Parkinson's Disease
Conditions
Keywords
GBA, genetic, progression, PD, glucocerebrosidase
Brief summary
In this longitudinal study, the investigators will follow Parkinson's disease (PD) patients with and without glucocerebrosidase (GBA) mutations. The investigators hypothesize that the rate of increase in brain network activity over time (network progression rate) is faster in patients with GBA gene mutations.
Detailed description
Parkinson's disease (PD) patients with mutations in the glucocerebrosidase gene (GBA) tend to have a more aggressive disease course. GBA may therefore provide a target for disease modifying therapies in mutation carriers. Using positron emission tomography (PET) and magnetic resonance imaging (MRI) brain imaging to measure network progression rates in mutation carriers will allow for the assessment of the potential disease modifying effects of new anti-GBA therapies. The investigators will also determine whether magnetic resonance imaging (MRI) network methods, which are less invasive and more broadly available than positron emission tomography (PET), produce comparable network progression measurements in individual patients. These determinations will be critical for the design of clinical trials of new disease-modifying drugs.
Interventions
GENETICDNA/GeneticTesting
Subjects will be tested for GBA and LRRK2 mutation status at baseline.
RADIATIONFDG PET scan
18F-Fluoro-2-deoxy-glucose (FDG) PET scan is a nuclear medicine test that measures glucose metabolism (energy) in your brain at baseline and 18 months later.
OTHERMRI scan
Magnetic Resonance Imaging (MRI) is a noninvasive scan which produces detailed pictures of the brain using a magnetic field. In addition, a special type of MRI, called resting state functional MRI (rs-fMRI), will measure and map brain activity. Conducted at baseline and 18 months later.
Investigator will evaluate subjects according to the Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS), the standard clinical tool used to measure the severity and progression of PD. Neuropsychological evaluation will assess how one's brain functions (via pencil and paper testing), which indirectly yields information about the structural and functional integrity of the brain. Conducted at baseline and 18 months later.
Sponsors
Northwell Health
Michael J. Fox Foundation for Parkinson's Research
Study design
Observational model
CASE_CONTROL
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
40 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Diagnosis of PD made according to United Kingdom (UK) Parkinson's Disease Society Brain Bank Criteria * Ability to provide written informed consent * Age 40-75 * Stable dose of antiparkinsonian medication for \>1 month prior to study entry
Exclusion criteria
* Subjects with pathogenic mutations in LRRK2 related PD mutations (subjects with variants of uncertain significance (VUS) are eligible * History of known causative factors such as encephalitis or neuroleptic treatment * Patients with dementia (defined as Mini-Mental Status Exam score \<24 or a Telephone Interview for Cognitive Status score \<26) * Atypical parkinsonian features including oculomotor abnormalities, incontinence, ataxia, sensory loss, or pyramidal signs * Known structural brain lesions * Patients with history of stroke, head injury, high intracranial pressure or severe headaches * Psychiatric disorder, including a history of major depression in the past 36 months * Pregnant or breastfeeding women (female subjects of child-bearing potential will be screened for pregnancy before imaging).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Increase in PD related metabolic pattern expression | Baseline and 18 months later | Changes in PD related and PD cognition related pattern expression in 18F-2-fluoro-2-deoxy-D-glucose (FDG) PET scans |
| Increase in PD related functional pattern expression | Baseline and 18 months later | Changes in PD related and PD cognition related pattern expression in resting state functional magnetic resonance imaging (rs-fMRI) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in motor function | Baseline and 18 months later | Change in motor function assessed with Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) III (The sum score ranges between 0-132 points. Higher scores indicate more severe impairment) |
| Change in cognitive function | Baseline and 18 months later | Change in cognitive function assessed with neuropsychological testing |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORDavid Eidelberg, MD
Head, Center for Neurosciences
Outcome results
None listed