5,124 results match your criteria disease prodromal

Mitochondrial Dysfunction in a Mouse Model of Prodromal Parkinson's Disease: A Metabolomic Analysis.

Neurosci Lett 2021 Sep 24:136267. Epub 2021 Sep 24.

Department of Neurology Kyoto University Graduate School of Medicine, Kyoto, Japan. Electronic address:

For the development of disease-modifying therapies for Parkinson's disease (PD) the identification of biomarkers in the prodromal stage is urgently required. Because PD is considered a systemic disease even in the early stage, we performed a metabolomic analysis of the plasma from a mouse model of prodromal PD (p-PD). Increased levels of isobutyrylcarnitine in p-PD mice imply an abnormality in β-oxidation in mitochondria, and increased levels of pyrimidine nucleoside can be associated with mitochondrial dysfunction. Read More

View Article and Full-Text PDF
September 2021

Investigating Auditory Electrophysiological Measures of Participants with Mild Cognitive Impairment and Alzheimer's Disease: A Systematic Review and Meta-Analysis of Event-Related Potential Studies.

J Alzheimers Dis 2021 Sep 18. Epub 2021 Sep 18.

Ear Science Institute Australia, Subiaco, WA, Australia.

Background: Objectively measuring auditory functions has been proposed as an avenue in differentiating normal age-related cognitive dysfunction from Alzheimer's disease (AD) and its prodromal states. Previous research has suggested auditory event-related potentials (AERPs) to be non-invasive, cost-effective, and efficient biomarkers for the diagnosis of AD.

Objective: The objective of this paper is to review the published literature on AERPs measures in older adults diagnosed with AD and those at higher risk of developing AD, i. Read More

View Article and Full-Text PDF
September 2021

Prodromal dysfunction of α5GABA-A receptor modulated hippocampal ripples occurs prior to neurodegeneration in the TgF344-AD rat model of Alzheimer's disease.

Heliyon 2021 Sep 1;7(9):e07895. Epub 2021 Sep 1.

Department of Pharmacology & Experimental Therapeutics, Boston University School of Medicine, Boston, Massachusetts, USA.

Decades of research attempting to slow the onset of Alzheimer's disease (AD) indicates that a better understanding of memory will be key to the discovery of effective therapeutic approaches. Here, we ask whether prodromal neural network dysfunction might occur in the hippocampal trisynaptic circuit by using α5IA (an established memory enhancer and selective negative allosteric modulator of extrasynaptic tonically active α5GABA-A receptors) as a probe drug in TgF344-AD transgenic rats, a model for β-amyloid induced early onset AD. The results demonstrate that orally bioavailable α5IA increases CA1 pyramidal cell mean firing rates during foraging and peak ripple amplitude during wakeful immobility in F344 rats in a familiar environment. Read More

View Article and Full-Text PDF
September 2021

Acetabular Fractures with Central Hip Dislocation: A Retrospective Consecutive 50 Case Series Study Based on AO/OTA 2018 Classification in Midterm Follow-Up.

Biomed Res Int 2021 17;2021:6659640. Epub 2021 Sep 17.

Department of Orthopedics, China Medical University Hospital, Taichung, Taiwan.

Introduction: Management of acetabular fractures is challenging, especially when a medial acetabular fracture is complicated by central hip dislocation. We retrospectively investigated the clinical outcome and risk factors of secondary hip osteoarthritis requiring total hip arthroplasty after the surgical treatment of acetabular fractures with central hip dislocation.

Materials And Methods: The medical records of all patients who had acetabular medial wall fractures with central hip dislocation treated with open reduction and internal fixation by a single surgeon between January 2015 and June 2017 were reviewed. Read More

View Article and Full-Text PDF
September 2021

Excellent Outcome of Acute Necrotizing Encephalopathy in an Adult With Bacterial Infections, Case Report.

Neurohospitalist 2021 Oct 5;11(4):351-355. Epub 2021 Feb 5.

Department of Pediatric Neurology, Washington University School of Medicine, Saint Louis, MO, USA.

Acute necrotizing encephalopathy (ANE) is a rare para-infectious encephalopathy that classically occurs in children. However, ANE should be considered in the differential diagnosis of adults with symmetric brain lesions after a prodromal illness given recent reports of coronavirus disease of 2019 (COVID-19) to presumably cause ANE in adults. We report a case of a 29-year-old male presenting with fever, malaise, and rapid deterioration into coma. Read More

View Article and Full-Text PDF
October 2021

Mild Parkinsonian Signs: A Systematic Review of Clinical, Imaging, and Pathological Associations.

Mov Disord 2021 Sep 25. Epub 2021 Sep 25.

Department of Clinical Neurosciences, UCL Institute of Neurology University College London, London, United Kingdom.

Mild parkinsonian signs (MPS) have been widely studied during the past 3 decades and proposed as a risk marker for neurodegenerative disease. This systematic review explores the epidemiology, clinical and prognostic associations, radiological features, and pathological findings associated with MPS in older adults free from neurodegenerative disease. We find that MPS as currently defined are strongly associated with increasing age and increased risk of development of Parkinson's disease (PD), all-cause dementia, disability, and death. Read More

View Article and Full-Text PDF
September 2021

Optimising classification of Parkinson's disease based on motor, olfactory, neuropsychiatric and sleep features.

NPJ Parkinsons Dis 2021 Sep 24;7(1):87. Epub 2021 Sep 24.

Preventive Neurology Unit, Wolfson Institute of Population Health, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UK.

Olfactory loss, motor impairment, anxiety/depression, and REM-sleep behaviour disorder (RBD) are prodromal Parkinson's disease (PD) features. PD risk prediction models typically dichotomize test results and apply likelihood ratios (LRs) to scores above and below cut-offs. We investigate whether LRs for specific test values could enhance classification between PD and controls. Read More

View Article and Full-Text PDF
September 2021

Plasma p-tau181 Level Predicts Neurodegeneration and Progression to Alzheimer's Dementia: A Longitudinal Study.

Front Neurol 2021 7;12:695696. Epub 2021 Sep 7.

Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.

Plasma-based biomarkers would be potential biomarkers for early diagnosis of Alzheimer's disease (AD) because they are more available and cost-effective than cerebrospinal fluid (CSF) or neuroimaging. Therefore, we aimed to evaluate whether phosphorylated tau181 (p-tau181) in plasma could be an accurate AD predictor. Participants from the ADNI database included 185 cognitively unimpaired subjects with negative Aβ (CU-), 66 subjects with pre-clinical AD (CU with positive Aβ), 164 subjects with mild cognitive impairment with negative Aβ (MCI-), 254 subjects with prodromal AD (MCI with positive Aβ), and 98 subjects with dementia. Read More

View Article and Full-Text PDF
September 2021

Characterizing the Retinal Phenotype of the Thy1-h[A30P]α-syn Mouse Model of Parkinson's Disease.

Front Neurosci 2021 7;15:726476. Epub 2021 Sep 7.

Research Group of Neural Circuit Development and Regeneration, Department of Biology, KU Leuven, Leuven, Belgium.

Despite decades of research, disease-modifying treatments of Parkinson's disease (PD), the second most common neurodegenerative disease worldwide, remain out of reach. One of the reasons for this treatment gap is the incomplete understanding of how misfolded alpha-synuclein (α-syn) contributes to PD pathology. The retina, as an integral part of the central nervous system, recapitulates the PD disease processes that are typically seen in the brain, and retinal manifestations have emerged as prodromal symptoms of the disease. Read More

View Article and Full-Text PDF
September 2021

Phase and amplitude EEG correlations change with disease progression in people with idiopathic rapid eye-movement sleep behavior disorder.

Sleep 2021 Sep 22. Epub 2021 Sep 22.

Department of Informatics, Bioengineering, Robotics and System engineering (DIBRIS), University of Genoa, Genoa, Italy.

Study Objectives: Increased phase synchronization in electroencephalography (EEG) bands might reflect the activation of compensatory mechanisms of cognitive decline in people with neurodegenerative diseases. Here, we investigated whether altered large-scale couplings of brain oscillations could be linked to the balancing of cognitive decline in a longitudinal cohort of people with idiopathic rapid eye-movement sleep behavior disorder (iRBD).

Methods: We analyzed 18 patients (17 males, 69. Read More

View Article and Full-Text PDF
September 2021

Glucocerebrosidase Activity is not Associated with Parkinson's Disease Risk or Severity.

Mov Disord 2021 Sep 22. Epub 2021 Sep 22.

Movement Disorders Unit, Neurological Institute, Tel-Aviv Medical Center, Tel-Aviv, Israel.

Background: Mutations in the GBA gene, which encodes the lysosomal enzyme glucocerebrosidase (GCase), are risk factors for Parkinson's disease (PD).

Objective: To explore the association between GCase activity, PD phenotype, and probability for prodromal PD among carriers of mutations in the GBA and LRRK2 genes.

Methods: Participants were genotyped for the G2019S-LRRK2 and nine GBA mutations common in Ashkenazi Jews. Read More

View Article and Full-Text PDF
September 2021

Different Sides of Depression in the Elderly: An In-depth View on the Role of Aβ Peptides.

Curr Med Chem 2021 Sep 21. Epub 2021 Sep 21.

Geriatric Psychiatry Department, Nathan S. Kline Institute, 140 Old Orangeburg Road, Orangeburg, NY 10962. United States.

Background: Late-onset depression (LOD) is the most common neuropsychiatric disorder associated with Alzheimer's disease (AD), often associated with structural and functional brain changes, neuropsychological impairments and negative family history for affective disorders. LOD could be a risk factor or a prodromal phase of AD; this has led to the investigation of the link between depression and amyloid-β (Aβ) peptides by measuring Aβ levels in plasma, cerebrospinal fluid (CSF) and brains of elderly depressed subjects.

Objective: Clarify the complex relationship between depression, Aβ peptides and AD. Read More

View Article and Full-Text PDF
September 2021

Heterozygous GBA D490V and ATP13a2 mutations do not exacerbate pathological α-synuclein spread in the prodromal preformed fibrils model in young mice.

Neurobiol Dis 2021 Sep 16;159:105513. Epub 2021 Sep 16.

Parkinson's Disease Center, Department of Neurodegenerative Science, Van Andel Institute, Grand Rapids, MI, USA. Electronic address:

Autophagic dysregulation and lysosomal impairment have been implicated in the pathogenesis of Parkinson's disease, partly due to the identification of mutations in multiple genes involved in these pathways such as GBA, SNCA, ATP13a2 (also known as PARK9), TMEM175 and LRRK2. Mutations resulting in lysosomal dysfunction are proposed to contribute to Parkinson's disease by increasing α-synuclein levels, that in turn may promote aggregation of this protein. Here, we used two different genetic models-one heterozygous for a mutated form of the GBA protein (D409V), and the other heterozygous for an ATP13a2 loss-of-function mutation, to test whether these mutations exacerbate the spread of α-synuclein pathology following injection of α-synuclein preformed fibrils in the olfactory bulb of 12-week-old mice. Read More

View Article and Full-Text PDF
September 2021

Parkinson's disease outside the brain: targeting the autonomic nervous system.

Lancet Neurol 2021 10;20(10):868-876

Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel; Sagol School of Neuroscience, Tel Aviv University, Tel Aviv, Israel. Electronic address:

Patients with Parkinson's disease present with signs and symptoms of dysregulation of the peripheral autonomic nervous system that can even precede motor deficits. This dysregulation might reflect early pathology and therefore could be targeted for the development of prodromal or diagnostic biomarkers. Only a few objective clinical tests assess disease progression and are used to evaluate the entire spectrum of autonomic dysregulation in patients with Parkinson's disease. Read More

View Article and Full-Text PDF
October 2021

Tau deposition and structural connectivity demonstrate differential association patterns with neurocognitive tests.

Brain Imaging Behav 2021 Sep 17. Epub 2021 Sep 17.

Department of Radiology and Imaging Sciences, Indiana University School of Medicine, 355 West 16th Street, Suite 4100, Indianapolis, IN, 46202, USA.

Tau neurofibrillary tangles have a central role in the pathogenesis of Alzheimer's Disease (AD). Mounting evidence indicates that the propagation of tau is assisted by brain connectivity with weakened white-matter integrity along the propagation pathways. Recent advances in tau positron emission tomography tracers and diffusion magnetic resonance imaging allow the visualization of tau pathology and white-matter connectivity of the brain in vivo. Read More

View Article and Full-Text PDF
September 2021

Stratification Tools for Disease-Modifying Trials in Prodromal Synucleinopathy.

Mov Disord 2021 Sep 17. Epub 2021 Sep 17.

Department of Neuroscience (DINOGMI), University of Genoa, Genoa, Italy.

Background: Dopamine transporter single photon-emission computed tomography (DAT-SPECT) is the strongest risk factor for phenoconversion in patients with idiopathic rapid eye movement (REM)-sleep behavior disorder (iRBD). However, it might be used as a second-line stratification tool in clinical trials, because it is expensive and mini-invasive.

Objective: Aim of the study is to investigate whether other cost-effective and non-invasive biomarkers may be proposed as first-line stratification tools. Read More

View Article and Full-Text PDF
September 2021

Circuit imaging biomarkers in preclinical and prodromal Parkinson's disease.

Mol Med 2021 09 16;27(1):111. Epub 2021 Sep 16.

Department of Nuclear Medicine and Molecular Imaging, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.

Parkinson's disease (PD) commences several years before the onset of motor features. Pathophysiological understanding of the pre-clinical or early prodromal stages of PD are essential for the development of new therapeutic strategies. Two categories of patients are ideal to study the early disease stages. Read More

View Article and Full-Text PDF
September 2021

Toll-like receptor 4 deficiency facilitates α-synuclein propagation and neurodegeneration in a mouse model of prodromal Parkinson's disease.

Parkinsonism Relat Disord 2021 Sep 11;91:59-65. Epub 2021 Sep 11.

Laboratory for Translational Neurodegeneration Research, Division of Neurobiology, Department of Neurology, Medical University of Innsbruck, Austria. Electronic address:

The evidence linking innate immunity mechanisms and neurodegenerative diseases is growing, but the specific mechanisms are incompletely understood. Experimental data suggest that microglial TLR4 mediates the uptake and clearance of α-synuclein also termed synucleinophagy. The accumulation of misfolded α-synuclein throughout the brain is central to Parkinson's disease (PD). Read More

View Article and Full-Text PDF
September 2021

The effects of cerebral amyloidopathy on regional glucose metabolism in older adults with depression and mild cognitive impairment while performing memory tasks.

Eur J Neurosci 2021 Sep 15. Epub 2021 Sep 15.

Department of Psychiatry, Korea University Guro Hospital, Korea University College of Medicine, Guro-gu, Seoul, Republic of Korea.

Co-occurring depression and mild cognitive impairment (MCI) in older adults is important because they have a high risk of conversion to dementia. In the present study, task-related F-18 fluorodeoxyglucose positron emission tomography (FDG-PET) was used to analyze older adults with concomitant depression and MCI. We recruited 20 older adults with simultaneous depression and MCI, and 10 older adults with normal cognition (NC). Read More

View Article and Full-Text PDF
September 2021

Altered Spontaneous Brain Activity in Subjects With Different Cognitive States of Biologically Defined Alzheimer's Disease: A Surface-Based Functional Brain Imaging Study.

Front Aging Neurosci 2021 30;13:683783. Epub 2021 Aug 30.

Department of Radiology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.

Before the apparent cognitive decline, subjects on the course of Alzheimer's disease (AD) can have significantly altered spontaneous brain activity, which could be potentially used for early diagnosis. As previous studies investigating local brain activity may suffer from the problem of cortical signal aliasing during volume-based analysis, we aimed to investigate the cortical functional alterations in the AD continuum using a surface-based approach. Based on biomarker profile "A/T," we included 11 healthy controls (HC, A-T-), 22 preclinical AD (CU, A+T+), 33 prodromal AD (MCI, A+T+), and 20 AD with dementia (d-AD, A+T+) from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database. Read More

View Article and Full-Text PDF

The Correlation Between Parkinson's Disease and Rapid Eye Movement Sleep Behavior Disorder: A Systematic Review.

Cureus 2021 Aug 9;13(8):e17026. Epub 2021 Aug 9.

Internal Medicine, California Institute of Behavioral Neurosciences & Psychology, Fairfield, USA.

Parkinson's disease (PD) is a neurodegenerative disease caused due to the destruction of dopaminergic neurons and the deposition of α-synuclein proteins, known as Lewy bodies. Generally, the diagnosis of PD is centered around motor symptoms. However, the early recognition of non-motor symptoms such as autonomic dysfunction, sleep disturbances, and cognitive and psychiatric disturbances are gaining increased attention for the early diagnosis of PD. Read More

View Article and Full-Text PDF

Assessment of Tau Pathology as Measured by 18F-THK5317 and 18F-Flortaucipir PET and Their Relation to Brain Atrophy and Cognition in Alzheimer's Disease.

J Alzheimers Dis 2021 Sep 9. Epub 2021 Sep 9.

Division of Clinical Geriatrics, Center for Alzheimer Research, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden.

Background: In Alzheimer's disease (AD), the abnormal aggregation of hyperphosphorylated tau leads to synaptic dysfunction and neurodegeneration. Recently developed tau PET imaging tracers are candidate biomarkers for diagnosis and staging of AD.

Objective: We aimed to investigate the discriminative ability of 18F-THK5317 and 18F-flortaucipir tracers and brain atrophy at different stages of AD, and their respective associations with cognition. Read More

View Article and Full-Text PDF
September 2021

Oxygen Sensing and Signaling in Alzheimer's Disease: A Breathtaking Story!

Cell Mol Neurobiol 2021 Sep 12. Epub 2021 Sep 12.

CNC - Center for Neuroscience and Cell Biology, Faculty of Medicine, University of Coimbra, Rua Larga, Polo I, 1st Floor, 3004-504, Coimbra, Portugal.

Oxygen sensing and homeostasis is indispensable for the maintenance of brain structural and functional integrity. Under low-oxygen tension, the non-diseased brain has the ability to cope with hypoxia by triggering a homeostatic response governed by the highly conserved hypoxia-inducible family (HIF) of transcription factors. With the advent of advanced neuroimaging tools, it is now recognized that cerebral hypoperfusion, and consequently hypoxia, is a consistent feature along the Alzheimer's disease (AD) continuum. Read More

View Article and Full-Text PDF
September 2021

Uncommon Presentation of Rasmussen's Encephalitis.

Neurol India 2021 Jul-Aug;69(4):1010-1013

Department of Neurology, SMS Medical College, Jaipur, Rajasthan, India.

Rasmussen's encephalopathy (RE) is an uncommon neurological disease of inflammatory origin which is characterized by intractable focal epilepsy, progressive limb weakness, and cognitive deterioration. RE presenting as movement disorder like hemidystonia or hemichorea is a rare occurrence. The duration of prodromal stage of RE is usually in weeks or months. Read More

View Article and Full-Text PDF
September 2021

Pharmaco-Magnetic Resonance as a Tool for Monitoring the Medication-Related Effects in the Brain May Provide Potential Biomarkers for Psychotic Disorders.

Int J Mol Sci 2021 Aug 27;22(17). Epub 2021 Aug 27.

Department of Psychiatry and Medical Psychology, Research Institute, Medical University Plovdiv, 4002 Plovdiv, Bulgaria.

The neurodegenerative and neurodevelopmental hypotheses represent the basic etiological framework for the origin of schizophrenia. Additionally, the dopamine hypothesis, adopted more than two decades ago, has repeatedly asserted the position of dopamine as a pathobiochemical substrate through the action of psychostimulants and neuroleptics on the mesolimbic and mesocortical systems, giving insight into the origin of positive and negative schizophrenic symptoms. Meanwhile, cognitive impairments in schizophrenia remain incompletely understood but are thought to be present during all stages of the disease, as well as in the prodromal, interictal and residual phases. Read More

View Article and Full-Text PDF

Heterogeneity of prodromal Parkinson symptoms in siblings of Parkinson disease patients.

NPJ Parkinsons Dis 2021 Sep 7;7(1):78. Epub 2021 Sep 7.

Department of Biomedical and NeuroMotor Sciences (DiBiNeM), University of Bologna, Bologna, Italy.

A prodromal phase of Parkinson's disease (PD) may precede motor manifestations by decades. PD patients' siblings are at higher risk for PD, but the prevalence and distribution of prodromal symptoms are unknown. The study objectives were (1) to assess motor and non-motor features estimating prodromal PD probability in PD siblings recruited within the European PROPAG-AGEING project; (2) to compare motor and non-motor symptoms to the well-established DeNoPa cohort. Read More

View Article and Full-Text PDF
September 2021

Factors associated with dropout in the longitudinal Vogel study of cognitive decline.

Eur J Neurosci 2021 Sep 7. Epub 2021 Sep 7.

Center for Mental Health, Department of Psychiatry, Psychosomatics and Psychotherapy, University Hospital Würzburg, Würzburg, Germany.

Dementia, including Alzheimer's disease, is a growing problem worldwide. Prevention or early detection of the disease or a prodromal cognitive decline is necessary. By means of our long-term follow-up 'Vogel study', we aim to predict the pathological cognitive decline of a German cohort (mean age was 73. Read More

View Article and Full-Text PDF
September 2021

Robust Discovery of Mild Cognitive Impairment Subtypes and Their Risk of Alzheimer's Disease Conversion Using Unsupervised Machine Learning and Gaussian Mixture Modeling.

Curr Alzheimer Res 2021 Aug 31. Epub 2021 Aug 31.

Tecnologico de Monterrey Ringgold standard institution - medical school Monterrey, new Leon. Mexico.

Background: Alzheimer's disease (AD) is an irreversible, progressive brain disorder that slowly destroys memory and thinking skills. The ability to correctly predict the diagnosis of Alzheimer's disease in its earliest stages can help physicians make more informed clinical decisions on therapy plans.

Objective: This study aimed to determine whether the unsupervised discovering of latent classes of subjects with mild cognitive impairment (MCI) may be useful in finding different prodromal AD stages and/or subjects with a low MCI to AD conversion risk. Read More

View Article and Full-Text PDF

Cohort Study in Parkinsonism: Delayed Transit, Accelerated Gastric Emptying, and Prodromal Dysmotility.

Neurol Clin Pract 2021 Aug;11(4):e407-e413

Clinical Enteric Neuroscience Translational and Epidemiological Research (CENTER) (KK, MC), Division of Gastroenterology and Hepatology; and Department of Neurology (AH); Mayo Clinic, Rochester, MN.

Objective: To evaluate gastric emptying (GE) and colonic transit in a cohort of patients with Parkinson disease and other parkinsonism disorders and to determine whether abnormal gut transit precedes motor onset of parkinsonism.

Methods: Medical record review of 84 patients with parkinsonism who underwent clinically indicated transit studies at Mayo Clinic (2001-2019) and 11 patients with transit studies who subsequently developed parkinsonism. Data are summarized as median (interquartile range). Read More

View Article and Full-Text PDF