Lewy body dementia (LBD) is situated at the convergence of neurodegenerative disorders, posing an intricate and diverse clinical dilemma. The accumulation of abnormal protein in the brain, namely, the Lewy body causes disturbances in typical neural functioning, leading to a range of cognitive, motor, and mental symptoms that have a substantial influence on the overall well-being and quality of life of affected individuals. There is no definitive cure for the disease; however, several nonpharmacological and pharmacological modalities have been tried with questionable efficacies. The aim of this study is to figure out the role of different interventional strategies in the disease. Donepezil, rivastigmine, memantine, and galantamine were the commonly used drugs for LBD. Together with that, levodopa, antipsychotics, armodafinil, piracetam, and traditional medications like yokukansan were also used, when indicated. Talking about nonpharmacological measures, exercise, physical therapy, multicomponent therapy, occupational therapy, psychobehavioral modification, transcranial stimulation, and deep brain stimulation have been used with variable efficacies. Talking about recent advances in the treatment of LBD, various disease-modifying therapies like ambroxol, neflamapimod, irsenontrine, nilotinib, bosutinib, vodobatinib, clenbuterol, terazosin, elayta, fosgonimeton, and anle138b are emerging out. However, there drugs are still in the different phases of clinical trials and are not commonly used in clinical practice. With the different pharmacological and nonpharmacological modalities we have for treatment of LBD, all of them offer symptomatic relief only. Being a degenerative disease, definite cure of the disease can only be possible with regenerative measures.
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http://dx.doi.org/10.1097/MS9.0000000000001664 | DOI Listing |
Mov Disord
January 2025
Department of Neurology, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
Background: Central synucleinopathies, including Parkinson's disease (PD), dementia with Lewy bodies (DLB), and multiple system atrophy (MSA), involve alpha-synuclein accumulation and dopaminergic cell loss in the substantia nigra (SN) and locus coeruleus (LC). Pure autonomic failure (PAF), a peripheral synucleinopathy, often precedes central synucleinopathies.
Objectives: To assess early brain involvement in PAF using neuromelanin-sensitive magnetic resonance imaging (NM-MRI) and fluorodopa-positron emission tomography (FDOPA-PET), and to determine whether PAF patients with a high likelihood ratio (LR) for conversion to a central synucleinopathy exhibit reduced NM-MRI contrast in the LC and SN compared with controls and low-LR patients.
Nat Commun
January 2025
NMR Based Structural Biology, Max Planck Institute for Multidisciplinary Sciences, Göttingen, Germany.
Aggregation intermediates play a pivotal role in the assembly of amyloid fibrils, which are central to the pathogenesis of neurodegenerative diseases. The structures of filamentous intermediates and mature fibrils are now efficiently determined by single-particle cryo-electron microscopy. By contrast, smaller pre-fibrillar α-Synuclein (αS) oligomers, crucial for initiating amyloidogenesis, remain largely uncharacterized.
View Article and Find Full Text PDFFree Neuropathol
January 2024
Department of Pathology, Nash Family Department of Neuroscience, Department of Artificial Intelligence & Human Health, Neuropathology Brain Bank & Research CoRE, Ronald M. Loeb Center for Alzheimer's Disease, Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
This review highlights a collection of both diverse and highly impactful studies published in the previous year selected by the author from the neurodegenerative neuropathology literature. As with previous reviews in this series, the focus is, to the best of my ability, to highlight human tissue-based experimentation most relevant to experimental and clinical neuropathologists. A concerted effort was made to balance the selected studies across neurodegenerative disease categories, approaches, and methodologies to capture the breadth of the research landscape.
View Article and Find Full Text PDFAlzheimers Dement (Amst)
January 2025
Biochemistry and Molecular Biology Department Neurodegenerative Pathologies LBMMS Hospices Civils de Lyon Lyon France.
Introduction: Seed amplification assays (SAAs) demonstrate remarkable diagnostic performance in alpha-synucleinopathies. However, existing protocols lack accessibility in routine laboratories, mainly due to the requirement for in-house production of recombinant alpha-synuclein (aSyn). This study proposes a cerebrospinal fluid (CSF) aSyn-SAA protocol using solely commercial reagents to facilitate its clinical implementation.
View Article and Find Full Text PDFGeroscience
January 2025
ICube Laboratory UMR-7357 and FMTS (Fédération de Médecine Translationnelle de Strasbourg), IMIS Team and IRIS Platform, University of Strasbourg and CNRS, Strasbourg, France.
The differential mechanisms between proteinopathies and neurodegeneration in Alzheimer's disease (AD) and dementia with Lewy bodies (DLB) remain unclear. To address this issue, we conducted a voxel-based morphometry and cerebrospinal fluid biomarker (α-synuclein, Aβ42, t-Tau and p-Tau) level correlation study in patients with DLB, AD and mixed cases (AD + DLB). Cerebrospinal fluid samples obtained by lumbar puncture and whole-brain T1-weighted images were collected in the AlphaLewyMA cohort.
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