Dementia with Lewy bodies: Impact of co‐pathologies and implications for clinical trial design

Toledo, Jon B.; Abdelnour, Carla; Weil, Rimona S; Ferreira, Daniel; Rodríguez‐Porcel, Federico; Pilotto, Andrea; Wyman‐Chick, Kathryn A.; Grothe, Michel J.; Kane, Joseph; Taylor, Angela; Rongve, Arvid; Scholz, Sonja W.; Leverenz, James B.; Boeve, Bradley F.; Aarsland, Dag; McKeith, Ian; Lewis, Simon J.G.; Leroi, Iracema

doi:10.1002/alz.12814

Cited by 18 publications

(19 citation statements)

References 172 publications

(462 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…More than half of DLB clinical trials have used biomarkers, more often for outcome measures than to support patient selection. There is growing recognition of the heterogenous neuropathological footprint in DLB, with copathology present in most patients, and the use of biomarkers as inclusion criteria is likely to be of increasing relevance [32]. Selection of participants based on biomarkers may be particularly beneficial for DMTs aim to target specific neuropathologies.…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2023

Self Cite

View full text Add to dashboard Cite

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

show abstract

Section: Discussionmentioning

confidence: 99%

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

et al. 2023

Self Cite

View full text Add to dashboard Cite

show abstract

“…88 Co-pathology is common in the dementia post mortem studies, and there is evidence that the presence of co-pathology can influence clinical presentation. 89 The influence of AD and other co-pathologies on clinical presentation and disease progression in MCI-LB should be investigated.…”

Section: Recommendationsmentioning

confidence: 99%

Research diagnostic criteria for mild cognitive impairment with Lewy bodies: A systematic review and meta‐analysis

Donaghy

Carrarini

Ferreira

et al. 2023

Alzheimer's & Dementia

Self Cite

View full text Add to dashboard Cite

Introduction Operationalized research criteria for mild cognitive impairment with Lewy bodies (MCI‐LB) were published in 2020. The aim of this systematic review and meta‐analysis was to review the evidence for the diagnostic clinical features and biomarkers in MCI‐LB set out in the criteria. Methods MEDLINE, PubMed, and Embase were searched on 9/28/22 for relevant articles. Articles were included if they presented original data reporting the rates of diagnostic features in MCI‐LB. Results Fifty‐seven articles were included. The meta‐analysis supported the inclusion of the current clinical features in the diagnostic criteria. Evidence for striatal dopaminergic imaging and meta‐iodobenzylguanidine cardiac scintigraphy, though limited, supports their inclusion. Quantitative electroencephalogram (EEG) and fluorodeoxyglucose positron emission tomography (PET) show promise as diagnostic biomarkers. Discussion The available evidence largely supports the current diagnostic criteria for MCI‐LB. Further evidence will help refine the diagnostic criteria and understand how best to apply them in clinical practice and research. Highlights A meta‐analysis of the diagnostic features of MCI‐LB was carried out. The four core clinical features were more common in MCI‐LB than MCI‐AD/stable MCI. Neuropsychiatric and autonomic features were also more common in MCI‐LB. More evidence is needed for the proposed biomarkers. FDG‐PET and quantitative EEG show promise as diagnostic biomarkers in MCI‐LB.

show abstract

“…Dementia with Lewy bodies (DLB) is a complex, heterogeneous, neurodegenerative dementia, with misfolded α-synuclein forming Lewy bodies (LB) and Lewy neurites as the neuropathological hallmark [1]. Clinical features are variable but a diagnosis of probable DLB requires the presence of dementia and two core features among recurrent visual hallucinations (VH), fluctuating cognition, REM sleep behaviour disorder (RBD) and parkinsonism.…”

Section: Introductionmentioning

confidence: 99%

Clinical trials in dementia with Lewy bodies: the evolving concept of co-pathologies, patient selection and biomarkers

Gibson

Abdelnour

Chong

et al. 2023

Current Opinion in Neurology

Self Cite

View full text Add to dashboard Cite

Purpose of review Currently, no disease modifying therapies (DMTs) have been approved for use in dementia with Lewy bodies (DLB). Clinical trials face difficulties due to the clinical and neuropathological heterogeneity of the condition with a diverse array of neuropathogenic mechanisms contributing to the clinical phenotype. The purpose of this review is to describe how recent advances in the development of biofluid biomarkers may be used in clinical trials to tackle some of these challenges. Recent findings Biomarkers are essential both to support the accurate diagnosis of DLB and to delineate the influence of coexisting pathologies. Recent advances in the development of α-synuclein seeding amplification assays (SAA) allow accurate identification of α-synuclein from the prodromal stages in DLB. Additionally, validation of plasma phosphorylated tau assays in DLB is ongoing and offers an accessible biomarker to indicate the existence of AD co-pathology. Use of biomarkers for diagnosis and group stratification in clinical trials of DLB is growing and likely to be of increasing importance in the future. Summary In vivo biomarkers can enhance patient selection in clinical trials allowing greater diagnostic accuracy, a more homogeneous trial population, and stratification by co-pathology to create subgroups most likely to derive therapeutic benefit from DMTs.

show abstract

Dementia with Lewy bodies: Impact of co‐pathologies and implications for clinical trial design

Cited by 18 publications

References 172 publications

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

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

Research diagnostic criteria for mild cognitive impairment with Lewy bodies: A systematic review and meta‐analysis

Clinical trials in dementia with Lewy bodies: the evolving concept of co-pathologies, patient selection and biomarkers

Contact Info

Product

Resources

About