Article
Clinical Neurology
Julia Schumacher, Jeffrey L. Gunter, Scott A. Przybelski, David T. Jones, Jonathan Graff-Radford, Rodolfo Savica, Christopher G. Schwarz, Matthew L. Senjem, Clifford R. Jack, Val J. Lowe, David S. Knopman, Julie A. Fields, Walter K. Kremers, Ronald C. Petersen, Neill R. Graff-Radford, Tanis J. Ferman, Bradley F. Boeve, Alan J. Thomas, John-Paul Taylor, Kejal Kantarci
Summary: The presence of concurrent Alzheimer's disease pathology in patients with DLB is associated with more severe loss of default mode network connectivity. Additionally, higher functional connectivity between brain regions is related to higher tau pathology levels in cognitively normal, Alzheimer's disease, and DLB patients.
Article
Neurosciences
Yueyi Yu, Xinyi Xia, Xiaosheng Meng, Dan Li, Qi Qin
Summary: This study investigated the feasibility of using plasma p-tau181 and A beta(42) as potential biomarkers to differentiate AD and DLB. The results showed that plasma p-tau181 was significantly lower in DLB than in AD and healthy controls, while plasma A beta(42) was significantly higher in DLB than in AD but lower than in healthy controls. Both plasma biomarkers showed good accuracy in distinguishing DLB from healthy controls, while A beta(42) had better accuracy than p-tau181 in discriminating DLB from AD. These findings confirm the high diagnostic value of plasma p-tau181 and A beta(42) for distinguishing patients with DLB from healthy controls.
JOURNAL OF ALZHEIMERS DISEASE
(2023)
Article
Clinical Neurology
Qin Chen, Scott A. Przybelski, Matthew L. Senjem, Christopher G. Schwarz, Timothy G. Lesnick, Hugo Botha, David S. Knopman, Jonathan Graff-Radford, Rodolfo Savica, David T. Jones, Julie A. Fields, Manoj K. Jain, Neill R. Graff-Radford, Tanis J. Ferman, Walter K. Kremers, Clifford R. Jack, Ronald C. Petersen, Bradley F. Boeve, Val J. Lowe, Kejal Kantarci
Summary: This study investigated the longitudinal rate of tau accumulation and its association with neurodegeneration and clinical disease progression in patients with dementia with Lewy bodies (DLB). The study found that DLB patients had a faster increase in flortaucipir SUVr compared to the control group, with increased accumulation rates in the lateral occipital and temporoparietal cortices. These increased rates of tau accumulation were associated with neurodegeneration and faster disease progression in DLB.
MOVEMENT DISORDERS
(2022)
Article
Geriatrics & Gerontology
Elijah Mak, Nicolas Nicastro, Maura Malpetti, George Savulich, Ajenthan Surendranathan, Negin Holland, Luca Passamonti, P. Simon Jones, Stephen F. Carter, Li Su, Young T. Hong, Tim D. Fryer, Guy B. Williams, Franklin Aigbirhio, James B. Rowe, John T. O'Brien
Summary: The study examined the distribution of tau burden in patients with DLB and AD, revealing a lower tau deposition in DLB patients compared to AD patients. The findings suggest that tau may interact synergistically with other pathologic processes to aggravate disease severity in DLB, as indicated by its associations with cognitive impairment.
NEUROBIOLOGY OF AGING
(2021)
Article
Geriatrics & Gerontology
Guili Zhang, Shuai Liu, Zhichao Chen, Zhihong Shi, Wenzheng Hu, Lingyun Ma, Xiaodan Wang, Xudong Li, Yong Ji
Summary: Elevated plasma total homocysteine (tHcy) levels were independently associated with dementia with Lewy bodies (DLB) and Alzheimer's disease (AD). The association was stronger for DLB than for AD, and future longitudinal studies are needed to confirm the causative role of tHcy in DLB.
FRONTIERS IN AGING NEUROSCIENCE
(2021)
Article
Clinical Neurology
Nicholas J. Ashton, Albert Puig-Pijoan, Marta Mila-Aloma, Aida Fernandez-Lebrero, Greta Garcia-Escobar, Fernando Gonzalez-Ortiz, Przemyslaw R. Kac, Wagner S. Brum, Andrea L. Benedet, Juan Lantero-Rodriguez, Theresa A. Day, Jeroen Vanbrabant, Erik Stoops, Eugeen Vanmechelen, Gallen Triana-Baltzer, Setareh Moughadam, Hartmuth Kolb, Paula Ortiz-Romero, Thomas K. Karikari, Carolina Minguillon, Juan Jose Hernandez Sanchez, Irene Navalpotro-Gomez, Oriol Grau-Rivera, Rosa Maria Manero, Victor Puente-Periz, Rafael de la Torre, Jaume Roquer, Jeff L. Dage, Henrik Zetterberg, Kaj Blennow, Marc Suarez-Calvet
Summary: This study compared the main blood phosphorylated tau immunoassays in a memory clinic population and found that several plasma p-tau biomarkers can be used as stand-alone biomarkers to detect Alzheimer's disease.
ALZHEIMERS & DEMENTIA
(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
Neurosciences
Rebecca R. Valentino, Chloe Ramnarine, Michael G. Heckman, Patrick W. Johnson, Alexandra I. Soto-Beasley, Ronald L. Walton, Shunsuke Koga, Koji Kasanuki, Melissa E. Murray, Ryan J. Uitti, Julie A. Fields, Hugo Botha, Vijay K. Ramanan, Kejal Kantarci, Val J. Lowe, Clifford R. Jack, Nilufer Ertekin-Taner, Rodolfo Savica, Jonathan Graff-Radford, Ronald C. Petersen, Joseph E. Parisi, R. Ross Reichard, Neill R. Graff-Radford, Tanis J. Ferman, Bradley F. Boeve, Zbigniew K. Wszolek, Dennis W. Dickson, Owen A. Ross
Summary: This study investigates the impact of mitochondrial DNA (mtDNA) haplogroup background on the risk of dementia with Lewy bodies (DLB) and the severity of neuropathological diseases. The results suggest that there are no significant associations between mtDNA haplogroups and the risk of DLB or Lewy body disease (LBD) with a high likelihood of having DLB (LBD-hDLB). However, haplogroup H may have a protective effect against DLB risk and neuronal loss in substantia nigra regions in LBD-hDLB cases, but further validation is needed.
ACTA NEUROPATHOLOGICA COMMUNICATIONS
(2022)
Article
Clinical Neurology
Paul C. Donaghy, Michael Firbank, George Petrides, Jim Lloyd, Nicola Barnett, Kirsty Olsen, Amanda Heslegrave, Henrik Zetterberg, Alan J. Thomas, John T. O'Brien
Summary: Plasma biomarkers are correlated with A beta deposition in DLB and can be used to identify A beta-positive cases and predict the rate of cognitive decline.
PARKINSONISM & RELATED DISORDERS
(2022)
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
Neurosciences
Jinghuan Gan, Shuai Liu, Zhichao Chen, Yaqi Yang, Lingyun Ma, Qingbo Meng, Xiao-Dan Wang, Chunyan Liu, Xudong Li, Wei Zhang, Yong Ji
Summary: Elevated plasma orexin-A levels were observed in patients with MCI-LB or DLB, while lower levels were found in DLB patients with fluctuating cognition or parkinsonism. Plasma orexin-A levels were associated with the presence of core features and motor and neuropsychiatric symptoms in patients with MCI-LB and DLB.
JOURNAL OF ALZHEIMERS DISEASE
(2022)
Article
Clinical Neurology
Sara Hall, Shorena Janelidze, Elisabet Londos, Antoine Leuzy, Erik Stomrud, Jeffrey L. Dage, Oskar Hansson
Summary: This study investigated plasma phospho-tau217 and phospho-tau181 in 35 patients with Lewy body disease with dementia, finding correlations with CSF and tau-PET imaging, and predictive value for pathological status. Plasma phospho-tau may serve as a useful marker for Alzheimer's co-pathology in Lewy body disease with dementia.
MOVEMENT DISORDERS
(2021)
Article
Psychiatry
Kai Sin Chin, Leonid Churilov, Vincent Dore, Victor L. Villemagne, Christopher C. Rowe, Nawaf Yassi, Rosie Watson
Summary: This study found that tau protein is commonly present in individuals with dementia with Lewy bodies and may be associated with worse cognition. The levels of plasma p-tau181 correlated with tau deposition and amyloid-beta binding, suggesting its potential as a marker for identifying co-morbid Alzheimer's disease-related pathology in dementia with Lewy bodies. Further research is needed to evaluate the clinical implications of tau in larger longitudinal studies.
AUSTRALIAN AND NEW ZEALAND JOURNAL OF PSYCHIATRY
(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)
Review
Neurosciences
Jay Amin, Daniel Erskine, Paul C. Donaghy, Ajenthan Surendranathan, Peter Swann, Amy P. Kunicki, Delphine Boche, Clive Holmes, Ian G. McKeith, John T. O'Brien, Jessica L. Teeling, Alan J. Thomas
Summary: This article provides a review of the role of inflammation in Dementia with Lewy bodies (DLB). The research suggests an increase in cerebral and peripheral inflammation in the early stages of DLB, which decreases as the disease progresses. Alpha-synuclein is found to directly promote inflammation, and the presence of Alzheimer's disease (AD) co-pathology contributes to the profile of neuroinflammation in DLB. Further longitudinal studies are recommended to enhance our understanding of the disease's pathogenesis and develop a composite biomarker for DLB diagnosis and identification of new therapeutic targets.
NEUROBIOLOGY OF DISEASE
(2022)
Article
Clinical Neurology
Jijing Wang, Cong Guo, Zhaowei Meng, Marissa D. Zwan, Xin Chen, Sven Seelow, Susanna L. Lundstrom, Sergey Rodin, Charlotte E. Teunissen, Roman A. Zubarev
Summary: This study strengthens the association between isoAsp and Alzheimer's disease (AD) using novel approaches to isoAsp analysis in blood samples. The findings demonstrate elevated isoAsp levels, reduced anti-isoAsp antibodies, increased A beta concentration, and more protein aggregation in AD blood compared to controls. Additionally, deamidation reduces the binding capacity of blood protein HSA with A beta and p-tau.
ALZHEIMERS & DEMENTIA
(2023)
Article
Clinical Neurology
Harald Hegen, Georgina Arrambide, Sharmilee Gnanapavan, Batia Kaplan, Michael Khalil, Ruba Saadeh, Charlotte Teunissen, Hayrettin Tumani, Luisa Maria Villar, Maria Alice Willrich, Henrik Zetterberg, Florian Deisenhammer
Summary: Cerebrospinal fluid (CSF) analysis is crucial for diagnosing and differentiating multiple sclerosis (MS) patients. Detection of CSF-restricted oligoclonal bands (OCBs) and kappa-free light chains (FLCs) proves the inflammatory nature of the disease and enhances diagnostic accuracy. Kappa-FLCs offer advantages such as fast, easy, cost-effective, reliable detection, and quantitative results, which can improve the prediction of MS disease activity. The international panel of experts recommends including intrathecal kappa-FLC synthesis in the next revision of MS diagnostic criteria.
MULTIPLE SCLEROSIS JOURNAL
(2023)
Review
Clinical Neurology
Harald Hegen, Janette Walde, Klaus Berek, Georgina Arrambide, Sharmilee Gnanapavan, Batia Kaplan, Michael Khalil, Ruba Saadeh, Charlotte Teunissen, Hayrettin Tumani, Luisa M. Villar, Maria Alice Willrich, Henrik Zetterberg, Florian Deisenhammer
Summary: This study conducted a systematic review and meta-analysis to evaluate the diagnostic value of kappa-FLC index compared to OCB in identifying patients with CIS or MS, and to determine the cut-off for kappa-FLC index. The findings indicate that kappa-FLC index has similar diagnostic accuracy in MS as OCB.
MULTIPLE SCLEROSIS JOURNAL
(2023)
Article
Clinical Neurology
Floor C. Loonstra, Lodewijk R. J. de Ruiter, Marleen J. A. Koel-Simmelink, Menno M. Schoonheim, Eva M. M. Strijbis, Bastiaan Moraal, Frederik Barkhof, Bernard M. J. Uitdehaag, Charlotte Teunissen, Joep Killestein
Summary: This study explores the association between novel blood biomarkers (sNfL, sGFAP, and sCNTN1) and disability outcome measures and MRI volumes in people with multiple sclerosis (MS). The results indicate that sNfL and sGFAP are associated with disease progression, while sCNTN1 is not related to clinical or MRI measures.
NEUROLOGY-NEUROIMMUNOLOGY & NEUROINFLAMMATION
(2023)
Article
Psychology, Educational
Thomas B. McGuckian, Peter H. Wilson, Rich D. Johnston, Shahin Rahimi-Golkhandan, Jan Piek, Dido Green, Jeffrey M. Rogers, Paul Maruff, Bert Steenbergen, Scott Ruddock
Summary: This longitudinal study examined the development of children's complex executive function (EF) using the Groton Maze Learning Task (GMLT). A total of 147 children (61 males, ages 5.5-11 years) were recruited from six multicultural primary schools in Melbourne and Perth, Australia. The study spanned from 2010 to 2012, with assessments on the GMLT conducted every 6 months. Growth curve models indicated a quadratic growth trajectory in each measure of error, reflecting visuospatial memory, executive control, and complex EF. The ability to apply rules for action, a key aspect of complex EF, developed rapidly during early-to-mid childhood.
Article
Clinical Neurology
Jelle Y. Broos, Floor C. Loonstra, Lodewijk R. J. de Ruiter, Mariam Gouda, Wing Hee Fung, Menno M. Schoonheim, Marieke Heijink, Eva M. M. Strijbis, Charlotte Teunissen, Joep Killestein, Helga E. de Vries, Martin Giera, Bernard M. J. Uitdehaag, Gijs Kooij
Summary: This study investigated the association between bioactive lipid mediators (LMs) and clinical, biochemical, and MRI parameters in patients with multiple sclerosis (MS). The LM profiles of patients with progressive MS (PMS) were significantly different from those of patients with relapsing remitting MS (RRMS) and healthy controls (HCs), particularly with elevated levels of arachidonic acid (AA) derivatives. Specifically, 15-hydroxyeicosatetraenoic acid (HETE) was correlated with clinical and biochemical parameters and associated with neurodegenerative processes in PMS patients.
Article
Clinical Neurology
Maarten J. Mackenbach, Eline A. J. Willemse, Jan J. A. van den Dorpel, Nadine A. M. E. van der Beek, Jordi Diaz-Manera, Dimitris Rizopoulos, Charlotte Teunissen, Ans T. van der Ploeg, Johanna M. P. van den Hout
Summary: This study examines the association between neurofilament light (NfL) and central nervous system (CNS) involvement in patients with classic infantile Pompe disease. The results suggest that NfL levels may serve as a potential biomarker for assessing CNS damage in this population.
Article
Psychology, Clinical
Lisa Bransby, Emily Rosenich, Rachel F. Buckley, Nawaf Yassi, Matthew P. Pase, Paul Maruff, Yen Ying Lim
Summary: This study aimed to determine the frequency and co-occurrence of modifiable dementia risk factors (MDRFs) in a large sample of middle-aged adults. The results showed that most individuals reported MDRFs in two or more domains, and these multidomain MDRFs were related to poorer cognition.
Article
Multidisciplinary Sciences
Dea Gogishvili, Eleonora M. Vromen, Sascha Koppes-den Hertog, Afina W. Lemstra, Yolande A. L. Pijnenburg, Pieter Jelle Visser, Betty M. Tijms, Marta Del Campo, Sanne Abeln, Charlotte E. Teunissen, Lisa Vermunt
Summary: This study used machine learning techniques to identify cerebrospinal fluid (CSF) biomarkers that predict the rate of cognitive decline in dementia patients. Longitudinal mini-mental state examination scores (MMSE) were used to create fast and slow progression groups. Random forest classifiers were trained on CSF proteomic profiles and a well-performing prediction model for the progression group was obtained. TNFRSF4 and TGF beta-1 emerged as the top markers for predicting cognitive decline.
SCIENTIFIC REPORTS
(2023)
Article
Clinical Neurology
Marie-Paule E. van Engelen, Hans Heijst, Eline A. J. Willemse, Mardien L. Oudega, Lisa Vermunt, Philip Scheltens, Everard G. B. Vijverberg, Yolande A. L. Pijnenburg, Charlotte E. Teunissen
Summary: The clinical overlap of frontotemporal dementia and primary psychiatric diseases makes diagnostic distinction difficult, leading to misdiagnosis and delay. Measurement of neurofilament light chain in urine is not suitable for differentiating frontotemporal dementia from psychiatric disorders, and serum neurofilament light chain remains the most patient-friendly matrix for differentiation.
BRAIN COMMUNICATIONS
(2023)
Editorial Material
Neurosciences
John J. Alam, Ralph A. Nixon
MOLECULAR NEURODEGENERATION
(2023)
Article
Clinical Neurology
Yanaika S. S. Hok-A-Hin, Katharina Bolsewig, Daimy N. N. Ruiters, Alberto Lleo, Daniel Alcolea, Afina W. W. Lemstra, Wiesje M. M. van der Flier, Charlotte E. E. Teunissen, Marta del Campo
Summary: Our study showed that THOP1 can serve as an early specific biomarker for Alzheimer's Disease (AD). We developed THOP1 immunoassays and validated our findings in two independent cohorts.
ALZHEIMER'S & DEMENTIA: DIAGNOSIS, ASSESSMENT & DISEASE MONITORING
(2023)
Article
Cell Biology
Wiesje M. van der Flier, Marjolein E. de Vugt, Ellen M. A. Smets, Marco Blom, Charlotte E. Teunissen
Summary: Alzheimer's disease is a significant healthcare challenge with no current cure. This perspective proposes a strategy to shift the focus towards the pre-dementia stages and invest in personalized medicine for diagnosis, prediction and prevention. It suggests empowering patients and the public to actively participate in managing their health and disease, and developing improved strategies for early intervention.