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Lewy bodies dementia

L Raposo Rodríguez, D J Tovar Salazar, N Fernández García, L Pastor Hernández, Ó Fernández Guinea
OBJECTIVE: To describe and illustrate the key findings on structural magnetic resonance imaging (MRI) in the most common dementias of neurodegenerative origin: Alzheimer's disease, vascular dementia, dementia with Lewy bodies, variants of frontotemporal dementia, progressive supranuclear palsy, variants of multiple system atrophy, Parkinson dementia, and corticobasal degeneration. CONCLUSION: Today the role of MRI is no longer limited to ruling out underlying causes of cognitive deterioration...
June 11, 2018: Radiología
Koji Kasanuki, Keith A Josephs, Tanis J Ferman, Melissa E Murray, Shunsuke Koga, Takuya Konno, Nobutaka Sakae, Adam Parks, Ryan J Uitti, Jay A Van Gerpen, Neill R Graff-Radford, Zbigniew K Wszolek, Dennis W Dickson
OBJECTIVE: To describe clinical and pathologic characteristics of diffuse Lewy body disease (DLBD) manifesting as corticobasal syndrome (CBS). METHODS: In 523 autopsy-confirmed cases of DLBD, we identified 11 patients diagnosed with CBS. For comparison, we studied 22 DLBD brains with antemortem presentation of dementia with Lewy bodies (DLB). Given previous studies suggesting the importance of pathology in peri-Rolandic cortices in CBS, we used digital pathology to count Lewy bodies and to quantify intracytoplasmic and neuritic α-synuclein and phospho-tau burden in the motor cortex...
June 13, 2018: Neurology
Laia Perez-Roca, Cristina Adame-Castillo, Jaume Campdelacreu, Lourdes Ispierto, Dolores Vilas, Ramon Rene, Ramiro Alvarez, Jordi Gascon-Bayarri, Maria A Serrano-Munoz, Aurelio Ariza, Katrin Beyer
Parkinson disease (PD) and dementia with Lewy bodies (DLB) are Lewy body diseases characterized by abnormal alpha-synuclein deposits and overlapping pathological features in the brain. Several studies have shown that glucocerebrosidase (GBA) deficiency is involved in the development of LB diseases. Here, we aimed to find out if this deficiency starts at the transcriptional level, also involves alternative splicing, and if GBA expression changes in brain are also detectable in blood of patients with LB diseases...
April 2018: Aging and Disease
Estrella Morenas-Rodríguez, Isabel Sala, Andrea Subirana, Elba Pascual-Goñi, MaBelén Sánchez-Saudinós, Daniel Alcolea, Ignacio Illán-Gala, María Carmona-Iragui, Roser Ribosa-Nogué, Valle Camacho, Rafael Blesa, Juan Fortea, Alberto Lleó
BACKGROUND: Dementia with Lewy bodies (DLB) is a heterogeneous disease in which clinical presentation, symptoms, and evolution widely varies between patients. OBJECTIVE: To investigate the existence of clinical subtypes in DLB based on the initial clinical presentation. METHODS: 81 patients with a clinical diagnosis of probable DLB were consecutively included. All patients underwent a neurological evaluation including a structured questionnaire about neuropsychiatric symptoms and sleep, an assessment of motor impairment (Unified Parkinson Disease Rating Scale subscale III), and a formal neuropsychological evaluation...
June 4, 2018: Journal of Alzheimer's Disease: JAD
Marialuisa Quadri, Wim Mandemakers, Martyna M Grochowska, Roy Masius, Hanneke Geut, Edito Fabrizio, Guido J Breedveld, Demy Kuipers, Michelle Minneboo, Leonie J M Vergouw, Ana Carreras Mascaro, Ekaterina Yonova-Doing, Erik Simons, Tianna Zhao, Alessio B Di Fonzo, Hsiu-Chen Chang, Piero Parchi, Marta Melis, Leonor Correia Guedes, Chiara Criscuolo, Astrid Thomas, Rutger W W Brouwer, Daphne Heijsman, Angela M T Ingrassia, Giovanna Calandra Buonaura, Janneke P Rood, Sabina Capellari, Annemieke J Rozemuller, Marianna Sarchioto, Hsin Fen Chien, Nicola Vanacore, Simone Olgiati, Yah-Huei Wu-Chou, Tu-Hsueh Yeh, Agnita J W Boon, Susanne E Hoogers, Mehrnaz Ghazvini, Arne S IJpma, Wilfred F J van IJcken, Marco Onofrj, Paolo Barone, David J Nicholl, Andreas Puschmann, Michele De Mari, Anneke J Kievit, Egberto Barbosa, Giuseppe De Michele, Danielle Majoor-Krakauer, John C van Swieten, Frank J de Jong, Joaquim J Ferreira, Giovanni Cossu, Chin-Song Lu, Giuseppe Meco, Pietro Cortelli, Wilma D J van de Berg, Vincenzo Bonifati
BACKGROUND: Most patients with Parkinson's disease, Parkinson's disease dementia, and dementia with Lewy bodies do not carry mutations in known disease-causing genes. The aim of this study was to identify a novel gene implicated in the development of these disorders. METHODS: Our study was done in three stages. First, we did genome-wide linkage analysis of an Italian family with dominantly inherited Parkinson's disease to identify the disease locus. Second, we sequenced the candidate gene in an international multicentre series of unrelated probands who were diagnosed either clinically or pathologically with Parkinson's disease, Parkinson's disease dementia, or dementia with Lewy bodies...
June 6, 2018: Lancet Neurology
Min Seung Kim, Jung Han Yoon, Ji Man Hong
OBJECTIVE: Our study aimed to investigate whether heart rate variability (HRV) could be a useful diagnostic screening tool at MCI (mild cognitive impairment) stage of Dementia with Lewy bodies (DLB) from Alzheimer's disease (AD). METHODS: This retrospective study used a selected sample from Ajou neurological registry. We identified MCI patients who underwent HRV testing at baseline, and who developed probable DLB (MCI-DLB: n = 23) or AD (MCI-AD: n = 32)...
May 29, 2018: Clinical Neurophysiology: Official Journal of the International Federation of Clinical Neurophysiology
Daniel A Barone, Claire Henchcliffe
Rapid eye movement (REM) sleep behavior disorder (RBD) involves REM sleep without atonia in conjunction with a recurrent nocturnal dream enactment behavior, with vocalizations such as shouting and screaming, and motor behaviors such as punching and kicking. Secondary RBD is well described in association with neurological disorders including Parkinson's disease (PD), multiple system atrophy (MSA), and other conditions involving brainstem structures such as tumors. However, RBD alone is now considered to be a potential harbinger of later development of neurodegenerative disorders, in particular PD, MSA, dementia with Lewy bodies (DLB), and pure autonomic failure...
May 29, 2018: Clinical Neurophysiology: Official Journal of the International Federation of Clinical Neurophysiology
Olivier Bousiges, Frédéric Blanc
Dementia with Lewy body (DLB) is the second most common form of dementia after Alzheimer's disease (AD), accounting for 15% to 20% of neuropathologically defined cases. Two-thirds of the patients affected are not or misdiagnosed. In this review, we evaluate the discriminatory power of cerebrospinal fluid (CSF) biomarkers by focusing more specifically on differential diagnosis between DLB and AD. Thus, among the AD biomarkers (t-Tau, phospho-Tau181 , Aβ42 and Aβ40) used routinely, t-Tau and phospho-Tau181 have shown excellent discrimination whatever the clinical stages severity...
June 1, 2018: Gériatrie et Psychologie Neuropsychiatrie du Vieillissement
Ryan A Townley, Hugo Botha, Jonathan Graff-Radford, Bradley F Boeve, Ronald C Petersen, Matthew L Senjem, David S Knopman, Val Lowe, Clifford R Jack, David T Jones
Background: Idiopathic normal pressure hydrocephalus (iNPH) is an important and treatable cause of neurologic impairment. Diagnosis is complicated due to symptoms overlapping with other age related disorders. The pathophysiology underlying iNPH is not well understood. We explored FDG-PET abnormalities in iNPH patients in order to determine if FDG-PET may serve as a biomarker to differentiate iNPH from common neurodegenerative disorders. Methods: We retrospectively compared 18 F-FDG PET-CT imaging patterns from seven iNPH patients (mean age 74 ± 6 years) to age and sex matched controls, as well as patients diagnosed with clinical Alzheimer's disease dementia (AD), Dementia with Lewy Bodies (DLB) and Parkinson's Disease Dementia (PDD), and behavioral variant frontotemporal dementia (bvFTD)...
2018: NeuroImage: Clinical
Christian Hohenfeld, Cornelius J Werner, Kathrin Reetz
Biomarkers in whichever modality are tremendously important in diagnosing of disease, tracking disease progression and clinical trials. This applies in particular for disorders with a long disease course including pre-symptomatic stages, in which only subtle signs of clinical progression can be observed. Magnetic resonance imaging (MRI) biomarkers hold particular promise due to their relative ease of use, cost-effectiveness and non-invasivity. Studies measuring resting-state functional MR connectivity have become increasingly common during recent years and are well established in neuroscience and related fields...
2018: NeuroImage: Clinical
S Gauthier, H Zhang, K P Ng, T A Pascoal, P Rosa-Neto
Background: The NIA-AA research framework proposes a biological definition of Alzheimer's disease, where asymptomatic persons with amyloid deposition would be considered as having this disease prior to symptoms. Discussion: Notwithstanding the fact that amyloid deposition in isolation is not associated with dementia, even the combined association of amyloid and tau pathology does not inevitably need to dementia over age 65. Other pathological factors may play a leading or an accelerating role in age-associated cognitive decline, including vascular small vessel disease, neuroinflammation and Lewy Body pathology...
2018: Translational Neurodegeneration
R C Hamdy, A Kinser, Tracey Kendall-Wilson, A Depelteau, R Copeland, K Whalen, J Culp
Visual well-formed hallucinations, fluctuations in the level of cognition, and alertness and extrapyramidal signs are core features of dementia with Lewy bodies. Some patients realize that what they are seeing or hearing are just hallucinations and learn to accept them. Others, however experience these hallucinations as quite real and cannot be dissuaded from the firm belief that they are. In fact, efforts to dissuade them often serve only to confirm the often associated paranoid delusions and this may lead to a catastrophic ending...
January 2018: Gerontology & Geriatric Medicine
Suzanne Chartier, Charles Duyckaerts
Misfolded α-synuclein accumulates in histological inclusions constituting "Lewy pathology" found in idiopathic Parkinson disease, Parkinson disease dementia and dementia with Lewy body. The mechanism inducing α-synuclein misfolding is still unknown. The misfolded molecules form oligomers that organize into fibrils. α-Synuclein fibrils, in vitro, are capable of initiating an auto-replicating process, transforming normal molecules into misfolded molecules that aggregate. Fibrils can cross the neuronal membrane and recruit α-synuclein molecules in connected neurons...
June 5, 2018: Cell and Tissue Research
Cindy Chi-Ching Pang, Clemens Kiecker, John T O'Brien, Wendy Noble, Raymond Chuen-Chung Chang
The hippocampus has a critical role in cognition and human memory and is one of the most studied structures in the brain. Despite more than 400 years of research, little is known about the Ammon's horn region cornu ammonis 2 (CA2) subfield in comparison to other subfield regions (CA1, CA3, and CA4). Recent findings have shown that CA2 plays a bigger role than previously thought. Here, we review understanding of hippocampus and CA2 ontogenesis, together with basic and clinical findings about the potential role of this region in neurodegenerative disease...
June 1, 2018: Neuroscientist: a Review Journal Bringing Neurobiology, Neurology and Psychiatry
Maria Paraskevaidi, Camilo L M Morais, Diane E Halliwell, David M A Mann, David Allsop, Pierre L Martin-Hirsch, Francis Luke Martin
Accurate identification of Alzheimer's disease (AD) is still of major clinical importance considering the current lack of non-invasive and low-cost diagnostic approaches. Detection of early-stage AD is particularly desirable as it would allow early intervention and/or recruitment of patients into clinical trials. There is also an unmet need for discrimination of AD from dementia with Lewy bodies (DLB), as many cases of the latter are misdiagnosed as AD. Biomarkers based on a simple blood test would be useful in research and clinical practice...
June 4, 2018: ACS Chemical Neuroscience
John J Hanfelt, Limin Peng, Felicia C Goldstein, James J Lah
Given the importance of identifying prodromes of dementia with specific etiologies, we assessed whether seven latent classes of mild cognitive impairment (MCI), defined empirically based on cognitive, functional, and neuropsychiatric information at initial visit, are associated with distinct clinical outcomes and neuropathological features. We separated 6034 participants with a baseline diagnosis of MCI into seven latent classes using previously defined criteria. We found that these latent classes of MCI differed significantly in their clinical outcomes, survival time, and neuropathology...
May 31, 2018: Neurobiology of Disease
David F Tang-Wai, Morris Freedman
PURPOSE OF REVIEW: This article presents a clinically useful approach to obtaining the history and performing the mental status examination of patients with cognitive, language, or behavioral problems. RECENT FINDINGS: Laboratory and imaging biomarkers are being developed for accurate diagnosis of neurobehavioral disorders, yet few are currently available for clinical use. Moreover, not all centers have access to these potential tools. Practicing clinicians are therefore left primarily with their skills of history taking and examination...
June 2018: Continuum: Lifelong Learning in Neurology
Kai Li, Wen Su, Shu-Hua Li, Ying Jin, Hai-Bo Chen
Cognitive impairment is a common disabling symptom in PD. Unlike motor symptoms, the mechanism underlying cognitive dysfunction in Parkinson's disease (PD) remains unclear and may involve multiple pathophysiological processes. Resting state functional magnetic resonance imaging (rs-fMRI) is a fast-developing research field, and its application in cognitive impairments in PD is rapidly growing. In this review, we summarize rs-fMRI studies on cognitive function in PD and discuss the strong potential of rs-fMRI in this area...
2018: Parkinson's Disease
Anthony Flamier, Jida El Hajjar, James Adjaye, Karl J Fernandes, Mohamed Abdouh, Gilbert Bernier
Late-onset sporadic Alzheimer's disease (AD) is the most prevalent form of dementia, but its origin remains poorly understood. The Bmi1/Ring1 protein complex maintains transcriptional repression of developmental genes through histone H2A mono-ubiquitination, and Bmi1 deficiency in mice results in growth retardation, progeria, and neurodegeneration. Here, we demonstrate that BMI1 is silenced in AD brains, but not in those with early-onset familial AD, frontotemporal dementia, or Lewy body dementia. BMI1 expression was also reduced in cortical neurons from AD patient-derived induced pluripotent stem cells but not in neurons overexpressing mutant APP and PSEN1...
May 29, 2018: Cell Reports
Yasmine Y Fathy, Allert J Jonker, Ellen Oudejans, Frank Jan J de Jong, Anne-Marie W van Dam, Annemieke J M Rozemuller, Wilma D J van de Berg
AIM: The insular cortex consists of a heterogenous cytoarchitecture and diverse connections and is thought to integrate autonomic, cognitive, emotional, and interoceptive functions to guide behaviour. In Parkinson's disease (PD) and Dementia with Lewy bodies (DLB), it reveals α-synuclein pathology in advanced stages. The aim of this study is to assess the insular cortex cellular and sub-regional vulnerability to α-synuclein pathology in well-characterized PD and DLB subjects. METHODS: We analysed post-mortem insular tissue from 24 donors with incidental Lewy body disease, PD, PD with dementia (PDD), DLB, and age-matched controls...
May 24, 2018: Neuropathology and Applied Neurobiology
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