Search Our Scientific Publications & Authors

PLoS One 2019 18;14(4):e0215384. Epub 2019 Apr 18.

Morton and Gloria Shulman Movement Disorders Centre and the Edmond J Safra Program in Parkinson's Research, Toronto Western Hospital, Toronto, Ontario, Canada.

Background: Successful patient-physician communication is critical for improving health outcomes, but research regarding optimal communication practices in Parkinson's disease is limited. The objective of the current study was to investigate barriers and facilitators of communication between persons with Parkinson's disease, carepartners, and physicians, specifically in the setting of off periods, with the goal of identifying ways to improve patient-carepartner-physician communication.

Method: We interviewed persons with Parkinson's, carepartners, and physicians (specialists and non-specialists) using a semi-structured questionnaire to identify and describe experiences, barriers, and facilitators relating to communication about off periods in Parkinson's disease. Read More

Psychogeriatrics 2019 Apr 17. Epub 2019 Apr 17.

Department of Psychiatry, Juntendo University School of Medicine, Tokyo, Japan.

Differentiating posterior cortical atrophy (PCA) from other diseases can be difficult and time-consuming, and there is a particularly high possibility of misdiagnosis when psychiatrists diagnose complaints related to visual perception. Here, a case of PCA involving prominent visual perceptual disorders is reported; PCA was difficult to distinguish from psychogenic disturbance of vision in this case. For a year, a 59-year-old woman had had visual perceptual disorders, including a distorted view and prosopagnosia. Read More

Int J Geriatr Psychiatry 2019 Apr 16. Epub 2019 Apr 16.

Institute of Neuroscience, Newcastle upon Tyne, United Kingdom.

Background: Inflammation appears to play a role in the progression of neurodegenerative diseases. However, little is known about inflammation during early stages of cognitive decline or whether this differs in different disease groups. We sought to investigate this by assessing the inflammatory profile in patients with Parkinson's disease with the early stages of cognitive impairment (PD-MCI), patients with prodromal Alzheimer's disease (MCI-AD), prodromal Lewy Body disease (MCI-LB) and controls. Read More

Neuroimage Clin 2019 Apr 3;22:101812. Epub 2019 Apr 3.

Institute of Neuroscience, Newcastle University, Campus for Ageing and Vitality, Newcastle upon Tyne NE4 5PL, United Kingdom.

We studied the dynamic functional connectivity profile of dementia with Lewy bodies (DLB) and Alzheimer's disease (AD) compared to controls, how it differs between the two dementia subtypes, and a possible relation between dynamic connectivity alterations and temporally transient clinical symptoms in DLB. Resting state fMRI data from 31 DLB, 29 AD, and 31 healthy control participants were analyzed using dual regression to determine between-network functional connectivity. Subsequently, we used a sliding window approach followed by k-means clustering and dynamic network analyses to study dynamic functional connectivity. Read More

Eur J Nucl Med Mol Imaging 2019 Apr 12. Epub 2019 Apr 12.

Department of Neurology, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun-gu, Seoul, 30722, South Korea.

Purpose: Little is known regarding the clinical relevance or neurobiology of subtle motor disturbance in Alzheimer's disease (AD). This study aims to investigate the patterns of striatal F-FP-CIT uptake in patients with AD-related cognitive impairment (ADCI) with mild parkinsonism.

Methods: We recruited 29 consecutive patients with ADCI with mild parkinsonism. Read More

Neuropathol Appl Neurobiol 2019 Apr 12. Epub 2019 Apr 12.

Reta Lila Weston Institute, UCL Queen Square Institute of Neurology, London.

Lewy body dementias are the second most common neurodegenerative dementias after Alzheimer's disease, and include dementia with Lewy bodies and Parkinson's disease dementia. They share similar clinical and neuropathological features but differ in the time of dementia and parkinsonism onset. Although Lewy bodies are their main pathological hallmark, several studies have shown the emerging importance of Alzheimer's disease pathology. Read More

Neurocase 2019 Apr 10:1-4. Epub 2019 Apr 10.

a Department of Neurology , Mayo Clinic , Rochester , MN , USA.

Hereditary diffuse leukoencephalopathy with spheroids (HDLS) is an adult-onset autosomal dominant leukoencephalopathy resulting from mutations affecting the tyrosine kinase domain of the colony stimulating factor receptor 1 protein (encoded by CSF1R). The clinical phenotypes reported with CSF1R mutations are variable. We present a case of a patient with a pathogenic variant in the CSF1R gene with clinical and imaging features suggestive of Dementia with Lewy Bodies (DLB). Read More

Mov Disord 2019 Apr 9. Epub 2019 Apr 9.

Department of Neurology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.

Background: Recently, the LRP10 gene has been identified as a novel genetic cause in individuals affected by Parkinson's disease (PD), Parkinson's disease dementia, or dementia with Lewy bodies.

Objective: We investigated the involvement of LRP10 mutations in Chinese patients with familial PD and reviewed previous studies of LRP10 mutations in patients with PD.

Methods: A mutation analysis of the LRP10 gene was performed in a cohort of 205 unrelated Chinese patients with familial PD. Read More

J Parkinsons Dis 2019 Apr 3. Epub 2019 Apr 3.

Department of Neurology, University of Pittsburgh, Pittsburgh, PA, USA.

Background: In patients with early parkinsonism, misdiagnosis may occur in >30% of cases. This can have detrimental consequences clinically and in clinical trials. Dopamine transporter (DAT) SPECT imaging can help improve diagnostic accuracy. Read More

J Psychiatr Res 2019 Mar 30;113:141-147. Epub 2019 Mar 30.

Center for Neurodegenerative Diseases, Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, 100050, China; China National Clinical Research Center for Neurological Diseases, Beijing, 100050, China; Parkinson's Disease Center, Beijing Institute for Brain Disorders, Capital Medical University, Beijing, 100050, China. Electronic address:

Alzheimer's disease (AD) is the most common cause of dementia in the elderly. It shares clinical and pathological features with other types of dementia, such as vascular dementia (VaD), Lewy body dementia (LBD), and frontotemporal dementia (FTD). We have hypothesized that there might be an overlapping molecular mechanism and genetic basis to the different types of dementia. Read More

Neurobiol Dis 2019 Apr 3;127:492-501. Epub 2019 Apr 3.

Department of Neurodegenerative Diseases, UCL Institute of Neurology, London, UK; UK Dementia Research Institute (UK DRI) at UCL, London, UK. Electronic address:

Recent large-scale genetic studies have allowed for the first glimpse of the effects of common genetic variability in dementia with Lewy bodies (DLB), identifying risk variants with appreciable effect sizes. However, it is currently well established that a substantial portion of the genetic heritable component of complex traits is not captured by genome-wide significant SNPs. To overcome this issue, we have estimated the proportion of phenotypic variance explained by genetic variability (SNP heritability) in DLB using a method that is unbiased by allele frequency or linkage disequilibrium properties of the underlying variants. Read More

Parkinsonism Relat Disord 2019 Mar 28. Epub 2019 Mar 28.

Department of Neurology, University of Pennsylvania School of Medicine, Philadelphia, PA, USA; Parkinson's Disease Research, Education and Clinical Center, Michael J. Crescenz Veterans Affairs Medical Center, Philadelphia, PA, USA. Electronic address:

Braak et al.'s 2003 paper detailing the caudo-rostral progression of Lewy body pathology (LP) formed the foundation of current understanding of disease spread in Parkinson's disease (PD); however, its methods are difficult to recreate and consequently multiple new staging systems emerged to recapitulate Braak's staging system using standard neuropathological methods and to account for other patterns of LP. Studies using these systems have documented widely variable rates of cases that 'fail to fit' expected patterns of LP spread. Read More

Sleep 2019 Apr 4. Epub 2019 Apr 4.

Neurology Service, Multidisciplinary Sleep Unit, Universitat de Barcelona, IDIBAPS, CIBERNED, Hospital Clinic de Barcelona, Spain.

Objective: To study REM sleep behavior disorder (RBD) and other sleep disorders in dementia with Lewy bodies (DLB).

Methods: Consecutive patients with DLB and mild dementia severity were recruited irrespective of sleep complaints. Patients underwent clinical interview, assessment of sleep scales and video-polysomnography. Read More

Neurology 2019 Apr 3. Epub 2019 Apr 3.

From the Departments of Neurology (S.W.K., H.S.Y., S.J.C., P.H.L., Y.H.S., B.S.Y.) and Nuclear Medicine (M.Y.), Yonsei University College of Medicine, Seoul, Korea; and McGill Centre for Integrative Neuroscience (S.J., A.C.E.), Montreal Neurological Institute, McGill University, Quebec, Canada.

Objectives: To investigate the independent and interaction effects of Alzheimer disease (AD) and Lewy body disease (LBD) on cognition and brain atrophy.

Methods: We consecutively recruited 38 controls and 108 patients with AD-related cognitive impairment (ADCI) and/or LBD-related cognitive impairment (LBCI) from university-based dementia and movement clinics. Diagnoses of ADCI and LBCI were supported by F-florbetaben PET and F-N-(3-fluoropropyl)-2β-carbon ethoxy-3β-(4-iodophenyl) nortropane-PET, respectively. Read More

J Proteome Res 2019 Apr 15. Epub 2019 Apr 15.

Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry , Sahlgrenska Academy at the University of Gothenburg , S-431 80 Mölndal , Sweden.

Parkinson's disease (PD) is characterized by intraneuronal inclusions of aggregated α-synuclein protein (so-called Lewy bodies) in distinct brain regions. Multiple posttranslational modifications may affect the structure and function of α-synuclein. Mass spectrometry-based analysis may be useful for the characterization and quantitation of α-synuclein forms, but has proven challenging, mainly due to the insolubility of Lewy bodies in aqueous buffer. Read More

Brain 2019 Apr 1. Epub 2019 Apr 1.

Institute of Neuroscience, Newcastle University, Campus for Ageing and Vitality, Newcastle upon Tyne, NE4 5PL, UK.

Lewy body dementia includes dementia with Lewy bodies and Parkinson's disease dementia and is characterized by transient clinical symptoms such as fluctuating cognition, which might be driven by dysfunction of the intrinsic dynamic properties of the brain. In this context we investigated whole-brain dynamics on a subsecond timescale in 42 Lewy body dementia compared to 27 Alzheimer's disease patients and 18 healthy controls using an EEG microstate analysis in a cross-sectional design. Microstates are transiently stable brain topographies whose temporal characteristics provide insight into the brain's dynamic repertoire. Read More

J Clin Neurol 2019 Apr;15(2):135-142

Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.

The common pathological features of synucleinopathies are abnormal aggregates of the synaptic protein alpha-synuclein (αSN) in the cytoplasm of neurons or glia. These abnormal aggregates appear several years before the onset of clinical manifestations, and so the early detection of αSN in body fluids or peripheral tissues (e.g. Read More

Biomolecules 2019 03 27;9(4). Epub 2019 Mar 27.

Parkinson's and Movement Disorders Center, Virginia Commonwealth University, P.O. Box 980539, Richmond, VA 23298, USA.

Parkinson's disease (PD) is a neurodegenerative disorder that exhibits aberrant protein aggregation and mitochondrial dysfunction. Ndi1, the yeast mitochondrial NADH dehydrogenase (complex I) enzyme, is a single subunit, internal matrix-facing protein. Previous studies have shown that Ndi1 expression leads to improved mitochondrial function in models of complex I-mediated mitochondrial dysfunction. Read More

BJR Case Rep 2018 Dec 30;4(4):20180030. Epub 2018 Jun 30.

Department of Neuroscience, Faculty of Medicine, Anglia Ruskin University, Chelmsford, Essex, , UK.

Despite some differences in clinical presentation, it is often difficult to differentiate between dementia with Lewy bodies (DLB), clinical Alzheimer's dementia (AD) and Parkinson's disease dementia. However, differentiation can be crucial, especially as patients with DLB characteristically have a hypersensitivity to most antiemetic and neuroleptic drugs as they affect the cholinergic and dopaminergic system, potentially leading to life-threatening catatonia, loss of cognitive function and muscle rigidity. The aim of this study is to evaluate if resting state (RS) functional MRI (fMRI) can be used in routine practice on a 1. Read More

Front Immunol 2019 15;10:480. Epub 2019 Mar 15.

Department of Neurology, Emory University, Atlanta, GA, United States.

Inflammation is a common process involved in aging, multiple sclerosis (MS), and age-related neurodegenerative disorders such as Alzheimer's disease (AD) and Parkinson's disease (PD), but there is limited evidence for the effects of aging on inflammation in the central nervous system. We collected cerebrospinal fluid (CSF) from 105 healthy control subjects representing a wide age range (23-86), and analyzed levels of cytokines associated innate immunity (TNF-α) and different T-helper subtypes: interferon-gamma induced protein 10 (IP-10) for Th1, interleukin-10 (IL-10) for Th2, and interleukin 8 (IL-8/CXCL8) for Th17. We show that CSF levels of TNF-α, IP-10, and IL-8 all increased linearly with age, but levels of IL-10 demonstrated a U-shaped relationship with age. Read More

Parkinsonism Relat Disord 2019 Mar 23. Epub 2019 Mar 23.

Sleep Medicine Centre, Department of Systems Medicine, University of Rome 'Tor Vergata", Rome, Italy.

Introduction: Several longitudinal studies revealed that patients affected by idiopathic REM behavior disorder (iRBD) trend to convert to α-synucleinopathies at follow-up, although the time and direction of conversion is currently unpredictable. This study aimed at evaluating brain glucose metabolism, measured by [18F]FDG-PET, in patients affected by iRBD and compared to Parkinson's Disease (PD), Lewy Body Dementia (DLB), Alzheimer's Disease (AD), and controls.

Methods: Differences in brain [18F]FDG uptake were analyzed using statistical parametric mapping implemented in Matlab R2012b among iRBD, PD, DLB, AD, and controls. Read More

Parkinsonism Relat Disord 2019 Mar 23. Epub 2019 Mar 23.

Department of Neurology, University of Florida College of Medicine, P.O. Box 100236, Gainesville, FL 32610, USA. Electronic address:

Introduction: Understanding hospitalization in Lewy body dementia (LBD) is a known knowledge gap. We aimed to identify common causes, medication profiles, complications, and outcomes of hospitalization in LBD.

Methods: A retrospective cohort study investigated details of academic medical center hospitalizations over a two-year period for patients with LBD. Read More

Dis Model Mech 2019 Apr 9;12(4). Epub 2019 Apr 9.

Biomedical Sciences Research Centre, Department of Bioscience and Chemistry, Sheffield Hallam University, Sheffield, South Yorkshire S1 1WB, UK

Extensive loss of dopaminergic neurons and aggregation of the protein α-synuclein into ubiquitin-positive Lewy bodies represents a major neuropathological hallmark of Parkinson's disease (PD). At present, the generation of large nuclear-associated Lewy bodies from endogenous wild-type α-synuclein, translationally regulated under its own promoter in human cell culture models, requires costly and time-consuming protocols. Here, we demonstrate that fully differentiated human SH-SY5Y neuroblastoma cells grown in three-dimensional cell culture develop Lewy-body-like pathology upon exposure to exogenous α-synuclein species. Read More

Semin Neurol 2019 Apr 29;39(2):274-282. Epub 2019 Mar 29.

Department of Neurology, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey.

Dementia with Lewy bodies (DLB) and Parkinson's disease dementia (PD-D) are Lewy body-related neurodegenerative disorders sharing common clinical and neuropathological findings. The clinical features of both conditions include cognitive impairment, behavioral symptoms, autonomic dysfunction, sleep disorders, and parkinsonism. The cognitive profile of both disorders is characterized by particularly severe deficits in executive and visuospatial functions as well as attention. Read More

Semin Neurol 2019 Apr 29;39(2):213-226. Epub 2019 Mar 29.

Department of Neurology, Institute of Memory and Alzheimer's Disease, Assistance Publique - Hopitaux de Paris, Pitié-Salpêtrière Hospital, Paris, France.

Alzheimer's disease (AD) is the commonest neurodegenerative disease and the most frequent cause of dementia. It affects 30 million people worldwide. Current research criteria focus on biomarkers' status for amyloid and tau using positron emission tomography and cerebrospinal fluid analysis, independent of clinical status. Read More

Semin Neurol 2019 Apr 29;39(2):188-199. Epub 2019 Mar 29.

Department of Radiology of Biomedical Imaging, Yale School of Medicine, New Haven, Connecticut.

Dementia is a global health issue, the burden of which will worsen with an increasingly aging population. Alzheimer's disease (AD) is the most common dementia, with 50 to 60% of all dementias attributable to AD alone, while the rest are mostly due to frontotemporal lobar dementia, dementia with Lewy bodies, Parkinson's disease dementia, and vascular dementia. Diagnosis of dementias is made clinically with the aid of other testing modalities including neuroimaging. Read More

Semin Neurol 2019 Apr 29;39(2):153-166. Epub 2019 Mar 29.

Department of Neurology, Yale School of Medicine, New Haven, Connecticut.

Dementia is a state of cognitive dysfunction which leads to functional decline. It is a syndrome caused by several medical and neurological causes, but most cases of dementia are due to "primary dementias." Primary dementias are neurological diseases whose manifestations are predominantly cognitive. Read More

Alzheimers Dement (Amst) 2019 Dec 15;11:270-276. Epub 2019 Mar 15.

Department of Neurology, Mayo Clinic, Jacksonville, FL, USA.

Introduction: We sought to determine if a proteomic profile approach developed to detect Alzheimer's disease would distinguish patients with Lewy body disease from normal controls, and if it would distinguish dementia with Lewy bodies (DLB) from Parkinson's disease (PD).

Methods: Stored plasma samples were obtained from 145 patients (DLB n = 57, PD without dementia n = 32, normal controls n = 56) enrolled from patients seen in the Behavioral Neurology or Movement Disorders clinics at the Mayo Clinic, Florida. Proteomic assays were conducted and analyzed as per our previously published protocols. Read More

Clin Chim Acta 2019 Mar 25;495:13-24. Epub 2019 Mar 25.

Laboratory of Clinical Neurochemistry, Department of Medicine, University of Perugia, Ospedale S. Maria della Misericordia, Perugia, Italy. Electronic address:

Mutations on the GBA gene, encoding for the lysosomal enzyme β-glucocerebrosidase (GCase), have been identified as the most common genetic risk factor involved in the development of Parkinson's disease (PD) and dementia with Lewy bodies (DLB), indicating a direct contribution of this enzyme to the pathogenesis of synucleinopathies. Decreased GCase activity has been observed repeatedly in brain tissues and biological fluids of both GBA mutation carrier and non-carrier PD and DLB patients, suggesting that lower GCase activity constitutes a typical feature of these disorders. Additional genetic, pathological and biochemical data on other lysosomal enzymes (e. Read More

Mov Disord 2019 Mar 28. Epub 2019 Mar 28.

Department of Neurology, Christian-Albrechts-University of Kiel, Kiel, Germany.

The past decade has seen a dramatic expansion of the field of prodromal PD. Ten years ago, there were only six known prodromal markers of disease, none of which had more than two studies documenting diagnostic value. We now have at least 16 markers, with as many as 10 prospective studies for a single marker. Read More

Drugs R D 2019 Mar 27. Epub 2019 Mar 27.

Department of Neurology, Laboratory for Dementia and Parkinsonism, Translational Neurotherapeutics Program, Parkinson's Foundation Center of Excellence, Georgetown University Medical Center, Washington, DC, USA.

Background And Objectives: Inhibition of Abelson (Abl) tyrosine kinase as a therapeutic target has been gaining attention in neurodegeneration. Post-mortem Alzheimer's and Parkinson's disease brains show that the levels of several other tyrosine kinases, including Discoidin Domain Receptors (DDR1/2) are elevated. Knockdown of these tyrosine kinases with shRNA reduces neurotoxic proteins, including alpha-synuclein, beta-amyloid and tau. Read More

ACS Chem Neurosci 2019 Apr 9. Epub 2019 Apr 9.

School of Biotechnology , Jawaharlal Nehru University , New Delhi 110067 , India.

Parkinson's disease is characterized by the deterioration of dopaminergic neurons of substantia nigra pars compacta along with a substantial loss of noradrenergic neurons of the locus coeruleus, which is the major source of noradrenaline (NA) in the brain. We have investigated the interaction of NA with α-synuclein (α-syn), the major protein constituent of Lewy bodies that are the pathological hallmark of Parkinson's disease (PD). It is expected that NA, like dopamine, could bind to α-syn and modulate its aggregation propensity and kinetics, which could also contribute to the onset of PD. Read More

J Neurophysiol 2019 Mar 27. Epub 2019 Mar 27.

Neural and Behavioral Sciences, Penn State College of Medicine, United States.

Parkinson's disease (PD) is predominantly idiopathic in origin, and a large body of evidence indicates that gastrointestinal (GI) dysfunctions are a significant co-morbid clinical feature; these dysfunctions include dysphagia, nausea, delayed gastric emptying and severe constipation, all of which occur commonly before the onset of the well-known motor symptoms of PD. Based on a distinct distribution pattern of Lewy bodies (LB) in the enteric nervous system (ENS) and in the preganglionic neurons of the dorsal motor nucleus of the vagus (DMV), and together with the early onset of GI symptoms, it was suggested that idiopathic PD begins in the ENS, spreads to the central nervous system (CNS) reaching the DMV and the substantia nigra pars compacta (SNpc). These two areas are connected by a recently discovered monosynaptic nigro-vagal pathway, which is dysfunctional in rodent models of PD. Read More

Brain Sci 2019 Mar 23;9(3). Epub 2019 Mar 23.

Department of Neurology, Mayo Clinic, Rochester, MN 55905, USA.

Background: The prevalence of dream enactment behavior and other risk factors for a parkinsonian disorder is not well documented.

Methods: A survey on prevalence of parkinsonism risk factors was designed using two validated instruments (REM behavior disorder single item question, bowel movement frequency for constipation) and three exploratory instruments (for hallucinations, cognitive and olfactory complaints.) It was sent by mail and email to patients aged 50 and over at two University of Utah community clinics in Salt Lake City. Read More

Pharmacol Res Perspect 2019 04 12;7(2):e00470. Epub 2019 Mar 12.

Translational Neurotherapeutics Program Laboratory for Dementia and Parkinsonism Department of Neurology Georgetown University Medical Center Washington District of Columbia.

Nilotinib is a broad-based tyrosine kinase inhibitor with the highest affinity to inhibit Abelson (c-Abl) and discoidin domain receptors (DDR1/2). Preclinical evidence indicates that Nilotinib reduces the level of brain alpha-synuclein and attenuates inflammation in models of Parkinson's disease (PD). We previously showed that Nilotinib penetrates the blood-brain barrier (BBB) and potentially improves clinical outcomes in individuals with PD and dementia with Lewy bodies (DLB). Read More

Parkinsonism Relat Disord 2019 Mar 15. Epub 2019 Mar 15.

Lou Ruvo Center for Brain Health, Cleveland Clinic, Cleveland, OH, 44195, USA; Neurological Institute, Cleveland Clinic, Cleveland, OH, 44195, USA.

Background: Biomarkers are being used increasingly to support the diagnosis of dementia with Lewy bodies (DLB). Novel biomarkers that increase diagnostic specificity of DLB are needed. We assessed previously known FDG-PET occipital cortex hypometabolism, and cingulate island sign biomarkers of DLB against a novel amygdala signature. Read More

Acta Neurol Scand 2019 Mar 23. Epub 2019 Mar 23.

Department of Neurology, Dokkyo Medical University, Mibu, Japan.

Background: We investigated serum insulin-like growth factor (IGF)-1 levels in patients with neurodegenerative diseases and correlated these levels with clinical parameters.

Methods: One hundred and fifty-six patients with neurodegenerative diseases were included in this study, and serum IGF-1 levels were determined.

Results: Serum IGF-1 levels (mean ± standard error) were not significantly different among the patients with different neurodegenerative diseases: Parkinson's disease (PD; n = 73), 112. Read More

Int J Geriatr Psychiatry 2019 Mar 22. Epub 2019 Mar 22.

Institute of Neuroscience, Newecastle University, Newcastle upon Tyne, United Kingdom.

Introduction: Lewy body disease is postulated, by the Braak model, to originate in the enteric nervous system, before spreading to the central nervous system. Therefore, a high prevalence of gastroparesis symptoms would be expected in prodromal dementia with Lewy bodies (DLB) and be highest in those with a dopaminergic deficit on imaging. The aim of this study was to explore whether gastroparesis was an early diagnostic marker of prodromal DLB and explore the relationship between symptoms and dopaminergic imaging findings on FP-CIT SPECT. Read More

Ann Nucl Med 2019 Mar 21. Epub 2019 Mar 21.

Institute of Neuroscience, Newcastle University, Biomedical Research Building, Campus for Ageing and Vitality, Newcastle upon Tyne, NE4 5PL, UK.

Objective: I-123-2β-Carbomethoxy-3β-(4-iodophenyl)-N-(3-fluoropropyl)nortropane (FP-CIT) imaging is an established biomarker used in the diagnosis of Lewy body disease. Images are often reported with the aid of striatal binding ratios (SBRs), comparing uptake to a normal database via Z scores. It is well known that SBRs are age dependent. Read More

J Neurochem 2019 Mar 20. Epub 2019 Mar 20.

Institute of Neuroscience, Campus for Ageing and Vitality, Newcastle University, Newcastle-upon-Tyne, NE4 5PL, UK.

Lewy body diseases (LBDs) share clinical, pathological, genetic, and biochemical signatures, and are regarded as a highly heterogeneous group of neurodegenerative disorders. Inclusive of Parkinson's disease (PD), Parkinson's disease dementia (PDD), and dementia with Lewy bodies (DLB), controversy still exists as to whether they should be considered as separate disease entities or as part of the same disease continuum. Here we discuss emerging knowledge relating to both clinical, and neuropathological differences and consider current biomarker strategies as we try to improve our diagnostic capabilities and design of disease modifying therapeutics for this group of debilitating neurodegenerative disorders. Read More

Psychogeriatrics 2019 Mar 19. Epub 2019 Mar 19.

Paris Diderot University - Paris VII, Paris, France.

Cochrane Database Syst Rev 2019 03 20;3:CD003154. Epub 2019 Mar 20.

Radcliffe Department of Medicine, University of Oxford, John Radcliffe Hospital, Level 4, Main Hospital, Room 4401C, Oxford, Oxfordshire, UK, OX3 9DU.

Background: Memantine is a moderate affinity uncompetitive antagonist of glutamate NMDA receptors. It is licensed for use in moderate and severe Alzheimer's disease (AD); in the USA, it is also widely used off-label for mild AD.

Objectives: To determine efficacy and safety of memantine for people with dementia. Read More

Subcell Biochem 2019;91:75-106

Institute of Neuroscience, Newcastle University, Newcastle upon Tyne, UK.

This chapter describes the main neuropathological features of the most common age associated neurodegenerative diseases including Alzheimer's disease, Lewy body diseases, vascular dementia and the various types of frontotemporal lobar degeneration. In addition, the more recent concepts of primary age-related tauopathy and ageing-related tau astrogliopathy as well as chronic traumatic encephalopathy are briefly described. One section is dedicated to cerebral multi-morbidity as it is becoming increasingly clear that the old brain is characterised by the presence of multiple pathologies (to varying extent) rather than by one single, disease specific pathology alone. Read More

Neuroimage Clin 2019 Mar 12;22:101755. Epub 2019 Mar 12.

Amsterdam UMC, Vrije Universiteit Amsterdam, Psychiatry, Amsterdam Neuroscience, De Boelelaan 1117, Amsterdam, Netherlands; Amsterdam UMC, Vrije Universiteit Amsterdam, Anatomy and Neurosciences, Amsterdam Neuroscience, De Boelelaan 1117, Amsterdam, Netherlands.

Parkinson's disease (PD) and dementia with Lewy bodies (DLB) are thought to be part of a spectrum: both have a clinical profile including symptoms associated with dopaminergic and serotonergic loss, yet few imaging studies have focused on serotonergic neurodegeneration in both disorders. We aimed to study degeneration of terminals with dopamine and serotonin transporter (DAT and SERT, respectively) in patients with early-stage PD and DLB relative to healthy controls, using I-N-ω-fluoropropyl-2β-carbomethoxy-3β-(4-iodophenyl)nortropane (I-FP-CIT) single photon emission computed tomography (SPECT). We conducted region of interest (ROI) and voxel-based analyses on I-FP-CIT SPECT scans. Read More

Psychogeriatrics 2019 Mar 18. Epub 2019 Mar 18.

Neurology Department, Brugmann University Hospital, Brussels, Belgium.

J Alzheimers Dis 2019 ;68(2):647-655

Department of Medicine, University of Washington School of Medicine, Seattle, WA, USA.

Background: The aging eye offers unique opportunities to study and understand the aging brain, in particular related to Alzheimer's disease (AD) and dementia. However, little is known about relationships between eye diseases and dementia-related neurodegeneration.

Objective: To determine the potential association between three age-related eye diseases and AD and dementia-related neuropathology. Read More

J Alzheimers Dis 2019 ;68(2):723-733

IRCCS Istituto delle Scienze Neurologiche di Bologna, Bologna, Italy.

Cerebrospinal fluid (CSF) biomarkers have been extensively investigated in idiopathic normal pressure hydrocephalus (iNPH) with the aim of a better differential diagnosis, but the pathophysiological mechanisms underlying CSF biomarker changes and the relationship between biomarker levels and clinical variables are still a matter of debate. We evaluated CSF amyloid-β (Aβ)42 and Aβ40, total (t)-tau, phosphorylated (p)-tau, total prion protein (t-PrP), and neurofilament light chain protein (NfL) in healthy controls (n = 50) and subjects with iNPH (n = 71), Alzheimer's disease (AD) (n = 60), and several other subtypes of dementia (n = 145). Patients with iNPH showed significantly lower levels of Aβ42, Aβ40, t-tau, and p-tau compared to controls. Read More

Eur J Med Chem 2019 May 8;169:185-199. Epub 2019 Mar 8.

Department of Chemistry, Dasaratha Deb Memorial College, Khowai, Tripura, 799201, India.

Alzheimer's disease (AD) and Parkinson's disease (PD) are the most common age-related neurodegenerative disorders, affecting several millions of aged people globally. Among these disorders, AD is more severe, affecting about 7% of individuals aged 65 and above. AD is primarily a dementia-related disorder from progressive cognitive deterioration and memory impairment, while PD is primarily a movement disorder illness having three major kinesia or movement disorder symptoms, bradykinesia (slowness of movements), hypokinesia (reduction of movement amplitude), and akinesia (absence of normal unconscious movements) along with muscle rigidity and tremor at rest. Read More

J Clin Neurol 2019 Apr 11;15(2):175-183. Epub 2019 Mar 11.

Department of Nuclear Medicine, Seoul Metropolitan Government-Seoul National University Boramae Medical Center, Seoul, Korea.

Background And Purpose: To identify a metabolic network reflecting neurodegeneration in patients with idiopathic rapid eye movement (REM) sleep behavior disorder (iRBD).

Methods: We recruited a prospective cohort comprising patients with Parkinson's disease (PD) with probable REM sleep behavior disorder (PDRBD, =21), polysomnography-confirmed iRBD patients (=28), and age-matched healthy controls (HC) (=24). PDRBD-related spatial covariance pattern (PDRBD-RP) were determined from ¹⁸F-fluorodeoxyglucose PET images of the PDRBD group and validated by reproduction in a separate PD cohort with polysomnography-confirmed REM sleep behavior disorder (=11). Read More

Acta Neuropathol Commun 2019 Mar 14;7(1):41. Epub 2019 Mar 14.

Center for Neurodegenerative Science, Van Andel Research Institute, 333 Bostwick Avenue N.E, Grand Rapids, MI, 49503, USA.

Misfolded alpha-synuclein (αSyn) is a major constituent of Lewy bodies and Lewy neurites, which are pathological hallmarks of Parkinson's disease (PD). The contribution of αSyn to PD is well established, but the detailed mechanism remains obscure. Using a model in which αSyn aggregation in primary neurons was seeded by exogenously added, preformed αSyn amyloid fibrils (PFF), we found that a majority of pathogenic αSyn (indicated by serine 129 phosphorylated αSyn, ps-αSyn) was membrane-bound and associated with mitochondria. Read More