Citations

Abstract Background Trials in Lewy body dementia (LBD) rely on scales and measurements created for Alzheimer’s disease and Parkinson’s disease. Industry and regulatory authority stakeholders and LBD triallists have recognised the absence of an LBD‐specific scale as critical unmet need in the drug development pipeline. Heterogeneity in LBD trials design, particularly concerning outcome measures, precludes effective evidence synthesis and data harmonisation. We describe the development of the Lewy Body Dementia‐Domain Rating Scale (LBD‐DRS) and a proposed roadmap for adoption and validation. Method Led by a core working group and steering committee, a three‐round Delphi survey process was used to establish consensus around the conceptual framework and preliminary content of the LBD‐DRS among invited LBD researchers and clinicians. “Consensus” was established when ≥75% of respondents concurred on any survey statement or questions. Result Consensus around the need for an LBD‐specific scale, specifically for use in early LBD, was established. After feedback was received for two early versions of LBD, a third version of LBD‐DRS has been further developed. This third version, and the results of the second Delphi survey round will be presented. A pragmatic approach, favouring an inclusive scoring approach for symptoms has been adopted, recognising that further iterations will be required once field data becomes available. Conclusion After consensus on the conceptual framework and preliminary content is established, the authors will consult with a broader range of stakeholders, including people living with LBD and their care partners, will be required to further develop LBD‐DRS. Engagement with regulatory bodies and the pharmaceutical industry will guide further development before validation studies are pursued.

Abstract Dementia with Lewy bodies (DLB), a progressive neurodegenerative disease with heterogeneous clinical presentations, greatly impacts patients, caregivers, and society. Despite its frequency, diagnosing and treating DLB remains challenging. Advances in in vivo biomarker assays reflecting underlying pathology are improving disease identification, diagnostic accuracy, and therapeutic development for biologically targeted, disease‐modifying agents. Consequently, definitions of Alzheimer's disease and Parkinson's disease (PD) have shifted to focus on pathological changes occurring before clinical features, with proposed frameworks for detecting pathological amyloid and tau, neurodegeneration, and other markers (National Institute on Aging‐Alzheimer's Association) and alpha‐synucleinopathy and dopaminergic degeneration (Neuronal α‐synuclein Disease Integrated Staging System, SynNeurGe). The biological frameworks, particularly those related to alpha‐synuclein (α‐synuclein), have sparked debate about unifying DLB and PD under a single pathobiologic disease. This paper discusses the implications of these biological frameworks for the DLB community, addressing topics regarding multiple pathologies and neurochemical systems, clinical heterogeneity, and functional impairment, and exploring the potential impact on clinical trials and care. Highlights DLB is a progressive neurodegenerative disease with varied clinical presentations. Diagnosing and treating DLB remains challenging despite its frequency. Biological frameworks are reshaping Alzheimer's and Parkinson's definitions. In vivo biomarkers are improving DLB identification and diagnostic accuracy. Debate exists regarding unifying DLB and Parkinson's under one pathobiology.

686 Background: Blue-light cystoscopy (BLC) is an established procedure for use in the diagnosis and surveillance of patients with non-muscle-invasive bladder cancer (NMIBC). It is associated with improved detection rates compared to white light cystoscopy (WLC); however, limited data is available regarding its role in upstaging and/or upgrading when used alongside WLC. The aim of this study is to assess the incidence and features of patients undergoing upstaging and/or risk-group migration with the implementation of BLC. Methods: Using data from the prospective multi-institutional Cysview Registry (2014-2024), patients with NMIBC who underwent transurethral resection or biopsy of bladder tumors were identified. The patients in whom malignant lesions were exclusively detected by BLC, as well as those experiencing an upward change in risk category (as defined by the American Urological Association [AUA] classification) based on BLC findings, were documented. The clinical features of these patients were subsequently reviewed. Results: In this study, 2,854 patients were enrolled, who collectively underwent 4,158 resections and provided 6,432 separate pathology samples. A total of 201 (7%) patients had at least one malignant lesion detected exclusively by BLC while having negative WLC. These lesions (total 335) included carcinoma in-situ (CIS) in 145 (43%), low-grade Ta in 53 (16%), high-grade Ta in 95 (28%), high-grade T1 in 37 (11%), and high-grade T2 in 5 (1%). In patients with multifocal disease, BLC resulted in AUA risk-group upward migration in 66 (2.3%) patients.Theclinical features of these two groups are presented in the table. Taken together, the total rate of upgrading or upstaging using BLC was 9.3%, including migration to low-risk in 1.2%, intermediate-risk in 2.1%, and high-risk in 6%. Conclusions: Using BLC during transurethral resection or biopsy of bladder tumors results in risk group migration in over 9% of patients with NMIBC. This impacts patient management, including the administration of intravesical therapy when it was not initially planned, an extension in the duration of therapy, or the decision to proceed with radical cystectomy. Clinical features of patients with malignant lesions detected by BLC only (A) and those with risk group migration (B). Clinical features A B Age, median (IQR), year 71 (63-76) 71 (61-77) Gender, n (%) Male Female 140 (74)49 (26) 54 (82)12 (18) History of smoking, n (%) 117 (62) 40 (61) Primary occurrence, n (%) 65 (34) 14 (21) History on intravesical therapy, n (%) 92 (49) 40 (61) Urine cytology * , n (%) Positive Suspicious Atypical Negative/NA 33 (17)21 (10)41 (20)106 (53) 13 (20)7 (11)10 (15)36 (54) IQR: interquartile range; NA: not available. *Detected by either voided urine or bladder wash.

Background: Regional analgesia is a critical component of enhanced recovery after surgery pathways for cystectomy, but there is little research comparing different modalities. Transversus abdominis plane block is a well-established procedure used for postoperative regional analgesia, whereas erector spinae plane block is a recently described technique that some contend improves pain control. Objective: We sought to compare these modalities in patients undergoing cystectomy, with primary end points of pain scores and total narcotic utilization measured in morphine milliequivalents. Methods: We retrospectively reviewed 77 consecutive patients who underwent open radical cystectomy. Patients who did not undergo erector spinae plane block or transversus abdominis plane block or who used chronic narcotics were excluded. Pain intensity scores were measured immediately postoperatively and in 24-hour intervals until 72 hours postoperatively. Cumulative narcotic utilization at 72 hours, return to bowel function, and length of stay were measured. Results: Fifty-one patients met inclusion criteria. Seventeen patients underwent erector spinae plane block and 34 transversus abdominis plane block. Erector spinae plane block patients reported lower pain scores immediately postoperatively (P = .046), at 48 hours (P = .019), and 72 hours (P = .019). Erector spinae plane block patients used less narcotics after 72 hours than transversus abdominis plane block patients (median: 62.50 morphine milliequivalents vs 146.25 morphine milliequivalents, P = .008). Conclusions: Compared with transversus abdominis plane block, erector spinae plane block reduced total narcotic utilization by 234% while also reducing subjective patient pain scores. Increased adoption of erector spinae plane block could have major impacts on both clinical outcomes and patient satisfaction in patients undergoing radical cystectomy.

The use of blue light cystoscopy (BLC) has been shown to improve bladder tumor detection. However, data demonstrating the efficacy of BLC across different races are limited. Herein, we aim to evaluate heterogeneity in the characteristics of BLC for the detection of malignant lesions among various races. Clinicopathologic information was collected from patients enrolled in the multi-institutional Cysview® registry (2014–2021) who underwent transurethral resection or biopsy of bladder tumors. Outcome variables included sensitivity and negative and positive predictive values of BLC and white light cystoscopy (WLC) for the detection of malignant lesions among various races. Overall, 2379 separate lesions/tumors were identified from 1292 patients, of whom 1095 (85%) were Caucasian, 96 (7%) were African American, 51 (4%) were Asian, and 50 (4%) were Hispanic. The sensitivity of BLC was higher than that of WLC in the total cohort, as well as in the Caucasian and Asian subgroups. The addition of BLC to WLC increased the detection rate by 10% for any malignant lesion in the total cohort, with the greatest increase in Asian patients (18%). Additionally, the positive predictive value of BLC was highest in Asian patients (94%), while Hispanic patients had the highest negative predictive value (86%). Our study showed that regardless of race, BLC increases the detection of bladder cancer when combined with WLC.

AbstractDespite its high prevalence among dementias, Lewy body dementia (LBD) remains poorly understood with a limited, albeit growing, evidence base. The public‐health burden that LBD imposes is worsened by overlapping pathologies, which contribute to misdiagnosis, and lack of treatments. For this report, we gathered and analyzed public‐domain information on advocacy, funding, research outputs, and the therapeutic pipeline to identify gaps in each of these key elements. To further understand the current gaps, we also conducted interviews with leading experts in regulatory/governmental agencies, LBD advocacy, academic research, and biopharmaceutical research, as well as with funding sources. We identified wide gaps across the entire landscape, the most critical being in research. Many of the experts participated in a workshop to discuss the prioritization of research areas with a view to accelerating therapeutic development and improving patient care. This white paper outlines the opportunities for bridging the major LBD gaps and creates the framework for collaboration in that endeavor.Highlights A group representing academia, government, industry, and consulting expertise was convened to discuss current progress in Dementia with Lewy Body care and research. Consideration of expert opinion,natural language processing of the literature as well as publicly available data bases, and Delphi inspired discussion led to a proposed consensus document of priorities for the field.

AbstractBackgroundNo specific clinical rating scale currently exists for Lewy body dementia (LBD). Clinical rating scales developed for other diseases are therefore used instead for LBD clinical trials. However, these scales are not optimized for LBD and may not sufficiently reflect the complex array of LBD‐related phenomenology, making it more difficult to interpret outcome data from LBD clinical trials.MethodA working group comprised of 14 members bridging various international LBD‐focused research groups was convened to develop the first iteration of the LBD‐DRS with a focus on inclusion of key LBD related symptom domains, ensuring that any scale is mapped to regulatory expectations, and an emphasis on being patient‐centered. This draft was then subsequently presented to a broader stakeholder group (»50 participants) at the International Lewy body Dementia Conference in June 2022 for further feedback, leading to a further iteration of the scale.ResultThe LBD‐DRS has been designed to capture ratings of the frequency and severity of symptoms across the key domains relevant to LBD – cognitive, neuropsychiatric, motor, autonomic and sleep – as well as the functional impact and perceived burden of symptoms for patients and their care partners. An international Delphi exercise is now planned with many LBD‐relevant stakeholders, which will be coupled with workgroup engagement (for example, with patient‐caregiver groups) to further develop the scale with the resulting final draft anticipated for pilot use in the near future.ConclusionsIn this presentation we will elaborate on the development of the scale, key areas that it will cover as well as challenge points and next steps. Upon completion of the development and refinement of the LBD‐DRS, we propose that this scale will have utility as valid and LBD specific outcome measure in LBD clinical trials.

Abstract INTRODUCTION Sex influences neurodegeneration, but it has been poorly investigated in dementia with Lewy bodies (DLB). We investigated sex differences in brain atrophy in DLB using magnetic resonance imaging (MRI). METHODS We included 436 patients from the European‐DLB consortium and the Mayo Clinic. Sex differences and sex‐by‐age interactions were assessed through visual atrophy rating scales ( n = 327; 73 ± 8 years, 62% males) and automated estimations of regional gray matter volume and cortical thickness ( n = 165; 69 ± 9 years, 72% males). RESULTS We found a higher likelihood of frontal atrophy and smaller volumes in six cortical regions in males and thinner olfactory cortices in females. There were significant sex‐by‐age interactions in volume (six regions) and cortical thickness (seven regions) across the entire cortex. DISCUSSION We demonstrate that males have more widespread cortical atrophy at younger ages, but differences tend to disappear with increasing age, with males and females converging around the age of 75. Highlights Male DLB patients had higher odds for frontal atrophy on radiological visual rating scales. Male DLB patients displayed a widespread pattern of cortical gray matter alterations on automated methods. Sex differences in gray matter measures in DLB tended to disappear with increasing age.

AbstractIn Lewy body dementia (LBD), disturbances of sleep and/or arousal including insomnia, excessive daytime sleepiness, rapid eye movement (REM) sleep behavior disorder, obstructive sleep apnea, and restless leg syndrome are common. These disorders can each exert a significant negative impact on both patient and caregiver quality of life; however, their etiology is poorly understood. Little guidance is available for assessing and managing sleep disorders in LBD, and they remain under‐diagnosed and under‐treated. This review aims to (1) describe the specific sleep disorders which occur in LBD, considering their putative or potential mechanisms; (2) describe the history and diagnostic process for these disorders in LBD; and (3) summarize current evidence for their management in LBD and consider some of the ongoing and unanswered questions in this field and future research directions.