Clinical outcome measures in dementia with Lewy bodies trials: critique and recommendations

Rodríguez‐Porcel, Federico; Wyman‐Chick, Kathryn A.; Ruiz, Carla Abdelnour; Toledo, Jon B.; Ferreira, Daniel; Urwyler, Prabitha; Weil, Rimona S; Kane, Joseph; Pilotto, Andrea; Rongve, Arvid; Boeve, Bradley F.; Taylor, John‐Paul; McKeith, Ian; Aarsland, Dag; Lewis, Simon J.G.

doi:10.1186/s40035-022-00299-w

Cited by 6 publications

(4 citation statements)

References 200 publications

(173 reference statements)

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“…More detailed neuropsychological testing could further inform brain regions involved in DLB, though the optimal clinical outcome measures in DLB remain unclear. 52,53 Finally, our current study has limited generalizability due to inclusion of predominantly male, White, non-Hispanic individuals.…”

Section: Discussionmentioning

confidence: 95%

Longitudinal Free‐Water Changes in Dementia with Lewy Bodies

Chiu,

Chen,

Wang

et al. 2024

Movement Disorders

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BackgroundDiffusion‐weighted magnetic resonance imaging (dMRI) examines tissue microstructure integrity in vivo. Prior dementia with Lewy bodies (DLB) diffusion tensor imaging studies yielded mixed results.ObjectiveWe employed free‐water (FW) imaging to assess DLB progression and correlate with clinical decline in DLB.MethodsBaseline and follow‐up MRIs were obtained at 12 and/or 24 months for 27 individuals with DLB or mild cognitive impairment with Lewy bodies (MCI‐LB). FW was analyzed using the Mayo Clinic Adult Lifespan Template. Primary outcomes were FW differences between baseline and 12 or 24 months. To compare FW change longitudinally, we included 20 cognitively unimpaired individuals from the Alzheimer's Disease Neuroimaging Initiative.ResultsWe followed 23 participants to 12 months and 16 participants to 24 months. Both groups had worsening in Montreal Cognitive Assessment (MoCA) and Movement Disorder Society‐Unified Parkinson's Disease Rating Scale (MDS‐UPDRS) scores. We found significant FW increases at both time points compared to baseline in the insula, amygdala, posterior cingulum, parahippocampal, entorhinal, supramarginal, fusiform, retrosplenial, and Rolandic operculum regions. At 24 months, we found more widespread microstructural changes in regions implicated in visuospatial processing, motor, and cholinergic functions. Between‐group analyses (DLB vs. controls) confirmed significant FW changes over 24 months in most of these regions. FW changes were associated with longitudinal worsening of MDS‐UPDRS and MoCA scores.ConclusionsFW increased in gray and white matter regions in DLB, likely due to neurodegenerative pathology associated with disease progression. FW change was associated with clinical decline. The findings support dMRI as a promising tool to track disease progression in DLB. © 2024 International Parkinson and Movement Disorder Society.

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Section: Discussionmentioning

confidence: 95%

Longitudinal Free‐Water Changes in Dementia with Lewy Bodies

Chiu,

Chen,

Wang

et al. 2024

Movement Disorders

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“…As noted in previous reviews, most of the clinical outcome measures used for primary endpoints in DLB clinical trials are not diseasespecific nor validated in this population [27], with most of them designed for AD or PD. We identified four instruments for assessing clinical outcome measures specific for DLB: the Dementia Cognitive Fluctuation Scale (DCFS) evaluating cognitive fluctuations to distinguish Lewy body dementias from AD and vascular dementia [28] used in the CST-103/CST-107 trial and various composite scores used in clinical trials of neflamapimod, ATH-1017 (fosgonimeton), and mevidalen.…”

Section: Discussionmentioning

confidence: 97%

Dementia with Lewy Bodies Drug Therapies in Clinical Trials: Systematic Review up to 2022

et al. 2023

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Introduction: Reviews of randomized clinical trials (RCTs) in dementia with Lewy bodies (DLB) are essential for informing ongoing research efforts of symptomatic therapies and potentially disease-modifying therapies (DMTs).Methods: We performed a systematic review of all clinical trials conducted until September 27, 2022, by examining 3 international registries: ClinicalTrials.gov, the European Union Drug Regulating Authorities Clinical Trials Database, and the International Clinical Trials Registry Platform, to identify drugs in trials in DLB. Results: We found 25 agents in 40 trials assessing symptomatic treatments and DMTs for DLB: 7 phase 3, 31 phase 2, and 2 phase 1 trials. We found an active pipeline for drug development in DLB, with most ongoing clinical trials in phase 2. We identified a recent trend

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“…Constellations of DLB symptoms can be used to inform the diagnosis, but the scales used to delineate the presence of symptoms and measure their severity are not optimized for DLB. For example, the routinely used Neuropsychiatric Inventory (NPI) is tuned to detect and measure the severity of a wide variety of hallucinations but not specifically visual hallucinations, a core symptom in DLB 22 – hence the need for better clinical tools to diagnose psychiatric symptoms in DLB. To make matters worse, there is little commonality across examinations used by clinicians – hence the need for standardized neuropsychiatric tools and metrics capable of dealing with DLB's complexities.…”

Section: The Current and Future State Of Lewy Body Dementiamentioning

confidence: 99%

Lewy body dementia: Overcoming barriers and identifying solutions

Agarwal,

Backler,

Bayram

et al. 2024

Alzheimer's & Dementia

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Despite 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.

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Clinical outcome measures in dementia with Lewy bodies trials: critique and recommendations

Cited by 6 publications

References 200 publications

Longitudinal Free‐Water Changes in Dementia with Lewy Bodies

Longitudinal Free‐Water Changes in Dementia with Lewy Bodies

Dementia with Lewy Bodies Drug Therapies in Clinical Trials: Systematic Review up to 2022

Lewy body dementia: Overcoming barriers and identifying solutions

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