Review
Cell Biology
Augoustos Tsamourgelis, Peter Swann, Leonidas Chouliaras, John T. O'Brien
Summary: Dementia with Lewy Bodies (DLB) is the second most common neurodegenerative dementia. Proteomics has revealed protein dysregulation in the brain and peripheral tissues in DLB, which shares common features with other dementias but also has unique protein signatures. Identifying novel protein targets and diagnostic biomarkers could lead to new therapeutics and improved clinical trials for DLB.
AGEING RESEARCH REVIEWS
(2023)
Review
Clinical Neurology
Melissa J. Armstrong
Summary: Dementia with Lewy bodies (DLB) is a specific presentation of a pathological alpha-synucleinopathy, with recent advances including updated diagnostic criteria and recognition of prodromal states. Research shows common co-occurrence of Alzheimer's disease pathology in individuals with DLB, impacting biomarker use and progression. Identifying biomarkers and effective therapies remain key areas of focus for future research in DLB.
THERAPEUTIC ADVANCES IN NEUROLOGICAL DISORDERS
(2021)
Article
Clinical Neurology
Monica Gagliardi, Radha Procopio, Giuseppe Nicoletti, Maurizio Morelli, Marco D'Amelio, Aldo Quattrone, Grazia Annesi
Summary: The study aimed to evaluate LRP10 gene mutations in PD and DLB patients from Southern Italy, finding only 2 missense and 3 synonymous variants in patients and control subjects, and a rare variant p.L622F in a PD case. These results indicate that LRP10 mutations are not a common cause of PD and DLB in Southern Italy.
NEUROLOGICAL SCIENCES
(2021)
Article
Clinical Neurology
Kurt A. Jellinger
Summary: PDD and DLB are two major neurocognitive disorders in the spectrum of Lewy body diseases with overlapping clinical and neuropathological features. DLB has higher Braak LB scores and neuritic Braak stages, as well as more severe neuropathological features like Thal A beta phases and neuritic Braak stages. Worse prognosis in DLB is linked to increased Braak neuritic stages and more severe cerebral amyloid angiopathy.
PARKINSONISM & RELATED DISORDERS
(2022)
Review
Clinical Neurology
Rotem Iris Orad, Tamara Shiner
Summary: Dementia with Lewy bodies presents a diagnostic challenge due to clinical overlap with other neurodegenerative conditions, such as Parkinson's disease dementia and Alzheimer's disease. Neuroimaging plays a central role in improving diagnostic accuracy and management of this disorder.
JOURNAL OF NEUROLOGY
(2022)
Article
Clinical Neurology
Martyna M. Grochowska, Ana Carreras Mascaro, Valerie Boumeester, Domenico Natale, Guido J. Breedveld, Hanneke Geut, Wiggert A. van Cappellen, Agnita J. W. Boon, Anneke J. A. Kievit, Esther Sammler, Piero Parchi, Pietro Cortelli, Dario R. Alessi, Wilma D. J. van de Berg, Vincenzo Bonifati, Wim Mandemakers
Summary: Loss-of-function variants in the LRP10 gene are linked to Parkinson's disease, dementia, and other neurodegenerative disorders. LRP10 is highly expressed in astrocytes and interacts with SORL1, potentially playing a crucial role in vesicle trafficking pathways. The specific pattern of LRP10 incorporation into Lewy bodies suggests its involvement in neurodegenerative diseases.
ACTA NEUROPATHOLOGICA
(2021)
Article
Clinical Neurology
Stephen Joza, Michele T. Hu, Ki-Young Jung, Dieter Kunz, Ambra Stefani, Petr Dusek, Michele Terzaghi, Dario Arnaldi, Aleksandar Videnovic, Mya C. Schiess, Wiebke Hermann, Jee-Young Lee, Luigi Ferini-Strambi, Simon J. G. Lewis, Laurene Leclair-Visonneau, Wolfgang H. Oertel, Elena Antelmi, Friederike Sixel-Doering, Valerie Cochen De Cock, Claudio Liguori, Jun Liu, Federica Provini, Monica Puligheddu, Alessandra Nicoletti, Claudio L. A. Bassetti, Jitka Buskova, Yves Dauvilliers, Raffaele Ferri, Jacques Y. Montplaisir, Michael Lawton, Han-Joon Kim, Frederik Bes, Birgit Hoegl, Karel Sonka, Giuseppe Fiamingo, Pietro Mattioli, Maria Lorena Lavadia, Jessika Suescun, Kyung Ah Woo, Sara Marelli, Kaylena Ehgoetz Martens, Annette Janzen, Giuseppe Plazzi, Brit Mollenhauer, Mariana Fernandes, Yuanyuan Li, Pietro Cortelli, Michela Figorilli, Calogero Edoardo Cicero, Carolin Schaefer, Lily Guiraud, Giuseppe Lanza, Jean-Francois Gagnon, Jun-Sang Sunwoo, Abubaker Ibrahim, Nicola Girtler, Claudia Trenkwalder, Luca Baldelli, Amelie Pelletier, Ronald B. Postuma
Summary: The synucleinopathies, such as Parkinson's disease and dementia with Lewy bodies, have a long prodromal period with progressive subclinical symptoms. Idiopathic REM sleep behavior disorder is an early predictor of these diseases and provides an opportunity for intervention with neuroprotective therapy.
Article
Clinical Neurology
Jing Xu, Jia Li, Ya-juan Sun, Wei Quan, Li Liu, Qing-hui Zhang, Yi-dan Qin, Xiao-chen Pei, Hang Su, Jia-jun Chen
Summary: In this study, mRNA expression profiles were analyzed to identify potential biomarkers and mechanisms distinguishing between Parkinson's disease dementia (PDD) and dementia with Lewy bodies (DLB). Seven hub genes were found to be significantly associated with PDD, suggesting their involvement in the heterogeneous pathogenesis of PDD and DLB. Additionally, several signaling pathways related to different diseases were identified.
FRONTIERS IN NEUROLOGY
(2023)
Review
Biochemistry & Molecular Biology
Noah J. Graves, Yann Gambin, Emma Sierecki
Summary: Like many neurodegenerative diseases, Parkinson's disease (PD) is characterized by the formation of proteinaceous aggregates in brain cells. Additionally, these aggregates are also found in other disorders, collectively referred to as synucleinopathies. Despite the diversity in pathologies and symptoms, aSyn aggregates are a common marker and potential driver of these diseases. This review compares PD, DLB, and MSA, highlighting the role of aSyn aggregates in each disorder and discussing the relationship between aSyn strains and the cellular environment.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Clinical Neurology
Alice Tisserand, Benjamin Cretin, Mary Mondino, Anne Botzung, Lea Sanna, Catherine Demuynck, Pierre Anthony, Candice Muller, Olivier Bousiges, Nathalie Philippi, Frederic Blanc
Summary: This study aimed to investigate the association between photophobia and dementia with Lewy bodies (DLB). The study found that photophobia was more frequent in DLB patients and was associated with decreased gray matter in the right precentral cortex and the eyelid motor region. This finding is important for understanding the pathological mechanism of DLB.
EUROPEAN JOURNAL OF NEUROLOGY
(2023)
Article
Clinical Neurology
Karri Kaivola, Zalak Shah, Ruth Chia, Sonja W. Scholz
Summary: The GBA gene is associated with risk for dementia with Lewy bodies (DLB) in patients without the APOE ε4 allele, while the APOE ε4 allele is associated with DLB co-pathology with Alzheimer's disease. APOE ε4 is not an independent driver of alpha-synuclein pathology in pure DLB, but GBA plays a significant role in the pure DLB subgroup.
Article
Behavioral Sciences
Stefania Pezzoli, Raquel Sanchez-Valle, Aleix Solanes, Matthew J. Kempton, Oliver Bandmann, Jae Il Shin, Annachiara Cagnin, Jennifer G. Goldman, Doug Merkitch, Michael J. Firbank, John-Paul Taylor, Javier Pagonabarraga, Jaime Kulisevsky, Frederic Blanc, Norma Verdolini, Annalena Venneri, Joaquim Radua
Summary: The study found that visual hallucinations in patients with Parkinson's disease and dementia with Lewy bodies are associated with reductions in grey matter volume in certain brain regions, as well as lower verbal immediate memory performance in Parkinson's disease patients.
NEUROSCIENCE AND BIOBEHAVIORAL REVIEWS
(2021)
Article
Geriatrics & Gerontology
E. Costantini, C. Carrarini, P. Borrelli, M. De Rosa, D. Calisi, S. Consoli, D. D'Ardes, F. Cipollone, M. Di Nicola, M. Onofrj, M. Reale, L. Bonanni
Summary: This study evaluated the expression levels of nAChR subunits and inflammatory cytokines in peripheral blood mononuclear cells (PBMCs) of DLB and AD patients. The results showed higher expression levels of TNF alpha, IL6, and IL1 beta in DLB and AD patients, and lower expression levels of nAChR alpha 4, nAChR beta 2, and nAChR beta 4 in DLB and AD patients. The findings suggest a peripheral link between inflammation and neurodegeneration.
Article
Neurosciences
Tatyana Dmitrievna Fedorova, Karoline Knudsen, Jacob Horsager, Allan K. Hansen, Niels Okkels, Hanne Gottrup, Kim Vang, Per Borghammer
Summary: The study compared the striatal dopaminergic dysfunction asymmetry between patients with dementia with Lewy bodies (DLB) and Parkinson's disease (PD). It found that DLB patients had more symmetric striatal degeneration compared to PD patients, which supports the hypothesis that DLB patients may conform to the body-first subtype while PD patients may conform to the brain-first subtype.
JOURNAL OF PARKINSONS DISEASE
(2023)
Review
Clinical Neurology
Shannon Y. Chiu, Kathryn A. Wyman-Chick, Tanis J. Ferman, Ece Bayram, Samantha K. Holden, Parichita Choudhury, Melissa J. Armstrong
Summary: This review summarizes the current knowledge on sex differences in dementia with Lewy bodies (DLB) in terms of epidemiology, clinical features, neuropathology, biomarkers, disease progression, and caregiving. The prevalence of DLB in men is higher in many studies, but this finding is inconsistent. Women with DLB may experience more visual hallucinations, while men may have a higher frequency of REM sleep behavior disorder and parkinsonism. Women tend to be older, have greater cognitive impairment, and meet DLB criteria later than men. The impact of sex on DLB progression and the lack of research on sex differences in biomarkers and treatment are mixed. Women provide the majority of caregiving in DLB, but the effects of this on the caregiving experience are uncertain. Understanding sex differences will aid in developing sex-specific strategies in DLB.
PARKINSONISM & RELATED DISORDERS
(2023)
Article
Biochemistry & Molecular Biology
Daniela Hartl, Patrick May, Wei Gu, Manuel Mayhaus, Sabrina Pichler, Christian Spaniol, Enrico Glaab, Dheeraj Reddy Bobbili, Paul Antony, Sandra Koegelsberger, Alexander Kurz, Timo Grimmer, Kevin Morgan, Badri N. Vardarajan, Christiane Reitz, John Hardy, Jose Bras, Rita Guerreiro, Rudi Balling, Jochen G. Schneider, Matthias Riemenschneider
MOLECULAR PSYCHIATRY
(2020)
Review
Clinical Neurology
John O'Brien, John Paul Taylor, Clive Ballard, Roger A. Barker, Clare Bradley, Alistair Burns, Daniel Collerton, Sonali Dave, Rob Dudley, Paul Francis, Andrea Gibbons, Kate Harris, Vanessa Lawrence, Iracema Leroi, Ian McKeith, Michel Michaelides, Chaitali Naik, Claire O'Callaghan, Kirsty Olsen, Marco Onofrj, Rebecca Pinto, Gregor Russell, Peter Swann, Alan Thomas, Prabitha Urwyler, Rimona Sharon Weil, Dominic Ffytche
JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY
(2020)
Article
Biochemistry & Molecular Biology
Ivan Alic, Pollyanna A. Goh, Aoife Murray, Erik Portelius, Eleni Gkanatsiou, Gillian Gough, Kin Y. Mok, David Koschut, Reinhard Brunmeir, Yee Jie Yeap, Niamh L. O'Brien, Jurgen Groet, Xiaowei Shao, Steven Havlicek, N. Ray Dunn, Hlin Kvartsberg, Gunnar Brinkmalm, Rosalyn Hithersay, Carla Startin, Sarah Hamburg, Margaret Phillips, Konstantin Pervushin, Mark Turmaine, David Wallon, Anne Rovelet-Lecrux, Hilkka Soininen, Emanuela Volpi, Joanne E. Martin, Jia Nee Foo, David L. Becker, Agueda Rostagno, Jorge Ghiso, Zeljka Krsnik, Goran Simic, Ivica Kostovi, Dinko Mitrecic, Paul T. Francis, Kaj Blennow, Andre Strydom, John Hardy, Henrik Zetterberg, Dean Nizetic
Summary: Research has shown that individuals with Down Syndrome exhibit Alzheimer's disease-like pathological changes, which can be successfully replicated in vitro cerebral organoids models. These findings suggest that DS cerebral organoids could serve as a potential detector for pre-morbid AD-risk populations, as well as a system for hypothesis-free drug screening and identification of natural suppressor genes for neurodegenerative diseases.
MOLECULAR PSYCHIATRY
(2021)
Article
Clinical Neurology
Danielle Wasserman, Dorothea Bindman, Alexander D. Nesbitt, Diana Cash, Milan Milosevic, Paul T. Francis, K. Ray Chaudhuri, Guy D. Leschziner, Luigi Ferini-Strambi, Clive Ballard, Amy Eccles, Ivana Rosenzweig
Summary: The study found that patients with idiopathic rapid eye movement (REM) sleep behavior disorder (iRBD) exhibited an increased number of periodic limb movements during sleep compared to healthy controls. It also revealed significant associations between striatal dopamine transporter uptake and sleep architecture, indicating that dopamine deficiency in the caudate nucleus may affect sleep quality.
NATURE AND SCIENCE OF SLEEP
(2021)
Article
Clinical Neurology
Kirsty E. McAleese, Sean J. Colloby, Alan J. Thomas, Safa Al-Sarraj, Olaf Ansorge, James Neal, Federico Roncaroli, Seth Love, Paul T. Francis, Johannes Attems
Summary: The aged brain often exhibits multiple pathologies, rather than a single pathology, and the presence of multiple pathologies can significantly worsen cognitive decline, increasing the risk of transitioning from mild cognitive impairment to dementia.
ALZHEIMERS & DEMENTIA
(2021)
Article
Clinical Neurology
Clara Y. B. Low, Jasinda H. Lee, Frances T. W. Lim, Chingli Lee, Clive Ballard, Paul T. Francis, Mitchell K. P. Lai, Michelle G. K. Tan
Summary: Studies have shown selective upregulation of FynT expression in the neocortex of patients with Alzheimer's disease, Parkinson's disease dementia, and dementia with Lewy bodies, which correlated with cognitive impairment, neuropathological lesions, soluble beta-amyloid, phosphorylated tau, and markers of microglia and astrocyte activation. This suggests that FynT may play a role in neurodegenerative dementias through effects on tauopathy and neuroinflammation.
Article
Multidisciplinary Sciences
Cigdem Gelegen, Diana Cash, Katarina Ilic, Millie Sander, Eugene Kim, Camilla Simmons, Michel Bernanos, Joana Lama, Karen Randall, Jonathan T. Brown, Svjetlana Kalanj-Bognar, Samuel Cooke, K. Ray Chaudhuri, Clive Ballard, Paul Francis, Ivana Rosenzweig
SCIENTIFIC REPORTS
(2022)
Article
Multidisciplinary Sciences
Gemma Shireby, Emma L. Dempster, Stefania Policicchio, Rebecca G. Smith, Ehsan Pishva, Barry Chioza, Jonathan P. Davies, Joe Burrage, Katie Lunnon, Dorothea Seiler Vellame, Seth Love, Alan Thomas, Keeley Brookes, Kevin Morgan, Paul Francis, Eilis Hannon, Jonathan Mill
Summary: This study identified differences in cortical DNA methylation associated with Alzheimer's disease pathology and found that most of these differences occurred in non-neuronal cells.
NATURE COMMUNICATIONS
(2022)
Article
Clinical Neurology
Zunera Khan, Miguel Vasconcelos Da Silva, Kayleigh-Marie Nunez, Chris Kalafatis, Steven Nowicki, Zuzana Walker, Ingelin Testad, Paul Francis, Clive Ballard
Summary: The study found that impairment of non-verbal communication among nursing home residents with dementia was independently associated with the severity of neuropsychiatric symptoms (NPS) and quality of life (QoL). This highlights a novel potential approach to improve NPS and QoL using elements of non-verbal communication, particularly for individuals with severe dementia.
ALZHEIMERS & DEMENTIA-TRANSLATIONAL RESEARCH & CLINICAL INTERVENTIONS
(2021)
Article
Medicine, General & Internal
Sube Banerjee, Juliet High, Susan Stirling, Lee Shepstone, Ann Marie Swart, Tanya Telling, Catherine Henderson, Clive Ballard, Peter Bentham, Alistair Burns, Nicolas Farina, Chris Fox, Paul Francis, Robert Howard, Martin Knapp, Iracema Leroi, Gill Livingston, Ramin Nilforooshan, Shirley Nurock, John O'Brien, Annabel Price, Alan J. Thomas, Naji Tabet
Summary: This study evaluated the efficacy and safety of mirtazapine, an antidepressant, for treating agitation in patients with dementia. The findings showed that mirtazapine did not reduce agitation symptoms compared to placebo, and there was a potentially higher mortality rate associated with mirtazapine use.
Article
Clinical Neurology
Eilis Hannon, Gemma L. Shireby, Keeley Brookes, Johannes Attems, Rebecca Sims, Nigel J. Cairns, Seth Love, Alan J. Thomas, Kevin Morgan, Paul T. Francis, Jonathan Mill
BRAIN COMMUNICATIONS
(2020)
Article
Clinical Neurology
Kathy Y. Liu, Suzanne Reeves, Kirsty E. McAleese, Johannes Attems, Paul Francis, Alan Thomas, Robert Howard
Article
Clinical Neurology
Gemma L. Shireby, Jonathan P. Davies, Paul T. Francis, Joe Burrage, Emma M. Walker, Grant W. A. Neilson, Aisha Dahir, Alan J. Thomas, Seth Love, Rebecca G. Smith, Katie Lunnon, Meena Kumari, Leonard C. Schalkwyk, Kevin Morgan, Keeley Brookes, Eilis Hannon, Jonathan Mill
Meeting Abstract
Clinical Neurology
K. E. McAleese, S. Colloby, J. Attems, A. Thomas, P. T. Francis
NEUROPATHOLOGY AND APPLIED NEUROBIOLOGY
(2020)
Meeting Abstract
Clinical Neurology
T. Eid, T. Lashley, T. Warner, R. Bandopadhyay, J. Hardy, J. Holton, P. Francis
NEUROPATHOLOGY AND APPLIED NEUROBIOLOGY
(2020)