower processing speed scores (multivariable-adjusted mean difference-4.32 [-5.09-3.56]).
Conclusion(s): In this large sample of AA and CA people with MS, self-reported AA identity was associated with indicators of lower socio-economic status and with greater disease severity across a broad array of neurological assessments

Introduction: Cognitive impairment is common and often disabling in multiple sclerosis (MS), but the risk factors and mechanisms underlying cognitive decline remain poorly understood. Pediatric MS (MS onset < 18 years of age) is unique due to the demyelinating process occurring in the context of development.
Objective(s): To compare cognitive functions in newly diagnosed patients with either adult- or pediatric-onset MS (AOMS vs. POMS).
Aim(s): To test performance in newly diagnosed MS patients using the Symbol Digit Modalities Test (SDMT) and a computer-based measure sensitive to processing speed deficits (Cogstate).
Method(s): As part of an ongoing multi-center longitudinal cognition trial, AOMS and POMS participants were recruited from outpatient visits and matched by years of disease. At the baseline evaluation, all participants were administered the Wide Range Achievement Test-4 (WRAT-4), the SDMT and the Cogstate Brief Battery, which includes three measures of information processing speed tasks:simple (DET) and choice (IDN) reaction time and working memory (ONB). Cogstate scores were converted to z-scores and then averaged for one composite z-score.
Result(s): A total of n=64 participants completed baseline assessments with n= 32 in the AOMS group (mean age 33.36 ?+/- 5.82) and n= 32 in the POMS group (mean age 11.31 ?+/- 3.64). All participants had relapsing remitting disease and the groups were matched for disease duration (4.91 ?+/- 3.05 years for AOMS vs. 6.38 ?+/- 3.54 for POMS). The POMS group had higher estimated premorbid IQ (WRAT-4 reading 112.7 ?+/- 18.5 vs. 105.4 ?+/- 13.4), though the result did not reach significance (p=0.07). Neither group's cognitive performances fell into the impaired range relative to age-normative means. However, the AOMS compared to the POMS group consistently performed significantly worse on the SDMT (mean z-score -0.26 ?+/- 1.15 for AOMS vs. 0.68 ?+/- 1.53 for POMS, p=0.01) and slower on the Cogstate composite (mean z-score of -1.04 ?+/- 1.09 for AOMS vs. 0.35 ?+/- 1.15 for POMS, p=0.04). Estimated premorbid IQ was correlated with SDMT, but not Cogstate performance (r=0.56 p=0.001 and r=0.13 p=0.35, respectively). Age of disease onset was significantly negatively correlated with cognitive processing (SDMT: r= -0.32, p= 0.01 and Cogstate DET: r= -0.33, p=0.02), further indicating that older age of onset is associated with greater cognitive impairment.
Conclusion(s): Adult MS is associated with larger cognitive involvement than pediatric MS