Article
Geriatrics & Gerontology
Niels Hansen, Claudia Lange, Charles Timaeus, Jens Wiltfang, Caroline Bouter
Summary: The study found that 55% of patients with positive 123I-FP-CIT SPECT and probable DLB exhibited psychiatric features, and there was a significant increase in the number of probable DLB patients with psychiatric symptoms after undergoing 123I-FP-CIT SPECT over a 6-year period. Additionally, there were no phenotypical differences between DLB patients with positive and negative 123I-FP-CIT SPECT.
FRONTIERS IN AGING NEUROSCIENCE
(2021)
Article
Geriatrics & Gerontology
Toji Miyagawa, Scott A. Przybelski, Daniela Maltais, Hoon-Ki Min, Lennon Jordan, Timothy G. Lesnick, Qin Chen, Jonathan Graff-Radford, David Jones, Rodolfo Savica, David Knopman, Ronald Petersen, Walter K. Kremers, Leah K. Forsberg, Julie A. Fields, Tanis J. Ferman, Laura Allen, Joseph Parisi, R. Ross Reichard, Melissa Murray, Dennis Dickson, Bradley F. Boeve, Kejal Kantarci, Val J. Lowe
Summary: Multimodal imaging with I-123-FP-CIT SPECT helps differentiate DLBs and ADem, providing additional diagnostic value and detecting complex pathology in patients with DLBs and ADem.
NEUROBIOLOGY OF AGING
(2021)
Article
Neurosciences
Young-gun Lee, Seun Jeon, Kyoungwon Baik, Sung Woo Kang, Byoung Seok Ye
Summary: This study used FP-CIT PET to analyze the DAT uptake patterns in patients with DLB and MCI-LB, as well as healthy controls. The results showed that evaluating nigral DAT uptake can improve the diagnostic accuracy of DLB and MCI-LB. Lower nigral DAT uptake was associated with visual hallucination, severe parkinsonism, cognitive dysfunction, and widespread gray matter atrophy in DLB and MCI-LB patients.
NPJ PARKINSONS DISEASE
(2023)
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
Radiology, Nuclear Medicine & Medical Imaging
Cecilia Boccalini, Nicolas Nicastro, Debora Elisa Peretti, Silvia Paola Caminiti, Daniela Perani, Valentina Garibotto
Summary: This study aimed to assess whether sex can influence neurotransmitter systems in patients with probable DLB. The results showed that females patients displayed lower I-123-FP-CIT binding and more extensive regional and spatial connectivity impairments compared to males.
EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING
(2023)
Article
Neurosciences
Lars Frings, Franziska Henninger, Martin Treppner, Goran Koeber, Martin Boeker, Philipp T. Meyer
Summary: DAT SPECT, commonly used in dementia diagnostics, has been found to provide valuable prognostic information. Patients with nigrostriatal degeneration (NSD) detected by DAT SPECT have a significantly higher mortality risk compared to those without NSD, with lower striatal DAT binding associated with increased mortality risk.
JOURNAL OF ALZHEIMERS DISEASE
(2021)
Article
Multidisciplinary Sciences
Mahmood Nazari, Andreas Kluge, Ivayla Apostolova, Susanne Klutmann, Sharok Kimiaei, Michael Schroeder, Ralph Buchert
Summary: This study utilized explainable artificial intelligence to identify extrastriatal brain regions that could assist in the interpretation of dopamine transporter SPECT in parkinsonian syndromes. The study found that besides the striatum, other brain regions like insula, amygdala, and prefrontal cortex also played a significant role in differentiating neurodegenerative and non-neurodegenerative parkinsonian syndromes.
SCIENTIFIC REPORTS
(2021)
Review
Biochemistry & Molecular Biology
Olivier Bousiges, Frederic Blanc
Summary: Dementia with Lewy Bodies (DLB) is a common cognitive neurodegenerative disease with clinical similarity to Alzheimer's disease (AD). This review examines the interest of different biomarkers in distinguishing DLB from AD, with a focus on cerebrospinal fluid (CSF), brain MRI, FP-CIT SPECT, MIBG SPECT, and PET. FP-CIT SPECT shows high interest in discriminating DLB and AD, while other biomarkers like MIBG SPECT, perfusion SPECT, FDG PET, and CSF biomarkers have lower validity. The potential of CSF synuclein RT-QuIC as a discrimination tool is highlighted, but its application in clinical routine needs further demonstration.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(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)
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
Computer Science, Artificial Intelligence
Diego Castillo-Barnes, Carmen Jimenez-Mesa, Francisco J. Martinez-Murcia, Diego Salas-Gonzalez, Javier Ramirez, Juan M. Gorriz
Summary: Spatial normalization allows quantitative comparison of brain scans and the quantification of bias introduced by nonlinear transformations is important for studying neurological disorders. Nonlinear transformations can alter diagnosis outcomes and introduce artificial information.
INTERNATIONAL JOURNAL OF NEURAL SYSTEMS
(2022)
Article
Multidisciplinary Sciences
Hiroki Nosaka, Masahisa Onoguchi, Hiroyuki Tsushima, Masaya Suda, Satoshi Kurata, Ayano Onoma, Ryosuke Murakawa
Summary: This study investigated the effect of brain atrophy on the analysis of N-omega-fluoropropyl-2 beta-carbomethoxy-3 beta-(4-[123I] iodophenyl) nortropane ([I-123]FP-CIT) single-photon emission computed tomography (SPECT) using Monte Carlo simulations. The results showed that as brain atrophy progressed, the specific binding ratio (SBR) was overestimated and the reference region value was more affected.
SCIENTIFIC REPORTS
(2022)
Review
Clinical Neurology
Balestrino Roberta, Barone Paolo, Filippi Massimo, Erro Roberto
Summary: Although the diagnosis of Parkinson's disease relies on clinical presentation, the use of imaging techniques, particularly DAT imaging, can aid in differential diagnosis. Structural lesions and certain medications may alter the results of DAT imaging, and unexpected findings such as SWEDD or SWIDD should be considered.
JOURNAL OF NEUROLOGY
(2022)
Review
Clinical Neurology
Stephen B. E. Wharton, Julie E. G. Simpson, Paul G. D. Ince, Connor D. Richardson, Richard E. Merrick, Fiona E. Matthews, Carol Brayne, CFAS
Summary: The epidemiological neuropathology perspective of population studies provides insights on the prevalence of different pathologies related to late-life dementia. Major findings from the Cognitive Function and Ageing Study (CFAS) and other studies indicate a high prevalence of Alzheimer's disease and vascular pathology in the ageing brain. Pathologies such as TDP-43 encephalopathy, ageing-related tau astrogliopathy, and primary age-related tauopathies also contribute to late-life dementia.
NEUROPATHOLOGY AND APPLIED NEUROBIOLOGY
(2023)
Review
Radiology, Nuclear Medicine & Medical Imaging
Mario Jreige, George K. K. Kurian, Jeremy Perriraz, Jevita Potheegadoo, Fosco Bernasconi, Sara Stampacchia, Olaf Blanke, Griffa Alessandra, Noemie Lejay, Paolo Salvioni Chiabotti, Olivier Rouaud, Marie Nicod Lalonde, Niklaus Schaefer, Giorgio Treglia, Gilles Allali, John O. O. Prior
Summary: This article is a systematic review of the application of dopaminergic scintigraphic imaging in the diagnosis of dementia with Lewy bodies. The results show that dopaminergic imaging plays a significant role in the assessment of dementia with Lewy bodies, aiding in early diagnosis and clinical evaluation. Most studies used a semi-quantitative analysis method to assess tracer uptake, and the superiority of purely quantitative analysis methods needs further investigation.
EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING
(2023)
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
Health Care Sciences & Services
Rebecca Gathercole, Rosie Bradley, Emma Harper, Lucy Davies, Lynn Pank, Natalie Lam, Anna Davies, Emma Talbot, Emma Hooper, Rachel Winson, Bethany Scutt, Victoria Ordonez Montano, Samantha Nunn, Grace Lavelle, Matthew Lariviere, Shashivadan Hirani, Stefano Brini, Andrew Bateman, Peter Bentham, Alistair Burns, Barbara Dunk, Kirsty Forsyth, Chris Fox, Catherine Henderson, Martin Knapp, Iracema Leroi, Stanton Newman, John O'Brien, Fiona Poland, John Woolham, Richard Gray, Robert Howard
Summary: This report includes parts reproduced with permission from the respective authors and published under open access licenses, allowing for free distribution and reproduction with proper citation. Minor modifications and formatting changes may have been made to the original text.
HEALTH TECHNOLOGY ASSESSMENT
(2021)
Article
Clinical Neurology
Negin Holland, Maura Malpetti, Timothy Rittman, Elijah E. Mak, Luca Passamonti, Sanne S. Kaalund, Frank H. Hezemans, P. Simon Jones, George Savulich, Young T. Hong, Tim D. Fryer, Franklin Aigbirhio, John T. O'Brien, James B. Rowe
Summary: The relationship between in vivo synaptic density and molecular pathology in primary tauopathies, especially in progressive supranuclear palsy and corticobasal degeneration, is investigated in this study. It is found that there is a biphasic correlation between synaptic density and molecular pathology, with regions rich in synapses more vulnerable to pathological aggregates accumulation, followed by synaptic loss as a response to the molecular pathology. These findings contribute to a better understanding of the pathophysiology of primary tauopathies and may inform the design of future clinical trials.
Article
Neurosciences
Kitty Pham, Anwar Mulugeta, Ang Zhou, John T. O'Brien, David J. Llewellyn, Elina Hypponen
Summary: The study found that high coffee consumption was associated with smaller total brain volumes and increased odds of dementia, but had less evidence for an association with stroke.
NUTRITIONAL NEUROSCIENCE
(2022)
Article
Clinical Neurology
Ramtin Mehraram, Luis R. Peraza, Nicholas R. E. Murphy, Ruth A. Cromarty, Sara Graziadio, John T. O'Brien, Alison Killen, Sean J. Colloby, Michael Firbank, Li Su, Daniel Collerton, John-Paul Taylor, Marcus Kaiser
Summary: This study investigates visual hallucinations in Lewy body dementia using EEG source localization and diffusion tensor imaging. The findings suggest consistent weakened connectivity within the visual ventral network and between this network and other networks in hallucinating patients. Structural analysis reveals affected white matter streamlines connecting cortical regions to the nucleus basalis of Meynert and the thalamus in hallucinating patients. This study provides empirical evidence for existing models of visual hallucinations in Lewy body dementia.
Article
Neurosciences
Andrea Luppi, Pedro A. M. Mediano, Fernando E. Rosas, Negin Holland, Tim D. Fryer, John T. O'Brien, James B. Rowe, David K. Menon, Daniel Bor, Emmanuel A. Stamatakis
Summary: This study decomposes neural information into synergistic and redundant components, showing the role of core brain regions in supporting higher cognition and demonstrating that humans leverage synergistic information more than macaques. The study also reveals the distinct roles of redundant and synergistic interactions in neural information processing.
NATURE NEUROSCIENCE
(2022)
Article
Geriatrics & Gerontology
Emad Sidhom, Mc Stephen Padilla, Jonathan Lewis, Simon White, John T. O'Brien, Giovanna R. Mallucci, Benjamin R. Underwood
Summary: The unfolded protein response has been identified as an important pathway and target for therapeutic intervention in neurodegeneration. However, the antidepressant trazodone, which has been proposed to act on this pathway, did not show disease modifying effects in previous studies. A new study examining electronic patient records of dementia patients in Cambridgeshire UK found that trazodone is rarely prescribed and at a lower dose than predicted. Patients prescribed trazodone had higher levels of neuropsychiatric symptoms and were in a late stage of the disease, suggesting that therapeutic intervention may no longer be effective.
INTERNATIONAL JOURNAL OF GERIATRIC PSYCHIATRY
(2022)
Article
Clinical Neurology
Daniel J. Tozer, Robin B. Brown, Jessica Walsh, Young T. Hong, Guy B. Williams, John T. O'Brien, Franklin I. Aigbirhio, Tim D. Fryer, Hugh S. Markus
Summary: Recent studies have found evidence of increased microglial activation, indicating inflammation, in cerebral small vessel disease. However, it is unclear whether these areas of neuroinflammation progress to tissue damage. This study showed that white matter destined to become white matter hyperintensities already exhibited signs of altered inflammation at baseline.
Article
Medicine, General & Internal
Shanquan Chen, Annabel C. Price, Rudolf N. Cardinal, Sinead Moylett, Anne D. Kershenbaum, James Fitzgerald, Christoph Mueller, Robert Stewart, John T. O'Brien
Summary: This study aimed to investigate the association between the use of acetylcholinesterase inhibitors (AChEIs) and/or memantine in patients with dementia with Lewy bodies (DLBs) and their hospital admissions and mortality rates. The results showed that the use of AChEIs and/or memantine was associated with a reduced risk of death and shorter hospital stays for DLB patients.
Article
Geriatrics & Gerontology
Anne D. Kershenbaum, Annabel C. Price, Rudolf N. Cardinal, Shanquan Chen, James M. Fitzgerald, Jonathan Lewis, Sinead Moylett, John T. O'Brien
Summary: Previous studies have shown reduced survival in Lewy body dementia (LBD) compared to Alzheimer's disease (AD), but the reasons for this are not known. This study aimed to identify cause of death categories accounting for the reduced survival in LBD. The findings indicated that PDD and DLB patients had higher hazard ratios for death compared to AD patients.
INTERNATIONAL JOURNAL OF GERIATRIC PSYCHIATRY
(2023)
Review
Biochemistry & Molecular Biology
Leonidas Chouliaras, John T. O'Brien
Summary: Dementia is a major cause of disability and death worldwide, with no disease modifying treatment available for common types such as Alzheimer's disease, Vascular dementia, Lewy Body Dementia, and Frontotemporal dementia. Early and accurate diagnosis of dementia subtype is crucial for improving clinical care and developing better treatments. Structural and molecular imaging methods, particularly multimodal magnetic resonance imaging (MRI) and positron emission tomography imaging (PET), have provided insight into the pathophysiology of neurodegenerative dementias and are increasingly being used for early and accurate diagnosis. However, there are still gaps in imaging tracers for certain protein abnormalities, and more extensive diagnostic imaging studies are needed.
MOLECULAR PSYCHIATRY
(2023)
Article
Clinical Neurology
Laura M. Wright, Paul C. Donaghy, David J. Burn, John -Paul Taylor, John T. O'Brien, Alison J. Yarnall, Fiona E. Matthews, Michael J. Firbank, Alan J. Thomas, Rachael A. Lawson
Summary: There is a limited longitudinal relationship between neuropsychiatric symptoms (NPS) and cognitive decline in prodromal Lewy body dementias (LBD). Core neuropsychiatric symptoms are not strongly associated with cognition, suggesting different underlying neuropathological mechanisms.
PARKINSONISM & RELATED DISORDERS
(2023)
Article
Clinical Neurology
Weijie Huang, Jianmin Zeng, Lina Jia, Dajiang Zhu, John O'Brien, Craig Ritchie, Ni Shu, Li Su
Summary: Genetic risk factors such as APOE ε4 and MAPT A allele are associated with changes in amyloid and tau pathways and cortical morphology in young healthy adults. Machine learning models showed that using all cortical features could accurately classify individuals with genetic risks of dementia. APOE ε4 carriers exhibited a more convoluted and thinner cortex across the cerebral cortex, while MAPT A allele carriers showed similar patterns in regions vulnerable to early tau pathology. There was a synergetic effect between APOE ε4 and MAPT A allele, with carriers of both risk factors showing the most deviation from the typical cortical pattern.
BRAIN COMMUNICATIONS
(2023)
Article
Clinical Neurology
Maria-Eleni Dounavi, Audrey Low, Graciela Muniz-Terrera, Karen Ritchie, Craig W. Ritchie, Li Su, Hugh S. Markus, John T. O'Brien
Summary: In healthy midlife adults, Dounavi and Low demonstrate that fluid-attenuated inversion recovery (FLAIR) MRI textural measures emerging from white matter hyperintensities (WMHs) and normal appearing white matter, related to WMH volume, reaction time and dementia risk. The observed associations suggest that FLAIR textural analysis might capture subtle white matter microstructural alterations.
BRAIN COMMUNICATIONS
(2022)
Article
Clinical Neurology
Jessica Walsh, Dan J. Tozer, Hasan Sari, Young T. Hong, Anna Drazyk, Guy Williams, N. Jon Shah, John T. O'Brien, Franklin Aigbirhio, Gary Rosenberg, Tim D. Fryer, Hugh S. Markus
Summary: Cerebral small vessel disease is a major cause of stroke and dementia. The study found that in sporadic SVD patients, microglial activation and increased blood-brain barrier permeability occur separately in spatial terms. No evidence of increased blood-brain barrier permeability was found in CADASIL.
