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)
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
Neurosciences
David J. Koss, Daniel Erskine, Andrew Porter, Pawel Palmoski, Hariharan Menon, Olivia G. J. Todd, Marta Leite, Johannes Attems, Tiago F. Outeiro
Summary: Through a multidisciplinary approach, this study confirms the presence of nuclear alpha-synuclein in the brains of patients with dementia with Lewy bodies, which may undergo pathogenic modifications and contribute to the disease phenotype.
ACTA NEUROPATHOLOGICA COMMUNICATIONS
(2022)
Article
Immunology
Kaibiao Xu, Dongmei Wang, Yan He, Shengnan Wang, Guanghui Liu, Yue Pan, Haishan Jiang, Yu Peng, Fenliang Xiao, Yihua Huang, Qiqi Wang, Yongming Wu, Suyue Pan, Yafang Hu
Summary: This study discovered a novel anti-CRMP2 antibody associated with suspected AE and suggested its significance for the diagnosis of AE.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Clinical Neurology
Hideki Oizumi, Kenshi Yamasaki, Hiroyoshi Suzuki, Saki Ohshiro, Yuko Saito, Shigeo Murayama, Yoko Sugimura, Takafumi Hasegawa, Kohji Fukunaga, Atsushi Takeda
Summary: The study suggests that p-alpha Syn accumulation in dermal macrophages is present in patients with IPD and may serve as an important biomarker for the disease. Additionally, the number of dermal macrophages was significantly positively correlated with the number of macrophages with p-alpha Syn deposits in the dermis of IPD patients.
ANNALS OF CLINICAL AND TRANSLATIONAL NEUROLOGY
(2022)
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)
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)
Article
Clinical Neurology
Ting-Ya Chang, Chun-Pai Yang, Yi-Huei Chen, Ching-Heng Lin, Ming-Hong Chang
Summary: This study showed that older age of onset in PD patients was associated with a higher incidence rate of dementia. In younger PD patients, the incidence rate of dementia was lower but the risk was higher compared to controls of the same age.
FRONTIERS IN NEUROLOGY
(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
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
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
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
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
Neurosciences
Bryan A. Killinger, Gabriela Mercado, Solji Choi, Tyler Tittle, Yaping Chu, Patrik Brundin, Jeffrey H. Kordower
Summary: This study used a sensitive tyramide signal amplification (TSA) technique to show the presence of PSER129 in the non-diseased mammalian brain, particularly in the mitral cells of the olfactory bulb (OB). PSER129 was found to interact with various proteins related to synaptic vesicle trafficking/recycling, SNARE, fatty acid oxidation, oxidative phosphorylation, and RNA binding. The accumulation of PSER129 in the OB may indicate the beginning of synucleinopathies or the natural tendency of the OB to accumulate this protein.
NPJ PARKINSONS DISEASE
(2023)
Article
Psychology, Multidisciplinary
Sandro Iannaccone, Elise Houdayer, Alfio Spina, Gianluca Nocera, Federica Alemanno
Summary: This study investigated the use of electroencephalography quantified with statistical pattern recognition (qEEG-SPR) as a tool for diagnosing dementia and differentiating dementia with Lewy bodies (DLB). The results showed that qEEG-SPR had high sensitivity and specificity for identifying dementia and DLB. It is a non-invasive, low-cost, and environmentally friendly method that can be implemented in healthcare settings.
FRONTIERS IN PSYCHOLOGY
(2023)
Article
Clinical Neurology
Ingrid Myrvoll Lorentzen, Jacob Espenes, Erik Hessen, Knut Waterloo, Geir Brathen, Santiago Timon, Dag Aarsland, Tormod Fladby, Bjorn-Eivind Kirsebom
Summary: The study developed regression-based norms for the FAS phonemic fluency test and found that years of education was the only significant predictor of test performance. The proposed norms provided a more accurate adjustment for demographics in the Norwegian population compared to American norms.
APPLIED NEUROPSYCHOLOGY-ADULT
(2023)
Article
Hematology
Arada Vinaiphat, Kalailingam Pazhanchamy, Gnanasekaran JebaMercy, SoFong Cam Ngan, Melvin Khee-Shing Leow, Hee Hwa Ho, Yong-Gui Gao, Kah Leong Lim, A. Mark Richards, Dominique P. V. de Kleijn, Christopher P. Chen, Raj N. Kalaria, Jian Liu, Deborah D. O'Leary, Neil E. McCarthy, Siu Kwan Sze
Summary: This study investigates the effects of high salt intake on endothelial cells and vascular structure. It shows that high salt diet decreases the expression of proteins in the endothelial glycocalyx and alters protein mediators in endothelial cells, leading to vascular pathology and increased cardiovascular risk.
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
(2023)
Article
Immunology
Yuek Ling Chai, Jasinda H. H. Lee, Joyce R. R. Chong, Clive Ballard, Paul T. Francis, Brian K. Kennedy, Thiruma V. Arumugam, Christopher P. P. Chen, Dag Aarsland, Mitchell K. P. Lai
Summary: This study compared the neuroinflammatory responses in Alzheimer's disease (AD) and Lewy body dementias (LBD). The findings showed elevated levels of inflammatory mediators in the brains of AD patients, while there were no significant changes in LBD patients. Furthermore, the increase in neuroinflammatory markers was associated with neurofibrillary tangle burden in AD, but not in LBD.
JOURNAL OF NEUROINFLAMMATION
(2023)
Article
Medicine, General & Internal
Lu Ma, Xin Hu, Lili Song, Xiaoying Chen, Menglu Ouyang, Laurent Billot, Qiang Li, Alejandra Malavera, Xi Li, Paula Munoz-Venturelli, Asita de Silva, Nguyen Huy Thang, Kolawole W. Wahab, Jeyaraj D. Pandian, Mohammad Wasay, Octavio M. Pontes-Neto, Carlos Abanto, Antonio Arauz, Haiping Shi, Guanghai Tang, Sheng Zhu, Xiaochun She, Leibo Liu, Yuki Sakamoto, Shoujiang You, Qiao Han, Bernard Crutzen, Emily Cheung, Yunke Li, Xia Wang, Chen Chen, Feifeng Liu, Yang Zhao, Hao Li, Yi Liu, Yan Jiang, Lei Chen, Bo Wu, Ming Liu, Jianguo Xu, Chao You, Craig S. Anderson
Summary: Implementing a goal-directed care bundle that focuses on early intensive blood pressure lowering, strict glucose control, antipyrexia, and rapid reversal of anticoagulation can improve outcomes for patients with acute intracerebral haemorrhage. This approach resulted in improved functional recovery and reduced serious adverse events in patients.
Article
Biochemistry & Molecular Biology
Kaung H. T. Salai, Liu-Yun Wu, Joyce R. R. Chong, Yuek Ling Chai, Bibek Gyanwali, Caroline Robert, Saima Hilal, Narayanaswamy Venketasubramanian, Gavin S. Dawe, Christopher P. P. Chen, Mitchell K. P. Lai
Summary: Tumor necrosis factor-receptor 1 (TNF-R1) signaling plays a critical role in regulating inflammatory responses. Elevated levels of soluble TNF-R1 (sTNF-R1) have been observed in predementia subjects, and specifically associated with cerebral small vessel disease (CSVD) and lower rates of cognitive decline. This suggests that sTNF-R1 interacts with vascular cognitive impairment in a complex manner, potentially providing protection against cognitive decline.
Article
Medicine, General & Internal
Sokratis Charisis, Tanweer Rashid, Hangfan Liu, Jeffrey B. Ware, Paul N. Jensen, Thomas R. Austin, Karl Li, Elyas Fadaee, Saima Hilal, Christopher Chen, Timothy M. Hughes, Jose Rafael Romero, Jon B. Toledo, Will T. Longstreth, Timothy J. Hohman, Ilya Nasrallah, R. Nick Bryan, Lenore J. Launer, Christos Davatzikos, Sudha Seshadri, Susan R. Heckbert, Mohamad Habes
Summary: This study conducted a whole-brain investigation of enlarged perivascular spaces (ePVSs) and found that increased ePVS burden in the basal ganglia and thalamus is associated with cerebral small vessel disease (cSVD), highlighting the clinical importance of ePVSs in these locations.
Article
Cardiac & Cardiovascular Systems
Narayanaswamy Venketasubramanian, Yogesh Pokharkar, Jia Hui Chai, Christopher Li Hsian Chen
Summary: Despite advances in revascularisation interventions for acute ischemic stroke, many patients continue to experience disability. A study analyzed data from a randomized, double-blind, placebo-controlled trial of a neuro-repair treatment (NeuroAiD/MLC601) and found that patients receiving a 3-month course of MLC601 had a significantly shorter time to functional recovery compared to those receiving placebo.
JOURNAL OF CARDIOVASCULAR DEVELOPMENT AND DISEASE
(2023)
Article
Clinical Neurology
Harald Hampel, Yan Hu, John Hardy, Kaj Blennow, Christopher Chen, George Perry, Seung Hyun Kim, Victor L. Villemagne, Paul Aisen, Michele Vendruscolo, Takeshi Iwatsubo, Colin L. Masters, Min Cho, Lars Lannfelt, Jeffrey L. Cummings, Andrea Vergallo
Summary: This summary reviews the evidence supporting the role of the amyloid-b (Ab) pathway in Alzheimer's disease (AD) and emphasizes the importance of targeting this pathway in early stages of the disease. Understanding and targeting the A beta pathway can lead to better therapeutic outcomes and management of AD.
NEURODEGENERATIVE DISEASE MANAGEMENT
(2023)
Review
Clinical Neurology
Marco Duering, Geert Jan Biessels, Amy Brodtmann, Christopher Chen, Charlotte Cordonnier, Frank-Erik de Leeuw, Stephanie Debette, Richard Frayne, Eric Jouvent, Natalia S. Rost, Annemieke ter Telgte, Rustam Al-Shahi Salman, Walter H. Backes, Hee-Joon Bae, Rosalind Brown, Hugues Chabriat, Alberto De Luca, Charles deCarli, Anna Dewenter, Fergus N. Doubal, Michael Ewers, Thalia S. Field, Aravind Ganesh, Steven Greenberg, Karl G. Helmer, Saima Hilal, Angela C. C. Jochems, Hanna Jokinen, Hugo Kuijf, Bonnie Y. K. Lam, Jessica Lebenberg, Bradley J. MacIntosh, Pauline Maillard, Vincent C. T. Mok, Leonardo Pantoni, Salvatore Rudilosso, Claudia L. Satizabal, Markus D. Schirmer, Reinhold Schmidt, Colin Smith, Julie Staals, Michael J. Thrippleton, Susanne J. van Veluw, Prashanthi Vemuri, Yilong Wang, David Werring, Marialuisa Zedde, Rufus O. Akinyemi, Oscar H. Del Brutto, Hugh S. Markus, Yi-Cheng Zhu, Eric E. Smith, Martin Dichgans, Joanna M. Wardlaw
Summary: Cerebral small vessel disease (SVD) is a common age-related condition that can cause stroke, cognitive decline, neurobehavioral symptoms, and functional impairment. STRIVE-1 classified and standardized the various visible features of SVD on structural MRI, but new information and imaging techniques have emerged since then. Quantitative imaging biomarkers and machine learning methods offer a more comprehensive understanding of the impact of SVD on the brain and can serve as intermediary outcomes in clinical trials and routine practice.
Article
Clinical Neurology
Joseph Giorgio, Ankeet Tanna, Maura Malpetti, Simon R. White, Jingshen Wang, Suzanne Baker, Susan Landau, Tomotaka Tanaka, Christopher Chen, James B. Rowe, John O'Brien, Jurgen Fripp, Michael Breakspear, William Jagust, Zoe Kourtzi
Summary: This study developed a two-stage approach to harmonize cognitive data across different cohorts and derived a cross-cohort score for cognitive impairment due to Alzheimer's disease. The results showed that the score was robust and sensitive, providing a better assessment for AD-related cognitive decline.
ALZHEIMER'S & DEMENTIA: DIAGNOSIS, ASSESSMENT & DISEASE MONITORING
(2023)
Article
Clinical Neurology
Rui Li, Eric L. Harshfield, Steven Bell, Michael Burkhart, Anil M. Tuladhar, Saima Hilal, Daniel J. Tozer, Francesca M. Chappell, Stephen D. J. Makin, Jessica W. Lo, Joanna M. Wardlaw, Frank-Erik de Leeuw, Christopher Chen, Zoe Kourtzi, Hugh S. Markus
Summary: This study investigated the feasibility of using machine learning methods to predict dementia caused by cerebral small vessel disease (SVD), and found that traditional statistical approaches performed better in prediction, especially with baseline cognitive abilities being highly predictive.
CEREBRAL CIRCULATION - COGNITION AND BEHAVIOR
(2023)
Article
Clinical Neurology
Elijah Mak, Liwen Zhang, Chin Hong Tan, Anthonin Reilhac, Hee Youn Shim, Marcus Ong Qin Wen, Zi Xuen Wong, Eddie Jun Yi Chong, Xin Xu, Mary Stephenson, Narayanaswamy Venketasubramanian, Juan Helen Zhou, John T. O'Brien, Christopher Li-Hsian Chen
Summary: This study investigated the influence of beta-amyloid accumulation on brain atrophy in Alzheimer's disease. The findings suggest that cortical thinning is correlated with amyloid deposition in individuals with mild cognitive impairment, indicating an increasing influence of amyloid on neurodegeneration and memory decline along the disease progression.
BRAIN COMMUNICATIONS
(2023)
Article
Clinical Neurology
Xin Ying Chua, Federico Torta, Joyce R. Chong, Narayanaswamy Venketasubramanian, Saima Hilal, Markus R. Wenk, Christopher P. Chen, Thiruma V. Arumugam, Deron R. Herr, Mitchell K. P. Lai
Summary: AD and VaD are associated with distinct changes of plasma sphingolipids, and specific combinations of sphingolipids panels have higher sensitivity and specificity for classification of AD and VaD, compared to NCI.
ALZHEIMERS RESEARCH & THERAPY
(2023)
Article
Medicine, Research & Experimental
Pazhanichamy Kalailingam, Khalilatul-Hanisah Mohd-Kahliab, SoFong Cam Ngan, Ranjith Iyappan, Evelin Melekh, Tian Lu, Gan Wei Zien, Bhargy Sharma, Tiannan Guo, Adam J. Macneil, Rebecca E. K. Macpherson, Evangelia Litsa Tsiani, Deborah D. O'Leary, Kah Leong Lim, I. Hsin Su, Yong-Gui Gao, A. Mark Richards, Raj N. Kalaria, Christopher P. Chen, Neil E. Mccarthy, Siu Kwan Sze
Summary: This study found that age-related protein damage can be mitigated by anti-isoDGR immunotherapy. The accumulation of isoDGR proteins is associated with increased expression of inflammatory cytokines and can be induced by injection of isoDGR-modified plasma proteins or synthetic peptides. However, treatment with anti-isoDGR monoclonal antibodies can significantly reduce the levels of isoDGR proteins in tissues, decrease the concentration of inflammatory cytokines in the plasma, improve cognitive/coordination metrics, and extend the lifespan of mice.
EMBO MOLECULAR MEDICINE
(2023)
Article
Biochemistry & Molecular Biology
Melanie Le Sayec, Diogo Carregosa, Khadija Khalifa, Chiara de Lucia, Dag Aarsland, Claudia N. Santos, Ana Rodriguez-Mateos
Summary: This study investigated the presence of (poly)phenol and methylxanthine metabolites in plasma and cerebrospinal fluid from individuals at risk of dementia and predicted their transport mechanism across the blood-brain barrier using in silico modeling. The results suggest that (poly)phenols and methylxanthines can cross the blood-brain barrier via passive diffusion or transport carriers to exert neuroprotective effects.