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Principal Investigator: Kathleen Lombard Poston
Organization: UNIVERSITY OF SOUTHERN CALIFORNIA
Fiscal Year: 2024
Award: $603,714
Funding agency: National Institute of Neurological Disorders and Stroke
ABSTRACT
Parkinson’s disease (PD) is a devastating, progressive neurodegenerative brain disease, with no known cure.
The disease afflicts 10 million people worldwide - ~1.5 million in the U.S. alone, and ~50k-60k new cases are
diagnosed annually. Risk factors or interventions are extremely hard to evaluate as we lack objective metrics of
how PD affects the brain. The vast global availability of brain imaging has led to several promising metrics to
gauge PD progression in the brain - structural changes in the basal ganglia and motor cortex, abnormalities in
neural connectivity seen with diffusion MRI (dMRI), and disruptions of the brain’s functional synchrony across
regions, seen with resting state functional MRI (fMRI). Despite these findings, factors that affect disease severity
are difficult to discover, as most imaging studies of PD scan <100 patients. Most PD research is conducted in
isolated cohorts from the US and Europe, limiting worldwide generalizability. Factors that affect PD progression
are hard to verify, leading to a crisis of reproducibility. Responding to NIH’s call for more reproducible studies,
here we launch ENIGMA’s Worldwide Parkinson’s Initiative. ENIGMA recently published the largest
neuroimaging studies of schizophrenia, bipolar disorder, major depression, epilepsy, and autism spectrum
disorder. With ENIGMA’s globally coordinated, highly powered consortium approach, we plan to overcome the
crisis of small studies with poor power and reproducibility. Pooling anatomic, diffusion and resting state functional
MRI metrics from 21 deeply assessed international cohorts - from the US, Brazil, Taiwan, New Zealand, the
Netherlands, Italy, Switzerland, South Africa, China, and Russia - we ask: How does the illness affect the brain's
structure, neural connectivity, and functional synchrony? What imaging biomarkers track disease progression
and consistently predict clinical outcomes? Do genetic risk loci for PD help predict brain decline? What PD
subtypes, or clusters, can imaging identify? Combining multimodal data from 2,307 patients and 1,264 controls,
we will thoroughly evaluate predictors and brain biomarkers in PD. Our aims are to: (1) Evaluate and rank
structural, diffusion, and resting state functional MRI biomarkers of PD worldwide; (2) Evaluate the added
value of polygenic risk scores (PRS) in predicting PD brain biomarkers; (3) Predict future functional
decline in PD with machine learning, multi-modal imaging and genomics. We will use genetic data and
baseline clinical variables from PD patients and healthy controls across our cohorts to construct an ensemble of
models to predict the annual rate of change in combined scores from the Movement Disorder Society—Unified
Parkinson's Disease Rating Scale parts II and III. We will rank the best predictors of decline, and assess how
robust they are internationally. By better modeling variance in patient outcomes, our multimodal predictive model
will empower PD clinical trials by ranking biomarkers of disease burden and determining the contexts where they
are reliable, accurate, and feasible to use.
Terms: <ASD><Affect><Africa><Age of Onset><Amygdala><Amygdaloid Body><Amygdaloid Nucleus><Amygdaloid structure><Anatomic Sites><Anatomic structures><Anatomy><Anterior><Area><Asia><Atrophic><Atrophy><Attenuated><Austria><Autism><Autistic Disorder><Basal Ganglia><Basal Nuclei><Belgium><Biological Markers><Bipolar Affective Psychosis><Bipolar Disorder><Bradykinesia><Brain><Brain Diseases><Brain Disorders><Brain Nervous System><Brain imaging><Brazil><China><Clinical><Clinical Trials><Cognitive><Cognitive Disturbance><Cognitive Impairment><Cognitive decline><Cognitive deficits><Cognitive function abnormal><Collaborations><Corpus Callosum><Corpus Callosums><Corpus Striatum><Corpus striatum structure><Corticospinal Tracts><Country><DWI (diffusion weighted imaging)><DWI-MRI><Data><Data Pooling><Data Set><Data Sources><Degenerative Neurologic Disorders><Development><Diagnosis><Diffusion><Diffusion MRI><Diffusion Magnetic Resonance Imaging><Diffusion Weighted MRI><Diffusion weighted imaging><Diffusion-weighted Magnetic Resonance Imaging><Dimensions><Disease><Disease Progression><Disorder><Disturbance in cognition><Drugs><Early Infantile Autism><Encephalon><Encephalon Diseases><Environmental Factor><Environmental Risk Factor><Epilepsy><Epileptic Seizures><Epileptics><Europe><Formosa><Foundations><Functional MRI><Functional Magnetic Resonance Imaging><Future><Gait><Genetic><Genetic Predisposition><Genetic Predisposition to Disease><Genetic Risk><Genetic Susceptibility><Genetic predisposing factor><Genetic propensity><Genomics><Head><Image><Impaired cognition><Impulsivity><Individual><Infantile Autism><Inferior Temporal Gyrus><Inherited Predisposition><Inherited Susceptibility><International><Intervention><Intervention Strategies><Intracranial CNS Disorders><Intracranial Central Nervous System Disorders><Investigation><Italy><Japan><Kanner's Syndrome><Learning><Least Squares><Least-Squares Analyses><Least-Squares Analysis><Letters><MDS-UPDRS><MDS-Unified Parkinson's Disease Rating Scale><MRI biomarker><MRI marker><Mainland China><Major Depressive Disorder><Manic-Depressive Psychosis><Measures><Medication><Mental Depression><Modeling><Motor><Motor Cortex><Movement><Movement Disorder Society Unified Parkinson's Disease Rating Scale><Multimodal Imaging><Multimodal ML><Multimodal machine learning><NIH><National Institutes of Health><Nerve Degeneration><Nervous System Degenerative Diseases><Netherlands><Neural Degenerative Diseases><Neural degenerative Disorders><Neurodegenerative Diseases><Neurodegenerative Disorders><Neurologic Degenerative Conditions><Neuron Degeneration><New Zealand><North America><Oceania><Paralysis Agitans><Parkinson><Parkinson Disease><Pathway interactions><Patient outcome><Patient-Centered Outcomes><Patient-Focused Outcomes><Patients><Pattern><Persons><Pharmaceutical Preparations><Phenotype><Posture><Predictive Factor><Predisposition gene><Primary Parkinsonism><Protocol><Protocols documentation><Publishing><Reproducibility><Republic of China><Research><Rest><Risk><Risk Factors><Risk-associated variant><Russia><Sample Size><Scanning><Schizophrenia><Schizophrenic Disorders><Seizure Disorder><Severities><Severity of illness><Source><South Africa><South America><Striate Body><Striatum><Structure><Structure of inferior temporal gyrus><Susceptibility Gene><Switzerland><Symptoms><Taiwan><Testing><Thalamic structure><Thalamus><Thick><Thickness><Treatment Efficacy><Tremor><UPDRS><Unified Parkinson's Disease Rating Scale><United States National Institutes of Health><amygdaloid nuclear complex><attenuate><attenuates><autism spectral disorder><autism spectrum disorder><autistic spectrum disorder><bio-markers><biobank><biologic marker><biological sex><biomarker><biorepository><biotypes><bipolar affective disorder><bipolar disease><bipolar illness><bipolar mood disorder><body movement><brain visualization><burden of disease><burden of illness><cholinergic><clinical 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