Buntanetap is an orally available small RNA targeting molecule that inhibits the translation of multiple neurotoxic aggregating proteins, including amyloid precursor protein (APP) and Tau. It has been evaluated in 13 clinical trials involving over 1000 participants, including healthy volunteers, patients with Alzheimer’s disease (AD) and Parkinson’s disease (PD), and has shown a favorable safety and tolerability profile. In two small studies in early AD, buntanetap demonstrated a trend toward cognitive improvement, despite being underpowered for efficacy. In a Phase2/3 study in early PD, it also improved PD patients’ cognitive functions. We evaluated safety and efficacy of buntanetap in treating mild to moderate AD patients in this 3-month randomized double-blind dose-ranging study (NCT05686044). Total of 351 Patients were equally randomized to either 7.5 mg, 15 mg, 30 mg buntanetap or placebo. Buntanetap had a favorable safety profile. The study did not meet its primary endpoints (ADAS-Cog-11 and ADCS-CGIC), as 40% of participants lacked amyloid pathology. However, in amyloid biomarker-positive mild AD patients, buntanetap demonstrated nominally statistically significant dose-dependent cognitive benefits, supported by biomarker evidence of target and pathway engagement. Further evaluation of buntanetap in this patient population are warranted. A Phase 3 trial is currently underway to confirm these findings (NCT06709014).

OBJECTIVE:To determine the test performance of cutaneous phosphorylated alpha-synuclein (P-SYN) in dementia with Lewy bodies (DLB), individuals with reduced Montreal Cognitive Assessment (MoCA) and healthy controls. METHODS:This is the first subgroup analysis of the Synuclein-One study, a prospective, blinded study evaluating P-SYN detection from skin biopsies in 218 subjects with a referral diagnosis of control (N = 151) and DLB (N = 67). All subjects completed detailed examinations, questionnaires, and had skin biopsies for detection of P-SYN. DLB patients were included if meeting the 4th DLB consensus probable criteria. Control subjects, aged 40-99, had no history, examination findings, or symptoms suggestive of a synucleinopathy or neurodegenerative disease. An expert review panel, blinded to pathological data, determined the final diagnosis. Controls with reduced MoCA (MoCA < 26, N = 26) at screening were analyzed separately. RESULTS:After expert panel review, only 50/67 patients met consensus criteria for DLB, 26/151 controls had a reduced MoCA, and 120/151 controls had a normal MoCA. The proportions of subjects with cutaneous P-SYN detected by skin biopsy were 96.0% (48 of 50) of the DLB group, 31% (8 of 26) of the controls with reduced MoCA, and 3.3% (4 of 120) of the controls with normal MoCA. INTERPRETATION:In this prospective, blinded, cross-sectional study, a high proportion of subjects meeting clinical consensus criteria for DLB had P-SYN detected in skin biopsies. Almost 1/3 of subjects with reduced MoCA testing also had P-SYN detected. These results support a role for skin biopsy detection of P-SYN in patients with DLB. TRIAL REGISTRATION:NCT04700722.

BackgroundThe Huntington's Disease (HD) Everyday Functioning (Hi-DEF) is a novel patient-reported outcome (PRO) scale developed to assess the impact of cognitive impairment on daily functioning in early HD patients.ObjectiveTo examine the psychometric properties, including reliability and validity, of the Hi-DEF. Findings from psychometric analyses using classical test theory (CTT) approach are presented here.MethodsA non-interventional validation study was conducted across nine HD Centers of Excellence across the US.ResultsPatients with HD (n = 151) were recruited: 59% were female, mean (SD) age was 47 (12) years, and mean (range) Total Functional Capacity (TFC) score was 11.4 (8-13). Excellent internal consistency reliability was observed for the Hi-DEF scale total score (Cronbach's alpha: 0.98) and across subscales (alpha range 0.87-0.96). Most targeting and scaling assumptions were met, although there were ceiling effects for three subscales. Construct validity was demonstrated by moderate to high Spearman's rank-order correlations with TFC scores (range r = -0.38 to -0.62) and known and validated measures such as the HD-PRO-TRIADTM (range r = 0.75-0.90), and ability to discriminate between levels of functional impairment (TFC 13, 12-11, and 10-8; p < 0.001). Correlations with Cambridge Neuropsychological Test Automated Battery (CANTAB) cognitive performance measures were low to moderate and ranged from 0.06 to 0.38.ConclusionsThe Hi-DEF is a reliable and valid PRO scale measuring the impact of cognitive impairment on daily functioning, assessing facets of cognitive functioning in context of activities of daily living impacted in early stages of HD.

Introduction: In the United States (US), prophylactic treatment with the antiemetic trimethobenzamide has been used before initiating apomorphine therapy. However, US trimethobenzamide stores have been depleted, leaving uncertainty regarding whether antiemetic pretreatment is needed. Methods: This modified Delphi panel aimed to inform circumstances when apomorphine is initiated without antiemetic pretreatment. During Round 1, a panel of 9 US movement disorder specialists rated the appropriateness of prescribing apomorphine therapy with and without antiemetic pretreatment across 192 patient scenarios and were able to review their scores in relation to other scores. During the Round 2, consensus was defined for each scenario as either strong (>75 % agreement) or moderate (66 % agreement). Results: There was strong consensus on 118 of 192 scenario’s (97 as appropriate and 21 as inappropriate), moderate consensus on 29 scenarios, some agreement on 32 scenarios, and lack of agreement on 13 scenarios. In the absence of an antiemetic, there was strong consensus that titration schedules should be flexible and based on dose response. However, the group only reached moderate consensus on the speed of titration, highlighting the need for more systematic information on this area. In the presence of an antiemetic, panelists considered usual initial dosing and flexible titration to be appropriate in most scenarios except for when the patient is already experiencing dopaminergic adverse events. Conclusions: Experts generally reached consensus that apomorphine can usually be prescribed without antiemetic pretreatment. Recommendations described here reflect the areas of greatest agreement among a panel of experts based on current available evidence.

Background and ObjectivesASPEN-1 was a phase 3, randomized, double-blind, placebo-controlled study to evaluate the efficacy, duration of response, and safety of 2 doses of DaxibotulinumtoxinA for Injection (DAXI), a novel botulinum toxin type A formulation in participants with cervical dystonia (CD).MethodsAdults (aged 18–80 years) with moderate-to-severe CD (Toronto Western Spasmodic Torticollis Rating Scale [TWSTRS] total score ≥20) were enrolled at 60 sites across 9 countries in Europe and North America. Participants were randomized (3:3:1) to single-dose intramuscular DAXI 125U, 250U, or placebo and followed for up to 36 weeks after injection. The primary end point was change from baseline in TWSTRS total score averaged across weeks 4 and 6. Key secondary end points included duration of effect, Clinical and Patient Global Impression of Change (CGIC, PGIC), TWSTRS subscale scores, and safety. Multiplicity-adjusted intent-to-treat hypothesis tests with multiple imputation were performed using ANCOVA and Cochran-Mantel-Haenszel analyses.ResultsOf 444 individuals screened, 301 were randomized to DAXI 125U (n = 125) or 250U (n = 130) or placebo (n = 46). DAXI 125U and 250U significantly improved the mean TWSTRS total score vs placebo (least squares mean [standard error] difference vs placebo: DAXI 125U, −8.5 [1.93], p < 0.0001; DAXI 250U, −6.6 [1.92], p = 0.0006). The median duration of effect (time from treatment until loss of ≥80% of the peak improvement in average TWSTRS total score achieved at weeks 4 and 6) was 24.0 (95% confidence interval 20.3–29.1) weeks with DAXI 125U and 20.3 (16.7–24.0) weeks with DAXI 250U. Significant improvements were also observed with DAXI in CGIC and PGIC responder rates and TWSTRS subscales. Treatment-related treatment-emergent adverse events (TEAEs) were reported by 29.6% of participants with DAXI 125U, 23.8% with DAXI 250U, and 17.4% with placebo, with injection site pain being the most common overall. The most frequently reported treatment-related TEAEs of interest in DAXI 125U, DAXI 250U, and placebo, respectively, were muscular weakness (4.8%, 2.3%, 0%), musculoskeletal pain (2.4%, 3.1%, 0%), and dysphagia (1.6%, 3.8%, 0%).DiscussionThis study demonstrated that DAXI, at doses of 125U and 250U, is an effective, safe, long-acting, and well-tolerated treatment for CD.Trial Registration InformationClinicalTrials.gov identifier (NCT03608397, submitted July 11, 2018) and EU Clinical Trials Register (ClinicalTrialsRegister.eu EudraCT identifier 2018-000446-19, submitted September 13, 2018). First participant enrolled on June 11, 2018. Trial registration was performed in accordance with the Food and Drug Administration Amendments Act (FDAAA 801), which stipulates that the responsible party register an applicable clinical trial not later than 21 calendar days after enrolling the first human participant (42 CFR 11.24).Classification of EvidenceThis study provides Class I evidence that in adults with moderate-to-severe idiopathic cervical dystonia, DAXI reduces dystonia more effectively than placebo.

To report interim results of a TREM2 (triggering receptor expressed on myeloid cells 2) agonist from the first interventional study in ALSP.

Objective: To evaluate neurologists' perception of PD patient attitudes towards injectable therapies and determine if education on these attitudes would alter neurologists' willingness to prescribe these therapies. Background: OFF episodes occur in majority of PD patients negatively impacting their day-to-day life. Subcutaneous injections of apomorphine have been shown to reduce OFF episodes with a rapid onset of action. Several other products are currently in development for the treatment of motor fluctuations requiring continuous subcutaneous infusion. We had previously reported that 89% of patients would be willing to self-inject, when there is an associated benefit. We hypothesized the following: 1. neurologists were unaware of this information (overestimating the impact of "needle phobia") and as a result may underutilize these effective therapies. 2. neurologists' willingness to prescribe injectable therapies would increase after learning this information. Design/Methods: Data were collected using an online survey. Our sample (n=200) comprised n=115 Movement Disorder Specialists (MDS) and n=85 General Neurologists. The sample had n=96 physicians who had previously prescribed APOKYN® and n=104 who had not. Results: 54% of general neurologists and 37% of MDS demonstrated a positive change in perceptions about patients' willingness to use self-injected therapies after reviewing patient survey data (all P<0.05). This was true amongst 53% of APOKYN® non-users and 35% of APOKYN® users (all P<0.05). In addition, 37% of general neurologists and 21% of MDS indicated a greater likelihood of prescribing these treatments (all P< 0.05). Conclusions: Neurologists may be overestimating the impact of "needle phobia" since there is a discrepancy between PD patients' willingness to self-inject medications and neurologists' perceptions. Educating neurologists about actual patient acceptance of injectable therapies appeared effective, might facilitate more discussions about injectable therapies with patients who have troublesome off time, and may result in greater utilization of these effective therapies. Disclosure: The institution of Dr. Kumar has received personal compensation in the range of $50,000-$99,999 for serving as a Consultant for Supernus. The institution of Dr. Kumar has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Abbvie. The institution of Dr. Kumar has received personal compensation in the range of $100,000-$499,999 for serving as a Consultant for Teva Pharmaceuticals. The institution of Dr. Kumar has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Annexon. The institution of Dr. Kumar has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Roche. The institution of Dr. Kumar has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Acorda Therapeutics. The institution of Dr. Kumar has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Cerevel Therapeutics. Dr. Kumar has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Impel Pharma. Dr. Kumar has received personal compensation in the range of $50,000-$99,999 for serving on a Speakers Bureau for Supernus. The institution of Dr. Kumar has received personal compensation in the range of $100,000-$499,999 for serving on a Speakers Bureau for Teva. The institution of Dr. Kumar has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Acorda Therapeutics. The institution of Dr. Kumar has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Kyowa Kirin. Dr. Kumar has received personal compensation in the range of $1,000,000+ for serving as an officer or member of the Board of Directors for Research Catalyst, LLC. Dr. Kumar has stock in Research Catalyst, LLC. Dr. Kumar has stock in CenExel. The institution of Dr. Kumar has received research support from Supernus. The institution of Dr. Kumar has received research support from Sage Therapeutics. The institution of Dr. Kumar has received research support from Prilenia Therapeutics. The institution of Dr. Kumar has received research support from Roche. The institution of Dr. Kumar has received research support from Triplet Therapeutics. The institution of Dr. Kumar has received research support from CHDI Foundation. The institution of Dr. Kumar has received research support from Neurocrine Biosciences. The institution of Dr. Kumar has received research support from Biovie. The institution of Dr. Kumar has received research support from Neuroderm. The institution of Dr. Kumar has received research support from Sanofi. The institution of Dr. Kumar has received research support from Addex Pharma. The institution of Dr. Kumar has received research support from Integrative Research Laboratories. The institution of Dr. Kumar has received research support from Takeda Pharmaceuticals. The institution of Dr. Kumar has received research support from Neuraly. The institution of Dr. Kumar has received research support from Abbvie. The institution of Dr. Kumar has received research support from Cerevel Therapeutics. The institution of Dr. Kumar has received research support from Transposon Therapeutics. The institution of Dr. Kumar has received research support from Lundbeck. The institution of Dr. Kumar has received research support from Biohaven. The institution of Dr. Kumar has received research support from Revance Therapeutics. The institution of Dr. Kumar has received research support from Impax Laboratories. The institution of Dr. Kumar has received research support from Pharma Two B. The institution of Dr. Kumar has received research support from Enterin. The institution of Dr. Kumar has received research support from CND Life Sciences. The institution of Dr. Kumar has received research support from Neuron23. The institution of Dr. Kumar has received research support from Annexon Biosciences. The institution of Dr. Kumar has received research support from Annovis. The institution of Dr. Kumar has received research support from PTC Therapeutics. The institution of Dr. Kumar has received research support from Uniqure. The institution of Dr. Kumar has received research support from Alexza. The institution of Dr. Kumar has received research support from SparkNeuro. The institution of Dr. Kumar has received research support from Praxis. The institution of Dr. Kumar has received research support from Scion Neurostim. The institution of Dr. Kumar has received research support from Cognition Therapeutics. The institution of Dr. Kumar has received research support from Eli Lilly. Dr. Kumar has received personal compensation in the range of $100,000-$499,999 for serving as a Medical Director with CenExel RMCR. Dr. Kumar has received personal compensation in the range of $1,000,000+ for serving as a Managing Member with Research Catalyst, LLC. Dr. Rossol has received personal compensation for serving as an employee of Mindfrog, a Market Research Company serving pharmaceutical clients. Dr. Rossol has received research support from Supernus. Dr. Rossol has received personal compensation in the range of $500,000-$999,999 for serving as a Market Research Vendor with Rigel. Dr. Rossol has received personal compensation in the range of $50,000-$99,999 for serving as a Market Research Vendor with AbbVie. Dr. Rossol has received personal compensation in the range of $500,000-$999,999 for serving as a Market Research Vendor with Supernus. Dr. Rossol has received personal compensation in the range of $50,000-$99,999 for serving as a Market Research Vendor with Santen. Dr. Rossol has received personal compensation in the range of $50,000-$99,999 for serving as a Market Research Vendor with Viatris. Dr. Rossol has received personal compensation in the range of $50,000-$99,999 for serving as a Market Research Vendor with Vistagen.

Objective: Tardive dyskinesia (TD) is a movement disorder that can negatively affect health-related quality of life. However, the impact of TD is not necessarily dependent solely on the objective severity of TD movements. There is currently no easy-to-use, standardized, clinician-rated assessment of the impact of TD on functioning. The aim of this consensus panel was to develop a scale (Impact-TD scale) to assess the impact of TD on patients' daily functioning in practice settings.Participants: Nine health care professionals with expertise in TD and clinical scale development met to discuss how TD negatively impacts the functional activities of patients.Evidence: This panel comprised 7 individuals from a previous panel that developed recommendations on the importance of optimally assessing the functional impact of TD. The previous panel published a narrative literature review that summarized the existing approaches to assess the impact of TD in clinical research and practice.Consensus Process: A modified Delphi process was used to assess agreement on the format and content of the Impact-TD scale. The panel discussed key features of the Impact-TD scale (ie, simplicity, usability, assessment of frequency of impact versus interference/distress). The scale aimed to describe specific consequences of TD symptoms with which patients may have difficulty.Conclusions: Consensus was reached on a list of consequences of TD symptoms that have a functional impact and were categorized in 4 functional domains: social, psychological/psychiatric, physical, and vocational/educational/recreational. The Impact-TD scale offers an easy-to-use clinical scale to measure the functional impact of TD in practice settings.

Objective: Characterize the natural history of ALSP by imaging, biomarkers, and standardized clinical measurements to inform the design of future clinical trials testing novel therapeutics for ALSP. Background: ALSP is a rare, rapidly progressing fatal neurologic disorder commonly caused by dominant variants in the CSF1R gene. The pathological hallmarks include demyelination of brain white matter, swollen axons, and pigmented glial cells. Clinically, ALSP is characterized by a constellation of symptoms including personality changes, cognitive dysfunction and motor impairments. There are no FDA approved treatments for ALSP. Limited natural history data is available to inform development of therapeutics for ALSP. Design/Methods: This is a prospective, multicenter, natural history study of patients with ALSP and asymptomatic carriers of CSF1R gene mutations. Up to 36 participants will be enrolled and followed for 24 months. Clinical assessments (cognitive, motor, functional, psychiatric, severity of illness, and caregiver burden) and MRI will be collected at Screening and at months 6, 12, 18, and 24. MRI severity score (Sundal et al 2012), white matter lesion and regional brain volumes will be derived. Blood and CSF (in a subset of participants) biomarkers of disease will be measured at specific visits. Results: 28 participants with confirmed CSF1R gene mutation meeting study eligibility criteria have been enrolled as of 9/2/2022. Among these, 17 were symptomatic and 11 were asymptomatic carriers, 13 were women and mean age at Screening visit was 46±13 years. Study enrollment is ongoing. Detailed study design and baseline characteristics of enrolled participants will be presented. Conclusions: This is the first systematic prospective study characterizing the natural history of ALSP due to CSF1R gene mutations leveraging standardized clinical, imaging and biomarker measurements. The outcome of this study is expected to inform on optimal biomarker and clinical endpoints and design of therapeutic intervention studies in ALSP. Disclosure: Dr. Rajagovindan has received personal compensation for serving as an employee of Biogen. Dr. Rajagovindan has received personal compensation for serving as an employee of Vigil. Dr. Rajagovindan has stock in Biogen. Dr. Rajagovindan has stock in Vigil . Mr. Matys has received personal compensation for serving as an employee of Vigil Neuroscience. Dr. Finger has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Vigil Neuro. Dr. Finger has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Denali Therapeutics. The institution of Dr. Finger has received research support from CIHR. The institution of Dr. Finger has received research support from Physician Servcices Incorporated. The institution of Dr. Finger has received research support from Weston Foundation. Dr. Finger has received personal compensation in the range of $500-$4,999 for serving as a Annual Meeting Course Director with American Academy of Neurology. An immediate family member of Dr. Gelfand has received personal compensation in the range of $50,000-$99,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Headache: The Journal of Head and Face Pain. The institution of Dr. Gelfand has received research support from Genentech/Roche. The institution of Dr. Gelfand has received research support from Vigil Neurosciences. An immediate family member of Dr. Gelfand has received publishing royalties from a publication relating to health care. Dr. Gelfand has received publishing royalties from a publication relating to health care. Dr. Gelfand has received publishing royalties from a publication relating to health care. Dr. Gelfand has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant and Expert, Vaccine Injury Compensation Program with United States Health and Human Services and Department of Justice. Dr. Gelfand has a non-compensated relationship as a Trial Steering Committee Chairperson and member with Roche / Genentech that is relevant to AAN interests or activities. Wolfgang Koehler has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Minoryx. Wolfgang Koehler has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Vigil. Wolfgang Koehler has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for United Leukodystrophy Foundation. Wolfgang Koehler has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for European Leukodystrophy Association. The institution of Wolfgang Koehler has received research support from Minoryx. The institution of Wolfgang Koehler has received research support from Vigil. The institution of Wolfgang Koehler has received research support from SwanBio. The institution of Wolfgang Koehler has received research support from Alexion. The institution of Dr. Kumar has received personal compensation in the range of $50,000-$99,999 for serving as a Consultant for Supernus. The institution of Dr. Kumar has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Abbvie. The institution of Dr. Kumar has received personal compensation in the range of $100,000-$499,999 for serving as a Consultant for Teva Pharmaceuticals. The institution of Dr. Kumar has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Annexon. The institution of Dr. Kumar has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Roche. The institution of Dr. Kumar has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Acorda Therapeutics. The institution of Dr. Kumar has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Cerevel Therapeutics. Dr. Kumar has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Impel Pharma. Dr. Kumar has received personal compensation in the range of $50,000-$99,999 for serving on a Speakers Bureau for Supernus. The institution of Dr. Kumar has received personal compensation in the range of $100,000-$499,999 for serving on a Speakers Bureau for Teva. The institution of Dr. Kumar has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Acorda Therapeutics. The institution of Dr. Kumar has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Kyowa Kirin. Dr. Kumar has received personal compensation in the range of $1,000,000+ for serving as an officer or member of the Board of Directors for Research Catalyst, LLC. Dr. Kumar has stock in Research Catalyst, LLC. Dr. Kumar has stock in CenExel. The institution of Dr. Kumar has received research support from Supernus. The institution of Dr. Kumar has received research support from Sage Therapeutics. The institution of Dr. Kumar has received research support from Prilenia Therapeutics. The institution of Dr. Kumar has received research support from Roche. The institution of Dr. Kumar has received research support from Triplet Therapeutics. The institution of Dr. Kumar has received research support from CHDI Foundation. The institution of Dr. Kumar has received research support from Neurocrine Biosciences. The institution of Dr. Kumar has received research support from Biovie. The institution of Dr. Kumar has received research support from Neuroderm. The institution of Dr. Kumar has received research support from Sanofi. The institution of Dr. Kumar has received research support from Addex Pharma. The institution of Dr. Kumar has received research support from Integrative Research Laboratories. The institution of Dr. Kumar has received research support from Takeda Pharmaceuticals. The institution of Dr. Kumar has received research support from Neuraly. The institution of Dr. Kumar has received research support from Abbvie. The institution of Dr. Kumar has received research support from Cerevel Therapeutics. The institution of Dr. Kumar has received research support from Transposon Therapeutics. The institution of Dr. Kumar has received research support from Lundbeck. The institution of Dr. Kumar has received research support from Biohaven. The institution of Dr. Kumar has received research support from Revance Therapeutics. The institution of Dr. Kumar has received research support from Impax Laboratories. The institution of Dr. Kumar has received research support from Pharma Two B. The institution of Dr. Kumar has received research support from Enterin. The institution of Dr. Kumar has received research support from CND Life Sciences. The institution of Dr. Kumar has received research support from Neuron23. The institution of Dr. Kumar has received research support from Annexon Biosciences. The institution of Dr. Kumar has received research support from Annovis. The institution of Dr. Kumar has received research support from PTC Therapeutics. The institution of Dr. Kumar has received research support from Uniqure. The institution of Dr. Kumar has received research support from Alexza. The institution of Dr. Kumar has received research support from SparkNeuro. The institution of Dr. Kumar has received research support from Praxis. The institution of Dr. Kumar has received research support from Scion Neurostim. The institution of Dr. Kumar has received research support from Cognition Therapeutics. The institution of Dr. Kumar has received research support from Eli Lilly. Dr. Kumar has received personal compensation in the range of $100,000-$499,999 for serving as a Medical Director with CenExel RMCR. Dr. Kumar has received personal compensation in the range of $1,000,000+ for serving as a Managing Member with Research Catalyst, LLC. Dr. Lynch has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Vigil Neuroscience. Dr. Orthmann Murphy has received research support from Conrad N. Hilton Foundation. Dr. Orthmann Murphy has received research support from Institute for Translational Medicine and Therapeutics' (ITMAT) Transdisciplinary Program in Translational Medicine and Therapeutics, University of Pennsylvania. The institution of Dr. Orthmann Murphy has received research support from Vigil Neurosciences. The institution of Dr. Orthmann Murphy has received research support from National MS Society. Dr. Orthmann Murphy has received personal compensation in the range of $500-$4,999 for serving as a Invited Speaker with Temple University . Dr. Orthmann Murphy has received personal compensation in the range of $0-$499 for serving as a Consultant with American Neurological Association. Dr. Schols has received personal compensation in the range of $500-$4,999 for serving as a Consultant for VICO Therapeutics. Dr. Schols has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis. The institution of Dr. Schols has received research support from Vigil. The institution of Nicole Wolf has received research support from ZonMW. Andreas Meier has received personal compensation for serving as an employee of Voyager Therapeutics. Andreas Meier has received personal compensation for serving as an employee of Biogen. Dr. Papapetropoulos has received personal compensation for serving as an employee of Vigil Neuroscience . Dr. Papapetropoulos has received personal compensation in the range of $100,000-$499,999 for serving as a Consultant for Acadia. Dr. Papapetropoulos has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Ventus Therapeutics Inc. Dr. Papapetropoulos has received personal compensation in the range of $10,000-$49,999 for serving as an officer or member of the Board of Directors for Adamas Pharmaceuticals. Dr. Papapetropoulos has received personal compensation in the range of $10,000-$49,999 for serving as an officer or member of the Board of Directors for Lipocine Inc. Dr. Papapetropoulos has stock in Vigil Neuroscience. Dr. Papapetropoulos has stock in Adamas. Dr. Papapetropoulos has stock in Lipocine. Dr. Wszolek has received personal compensation in the range of $5,000-$9,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Polish Neurological Society/Via Medica.

Background: Prognostic factors for acute myocardial infarction include diabetes mellitus and renal im- pairment (AMI). Few studies, meanwhile, have examined the impact of renal insufficiency in the setting of diabetes and AMI. Here, we looked into the clinical outcomes for individuals with AMI who also had renal impairment and diabetes mellitus. Method: 400 AMI patients (62 ± 12 years; 71% men) were included in this study from March 2022 to February 2023 and divided into 4 groups as follows: Group I (n = 100) did not have either diabetes or renal insufficiency (glomerular filtration rate [GFR] 50 ml/min/1.72m2), Group II (n = 100) did not have either condition, Group III (n = 100) did not have either condition but did have renal insufficiency, and Group IV (n = 100) did. Major adverse cardiac events included myocardial infarction, target lesion revascularization, and coronary artery bypass graft. Results: 180 (18.1%) patients experienced the primary objectives. In terms of composite MACE, there were differences between the 4 groups that were statistically significant (Group I: 12.4%; Group II: 15.6%; Group III: 30.4%; Group IV: 36.6%; p <0.002). The 12-month mortality increased stepwise from Group III to IV as compared with Group I in a Cox proportional hazards model after multiple covariates were taken into account (hazard ratio [HR], 1.95; 95% confidence interval [CI], 1.33-2.85; p = 0.002; and HR, 2.41; 95% CI, 1.61-3.61; p <0.002, respectively). However, Kaplan-Meier analysis found no significant difference between Group III and IV in the chance of mortality at 1 year (p = 0.287). Conclusion: Composite MACE is linked to renal insufficiency, particularly in conjunction with diabetes, and implies a bad prognosis in individuals with AMI. Patients with diabetes and/or renal insufficiency are classified, which is useful data for early risk stratification of AMI patients.

Objective: Tardive dyskinesia (TD) is a movement disorder that can negatively affect health-related quality of life. However, the impact of TD is not necessarily dependent solely on the objective severity of TD movements. There is currently no easy-to-use, standardized, clinician-rated assessment of the impact of TD on functioning. The aim of this consensus panel was to develop a scale (Impact-TD scale) to assess the impact of TD on patients' daily functioning in practice settings.Participants: Nine health care professionals with expertise in TD and clinical scale development met to discuss how TD negatively impacts the functional activities of patients.Evidence: This panel comprised 7 individuals from a previous panel that developed recommendations on the importance of optimally assessing the functional impact of TD. The previous panel published a narrative literature review that summarized the existing approaches to assess the impact of TD in clinical research and practice.Consensus Process: A modified Delphi process was used to assess agreement on the format and content of the Impact-TD scale. The panel discussed key features of the Impact-TD scale (ie, simplicity, usability, assessment of frequency of impact versus interference/distress). The scale aimed to describe specific consequences of TD symptoms with which patients may have difficulty.Conclusions: Consensus was reached on a list of consequences of TD symptoms that have a functional impact and were categorized in 4 functional domains: social, psychological/psychiatric, physical, and vocational/educational/recreational. The Impact-TD scale offers an easy-to-use clinical scale to measure the functional impact of TD in practice settings.

BACKGROUNDParkinson disease (PD) is associated with α-synuclein (αS) aggregation within enteric neurons. ENT-01 inhibits the formation of αS aggregates and improved constipation in an open-label study in patients with PD.OBJECTIVETo evaluate the safety and efficacy of oral ENT-01 for constipation and neurologic symptoms in patients with PD and constipation.DESIGNRandomized, placebo-controlled phase 2b study. (ClinicalTrials.gov: NCT03781791).SETTINGOutpatient.PATIENTS150 patients with PD and constipation.INTERVENTIONENT-01 or placebo daily for up to 25 days. After baseline assessment of constipation severity, daily dosing was escalated to the prokinetic dose, the maximum dose (250 mg), or the tolerability limit, followed by a washout period.MEASUREMENTSThe primary efficacy end point was the number of complete spontaneous bowel movements (CSBMs) per week. Neurologic end points included dementia (assessed using the Mini-Mental State Examination [MMSE]) and psychosis (assessed using the Scale for the Assessment of Positive Symptoms adapted for PD [SAPS-PD]).RESULTSThe weekly CSBM rate increased from 0.7 to 3.2 in the ENT-01 group versus 0.7 to 1.2 in the placebo group (P < 0.001). Improvement in secondary end points included SBMs (P = 0.002), stool consistency (P < 0.001), ease of passage (P = 0.006), and laxative use (P = 0.041). In patients with dementia, MMSE scores improved by 3.4 points 6 weeks after treatment in the ENT-01 group (n = 14) versus 2.0 points in the placebo group (n = 14). Among patients with psychosis, SAPS-PD scores improved from 6.5 to 1.7 six weeks after treatment in the ENT-01 group (n = 5) and from 6.3 to 4.4 in the placebo group (n = 6). ENT-01 was well tolerated, with no deaths or drug-related serious adverse events. Adverse events were predominantly gastrointestinal, including nausea (34.4% [ENT-01] vs. 5.3% [placebo]; P < 0.001) and diarrhea (19.4% [ENT-01] vs. 5.3% [placebo]; P = 0.016).LIMITATIONLonger treatment periods need to be investigated in future studies.CONCLUSIONENT-01 was safe and significantly improved constipation.PRIMARY FUNDING SOURCEEnterin, Inc.

Aims Coronavirus disease 2019 (COVID-19) is associated with higher rates of psychiatric morbidity due to various factors, including quarantine, social isolation, stigma, financial difficulties and direct and indirect central nervous system impact of severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2). This study aimed to describe the psychiatric morbidity of patients with COVID-19 referred to liaison psychiatry services in Qatar. Method This study was a retrospective review of patient records of the first 100 consecutive SARS-Cov-2 positive patients referred to liaison psychiatry services. The study was approved by the Hamad Medical Corporation Institutional Review Board (IRB) (MRC-05–072). Data were analysed using descriptive statistics. Result The majority (n = 92) of 100 included patients were male and median age was 43 years. Patients were of diverse background with majority of South Asian (Indian, Pakistani, Bengali, Nepalese, and Afghan) (n = 60), followed by Qatari (n = 18) background. Mean length of hospital stay was 26.51 days. 35 patients had severe or critical COVID-19 pneumonia, and 67 had at least one underlying physical comorbidity. Significant psychosocial stressors other than positive SARS-Cov-2 status, including lockdown, quarantine, finances and relationships issues were identified in 48 patients. A total of 35 patients had a positive past psychiatric history, out of which 17 were on maintenance psychotropic medications. Insomnia was the commonest psychiatric symptom (n = 65), followed by anxiety (n = 52), agitation (n = 42), depression (n = 39), changes in appetite (n = 32) and irritability (n = 30). The principal psychiatric diagnoses made were delirium (n = 29), acute stress reaction or adjustment disorder (n = 25), depression (n = 16), mania (n = 15), anxiety (n = 14), non-affective psychosis (n = 13), and dementia (n = 6). Approximately half of the patients with mania or non-affective psychosis had it as their first-onset disorder. Conclusion SARS-CoV-2, in both symptomatic and asymptomatic patients, is associated with a wide range of psychiatric morbidity which emphasizes clinicians’ vigilance for psychiatric symptoms. Insomnia was the commonest neuropsychiatric symptom which may have clinical practice and potential preventive strategies implications. Delirium, the commonest diagnosis in the study carries high morbidity and mortality and may reflect SARS-Cov-2 propensity to affect the brain directly and indirectly through a cytokine storm, organ failure, and prothrombotic state. Patients can also present with new-onset mania or non-affective psychosis. It is noteworthy that about two-thirds of the patients had no past psychiatric history. This study, along with expanding body of evidence may assist with resource allocation and liaison psychiatry services planning. It also underscores the importance of designing future studies to better understand longer-term psychiatric sequelae of COVID-19.

PURPOSE:Tardive dyskinesia (TD) is a hyperkinetic movement disorder in which patients experience abnormal involuntary movements that can have profound negative impacts on physical, cognitive, and psychosocial functioning. Use of measures to assess the functional impact of TD in routine clinical practice is lacking. To address this gap, an advisory panel of experts in psychiatry and movement disorder neurology was convened to develop consensus recommendations on assessment of the impact of TD on patients' functioning that can be used in clinical practice.METHODS:An advisory panel provided recommendations using an iterative process, beginning with a narrative literature review regarding current practices for assessing the impact of TD in clinical settings. A detailed summary was generated, and the advisory panel provided comments about the content and answered questions about assessing TD impact in clinical practice. The panelists' responses were discussed during a virtual meeting held on August 28, 2020. A second meeting on September 25, 2020, focused on developing and refining recommendations for assessment of the impact of TD in clinical practice. At the conclusion of the second meeting, general consensus was reached on all recommendation statements.RESULTS:As part of routine clinical practice, it is imperative to assess the impact of TD on the patient's life to help guide treatment decisions. Key domains for assessing the overall impact of TD include social, physical, vocational, and psychological functioning and the impact of TD on the underlying psychiatric disorder. Assessment of TD impact should be performed at every patient visit. Impact assessments should include consultation with patients, caregivers, and family members. Shared decision-making to initiate TD treatment should consider impact.CONCLUSION:The impact of TD should be assessed routinely, including the key domains of social, physical, vocational, and psychological functioning and the impact of TD on the underlying psychiatric disorder.

significant cognitive impairment.Dementia is the main cause of cognitive impairment among people aged 65 years and over.The prevalence of dementia increases with age.It is essential to differentiate dementia from other clinical states like mild cognitive impairment (MCI) and other prevalent mental health conditions like depression.Dementia is a clinical syndrome that many diseases can cause.The onset and progression vary depending on the etiology, but onset is usually insidious with slow progression.Dementia often remains a hidden problem, more so in societies with low public awareness about dementia.Often, people with mild to moderate dementia do not get identified.Clinical recognition of dementia is easier in the clinical setting when its severity is moderate or severe.However, the diagnosis can be challenging in the case of MCI and mild dementia.As dementia impacts the individual's mental capacity, a thorough understanding of the implications of such impairments is necessary to clarify the issues related to the application of the current Indian laws.

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BACKGROUND:The effectiveness and portability of the collaborative care model in the primary care treatment of depression has not been demonstrated in many randomized controlled trials in healthcare settings across the world. We determined the effectiveness of collaborative care management of elderly depression in the primary care setting in Singapore.METHOD:Eligible participants with depressive symptoms were randomized to 6-month duration usual care (UC, N = 112) or collaborative care (CC, N = 102). Outcome measures were HDRS-17, GDS, BDI and SF-12 MCS QOL measured at 3, 6, and 12-month, care satisfaction at 6-month, and also measured on 120 participants who refused referral (non-receipt of care, NC). Primary outcome was HDRS-17 measure of depression severity, response and remission at 6-month.RESULTS:HDRS scores in CC group compared to UC group were reduced more at 6-month (1.5 points difference in change from baseline), and also at 3 and 12-month, with similar observations of differences for GDS and BDI. There was significantly greater improvement for both CC and UC groups compared to NC group. The CC group was about 1.5 times more likely to show HDRS treatment response and remission, and more than two times likely to show GDS treatment response and remission than the UC and NC groups, as well as better quality of life improvement (P < .001) and better care satisfaction (P < .001).CONCLUSION:Collaborative care is effective for primary care treatment of older persons with depression and is portable in diverse health care settings.

Highlights This prospective study is one of the largest clinical trials in essential tremor to date. Study findings suggest that individualized non-invasive neuromodulation therapy used repeatedly at home over three months results in safe and effective hand tremor reduction and improves quality of life for many essential tremor patients. Background: Two previous randomized, controlled, single-session trials demonstrated efficacy of non-invasive neuromodulation therapy targeting the median and radial nerves for reducing hand tremor. This current study evaluated efficacy and safety of the therapy over three months of repeated home use. Methods: This was a prospective, open-label, post-clearance, single-arm study with 263 patients enrolled across 26 sites. Patients were instructed to use the therapy twice daily for three months. Pre-specified co-primary endpoints were improvements on clinician-rated Tremor Research Group Essential Tremor Rating Assessment Scale (TETRAS) and patient-rated Bain & Findley Activities of Daily Living (BF-ADL) dominant hand scores. Other endpoints included improvement in the tremor power detected by an accelerometer on the therapeutic device, Clinical and Patient Global Impression scores (CGI-I, PGI-I), and Quality of Life in Essential Tremor (QUEST) survey. Results: 205 patients completed the study. The co-primary endpoints were met (p << 0.0001), with 62% (TET-RAS) and 68% (BF-ADL) of 'severe' or 'moderate' patients improving to 'mild' or 'slight'. Clinicians (CGI-I) reported improvement in 68% of patients, 60% (PGI-I) of patients reported improvement, and QUEST improved (p = 0.0019). Wrist-worn accelerometer recordings before and after 21,806 therapy sessions showed that 92% of patients improved, and 54% of patients experienced >= 50% improvement in tremor power. Device-related adverse events (e.g., wrist discomfort, skin irritation, pain) occurred in 18% of patients. No device-related serious adverse events were reported. Discussion: This study suggests that non-invasive neuromodulation therapy used repeatedly at home over three months results in safe and effective hand tremor reduction in many essential tremor patients.