11,124 results match your criteria: "Dementia With Lewy Bodies"

Cognitive decline profiles associated with lewy pathology in the context of Alzheimer's disease neuropathologic change.

Alzheimers Res Ther

December 2024

Shiley-Marcos Alzheimer's Disease Research Center, Department of Neurosciences, University of California, San Diego, CA, USA.

Background: Alzheimer's disease neuropathologic change (ADNC) and Lewy pathology (LP) often coexist in cognitively impaired individuals. These pathologies' relative distribution and severity may modify these individuals' clinical presentation, cognitive profile, and prognosis. Therefore, we examined the contributions of LP and concomitant ADNC to disease survival and profiles of cognitive decline in preclinical and clinical stages in a large neuropathologically diagnosed group.

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A recent paper concluded that cholesteryl ester transfer protein (CETP) inhibition may be a viable target to treat dementia, based on human genetic evidence of a protective effect of target inhibition on risk of Lewy body and Parkinson's dementia. Alzheimer's disease, which is by far the most prevalent cause of dementia (around 80% of all dementia cases) was not included as an outcome. Evidence shows CETP inhibition is unlikely to affect Alzheimer's risk and may even potentially modestly increase risk.

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Background: Dementia with Lewy bodies (DLB) and Alzheimer's disease (AD) are common forms of dementia, characterized by overlapping clinical symptoms. Functional neuroimaging can provide valuable information for precise diagnosis. Our objective was to explore cerebral perfusion alterations in DLB and AD, and to determine which perfusion parameters are helpful in distinguishing DLB and AD.

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Dementia with lewy bodies patients with high tau levels display unique proteome profiles.

Mol Neurodegener

December 2024

F.M. Kirby Neurobiology Center, Department of Neurobiology, Boston Children's Hospital, Harvard Medical School, Boston, MA, 02115, USA.

Background: Clinical studies have long observed that neurodegenerative disorders display a range of symptoms and pathological features and, in some cases, overlap, suggesting that these diseases exist on a spectrum. Dementia with Lewy Bodies (DLB), a synucleinopathy, is a prominent example, where symptomatic similarities with tauopathy, Alzheimer's disease, are observed. Although tau pathology has been observed in DLB, the interplay between tau and α-synuclein is poorly understood at a molecular level.

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Aggregation of alpha-synuclein (α-Syn) is implicated in the pathogenesis of several neurodegenerative disorders, such as Parkinson's disease and Dementia with Lewy bodies, collectively termed synucleinopathies. Thus, tremendous efforts are being made to develop strategies to prevent or inhibit α-Syn aggregation. Here, we genetically engineered fission yeast to express human α-Syn C-terminally fused to green fluorescent protein (GFP) at low and high levels.

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Central nervous system parvalbumin-positive interneurons (PV-INs) are crucial and highly vulnerable to various stressors. They also play a significant role in the pathological processes of many neuropsychiatric diseases, especially those associated with cognitive impairment, such as Alzheimer's disease (AD), vascular dementia (VD), Lewy body dementia, and schizophrenia. Although accumulating evidence suggests that the loss of PV-INs is associated with memory impairment in dementia, the precise molecular mechanisms remain elusive.

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Evidence from neuropathological cohorts indicates that a CSF α-synuclein (α-syn) seed amplification assay (SAA) may provide quantitative kinetic parameters correlating with α-syn pathology burden in patients with Lewy body disease (LBD). Studies are needed to assess their longitudinal trend during the pre-symptomatic and clinical disease phases and their correlation with measures of disease progression. We aimed to assess the baseline α-syn CSF SAA kinetic parameters, their longitudinal variations and associations with clinical outcomes in a cohort of longitudinally repeatedly sampled Lewy Body disease patients, including clinically unimpaired (asymptomatic LBD) and neurologically impaired individuals.

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Background: Loss of dorsolateral nigral hyperintensity (DNH) in iron-sensitive sequences of Magnetic Resonance Imaging (MRI), also described as "swallow tail sign" (STS) loss, has shown promising diagnostic value in Parkinson's Disease (PD) and Atypical Parkinsonian Syndromes (APS).

Objective: To conduct a bibliometric analysis on substantia nigra MRI and a systematic review on the clinical utility of STS visual assessment on Susceptibility-Weighted Imaging in various clinical entities.

Methods: VOSviewer's keyword co-occurrence network was employed using Web of Science (WOS).

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Use of Artificial Intelligence in Imaging Dementia.

Cells

November 2024

Division of Neurology, Department of Brain Sciences, Faculty of Medicine, Imperial College London, London W12 0NN, UK.

Alzheimer's disease is the most common cause of dementia in the elderly population (aged 65 years and over), followed by vascular dementia, Lewy body dementia, and rare types of neurodegenerative diseases, including frontotemporal dementia. There is an unmet need to improve diagnosis and prognosis for patients with dementia, as cycles of misdiagnosis and diagnostic delays are challenging scenarios in neurodegenerative diseases. Neuroimaging is routinely used in clinical practice to support the diagnosis of neurodegenerative diseases.

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Isolated rapid-eye-movement sleep behavior disorder (iRBD) is a strong predictor of Parkinson's disease and Dementia with Lewy bodies. Previous studies indicate that cortical atrophy in iRBD patients may be linked to cognitive impairment, but the pattern of atrophy is inconsistently reported. This study aimed to elucidate cortical atrophy patterns in a cognitively unimpaired iRBD cohort, focusing on regions associated with cognitive functions, particularly the cuneus/precuneus, and evaluated the predictive value for future phenoconversion.

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Introduction: Little is known regarding the relationship between anticholinergic medications and frailty in dementia with Lewy bodies (DLB).

Methods: Anticholinergic Cognitive Burden Scale (ACB) and Claims-based Frailty Index scores were calculated for 12 months prior to the dementia diagnosis using electronic medical record and claims data. Logistic regression was used to estimate the association between ACB and odds of frailty.

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Background: Lewy body disorders (LBD), encompassing Parkinson disease (PD), PD dementia (PDD), and dementia with Lewy bodies (DLB), are characterized by alpha-synuclein pathology but often are accompanied by Alzheimer's disease (AD) neuropathological change (ADNC). The medial temporal lobe (MTL) is a primary locus of tau accumulation and associated neurodegeneration in AD. However, it is unclear the extent to which AD copathology in LBD (LBD/AD+) contributes to MTL-specific patterns of degeneration.

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The differential diagnosis of neurocognitive and psychiatric disorders, particularly when symptoms overlap significantly, poses a substantial challenge in clinical practice. Parkinson's disease (PD), Lewy body dementia, and catatonia are distinct conditions that can present with similar motor and cognitive symptoms, complicating accurate diagnosis and effective treatment. We report the case of a 45-year-old male patient who presented for electroconvulsive therapy (ECT) evaluation.

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African ancestry neurodegeneration risk variant disrupts an intronic branchpoint in GBA1.

Nat Struct Mol Biol

December 2024

Center for Alzheimer's and Related Dementias, National Institute on Aging and National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA.

Recently, an African ancestry-specific Parkinson disease (PD) risk signal was identified at the gene encoding glucocerebrosidase (GBA1). This variant ( rs3115534 -G) is carried by ~50% of West African PD cases and imparts a dose-dependent increase in risk for disease. The risk variant has varied frequencies across African ancestry groups but is almost absent in European and Asian ancestry populations.

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From onset to advancement: the temporal spectrum of α-synuclein in synucleinopathies.

Ageing Res Rev

December 2024

Department of Anatomy and Medical Imaging, University of Auckland, Auckland, New Zealand; Centre for Brain Research, University of Auckland, Auckland, 1023, New Zealand; Brain and Mind Centre & Faculty of Medicine and Health School of Medical Sciences, The University of Sydney, Sydney, NSW 2050, Australia. Electronic address:

This review provides an in-depth analysis of the complex role of alpha-synuclein (α-Syn) in the development of α-synucleinopathies, with a particular focus on its structural diversity and the resulting clinical variability. The ability of α-Syn to form different strains or polymorphs and undergo various post-translational modifications significantly contributes to the wide range of symptoms observed in disorders such as Parkinson's disease (PD), dementia with Lewy bodies (DLB), and multiple system atrophy (MSA), as well as in lesser-known non-classical α-synucleinopathies. The interaction between genetic predispositions and environmental factors further complicates α-synucleinopathic disease pathogenesis, influencing the disease-specific onset and progression.

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Neuroanatomical and clinical correlates of prodromal dementia with Lewy bodies: a systematic literature review of neuroimaging findings.

J Neurol

December 2024

Cognitive and Motor Rehabilitation and Neuroimaging Unit, Santa Lucia Foundation (IRCCS Fondazione Santa Lucia), Rome, Italy.

Prodromal Dementia with Lewy bodies (pro-DLB) has been recently defined; however, the neuroanatomical and functional correlates of this stage have not yet been univocally established. This study aimed to systematically review neuroimaging findings focused on pro-DLB. A literature search of works employing MRI, PET, and SPECT was performed.

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What is the future for dementia with Lewy bodies?

J Neurol

December 2024

Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA, USA.

Dementia with Lewy bodies (DLB) is the second most common neurodegenerative dementia after Alzheimer's disease (AD), yet it remains under-recognized and frequently misdiagnosed due to heterogenous clinical presentations, the presence of co-pathology, and the lack of specific diagnostic tools. Pathologically, DLB is characterized by the accumulation of misfolded alpha-synuclein (aSyn) aggregates, known as Lewy bodies. Recent advancements have improved in vivo detection of aSyn pathology through techniques such as seed amplification assays, monoclonal antibodies, and positron emission tomography using novel small-molecule ligands.

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Amygdala-predominant α-synuclein pathology is associated with exacerbated hippocampal neuron loss in Alzheimer's disease.

Brain Commun

December 2024

Laboratory for Neuropathology, Department of Imaging and Pathology, KU Leuven, Leuven 3000, Belgium.

Misfolded α-synuclein protein accumulates in 43-63% of individuals with symptomatic Alzheimer's disease. Two main patterns of comorbid α-synuclein pathology have been identified: caudo-rostral and amygdala-predominant. α-Synuclein aggregates have been shown to interact with the transactive response DNA-binding protein 43 (TDP-43) and abnormally phosphorylated tau protein.

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Introduction: Cardiac sympathetic denervation is specific to Lewy body disease (LBD). In Parkinson's disease (PD), sympathetic denervation in the major salivary glands (parotid glands [PG] and submandibular glands [SMG]) has been demonstrated by I-metaiodobenzylguanidine (MIBG) scintigraphy. We compared sympathetic denervation in the MSG between PD, dementia with Lewy bodies (DLB), and progressive supranuclear palsy (PSP).

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Behavioral variant frontotemporal dementia with pathogenic variant in presenting as dementia with Lewy body disease.

Neurocase

December 2024

Department of Neurology, The Barbara and Maurice Deane Center for Wellness and Cognitive Health, Icahn School of Medicine at Mount Sinai, New York, USA.

A 75-year-old Chinese American man presented to behavioral neurology clinic for a second opinion of dementia with Lewy body disease (DLB). The clinical manifestations met the criteria for a probable DLB diagnosis. Yet, in-depth evaluation unveiled clinical history, family history, and neuroimaging evidences that suggested a diagnosis of behavioral variant frontotemporal dementia (FTD).

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Article Synopsis
  • Single-nucleus RNA-sequencing (snRNA-seq) was used to explore cellular diversity in the human brain, but traditional methods couldn't capture full-length mRNA isoforms due to short-read limitations.
  • The study combined standard snRNA-seq techniques with long-read sequencing to analyze over 165,000 cells from individuals with Alzheimer's, Lewy body dementia, and Parkinson's disease, revealing distinct gene expression changes and a wide variety of mRNA isoforms.
  • This research enhances our understanding of the human prefrontal cortex's transcriptome and suggests that increased mRNA isoform diversity could offer insights into neurodegenerative diseases and potential therapeutic targets.
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Deep learning reveals pathology-confirmed neuroimaging signatures in Alzheimer's, vascular and Lewy body dementias.

Brain

December 2024

Neuroimage Analytics Laboratory and Biggs Institute Neuroimaging Core, Glenn Biggs Institute for Neurodegenerative Disorders, University of Texas Health Science Center at San Antonio, San Antonio, Texas 78229, USA.

Concurrent neurodegenerative and vascular pathologies pose a diagnostic challenge in the clinical setting, with histopathology remaining the definitive modality for dementia-type diagnosis. To address this clinical challenge, we introduce a neuropathology-based, data-driven, multi-label deep learning framework to identify and quantify in-vivo biomarkers for Alzheimer's disease (AD), vascular dementia (VD), and Lewy body dementia (LBD) using antemortem T1-weighted MRI scans of 423 demented and 361 control participants from NACC and ADNI datasets. Based on the best-performing deep learning model, explainable heatmaps are extracted to visualize disease patterns, and the novel Deep Signature of Pathology Atrophy REcognition (DeepSPARE) indices are developed, where a higher DeepSPARE score indicates more brain alterations associated with that specific pathology.

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Primary Progressive Aphasia Lacking Core Features of Nonfluent and Semantic Variants: Clinical, Neuroimaging, and Neuropathologic Features.

Neurology

November 2024

From the Departments of Neurology (H.W., J.R.D., H.C., J.G.-R., K.A.J.), Psychology (M.M.M.), and Radiology (N.T.T.P., V.J.L., J.L.W.), Mayo Clinic, Rochester, MN; and Department of Neuroscience (Neuropathology) (D.W.D.), Mayo Clinic, Jacksonville, FL.

Background And Objectives: Evidence has accumulated that the 2011 consensus criteria for primary progressive aphasia (PPA) do not fully capture features of logopenic variant PPA (lvPPA/LPA). We aimed to examine clinical, neuroimaging, and neuropathologic features of PPA lacking features of nonfluent/semantic variants and to provide practical additions to the 2011 consensus criteria.

Methods: This was a retrospective examination of data from 2 observational cohort studies where patients with PPA were prospectively recruited at Mayo Clinic.

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Decreased urinary excretion of norepinephrine and dopamine in autonomic synucleinopathies.

Clin Auton Res

December 2024

Autonomic Medicine Section (AMS), Clinical Neurosciences Program (CNP), Division of Intramural Research (DIR), National Institute of Neurological Disorders and Stroke (NINDS), National Institutes of Health (NIH), 10 Center Drive MSC-1620, Building 10 Room 8N260, Bethesda, MD, 20892-1620, USA.

Article Synopsis
  • Autonomic synucleinopathies like Parkinson's disease (PD), pure autonomic failure (PAF), and multiple system atrophy (MSA) are characterized by autonomic failure and the abnormal buildup of alpha-synuclein protein in the body. !* -
  • Research showed that patients with these conditions had significantly lower urinary excretion rates of norepinephrine and dopamine compared to controls, suggesting a potential dysfunction in their renal sympathetic function. !* -
  • The study analyzed urine samples from participants at the NIH over nearly three decades and found no significant differences in DOPA and epinephrine levels among the groups, indicating that only norepinephrine and dopamine were impacted by these diseases. !*
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