grant

Precision-Mapping Functional Connectivity in Parkinson's Disease

Organization WASHINGTON UNIVERSITYLocation SAINT LOUIS, UNITED STATESPosted 1 Feb 2023Deadline 31 Dec 2027
NIHUS FederalResearch GrantFY2026APOEAbnormal gaitAddressAffectAgeAlzheimer beta-ProteinAlzheimer's Amyloid beta-ProteinAlzheimer's amyloidAmentiaAmyloid Alzheimer's Dementia Amyloid ProteinAmyloid Beta-PeptideAmyloid Protein A4Amyloid beta-ProteinAmyloid βAmyloid β-PeptideAmyloid β-ProteinApo-EApoE proteinApolipoprotein EAttentionBehavioralBiological MarkersBrainBrain Nervous SystemBrain PathologyClinicalClinical EvaluationClinical TestingCognitionCognitiveCognitive DisturbanceCognitive ImpairmentCognitive declineCognitive deficitsCognitive function abnormalComplexDataDefectDegenerative Neurologic DisordersDementiaDepositDepositionDisease ProgressionDisturbance in cognitionDorsalDysfunctionEconomic BurdenEncephalonEvaluationExhibitsFamilyFoundationsFunctional MRIFunctional Magnetic Resonance ImagingFunctional disorderFutureGait abnormalityGait disorderGait disturbancesGait dysfunctionGait impairmentGeneticImpaired cognitionIndividualLinkLocationMR ImagingMR TomographyMRIMRI biomarkerMRI markerMRIsMT-bound tauMagnetic Resonance ImagingMapsMeasuresMedical Imaging, Magnetic Resonance / Nuclear Magnetic ResonanceMental disordersMental health disordersMethodsMorbidityMotorMotor CortexNAC precursorNMR ImagingNMR TomographyNerve Transmitter SubstancesNervous System Degenerative DiseasesNetwork AnalysisNeural Degenerative DiseasesNeural degenerative DisordersNeurodegenerative DiseasesNeurodegenerative DisordersNeurologic Degenerative ConditionsNeurotransmittersNuclear Magnetic Resonance ImagingPARK1 proteinPARK4 proteinPD dementiaPD with dementiaPETPET ScanPET imagingPETSCANPETTParalysis AgitansParkinsonParkinson DiseaseParkinson Disease dementiaParkinson's DementiaParkinson's disease with dementiaParticipantPathologyPathway AnalysisPatient SelectionPatientsPersonsPhenotypePhysiopathologyPositron Emission Tomography Medical ImagingPositron Emission Tomography ScanPositron-Emission TomographyPrimary ParkinsonismPrognostic MarkerProteinsPsychiatric DiseasePsychiatric DisorderRad.-PETResearch DesignRestRewardsSNCASNCA proteinScanningSocietiesStudy TypeSymptomsSystemTestingTimeWalking impairmentWorkZeugmatographya beta peptidea-syna-synucleinabetaabeta depositionabnormal brain functionagesalpha synucleinalpha synuclein genealphaSP22amyloid betaamyloid beta depositionamyloid β depositionamyloid-b proteinasynaβ depositionbehavioral impairmentbeta amyloid fibrilbio-markersbiologic markerbiomarkerbrain dysfunctionbrain impairmentcholinergicclinical applicabilityclinical applicationclinical developmentclinical heterogeneityclinical testcognitive defectscognitive dysfunctioncognitive losscohortde-noisingdegenerative diseases of motor and sensory neuronsdegenerative neurological diseasesdementia due to Parkinson diseasedementia in PDdementia in Parkinson diseasedenoisingdisease heterogeneitydysfunctional brainfMRIimpaired behaviorimprovedindividual heterogeneityindividual variabilityindividual variationinnovateinnovationinnovativemagnetic resonance imaging biomarkermagnetic resonance imaging markermental illnessmicrotubule bound taumicrotubule-bound taumortalitymotor deficitnetwork dysfunctionneural imagingneuro-imagingneurodegenerative illnessneuroimagingneurological imagingneuropathologicneuropathologicalneuropathologyneurophysiologicalneurophysiologynew approachesnon A-beta component of AD amyloidnon A4 component of amyloid precursornon-dementednon-motor symptomnondementednonmotor symptomnovelnovel approachesnovel strategiesnovel strategypathophysiologypatient stratificationpersonalization of treatmentpersonalized health interventionpersonalized interventionpersonalized medicinepersonalized therapypersonalized treatmentpositron emission tomographic (PET) imagingpositron emission tomographic imagingpositron emitting tomographyprecision interventionspredictive biological markerpredictive biomarkerspredictive markerpredictive molecular biomarkerprognostic biomarkerprognostic indicatorpsychiatric illnesspsychiatric symptompsychological disorderrecruitresearch clinical testingsoluble amyloid precursor proteinstratified patientstudy designtautau Proteinstau factorα synuclein geneα-synα-synucleinτ Proteins
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Full Description

ABSTRACT
Parkinson disease (PD) is a progressive neurodegenerative disease characterized by motor, cognitive, and

psychiatric manifestations resulting from abnormal protein deposition and neurotransmitter deficits. The

variability in clinical presentation and progression in PD likely reflects underlying variability in brain pathology.

Although current treatments provide dramatic motor benefit in PD, they fail to fully alleviate gait impairment and

non-motor symptoms and may exacerbate cognitive and psychiatric features. These more complex symptoms

are linked to the function of large-scale brain networks, which can be measured with resting-state functional

connectivity MRI (RSFC). In our past work, we demonstrated that PD participants, as a group, show differences

in RSFC relative to healthy controls. However, development of clinical applications requires reliable individual-

level biomarkers that capture the widespread neuropathology and respects the clinical heterogeneity of PD,

opening the avenue to “personalized medicine” in PD. Recently developed precision-mapping RSFC approaches

now permit identification of individual-level differences in brain network organization with high reliability and may

provide a non-invasive biomarker for PD. Therefore, we propose to identify individual-level RSFC markers of

PD, examine the relationship of these precision RSFC markers with the clinical manifestations and

neuropathology of PD, and determine if precision RSFC markers predict cognitive decline and dementia in PD.

Grant Number: 5R01NS124738-04
NIH Institute/Center: NIH

Principal Investigator: MEGHAN CAMPBELL

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