243 results match your criteria: "Institute for Neurodegenerative Disorders[Affiliation]"

Introduction: The effects of sex and apolipoprotein E (APOE)-Alzheimer's disease (AD) risk factors-on white matter microstructure are not well characterized.

Methods: Diffusion magnetic resonance imaging data from nine well-established longitudinal cohorts of aging were free water (FW)-corrected and harmonized. This dataset included 4741 participants (age = 73.

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Deep learning reveals pathology-confirmed neuroimaging signatures in Alzheimer's, vascular and Lewy body dementias.

Brain

December 2024

Neuroimage Analytics Laboratory and Biggs Institute Neuroimaging Core, Glenn Biggs Institute for Neurodegenerative Disorders, University of Texas Health Science Center at San Antonio, San Antonio, Texas 78229, USA.

Concurrent neurodegenerative and vascular pathologies pose a diagnostic challenge in the clinical setting, with histopathology remaining the definitive modality for dementia-type diagnosis. To address this clinical challenge, we introduce a neuropathology-based, data-driven, multi-label deep learning framework to identify and quantify in-vivo biomarkers for Alzheimer's disease (AD), vascular dementia (VD), and Lewy body dementia (LBD) using antemortem T1-weighted MRI scans of 423 demented and 361 control participants from NACC and ADNI datasets. Based on the best-performing deep learning model, explainable heatmaps are extracted to visualize disease patterns, and the novel Deep Signature of Pathology Atrophy REcognition (DeepSPARE) indices are developed, where a higher DeepSPARE score indicates more brain alterations associated with that specific pathology.

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Parkinson's Disease is a progressive neurodegenerative disorder afflicting almost 12 million people. Increased understanding of its complex and heterogenous disease pathology, etiology and symptom manifestations has resulted in the need to design, capture and interrogate substantial clinical datasets. Herein we advocate how advances in the deployment of artificial intelligence models for Federated Data Analysis and Federated Learning can help spearhead coordinated and sustainable approaches to address this grand challenge.

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Association of Self-Reported Sleep Characteristics With Neuroimaging Markers of Brain Aging Years Later in Middle-Aged Adults.

Neurology

November 2024

From the Departments of Psychiatry and Behavioral Sciences (C.C., C.D., Y.L., K.Y.), Neurology (K.Y.), and Epidemiology (K.Y.), University of California, San Francisco; Neuroimage Analytics Laboratory and Biggs Institute Neuroimaging Core (M.H.), Glenn Biggs Institute for Neurodegenerative Disorders, University of Texas Health Science Center at San Antonio; Center for AI and Data Science for Integrated Diagnostics and Center for Biomedical Image Computing and Analytics (M.H.), University of Pennsylvania, Philadelphia; and Department of Preventive Medicine (M.R.C.), Northwestern University Feinberg School of Medicine, Chicago, IL.

Article Synopsis
  • The study aimed to explore how sleep patterns in early midlife affect brain aging in late midlife using data from the CARDIA study.
  • Researchers analyzed sleep data, focusing on factors like sleep duration and quality, and later assessed brain age through MRIs taken 15 years later.
  • Results showed that individuals with more poor sleep characteristics had significantly older brain ages, emphasizing the need for sleep interventions to support brain health.*
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The Phase II trial of Anti-alpha-Synuclein Antibody in Early Parkinson's Disease (PASADENA) is an ongoing double-blind, placebo-controlled trial evaluating the safety and efficacy of prasinezumab in early-stage Parkinson's disease (PD). During the double-blind period, prasinezumab-treated individuals showed less progression of motor signs (Movement Disorders Society-sponsored revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part III) than placebo-treated individuals. We evaluated whether the effect of prasinezumab on motor progression, assessed as a change in MDS-UPDRS Part III score in the OFF and ON states, and MDS-UPDRS Part II score, was sustained for 4 years from the start of the trial.

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The Neuronal alpha-Synuclein Disease (NSD) biological definition and Integrated Staging System (NSD-ISS) provide a research framework to identify individuals with Lewy body pathology and stage them based on underlying biology and increasing degree of functional impairment. Utilizing data from the PPMI, PASADENA, and SPARK studies, we developed and applied biologic and clinical data-informed definitions for the NSD-ISS across the disease continuum. Individuals enrolled as Parkinson's disease, Prodromal, or Healthy Controls were defined and staged based on biological, clinical, and functional anchors at baseline.

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Article Synopsis
  • The Neuronal alpha-Synuclein Disease (NSD) and its Integrated Staging System (NSD-ISS) aim to identify and classify individuals with Lewy body pathology according to biological and functional factors.
  • Data from multiple studies reveal that a significant percentage of participants with Parkinson’s disease (PD) were classified as S+ (consistent with NSD), indicating a strong link between biological markers and disease staging.
  • Findings suggest that the baseline stage of individuals influences the timeline for progression to significant clinical outcomes, highlighting the need for further validation of the staging anchors in longer-term studies.
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Introduction: Recent advances in biomarker research have improved the diagnosis and monitoring of Alzheimer's disease (AD), but in vivo biomarker-based workflows to assess 4R-tauopathy (4RT) patients are currently missing. We suggest a novel biomarker-based algorithm to characterize AD and 4RTs.

Methods: We cross-sectionally assessed combinations of cerebrospinal fluid measures (CSF p-tau and t-tau) and F-PI-2620 tau-positron emission tomography (PET) in patients with AD (n = 64), clinically suspected 4RTs (progressive supranuclear palsy or corticobasal syndrome, n = 82) and healthy controls (n = 19).

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Carotid artery vascular stenosis causes the blood-CSF barrier damage and neuroinflammation.

J Neuroinflammation

September 2024

Department of Neurology, University of Pittsburgh Medical Center, 7016 Biomedical Science Tower 3, 3501 Fifth Ave., Pittsburgh, PA, 15213, USA.

Background: The choroid plexus (ChP) helps maintain the homeostasis of the brain by forming the blood-CSF barrier via tight junctions (TJ) at the choroid plexus epithelial cells, and subsequently preventing neuroinflammation by restricting immune cells infiltration into the central nervous system. However, whether chronic cerebral hypoperfusion causes ChP structural damage and blood-CSF barrier impairment remains understudied.

Methods: The bilateral carotid stenosis (BCAS) model in adult male C57BL/6 J mice was used to induce cerebral hypoperfusion, a model for vascular contributions to cognitive impairment and dementia (VCID).

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Article Synopsis
  • The study explores the connection between Parkinson's disease (PD) and multiple sclerosis (MS), examining cases of individuals with the G2019S genetic variant associated with both conditions.
  • Out of a research cohort, 1.4% of participants had MS develop before PD, and one case showed significant brain degeneration linked to PD without typical Lewy body formation.
  • The findings suggest a complex interplay between immune dysfunction and these neurodegenerative diseases, indicating that MS may occur independently and prior to PD in certain genetic carriers.
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Brain aging patterns in a large and diverse cohort of 49,482 individuals.

Nat Med

October 2024

Artificial Intelligence in Biomedical Imaging Laboratory (AIBIL), Center for and Data Science for Integrated Diagnostics (AI2D), Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.

Article Synopsis
  • - The aging process of the brain is affected by lifestyle, environmental, genetic factors, and age-related diseases, with advanced imaging and AI techniques helping to reveal the complexities of neuroanatomical changes.
  • - A study involving nearly 50,000 participants identified five major patterns of brain atrophy, which are quantified using R-indices to analyze their connections to various biomedical, lifestyle, and genetic factors.
  • - These R-indices not only predict disease progression and mortality but also offer a new, nuanced framework for understanding brain aging, which may enhance personalized diagnostics and improve clinical trial strategies.
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Background: Among LRRK2-associated parkinsonism cases with nigral degeneration, over two-thirds demonstrate evidence of pathologic alpha-synuclein, but many do not. Understanding the clinical phenotype and underlying biology in such individuals is critical for therapeutic development. Our objective was to compare clinical and biomarker features, and rate of progression over 4 years follow-up, among LRRK2-associated parkinsonism cases with and without evidence of alpha-synuclein aggregates.

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New insights into metabolism dysregulation after TBI.

J Neuroinflammation

July 2024

Department of Neurology, University of Pittsburgh, 3501 Fifth Avenue, Pittsburgh, PA, 15213, USA.

Traumatic brain injury (TBI) remains a leading cause of death and disability that places a great physical, social, and financial burden on individuals and the health system. In this review, we summarize new research into the metabolic changes described in clinical TBI trials, some of which have already shown promise for informing injury classification and staging. We focus our discussion on derangements in glucose metabolism, cell respiration/mitochondrial function and changes to ketone and lipid metabolism/oxidation to emphasize potentially novel biomarkers for clinical outcome prediction and intervention and offer new insights into possible underlying mechanisms from preclinical research of TBI pathology.

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Mild traumatic brain injuries (mTBIs) are highly prevalent and can lead to chronic behavioral and cognitive deficits often associated with the development of neurodegenerative diseases. Oxidative stress and formation of reactive oxygen species (ROS) have been implicated in mTBI-mediated axonal injury and pathogenesis. However, the underlying mechanisms and contributing factors are not completely understood.

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Background: Objectively measuring Parkinson's disease (PD) signs and symptoms over time is critical for the successful development of treatments aimed at halting the disease progression of people with PD.

Objective: To create a clinical trial simulation tool that characterizes the natural history of PD progression and enables a data-driven design of randomized controlled studies testing potential disease-modifying treatments (DMT) in early-stage PD.

Methods: Data from the Parkinson's Progression Markers Initiative (PPMI) were analyzed with nonlinear mixed-effect modeling techniques to characterize the progression of MDS-UPDRS part I (non-motor aspects of experiences of daily living), part II (motor aspects of experiences of daily living), and part III (motor signs).

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Background: The penetrance of common genetic risk variants for Parkinson's disease (PD) is low. Pesticide exposure increases PD risk, but how exposure affects penetrance is not well understood.

Objective: To determine the relationship between occupational pesticide exposure and PD in people with LRRK2 and GBA risk variants.

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Prasinezumab slows motor progression in rapidly progressing early-stage Parkinson's disease.

Nat Med

April 2024

Roche Pharma Research and Early Development (pRED), Neuroscience and Rare Diseases Discovery and Translational Area, Roche Innovation Center Basel, Basel, Switzerland.

Prasinezumab, a monoclonal antibody that binds aggregated α-synuclein, is being investigated as a potential disease-modifying therapy in early-stage Parkinson's disease. Although in the PASADENA phase 2 study, the primary endpoint (Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) sum of Parts I + II + III) was not met, prasinezumab-treated individuals exhibited slower progression of motor signs than placebo-treated participants (MDS-UPDRS Part III). We report here an exploratory analysis assessing whether prasinezumab showed greater benefits on motor signs progression in prespecified subgroups with faster motor progression.

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Microglial Na/H exchanger-1 (NHE1) protein, encoded by Slc9a1, plays a role in white matter demyelination of ischemic stroke brains. To explore underlying mechanisms, we conducted single cell RNA-seq transcriptome analysis in conditional Slc9a1 knockout (cKO) and wild-type (WT) mouse white matter tissues at 3 days post-stroke. Compared to WT, Nhe1 cKO brains expanded a microglial subgroup with elevated transcription of white matter myelination genes including Spp1, Lgals3, Gpnmb, and Fabp5.

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Background: Astrogliosis and white matter lesions (WML) are key characteristics of vascular contributions to cognitive impairment and dementia (VCID). However, the molecular mechanisms underlying VCID remain poorly understood. Stimulation of Na-K-Cl cotransport 1 (NKCC1) and its upstream kinases WNK (with no lysine) and SPAK (the STE20/SPS1-related proline/alanine-rich kinase) play a role in astrocytic intracellular Na overload, hypertrophy, and swelling.

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Evaluation of ATN Framework and Biofluid Markers to Predict Cognitive Decline in Early Parkinson Disease.

Neurology

February 2024

From the Department of Neurology (K.A.Q.C., D.J.I., T.F.T., E.R., J.P., A.S.C.-P., D.W.), University of Pennsylvania, Philadelphia; Department of Biostatistics (M.C.B., C.S.C.), College of Public Health, University of Iowa, Iowa City; Department of Pharmacology and Clinical Pharmacology (J.H.K.), Inha University, Incheon, South Korea; Feinberg School of Medicine (T.S.), Northwestern University, Chicago, IL; Department of Medical and Molecular Genetics (T.M.F.), Indiana University, Indianapolis; Laboratory of Neuro Imaging (A.W.T.), University of Southern California, Los Angeles; Department of Neurology (C.M.T.), Weill Institute for Neurosciences, University of California San Francisco; Department of Neurology (K.D.K.), University of Rochester Medical Center, NY; Department of Neurology (B.M.), University Medical Center, Göttingen, Paracelsus-Elena-Klinik, Germany; Department of Neurology (D.G.), University of California San Diego; The Michael J. Fox Foundation (S.H.), New York, NY; Department of Psychiatry (D.W.), School of Medicine at the University of Pennsylvania; Michael J. Crescenz VA Medical Center (D.W.), Parkinson's Disease Research, Education, and Clinical Center; Department of Neurology (A.D.S.), Perelman School of Medicine, University of Pennsylvania, Philadelphia; Institute for Neurodegenerative Disorders (K.M.), New Haven, CT; Department of Neurology (K.L.P.), Stanford University, Palo Alto, CA; and Department of Pathology and Laboratory Medicine (L.M.S.), University of Pennsylvania, Philadelphia.

Background And Objectives: In Parkinson disease (PD), Alzheimer disease (AD) copathology is common and clinically relevant. However, the longitudinal progression of AD CSF biomarkers-β-amyloid 1-42 (Aβ), phosphorylated tau 181 (p-tau), and total tau (t-tau)-in PD is poorly understood and may be distinct from clinical AD. Moreover, it is unclear whether CSF p-tau and serum neurofilament light (NfL) have added prognostic utility in PD, when combined with CSF Aβ.

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Parkinson's disease and dementia with Lewy bodies are currently defined by their clinical features, with α-synuclein pathology as the gold standard to establish the definitive diagnosis. We propose that, given biomarker advances enabling accurate detection of pathological α-synuclein (ie, misfolded and aggregated) in CSF using the seed amplification assay, it is time to redefine Parkinson's disease and dementia with Lewy bodies as neuronal α-synuclein disease rather than as clinical syndromes. This major shift from a clinical to a biological definition of Parkinson's disease and dementia with Lewy bodies takes advantage of the availability of tools to assess the gold standard for diagnosis of neuronal α-synuclein (n-αsyn) in human beings during life.

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Sleep apnea, affecting an estimated 1 in 4 American adults, has been reported to be associated with both brain structural abnormality and impaired cognitive function. Obstructive sleep apnea is known to be affected by upper airway anatomy. To better understand the contribution of upper airway anatomy to pathways linking sleep apnea with impaired cognitive function, we investigated the association of upper airway anatomy with structural brain abnormalities.

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Article Synopsis
  • - The study investigates tau pathology in chronic traumatic encephalopathy (CTE) using tau PET imaging from 218 participants, including former professional and college football players, and a control group of individuals without head impact exposure.
  • - Elevated tau levels were found in former football players compared to controls, especially in older players over 60 with cumulative head impact exposure, but PET imaging didn't effectively distinguish between individuals with and without traumatic encephalopathy syndrome.
  • - The authors emphasize the need for further research to better understand the link between tau pathology and chronic traumatic brain injuries, as current findings only partially clarify these relationships.
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