Review
Pharmacology & Pharmacy
Ritam Bandopadhyay, Nainshi Mishra, Ruhi Rana, Gagandeep Kaur, Mohammed M. Ghoneim, Sultan Alshehri, Gulam Mustafa, Javed Ahmad, Nabil. A. Alhakamy, Awanish Mishra
Summary: This study focuses on the recent updates in molecular mechanisms and therapeutic approaches for the effective management of levodopa-induced dyskinesia (LID) in Parkinson's disease patients.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Clinical Neurology
Francesco Cavallieri, Carla Budriesi, Annalisa Gessani, Sara Contardi, Valentina Fioravanti, Elisa Menozzi, Serge Pinto, Elena Moro, Franco Valzania, Francesca Antonelli
Summary: The study demonstrates that levodopa has a negative effect on speech acoustic parameters in Parkinson's disease patients. The intensity and location of dyskinesia negatively impact speech quality.
FRONTIERS IN NEUROLOGY
(2021)
Article
Medicine, General & Internal
Yang Luo, Huiqin Chen, Mingzhen Gui
Summary: This study aimed to predict early levodopa-induced dyskinesia (LID) in Parkinson's disease (PD) using radiomics and machine learning models. The results showed that hybrid models combining radiomics features and clinical features had good performance in predicting early LID in PD.
Article
Neurosciences
Melina P. Bordone, Ana Damianich, Alejandra Bernardi, Tomas Eidelman, Sara Sanz-Blasco, Oscar S. Gershanik, M. Elena Avale, Juan E. Ferrario
Summary: The study aimed to alleviate levodopa-induced dyskinesia in Parkinson's disease by reducing Fyn expression. Preadministration of miRNA-Fyn was effective in reducing LID, while post-L-DOPA delivery of miRNA-Fyn was less effective in reverting established dyskinesia. The findings suggest that early blocking of Fyn activity may be a more efficient therapeutic approach.
Article
Clinical Neurology
Jessie F. Fu, Michele Matarazzo, Jessamyn McKenzie, Nicole Neilson, Nasim Vafai, Katie Dinelle, Andre C. Felicio, Martin J. McKeown, A. Jon Stoessl, Vesna Sossi
Summary: The study found that the serotonergic system contributes to dopamine release and increases the risk for motor complications in early Parkinson's disease. Moreover, this contribution fails to provide sustained therapeutic advantage in early disease.
MOVEMENT DISORDERS
(2021)
Article
Biochemistry & Molecular Biology
Ana Gabrielle Bispo, Caio S. Silva, Camille Sena-dos-Santos, Dafne Dalledone Moura, Brenda Hanae Bentes Koshimoto, Bruno Lopes Santos-Lobato, Andrea Ribeiro-dos-Santos, Giovanna C. Cavalcante
Summary: Mitophagy dysfunction caused by gene mutations is associated with the development of Parkinson's Disease (PD). However, the association between the variants of mitophagy-related genes and the treatment with levodopa (LD) in PD patients has not been well explored. This study investigated the association of 14 variants of the PRKN gene with LD treatment in PD patients. The results suggest that while age at onset of symptoms, duration of PD, and LD treatment and dosage can influence the occurrence of dyskinesia, the investigated PRKN variants did not show a significant association.
Review
Neurosciences
Nayoung Kwak, Jinyoung Park, Hye-Young Kang, Myung-Jun Lee, Jae Kyung Suh, Hankil Lee
Summary: The results of the study indicate that as an adjuvant therapy to levodopa, opicapone can reduce dyskinesias and prolong the symptom-free on-time in patients with Parkinson's disease.
JOURNAL OF PARKINSONS DISEASE
(2022)
Review
Clinical Neurology
Ahmed Negida, Hazem S. Ghaith, Salma Yousry Fala, Hussien Ahmed, Eshak Bahbah, Mahmoud Ahmed Ebada, Mohamed Abd Elalem Aziz
Summary: This meta-analysis of six randomized controlled trials found that Mavoglurant was not superior to placebo in treating levodopa-induced dyskinesia in patients with Parkinson's Disease.
NEUROLOGICAL SCIENCES
(2021)
Article
Clinical Neurology
Chi-Chuan Wang, Tsai-Ling Wu, Fang-Ju Lin, Chun-Hwei Tai, Chin-Hsien Lin, Ruey-Meei Wu
Summary: The study found that early treatment with amantadine may delay the onset of levodopa-induced dyskinesia in patients with Parkinson's disease more effectively than treatment with other symptomatic agents. Further research is needed to validate this finding and explore the mechanism by which amantadine delays LID onset.
EUROPEAN JOURNAL OF NEUROLOGY
(2022)
Article
Neurosciences
Matthias Loehle, Alexander Bremer, Florin Gandor, Jonathan Timpka, Per Odin, Georg Ebersbach, Alexander Storch
Summary: This study compared the validity of motor state quantification between the Parkinson's disease (PD) home diary and direct clinical observation in fluctuating PD patients. The results showed that the home diary inadequately reflects actual motor states compared to direct clinical observation.
NPJ PARKINSONS DISEASE
(2022)
Article
Neurosciences
Piniel Alphayo Kambey, Wen Ya Liu, Jiao Wu, Chuanxi Tang, Wokuheleza Buberwa, Adonira Saro, Alphonce M. K. Nyalali, Dianshuai Gao
Summary: This study revealed the crucial role of Amphiregulin (Areg) gene in levodopa-induced dyskinesia in Parkinson's disease. Inhibition of Areg was found to alleviate dyskinetic movements and decrease the expression of related proteins. Therefore, Areg may serve as a potential target for therapy development.
CNS NEUROSCIENCE & THERAPEUTICS
(2023)
Article
Neurosciences
Nayron Medeiros Soares, Gabriela Magalhaes Pereira, Ana Carolina Leonardi Dutra, Nathalie Ribeiro Artigas, Julia Schneider Krimberg, Bruno Elkfury Monticelli, Artur Francisco Schumacher-Schuh, Rosa Maria Martins de Almeida, Carlos Roberto de Mello Rieder
Summary: This study investigated the relationship between serum uric acid (UA) levels and levodopa-induced dyskinesia (LID) in Parkinson's disease (PD) patients, as well as the associations between UA levels and clinical features of PD. The results showed that the dyskinesia group had lower serum UA levels compared to the no dyskinesia group, which was also observed in both men and women. Multivariate analysis demonstrated that lower UA levels were significantly associated with the presence of dyskinesia. Additional analysis revealed that serum UA levels were inversely correlated with depressive symptoms, disease duration, MDS-UPDRS IV, and time spent with dyskinesia, while positively correlated with age at onset of PD symptoms.
ARQUIVOS DE NEURO-PSIQUIATRIA
(2023)
Article
Neurosciences
Nayron Medeiros Soares, Gabriela Magalhaes Pereira, Ana Carolina Leonardi Dutra, Nathalie Ribeiro Artigas, Julia Schneider Krimberg, Bruno Elkfury Monticelli, Artur Francisco Schumacher-Schuh, Rosa Maria Martins de Almeida, Carlos Roberto de Mello Rieder
Summary: This study investigated the relationship between serum uric acid (UA) levels and levodopa-induced dyskinesia (LID) in Parkinson's disease (PD) patients, as well as the associations between UA levels and clinical features of PD. The results showed that serum UA levels were lower in the LID group compared to the non-LID group, and this difference was observed in both men and women. Multivariate analysis revealed that lower UA levels were significantly associated with the occurrence of LID. Furthermore, serum UA levels were inversely correlated with depressive symptoms, disease duration, disease severity, and time spent with dyskinesia, and positively correlated with age at onset of PD symptoms.
ARQUIVOS DE NEURO-PSIQUIATRIA
(2023)
Article
Clinical Neurology
Emilio Fernandez-Espejo, Fernando Rodriguez de Fonseca, Juan Suarez, Ramiro Gonzalez-Aparicio, Ana Santurtun
Summary: The study found that increasing levodopa equivalent dose (LED) would increase serum ATP13A2 concentration and facilitate the development of motor complications. There is a direct relationship between serum ATP13A2 level and the dose intensity of the antiparkinsonian dopaminergic medication, suggesting that serum ATP13A2 content might serve as a marker for dopamine replacement therapy.
PARKINSONISM & RELATED DISORDERS
(2021)
Article
Neurosciences
Bruno L. Santos-Lobato, Luiz Gustavo Gardinassi, Mariza Bortolanza, Ana Paula Ferranti Peti, Angela V. Pimentel, Lucia Helena Faccioli, Elaine A. Del-Bel, Vitor Tumas
Summary: Metabolomic analysis revealed a distinct metabolic profile associated with levodopa-induced dyskinesia (LID) in Parkinson's disease (PD), particularly characterized by dysregulation of the glycosphingolipid metabolic pathway and bile acid biosynthesis metabolites in plasma and CSF. These findings suggest a potential link between lipid metabolism dysregulation and LID in PD.
MOLECULAR NEUROBIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Maria Rogdaki, Celine Devroye, Mariasole Ciampoli, Mattia Veronese, Abhishekh Ashok, Robert A. McCutcheon, Sameer Jauhar, Ilaria Bonoldi, Maria Gudbrandsen, Eileen Daly, Therese van Amelsvoort, Marianne Van Den Bree, Michael J. Owen, Federico Turkheimer, Francesco Papaleo, Oliver D. Howes
Summary: Dopaminergic dysfunction is associated with genetic risk for psychosis, particularly in individuals with 22q11.2 deletion. This study found increased striatal dopamine synthesis capacity in individuals with 22q11.2 deletion compared to healthy controls and individuals with 22q11.2 duplication. Furthermore, dopamine synthesis was positively correlated with the severity of psychosis-risk symptoms.
MOLECULAR PSYCHIATRY
(2023)
Correction
Biochemistry & Molecular Biology
Maria Rogdaki, Celine Devroye, Mariasole Ciampoli, Mattia Veronese, Abhishekh H. Ashok, Robert A. McCutcheon, Sameer Jauhar, Ilaria Bonoldi, Maria Gudbrandsen, Eileen Daly, Therese van Amelsvoort, Marianne Van Den Bree, Michael J. Owen, Federico Turkheimer, Francesco Papaleo, Oliver D. Howes
MOLECULAR PSYCHIATRY
(2023)
Review
Psychology, Clinical
Leigh Townsend, Toby Pillinger, Pierluigi Selvaggi, Mattia Veronese, Federico Turkheimer, Oliver Howes
Summary: This study investigates brain metabolism in patients with schizophrenia and finds evidence of lower glucose metabolism in the frontal cortex, supporting the hypothesis of hypofrontality in schizophrenia. However, there were no consistent alterations in other brain regions.
PSYCHOLOGICAL MEDICINE
(2023)
Article
Biochemistry & Molecular Biology
Fangda Leng, Rainer Hinz, Steve Gentleman, Adam Hampshire, Melanie Dani, David J. Brooks, Paul Edison
Summary: Brain network dysfunction in Alzheimer's disease is associated with neuroinflammation, independent of A beta deposition and cortical atrophy. This study found that increased microglial activation correlated with disrupted structural and functional networks, while A beta did not, suggesting a link between neuroinflammation and systemic brain dysfunction in AD.
MOLECULAR PSYCHIATRY
(2023)
Article
Clinical Neurology
Tom Foltynie, Sonia Gandhi, Cristina Gonzalez-Robles, Marie-Louise Zeissler, Georgia Mills, Roger Barker, James Carpenter, Anette Schrag, Anthony Schapira, Oliver Bandmann, Stephen Mullin, Joy Duffen, Kevin McFarthing, Jeremy Chataway, Mahesh Parmar, Camille Carroll
Summary: Multi-arm, multi-stage platform designs have improved the efficiency of clinical trials in the field of oncology. Foltynie et al. discuss the challenges and considerations of using this approach to assess potential disease-modifying treatments in progressive neurological conditions such as Parkinson's disease.
Review
Clinical Neurology
K. Ray Chaudhuri, Valentina Leta, Kirsty Bannister, David J. J. Brooks, Per Svenningsson
Summary: In Parkinson disease (PD), some patients have non-motor symptoms that are related to abnormalities in noradrenergic function. Research suggests the existence of a noradrenergic subtype of PD, characterized by specific non-motor symptoms such as rapid eye movement sleep behavior disorder, pain, anxiety, and dysautonomia. Understanding this subtype could lead to personalized treatments for PD.
NATURE REVIEWS NEUROLOGY
(2023)
Article
Geriatrics & Gerontology
Lasse S. Madsen, Peter Parbo, Rola Ismail, Hanne Gottrup, Leif Ostergaard, David J. Brooks, Simon F. Eskildsen
Summary: Alterations in cerebral perfusion play a crucial role in Alzheimer's disease (AD). Deficiencies in brain microvascular circulation, together with accumulated amyloid-β, may result in local hypoxia. This study investigated alterations in cerebral circulation and the correlation with amyloid-β load in prodromal AD (pAD). The results showed that the pAD-MCI group had significantly lower microvascular blood flow and higher heterogeneity of microvascular blood transit times compared to other groups. Additionally, elevated amyloid-β levels correlated with decreased microvascular blood flow and increased heterogeneity in frontal and temporal areas of the pAD-MCI group.
NEUROBIOLOGY OF AGING
(2023)
Article
Behavioral Sciences
Erik D. Fagerholm, Zalina Dezhina, Rosalyn J. Moran, Federico E. Turkheimer, Robert Leech
Summary: Entropy is a property of both a system and an observer, measuring the hidden information in a system due to the observer's limitations. This article provides a theory of entropy based on statistical mechanics and toy models of neural systems. It explains the distinction between micro and macrostates, the characteristics of entropy for capturing hidden information, and the mathematical form of entropy derived from arrangements of discrete-state neurons. The article also discusses the increase in entropy over time in neural systems due to limitations in neuroimaging resolution. It aims to support using entropy as a method for characterizing neuroimaging timeseries and making inferences about brain states.
NEUROSCIENCE AND BIOBEHAVIORAL REVIEWS
(2023)
Article
Multidisciplinary Sciences
Fran Hancock, Fernando E. Rosas, Robert A. E. McCutcheon, Joana Cabral, Ottavia Dipasquale, Federico E. Turkheimer
Summary: This study demonstrates the reliability and face validity of using metastability as a potential neuromechanistic biomarker for schizophrenia pathology, providing new insights into the mechanisms of the disorder and potentially aiding in its diagnosis and treatment.
Article
Clinical Neurology
Andreas-Antonios Roussakis, Marta Gennaro, Mark Forrest Gordon, Ralf Reilmann, Beth Borowsky, Gail Rynkowski, Nicholas P. Lao-Kaim, Zoe Papoutsou, Juha-Matti Savola, Michael R. Hayden, David R. Owen, Nicola Kalk, Anne Lingford-Hughes, Roger N. Gunn, Graham Searle, Sarah J. Tabrizi, Paola Piccini
Summary: This longitudinal study demonstrates that the treatment of laquinimod in Huntington's disease does not affect regional microglia activation. Microglia activation is believed to be related to inflammation in the central nervous system and the progression of Huntington's disease. However, laquinimod is capable of regulating microglia. The study also shows that C-11-PBR28 PET-CT imaging can be used to assess regional gliosis and the effects of laquinimod treatment.
BRAIN COMMUNICATIONS
(2023)
Article
Immunology
M. R. Williams, C. M. Macdonald, F. E. Turkheimer
Summary: This study histologically examines the morphology of choroid plexus (CP) epithelial cells in patients with psychosis, schizophrenia and depression. It found increased somal width in the CP epithelial cells of schizophrenia patients without psychotic medication, indicating an illness-specific change mediated through the DA-system. No significant changes were observed in the CP epithelial cells of patients with major depressive disorder (MDD).
BRAIN BEHAVIOR AND IMMUNITY
(2023)
Review
Behavioral Sciences
Timothy Lawn, Matthew A. Howard, Federico Turkheimer, Bratislav Misic, Gustavo Deco, Daniel Martins, Ottavia Dipasquale
Summary: The human brain exhibits complex interactions across micro, meso-, and macro-scale organisational principles. Recent synergistic multi-modal approaches have begun to link micro-scale information to system level dynamics, transcending organisational hierarchies and offering novel perspectives into the brain's function and dysfunction. Methodological approaches to enrich functional imaging analyses with molecular information are rapidly evolving, with several streams of research having developed relatively independently, each offering unique potential to explore the trans-hierarchical functioning of the brain.
NEUROSCIENCE AND BIOBEHAVIORAL REVIEWS
(2023)
Article
Neurosciences
Cristina Gonzalez-Robles, Rimona S. Weil, Daniel van Wamelen, Michele Bartlett, Matthew Burnell, Caroline S. Clarke, Michele T. Hu, Brook Huxford, Ashwani Jha, Christian Lambert, Michael Lawton, Georgia Mills, Alastair Noyce, Paola Piccini, Kuhan Pushparatnam, Lynn Rochester, Carroll Siu, Caroline H. Williams-Gray, Marie-Louise Zeissler, Henrik Zetterberg, Camille B. Carroll, Thomas Foltynie, Anette Schrag
Summary: This study aims to provide an inventory of outcome measures (OM) for disease-modifying trials in Parkinson's disease and a framework for future selection of OM. An extensive inventory of OM was created based on evidence evaluation. Patient and public involvement emphasized the need for OM reflecting their disease experience and applicable to diverse populations and disease stages.
JOURNAL OF PARKINSONS DISEASE
(2023)
Article
Physics, Multidisciplinary
Erik D. Fagerholm, Zalina Dezhina, Rosalyn J. Moran, Karl J. Friston, Federico Turkheimer, Robert Leech
Summary: Boltzmann entropy measures hidden information in a system. In neuroimaging, information can be hidden in multiple indistinguishable brain states and neuronal pattern selections between regions. Selection entropy is more sensitive to small changes in probability distributions compared to the KL divergence. It identifies a principal gradient between sensorimotor and transmodal brain regions more effectively than the KL divergence in resting-state functional magnetic resonance imaging time series. Therefore, selection entropy is introduced as an additional asset in analyzing neuronal functional selectivity.
PHYSICAL REVIEW RESEARCH
(2023)
Article
Immunology
Oliver Cousins, Julia J. Schubert, Avinash Chandra, Mattia Veronese, Polena Valkimadi, Byron Creese, Zunera Khan, Ryan Arathimos, Adam Hampshire, Ivana Rosenzweig, Clive Ballard, Anne Corbett, Dag Aasland, Latha Velayudhan, Michael O'Neill, David Collier, Ramla Awais, Kerstin Sander, Erik Arstad, Oliver Howes, Federico Turkheimer, Angela Hodges
Summary: In this study, the impact of the TREM2 p.R47H variant on microglial activation, tau and amyloid deposition, brain structure, and cognitive profile in Alzheimer's disease was investigated. The results showed that TREM2 p.R47H carriers had reduced microglial activation levels in brain regions affected early in the Alzheimer's disease course, as well as differences in brain structure and cognition. Changes in microglial response may contribute to the increased risk of Alzheimer's disease in TREM2 p.R47H carriers. Future therapeutic approaches should aim to enhance protective microglial actions.
JOURNAL OF NEUROINFLAMMATION
(2023)
