Citations

Abstract Background Dementia with Lewy bodies (DLB) is a prevalent form of dementia associated with neuronal alpha‐synuclein aggregates (Lewy bodies). Symptoms include cognitive impairment, fluctuations, neuropsychiatric features including psychosis, sleep disorders, and dysautonomia. DLB is the most expensive form of dementia, and there are currently no treatments approved by the US FDA. Given the advent of sensitive and specific in vivo biomarkers for synuclein aggregation, drug developers are increasingly interested in DLB. FDA instituted Patient‐Focused Drug Development (PFDD) meetings in 2012 with the purpose of ensuring that patients’ experiences, perspectives, needs, and preferences are captured and meaningfully incorporated into drug development and evaluation. Method In October 2024, the Lewy Body Dementia Association (LBDA) and the Alzheimer’s Association (ALZ) co‐hosted an externally‐led PFDD (EL‐PFDD) meeting on DLB. Thirty days before the event, LBDA solicited public comment on the lived experience of DLB, the current state of treatment, and what people with DLB value in potential future therapies. During the live meeting, people with DLB, care partners and family members described their experiences and responded to live polling questions. Result The EL‐PFDD was attended by 347 people with DLB and care partners, drug developers (both industry and academic), FDA staff, and NIH staff. Preliminary analysis of the discussion content and survey responses shows several themes emerging from the meeting. The most bothersome and impactful symptoms varied over the course of the disease, but included cognitive impairment and fluctuations, neuropsychiatric symptoms, and sleepiness. Concerns for the future included progressive decline in cognition, changes in behavior/mood, and cost of care. Limitations to current treatments included lack of FDA‐approved medications, and side effects and lack of efficacy associated with “off label” medications. Priorities for future treatments included symptomatic treatments that do not worsen other DLB symptoms, slowing disease progression, accessibility/insurance coverage, and avoiding side effects. Conclusion The EL‐PFDD on DLB provided valuable information for drug developers and regulators to understand the lived experience of people with DLB and care partners. The results will be documented in a “Voice of the Patient” report that will be hosted at www.lbda.org/el‐pfdd .

Background Dementia with Lewy bodies (DLB) is a common degenerative dementia, but no studies investigate bereaved caregiver experiences. Objective To investigate the experiences of caregivers three months after the death of persons with DLB using a mixed-methods approach. Methods Dyads of individuals with moderate-advanced DLB and their primary informal caregivers were followed prospectively every 6 months until the person with DLB died. Caregivers completed a study visit with questionnaires and a semi-structured interview ∼3 months later. Spearman correlation coefficients and Wilcoxon rank-sum tests evaluated the relationships of post-death measures with pre-death patient and caregiver variables. Thematic analysis was used to analyze the interviews. Results Seventy-three caregivers completed visits (mean 3.5 months post-death). Most of the caregivers were women (82.2%) and spouses (76.7%) or adult children (17.8%). Over 40% had scores indicating risk for clinical depression. Post-death caregiver experiences (depression, quality of life, grief, resilience) correlated with pre-death caregiver experiences. Post-death experiences did not associate with patient characteristics, disease-related symptoms, or healthcare services used in the last 6 months of life. Trajectories for caregiver measures from pre- to post-death visits varied widely. Interview themes included grief and sadness, anger, guilt and regret, relief, appreciation/gratitude, and adjusting to a new normal. Conclusions The finding that pre-death caregiving experiences have the strongest association with post-death experiences emphasizes the critical importance of accessible and evidence-based caregiver support before and after the death of a person with DLB. Research is needed to develop interventions for current and bereaved caregivers of individuals with DLB. Trial registration information NCT04829656 (submitted 2021-03-22).

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.

Objectives: Many individuals with dementia with Lewy bodies (DLB) die of disease-related complications, but predicting the end of life can be challenging. We identified a phenotype associated with approaching end of life. Methods: We present 4 exemplar cases where individuals with DLB experienced refractory psychosis before death. We reviewed codebooks and quotes from 3 studies regarding end-of-life experiences in DLB to identify experiences that aligned with this phenotype. Results: In addition to the 4 cases, family caregivers in prior studies described prominent worsening of psychosis before death in some individuals with DLB. The worsening often occurred several months before death and was sometimes associated with rapid deterioration. Worsening psychosis was the prominent symptom and was not initially accompanied by cognitive or physical decline. In many cases, the refractory psychosis resulted in inpatient psychiatric hospitalization or residential care, but these scenarios were challenging because of the individual’s behavior. Conclusion: Refractory psychosis in DLB, particularly out of proportion to other symptoms, may be a signal of approaching the end of life. More research is needed to understand this phenomenon and to develop effective and safe treatments for psychosis in DLB.

AbstractINTRODUCTIONLittle is known regarding quality of life (QoL) in dementia with Lewy bodies (DLB), particularly in advanced stages.METHODSDyads of individuals with moderate–advanced DLB and their primary caregivers were recruited from specialty clinics, advocacy organizations, and research registries. The study collected demographics, disease‐related measures, and measures of patient/caregiver experiences.RESULTSThe Quality of Life in Alzheimer's Disease (QoL‐AD) was completed by the person with DLB and the caregiver (proxy) in 61 dyads; 85 dyads had only a proxy‐completed QoL‐AD. Patient‐ and proxy‐reported scores were moderately correlated (r = 0.57, P < 0.0001). Worse patient‐reported QoL correlated with daytime sleepiness, autonomic symptom burden, and behavioral symptoms. Proxy ratings correlated with dementia severity, daytime sleepiness, behavioral symptoms, dependence in activities of daily living, and caregiver experience measures.DISCUSSIONPatient‐ and proxy‐reported quality of life (QoL) should be assessed separately in advanced DLB. Some symptoms associated with QoL have available therapeutic options. Research is needed regarding strategies to optimally improve QoL in DLB.Highlights Patient and proxy quality of life (QoL) ratings had moderate correlation in advanced dementia with Lewy bodies. Daytime sleepiness affected patient‐ and proxy‐reported QoL. Behavioral symptoms affected patient‐ and proxy‐reported QoL. Autonomic symptom burden affected patient‐reported QoL. Dementia severity, dependence, and caregiver experiences affected proxy ratings.

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.