The presence and burden of cognitive issues: discordance between the perception of neurologists and people living with multiple sclerosis.

BACKGROUND AND PURPOSE: Cognitive impairment is a common symptom of multiple sclerosis (MS) and occurs in more than 40% of people living with MS (plwMS). No real-world study has assessed the perception of neurologists and plwMS on cognitive issues. METHODS: Using data from the 2011-2019 Adelphi MS Disease Specific Programme database, this real-world, retrospective, cross-sectional multi-cohort study included people aged ≥18 years with relapsing-remitting MS and secondary progressive MS from the United States, UK and the EU. Neurologists provided data on the patient record form for plwMS, with the same plwMS invited to voluntarily complete a patient self-completion form: a questionnaire about their experiences with MS. RESULTS: Of 25,374 plwMS, 4817 who provided information on cognitive and mood symptoms were included in the analysis. Of the plwMS, 68% and 59% reported feeling 'mentally fatigued' and having 'difficulty concentrating', respectively. Neurologists reported only 27% of plwMS as having 'difficulty concentrating' and 15% of plwMS as having 'short-/long-term memory problems'. Neurologists reported cognitive or mood symptoms as 'not experienced' by a higher percentage of participants with relapsing-remitting MS than secondary progressive MS. Of the plwMS who experienced 'difficulty concentrating', most had a concomitant feeling of being 'mentally fatigued' (52%), followed by 'feeling anxious or tense' (49%) and 'feeling depressed' (44%). In plwMS, caregivers reported 'difficulty concentrating' (16%) as the most common cognitive issue. CONCLUSION: A clear discordance was observed between neurologists and plwMS regarding the perception of the cognitive and neuropsychiatric issues. These results underline the under-perception of cognitive and emotional affective symptoms in plwMS during neurological consultations.

Does effort increase or decrease reward valuation? Considerations from cognitive dissonance theory.

The present research tested the effect of manipulated perceived control (over obtaining the outcomes) and effort on reward valuation using the event-related potential known as the Reward Positivity (RewP). This test was conducted in an attempt to integrate two research literatures with opposite findings: Effort justification occurs when high effort leads to high reward valuation, whereas effort discounting occurs when high effort leads to low reward valuation. Based on an examination of past methods used in these literatures, we predicted that perceived control and effort would interactively influence RewP. Consistent with the effort justification literature (cognitive dissonance theory), when individuals have high perceived control, high effort should lead to more reward valuation than low effort should. Consistent with the effort discounting literature, when individuals have low perceived control, low effort should lead to more reward valuation than high effort should. Results supported these interactive and integrative predictions.

The effort-doors task: Examining the temporal dynamics of effort-based reward processing using ERPs.

Aberrant reward processing is a cardinal feature of various forms of psychopathology. However, recent research indicates that aberrant reward processing may manifest at temporally distinct substages and involve interdependent subcomponents of reward processing. To improve our understanding of both the temporal dynamics and distinct subcomponents of reward processing, we added an effort manipulation to the "doors" reward-task paradigm, to derive behavioral and event-related potential (ERP) measures of effort-based reward processing. Behavioral measures consisting of reaction time, response rate, and response rate change were used to index effort expenditure, and ERP measures were used to index attention allocated toward effort-completion cues, anticipation of reward, valuation of reward, and attention toward monetary feedback. Reduced response rate and slowing of response were evident during the high effort versus the low effort condition. ERP findings indicated increased attention to signals of high- compared to low-effort completion cues-as well as reduced anticipation of rewards, and reduced attention toward feedback information following high effort expenditure. Participants showing the most response-rate slowing evidenced the greatest reward devaluation following high versus low effort. Findings demonstrate that the addition of an effort expenditure manipulation to the doors reward paradigm produced reliable ERP and behavioral measures of effort-based reward processing, providing opportunities for future researchers to utilize the effort-doors task to parse the temporal dynamics of both anticipatory and consummatory reward processing components.

Real-world assessment of the impact of "OFF" episodes on health-related quality of life among patients with Parkinson's disease in the United States.

BACKGROUND: Many patients with Parkinson's disease (PD) who receive carbidopa/levodopa experience symptom reemergence or worsening, or "OFF" episodes. This study assessed the association of "OFF" episodes with health-related quality of life (HRQoL). METHODS: US-specific data from the 2017 and 2019 Adelphi Real World Disease Specific Programme for PD, a real-world cross-sectional survey, were used. Neurologists provided data for 10-12 consecutive patients with PD who completed the 39-item Parkinson's Disease Questionnaire (PDQ-39) and the EuroQol 5-Dimension (EQ-5D). Data were grouped by patients who experienced "OFF" episodes versus those who did not and by average hours of daily "OFF" time. Differences between patient groups were assessed for demographics and clinical characteristics; regression analyses were used to model the relationship between HRQoL and "OFF" episodes with age, sex, body mass index, current PD stage on the Hoehn and Yahr scale, and number of concomitant conditions related and unrelated to mobility as covariates. RESULTS: Data from 722 patients were analyzed. Overall, 321 patients (44%) had "OFF" episodes (mean of 2.9 h of daily "OFF" time). Patients who experienced "OFF" episodes were less likely to work full-time and more likely to live with family members other than their spouse/partner or reside in a long-term care facility than those without "OFF" episodes. The presence of "OFF" episodes, regardless of the average hours of daily "OFF" time, was significantly associated with high scores (reflecting poor HRQoL) on most PDQ-39 dimensions and the summary index and low scores (reflecting poor health status) on the EQ-5D health utility index, visual analog scale (VAS), and all dimensions. Furthermore, increased average hours of daily "OFF" time was significantly correlated with higher scores for all PDQ-39 dimensions and the summary index, as well as with the EQ-5D health utility index and VAS scores. Patients with "OFF" episodes experienced reduced HRQoL even after correcting for potentially confounding variables. CONCLUSIONS: This study demonstrated that the occurrence of "OFF" episodes in patients with PD is associated with reduced HRQoL and that the impact on HRQoL increased incrementally with increasing average hours of daily "OFF" time.

Modulatory effects of positive mood and approach motivation on reward processing: Two sides of the same coin?

In a previous study (Paul & Pourtois, 2017), we found that positive mood substantially influenced the neural processing of reward, mostly by altering expectations and creating an optimistic bias. Under positive mood, the Reward Positivity (RewP) component and fronto-medial theta activity (FMθ) in response to monetary feedback were both changed compared with neutral mood. Nevertheless, whether positive valence per se or motivational intensity drove these neurophysiological effects remained unclear. To address this question, we combined a mindset manipulation with an imagery procedure to create and maintain three different affective states using a between-subjects design: a neutral mood, and positive mood with either high or low motivational intensity. After mood induction, 161 participants performed a simple gambling task while 64-channel EEG was recorded. FMθ activity results showed that irrespective of motivational intensity, positive compared with neutral mood altered reward expectancy. By comparison, RewP was not affected by positive mood nor motivational intensity. These results suggest that positive mood, rather than motivational intensity, is likely driving the change in reward expectation during gambling, which could reflect the presence of an optimistic bias. Moreover, at the methodological level, they confirm that the RewP ERP component and FMθ activity can capture dissociable effects during reward processing.

Quantifying the diagnostic pathway for patients with cognitive impairment: real-world data from Australia.

OBJECTIVES: Rapid diagnosis of dementia is essential to ensure optimum patient care. This study used real-world data to quantify the dementia diagnostic pathway in Australia. DESIGN: A real-world, cross-sectional survey of physicians and patients. SETTING: Clinical practice. PARTICIPANTS: Primary care or specialist physicians managing patients with cognitive impairment (CI). MEASUREMENTS: Descriptive analyses focused on key events in the diagnostic pathway. Regression modeling compared the duration between first consultation and formal diagnosis with various factors. RESULTS: Data for 600 patients were provided by 60 physicians. Mean time from initial symptoms to first consultation was 6.1 ± 4.4 months; 20% of patients had moderate or severe CI at first consultation. Mean time from first consultation to formal diagnosis was 4.0 ± 7.4 months (1.2 ± 3.6 months if not referred to a secondary physician, and 5.3 ± 8.3 months if referred). Time from first consultation to diagnosis was significantly associated with CI severity at first consultation; time was shorter with more severe CI. There was no association of disease severity and referral to a secondary physician; 69.5% of patients were referred, the majority (57.1%) to a geriatrician. The highest proportion of patients were diagnosed by geriatricians (47.4%). Some form of test or scale was used to aid diagnosis in 98.8% of patients. CONCLUSIONS: A substantial number of Australians experience cognitive decline and behavioral changes some time before consulting a physician or being diagnosed with dementia. Increasing public awareness of the importance of early diagnosis is essential to improve the proportion of patients receiving comprehensive support prior to disease progression.

Cognitive dissonance processes serve an action-oriented adaptive function.

The action-based model of cognitive dissonance proposes an adaptive function for rationalization that differs from the one offered by Cushman. The one proposed by Cushman is concerned more with the cold construction of cognitions, whereas the one proposed by the action-based model is a motivated protection of a strongly held cognition.

The Diagnostic Pathway From Cognitive Impairment to Dementia in Japan: Quantification Using Real-World Data.

OBJECTIVE: This study aimed to quantify the diagnostic pathway from cognitive impairment (CI) to dementia in Japan. METHODS: This was a real-world, cross-sectional survey of patients with CI and their physicians. RESULTS: Data for 1107 patients were provided by 106 physicians. Mean time from initial symptoms to the first consultation was 7.4±6.9 months; 42% of patients had moderate/severe CI at first consultation. Mean time from the first consultation to formal diagnosis was 2.9±11.0 months (1.9±8.8 mo if not referred to a secondary physician, and 5.1±14.6 mo if referred). Time from the first consultation to diagnosis was shorter with more severe CI at first consultation (P=0.0072). The highest proportion of patients were diagnosed by neurologists (45.8%). Tests or scales were used to aid diagnosis in 81.2% of patients. There was no association of disease severity and referral to a secondary physician; 30.9% of patients were referred, the majority (57.7%) to a neurologist. CONCLUSIONS: A substantial proportion of patients with dementia in Japan experience CI for some time before consulting a physician. Government policy to increase public understanding and awareness of dementia, and a proposed dementia screening system, should increase the proportion of individuals consulting physicians before disease progression.

On motivational influences, moving beyond valence, and integrating dimensional and discrete views of emotion.

The field of cognition and emotion has grown considerably over the past 30 years, with an increased emphasis on the relationships between emotional and motivational components and how they contribute to basic perceptual, cognitive, and neural processes. For instance, research has revealed that emotion often influences these processes via emotion's relationship with motivational dimensions, as when positive emotions low versus high in approach motivational intensity have different influences on attentional and other cognitive processes. Research has also revealed that motivational direction (approach vs. withdrawal) and affective valence (positive vs. negative) are not as closely related as once was theorised; that is, positive affect is not inevitably associated with approach motivation and negative affect is not inevitably associated with withdrawal motivation. These and other lines of research with anger have suggested that the field needs to move beyond a focus on affective valence and it needs to consider an integration of dimensional and discrete models of emotion. The article also includes some suggestions for improving methods of measuring and inducing emotions and some recommendations for future researchers.

Laboratory-induced learned helplessness attenuates approach motivation as indexed by posterior versus frontal theta activity.

Research suggests that midline posterior versus frontal electroencephalographic (EEG) theta activity (PFTA) may reflect a novel neurophysiological index of approach motivation. Elevated PFTA has been associated with approach-related tendencies both at rest and during laboratory tasks designed to enhance approach motivation. PFTA is sensitive to changes in dopamine signaling within the fronto-striatal neural circuit, which is centrally involved in approach motivation, reward processing, and goal-directed behavior. To date, however, no studies have examined PFTA during a laboratory task designed to reduce approach motivation or goal-directed behavior. Considerable animal and human research supports the hypothesis put forth by the learned helplessness theory that exposure to uncontrollable aversive stimuli decreases approach motivation by inducing a state of perceived uncontrollability. Accordingly, the present study examined the effect of perceived uncontrollability (i.e., learned helplessness) on PFTA. EEG data were collected from 74 participants (mean age = 19.21 years; 40 females) exposed to either Controllable (n = 26) or Uncontrollable (n = 25) aversive noise bursts, or a No-Noise Condition (n = 23). In line with prediction, individuals exposed to uncontrollable aversive noise bursts displayed a significant decrease in PFTA, reflecting reduced approach motivation, relative to both individuals exposed to controllable noise bursts or the No-Noise Condition. There was no relationship between perceived uncontrollability and frontal EEG alpha asymmetry, another commonly used neurophysiological index of approach motivation. Results have implications for understanding the neurophysiology of approach motivation and establishing PFTA as a neurophysiological index of approach-related tendencies.

The Influence of Agreeableness and Ego Depletion on Emotional Responding.

OBJECTIVE: Agreeable individuals report more intense withdrawal-oriented negative emotions across aversive situations. Two studies tested the hypothesis that self-regulatory depletion (i.e., ego depletion) moderates the relationship between trait Agreeableness and negative emotional responding. METHOD: Ego depletion was manipulated using a writing task. Emotional responding was measured with startle eye-blink responses (Study 1, N = 71) and self-reported valence, arousal, and empathic concern (Study 2, N = 256) during emotional picture viewing. Trait Agreeableness was measured using a questionnaire. RESULTS: In Study 1, Agreeableness predicted especially large startle responses during aversive images and especially small startles during appetitive images. After exercising self-control, the relationship between startle magnitudes and Agreeableness decreased. In Study 2, Agreeableness predicted more empathic concern for aversive images, which in turn predicted heightened self-reported negative emotions. After exercising self-control, the relationship between Agreeableness and empathic concern decreased. CONCLUSIONS: Agreeable individuals exhibit heightened negative emotional responding. Ego depletion reduced the link between Agreeableness and negative emotional responding in Study 1 and moderated the indirect effect of Agreeableness on negative emotional responding via empathic concern in Study 2. Empathic concern appears to be a resource-intensive process underlying heightened responding to aversive stimuli among agreeable persons.

Influence of the BDNF genotype on amygdalo-prefrontal white matter microstructure is linked to nonconscious attention bias to threat.

Cognitive processing biases, such as increased attention to threat, are gaining recognition as causal factors in anxiety. Yet, little is known about the anatomical pathway by which threat biases cognition and how genetic factors might influence the integrity of this pathway, and thus, behavior. For 40 normative adults, we reconstructed the entire amygdalo-prefrontal white matter tract (uncinate fasciculus) using diffusion tensor weighted MRI and probabilistic tractography to test the hypothesis that greater fiber integrity correlates with greater nonconscious attention bias to threat as measured by a backward masked dot-probe task. We used path analysis to investigate the relationship between brain-derived nerve growth factor genotype, uncinate fasciculus integrity, and attention bias behavior. Greater structural integrity of the amygdalo-prefrontal tract correlates with facilitated attention bias to nonconscious threat. Genetic variability associated with brain-derived nerve growth factor appears to influence the microstructure of this pathway and, in turn, attention bias to nonconscious threat. These results suggest that the integrity of amygdalo-prefrontal projections underlie nonconscious attention bias to threat and mediate genetic influence on attention bias behavior. Prefrontal cognition and attentional processing in high bias individuals appear to be heavily influenced by nonconscious threat signals relayed via the uncinate fasciculus.

Preferences and motivations with and without inferences.

Pessoa (2013) makes an impressive case that emotion, motivation, and cognition are neurally intertwined. Our commentary broadens the discussion to the functional, "mind" level. We argue that philosophical and computational considerations justify some modern "separatist" views. We highlight several psychological phenomena that illustrate independence, including affective and motivational reactions to rudimentary inputs, and the guiding role of such reactions in cognition.

Motivational intensity and valence are married, but they are not the same person: Commentary on Campbell et al. (2021).

Comments on the article by Campbell et al. (see record 2021-21096-001). Campbell et al. (2021) claimed motivational intensity (approach-avoidance) is a redundant construct that is merely another label for valence (positive-negative). They based their conclusion on a high correlation between valence and motivational intensity when participants rated pictures. We present arguments that their conclusion was based on inadequate evidence. First, we explain how high correlation fails to identify meaningful and consistent affective states where motivational intensity is essential. As a counterargument, we present replicated and cumulative empirical evidence of differences between affective states with equal valence and arousal but different motivational intensities such as desire or enthusiasm versus amusement. Second, we emphasize that correlations do not account for relative differences between valence and motivational intensity levels (which we termed undermotivated and overmotivated affect). We illustrate this by presenting how valence and motivational intensity diverge during watching affective video clips. We conclude the opposite of Campbell's team, that is, motivational intensity is a viable concept deserving further attention. However, studying motivational intensity requires specific strategies to dissect what is possible within affect from the most frequent. We formulate several recommendations regarding the choice of stimuli (overrepresentation of specific categories) and measurement (e.g., measuring dimensions of affect along with a broad range of discrete emotions and motivational concepts). This might improve the study in affective science toward stronger differentiation within the core of human affect. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Shared Decision-Making in the Treatment of Multiple Sclerosis: Results of a Cross-Sectional, Real-World Survey in Europe and the United States.

Introduction: Multiple sclerosis (MS) is a neurodegenerative disease characterized by progressive deterioration of cognitive and physical functioning, reducing activities of daily living and quality of life (QoL). Several treatments are available that modify the course of the disease and reduce the frequency of relapses. Although effective, all treatment options are accompanied by adverse events, and this study aimed to assess the extent to which patients were involved in the choice of treatment. Methods: Data were drawn from the Adelphi Multiple Sclerosis Disease Specific Program (DSP)™, a cross-sectional survey of healthcare practitioners (HCP) and their patients with MS in real-world clinical settings in Europe and the United States (US) between December 2020 and July 2021. HCPs reported patient demographics, clinical characteristics, current and previous treatment, and treatment outcomes. Patients voluntarily completed questionnaires reporting the physical and psychological impact of their MS and its treatment. Regression analysis with inverse probability of treatment weighting was used to compare treatment outcomes in patients actively involved in their current treatment choice with those who were not. Results: Of a total of 692 patients, median age 40 years and 64% female, mostly diagnosed with relapsing-remitting MS, those who were involved in shared decision-making tended to choose oral therapies such as dimethyl fumarate more often than HCPs. MS had greater impact on physical and psychological functioning in patients whose HCP made treatment decisions solely. Patients involved in decision-making reported greater satisfaction with their treatment and a better QoL. Discussion: Because no single optimal therapy exists for patients with MS, treatments should be individualized with consideration of patients' preferences. Our study shows that shared decision-making is under-utilized in the management of MS and supports the benefits of patient involvement. Conclusion: Patients who have an active role in treatment decision-making show improved wellbeing and QoL, and overall treatment satisfaction.

Associations Among Tremor Amplitude, Activities of Daily Living, and Quality of Life in Patients with Essential Tremor.

Background: Essential tremor (ET) is a disabling syndrome consisting of tremor, primarily in the upper limbs. We assessed the correlation of The Essential Tremor Rating Assessment Scale (TETRAS) Performance Item 4 ratings of upper limb tremor with the TETRAS activities of daily living (ADL) subscale and with 2 quality of life (QoL) scales. Methods: This noninterventional, cross-sectional, point-in-time survey of neurologists(n = 60), primary care physicians (n = 38), and their patients with ET (n = 1,003) used real-world data collected through the Adelphi ET Disease Specific Programme™. Physician-reported measures (TETRAS Performance Item 4 and TETRAS ADL total) and patient-reported QoL measures (generic EuroQol-5 Dimension 5 Level [EQ-5D-5 L] and ET-specific Quality of Life in Essential Tremor Questionnaire (QUEST)) were assessed with bivariate and multivariable analyses. Sensitivity analyses were also conducted. Results: The bivariate association between TETRAS Performance Item 4 score and TETRAS ADL total score was high (Pearson r = 0.761, P < 0.001). The bivariate associations between TETRAS Performance Item 4 score and EQ-5D-5 L index score (r = -0.410, P < 0.001) and between TETRAS ADL total score and EQ-5D-5 L index score (r = -0.543, P < 0.001) were moderate. The bivariate associations between TETRAS Performance Item 4 score and QUEST total score (r = 0.457, P < 0.001), and between TETRAS ADL total score and QUEST total score (r = 0.630, P < 0.001) were also moderate. These associations were unaltered by the inclusion of covariates. Discussion: This study showed that greater tremor severity (TETRAS Performance Item 4) was positively correlated with ADL impairment (TETRAS ADL) and negatively associated with QoL (EQ-5D-5 L and QUEST). TETRAS Performance Item 4 score is a robust predictor of TETRAS ADL total score, and TETRAS Performance Item 4 and TETRAS ADL total scores were robust predictors of the 2 QoL scales. The results demonstrate the value of TETRAS scores as valid endpoints for future clinical trials. Highlights: This real-world study assessed TETRAS scores as predictors of impaired QoL in ET. TETRAS Performance Item 4 and ADL were associated with EQ-5D-5 L and QUEST. TETRAS scores may serve as valid endpoints for future clinical trials.

When anger leads to rumination: induction of relative right frontal cortical activity with transcranial direct current stimulation increases anger-related rumination.

Anger is associated with various responses. Research on the neuroscience of anger has revealed that greater left than right frontal cortical activity is associated with angry approach-oriented responses, such as aggression, whereas greater right than left frontal cortical activity is associated with inhibited angry responses mixed with anxiety. In the current research, we extended these past studies by manipulating asymmetric frontal cortical activity using transcranial direct current stimulation and assessing its influence on ruminative responses to an interpersonal insult. Results revealed that self-reported rumination was greatest for participants who received a manipulated increase in relative right frontal cortical activity compared with those who received either a manipulated increase in relative left frontal cortical activity or sham stimulation. Taken together with past findings, the current results suggest that anger associated with greater relative left frontal cortical activity predicts approach-oriented aggressive action, whereas anger associated with greater relative right frontal cortical activity predicts inhibited rumination.

Treatment Patterns and Unmet Need for Patients with Progressive Multiple Sclerosis in the United States: Survey Results from 2016 to 2021.

INTRODUCTION: Much of the current literature on treatment patterns and disability progression in multiple sclerosis (MS) does not distinguish between the relapsing-remitting and progressive subtypes (including primary [PPMS] and secondary progressive MS [SPMS]), or between active/nonactive disease. Current treatment options for progressive MS are limited, with only one approved product for PPMS and none specifically for nonactive SPMS. Here we report treatment patterns, disability progression, and unmet needs among patients with active and nonactive PPMS and SPMS. METHODS: The annual, cross-sectional survey from the Adelphi Disease Specific Program was used to collect physician-reported data on US adult patients with PPMS and SPMS, including active and nonactive disease. Treatment patterns (including the proportion of patients who were untreated with a disease-modifying therapy [DMT]), disability progression, and unmet need are described from 2016 to 2021. RESULTS: Data were collected for 2067 patients with progressive MS (PPMS, 1583; SPMS, 484). A substantial proportion of patients were untreated across all groups, and this was highest for nonactive PPMS (~ 43%). The proportion of untreated patients generally declined over time but remained high in 2018-2021 (~ 10-38%). Among treated patients, the proportion receiving infusions increased over time to ~ 34-46%, largely driven by ocrelizumab use after approval. Disability progression was reported for most patients (> 50%), including many who were receiving a DMT. Across all disease subtypes, when physicians were asked about the greatest unmet need with current DMTs, they most frequently cited effectiveness (~ 63-87%), and specifically slowing disease progression (~ 32-59%). CONCLUSIONS: This analysis of physician-reported data reveals that patients with progressive MS, particularly those with nonactive disease, frequently remain untreated or continue to decline despite treatment with available DMTs. Thus there is an enduring need for safe and effective treatments for this underserved population.

Further examinations of attitudes toward discrete emotions, with a focus on attitudes toward anger.

The present research aimed to better understand individual differences in attitudes towards emotions with a focus on anger. We report findings of four studies conducted with American and Polish individuals. Results showed that individuals who have more positive attitudes toward anger are higher in trait anger (Studies 1-4), are more likely to think about getting revenge (Study 1), and expect that getting revenge will make them feel good (Studies 1-2). In addition, these individuals are lower in agreeableness and lower in the tendency to engage in avoidance when angered (Studies 1-4). They score lower in humility (Studies 3-4), lower in secure romantic attachment but higher in anxious and avoidance attachment (Study 3). Finally, they are more likely to believe a wide range of conspiracies (Studies 2-4). Discussion focuses on the implications of these results.

Influence of physicians' risk perception on switching treatments between high- efficacy and non-high-efficacy disease­modifying therapies in multiple sclerosis.

BACKGROUND: The decision of initiating treatment for multiple sclerosis (MS) with a high-efficacy DMT (HE DMT) or non-high-efficacy DMT (non-HE DMT) is influenced by several factors, including risk perception of patients and physicians. OBJECTIVE: Investigate the influence of physicians' risk perception on decision-making when switching treatments for MS and the reasons for switching. METHODS: Data were drawn from the Adelphi Real-World MS Disease-Specific Program (a retrospective survey) and analysis included people with RMS identified between 2017- 2021. RESULTS: Of 4129 patients with reasons for switch available, 3538 switched from non-HE DMT and 591 from HE DMT. Overall, 4.7% of patients were switched treatment by their physicians due to the risk of malignancies and infections including PML risk. The proportion of switches that were made due to the risk of PML were 23.9% in the HE DMT and 0.5% in the non-HE DMT groups. The top reasons for switching were relapse frequency (non-HE DMT vs HE-DMT: 26.8% vs 15.2%), lack of efficacy (20.9 vs 11.7) and increased number of MRI lesions (20.3% vs 12.4%). CONCLUSIONS: Physicians' risk perception of malignancies and infection excluding PML was not a leading factor when switching treatment. The risk of PML was a key factor, especially for switching patients from HE DMTs. In both groups, lack of efficacy was the key contributing factor for switching. Initiating the treatment with HE DMTs may potentially reduce the number of switches due to sub-optimal efficacy. These findings might help physicians to engage more in discussions with patients about the benefit/risk profile of DMTs.