Identifying Biomarkers of Parkinson's Disease Using Magnetic Resonance Imaging (MRI)

Multimodal MRI Markers of Nigrostriatal Pathology in Parkinson's Disease

This study is designed to determine if magnetic resonance imaging (MRI) measures can be used to diagnose and monitor the progression of Parkinson's disease (PD) while distinguishing between PD and parkinsonisms [conditions that are PD look-a-like diseases such as progressive supranuclear palsy (PSP) or multiple system atrophy (MSA)] when combined with changes in certain proteins in body fluids that are related to iron (Fe).

The lack of in vivo biomarker(s) reflecting Parkinson's disease (PD)-related cell loss and associated pathoetiological/physiological processes in nigrostriatal structures has hindered discovery research and limited the ability to evaluate disease-modifying therapies. Recent research has generated excitement for using DTI and R2* MRI measures as biomarker(s) for PD-related pathology in nigrostriatal pathways, but they fall short by the lack of understanding of their clinical implications and biological/pathological underpinnings. Working closely with the National Institute of Neurological Disorders and Stroke (NINDS) Parkinson's Disease Biomarkers Program (PDBP), the proposed work will investigate multimodal MRI techniques in combination with fluid-based iron (Fe) protein profiles to serve as in vivo markers for PD-related nigrostriatal pathology that can be used as biomarkers for diagnosing PD, following its progression, and gaining mechanistic understanding of PD pathoetiology and pathophysiology.

Inclusion Criteria:

PD Subjects:

1. Able and willing to sign the consent form at time of initial enrollment or if the subject is decisionally impaired and has a legal representative that is able and willing to sign a consent form at the time of the enrollment. If the subject becomes decisionally impaired during the course of the study, their legal representative may sign an addendum to consent for continued participation.
2. MMSE score of 15 or greater unless a legal representative is present.
3. Idiopathic PD according to published criteria.
4. History of adequate response to dopaminergic therapy.
5. History of asymmetrical symptom onset

MSA Subjects:

1. Older than 30 yrs.
2. Able and willing to sign the consent form at time of initial enrollment or if the subject is decisionally impaired and has a legal representative that is able and willing to sign a consent form at the time of the enrollment. If the subject becomes decisionally impaired during the course of the study, their legal representative may sign an addendum to consent for continued participation.
3. MMSE score of 15 or greater unless a legal representative is present.
4. MSA according to published criteria.
5. History of autonomic & urinary dysfunction and/or severe cerebellar ataxia.

PSP Subjects:

1. Older than 40 yrs.
2. Able and willing to sign the consent form at time of initial enrollment or if the subject is decisionally impaired and has a legal representative that is able and willing to sign a consent form at the time of the enrollment. If the subject becomes decisionally impaired during the course of the study, their legal representative may sign an addendum to consent for continued participation.
3. PSP according to published criteria.
4. Vertical gaze palsy and/or slow vertical gaze/postural instability during first year of diagnosis.
5. MMSE score of 15 or greater unless a legal representative is present

Controls:

1. Older than 21 yrs.
2. Able and willing to sign the consent form.
3. MMSE greater than 24.

Exclusion Criteria:

PD Subjects:

1. Unable or does not have a legal representative/unwilling to provide consent.
2. Any condition that precludes a routine MRI (e.g., claustrophobia, pacemaker, severe scoliosis, etc.).
3. History of cerebrovascular diseases or other neurological disorders.
4. Major medical problems such as renal or liver failure.
5. Unstable, non-PD-related medical conditions.
6. MMSE score less than 15 unless a legal representative is present
7. Use of anticoagulant medications.
8. Signs of dementia.

MSA Subjects:

1. Unable or does not have a legal representative /unwilling to provide consent.
2. Any condition that precludes a routine MRI (e.g., claustrophobia, pacemaker, severe scoliosis, etc.).
3. History of cerebrovascular diseases or other neurological disorders.
4. Major medical problems such as renal or liver failure.
5. Unstable, non-MSA-related medical conditions.
6. MMSE score less than 15 unless a legal representative is present
7. Use of anticoagulant medications.
8. Signs of dementia.

PSP Subjects:

1. Unable or does not have a legal representative /unwilling to provide consent.
2. Any condition that precludes a routine MRI (e.g., claustrophobia, pacemaker, severe scoliosis, etc.).
3. History of cerebrovascular diseases or other neurological disorders.
4. Major medical problems such as renal or liver failure.
5. Unstable, non-PSP-related medical conditions.
6. MMSE score less than 15 unless a legal representative is present
7. Use of anticoagulant medications.
8. Signs of dementia.

Controls:

1. Unable/unwilling to provide consent.
2. Evidence of severe memory impairment or signs of dementia (MMSE < 24).
3. Any condition that precludes a routine MRI (e.g., claustrophobia, pacemaker, severe scoliosis, etc.).
4. History of cerebrovascular diseases or other neurological disorders.
5. Major medical problems such as renal or liver failure.
6. Unstable medical conditions.
7. Use of anticoagulant medications.
8. Signs of dementia.