Striatal and Extra-striatal Mechanisms of Falling in Parkinson's Disease

Although most research in PD has a focus on presynaptic dopaminergic denervation, new lessons may be learned by exploring to what extent alterations in non-motor and non-dopaminergic systems may play a role in the balance impairment in this disorder. This project is designed to evaluate striatal pre-synaptic dopaminergic, cortical, thalamic, and brainstem cholinergic, cognitive, and oculomotor mechanisms underlying the risk of falling and imbalance in PD. The proposed study will exploit advances in our center in the development of dynamic biomathematical modeling of electronic platform data, application of specialized cognitive and oculomotor assessments, and positron emission tomography (PET). This novel multi-system approach holds promise for understanding mechanisms of falling in PD beyond pre-synaptic dopaminergic nigrostriatal denervation.

Inclusion criteria

• Subjects considered for inclusion will be female or male subjects either currently enrolled or eligible for care at the VA aged 50-85 years, or community volunteers.
• The racial, gender and ethnic characteristics of the proposed subjects population reflect the demographics of the patient population of the VA. However, extra efforts will be made to recruit women and minorities (see table 5).
• Children will be excluded from the study.
• No exclusion criteria shall be based on race, ethnicity, gender, or asymptomatic HIV status.

Exclusion criteria

• Inability to stand or walk independently (i.e., patients in Hoehn and Yahr stage IV and V).
• Vertiginous disorder.
• Orthostatic hypotension or unstable cardiovascular disease at risk of syncope (drop in systolic blood pressure of > 20 mm Hg upon standing).
• History of stroke with focal cortical lesions.
• Cerebellar, myelopathic or significant radiculopathy syndrome.
• Diminished light perception in both eyes (< 20/40 corrected OU).
• Intracranial surgery.
• Subjects who have participated in other research protocols such that their cumulative radiation absorbed dose to whole body, gonads, bone marrow or lens of the eye would exceed 5 Rem, or dose to other body organs is more than 15 Rem in preceding 12 months.
• Pregnancy (beta-HCG test within 48 hours of PET study) or breastfeeding.
• Contra-indications to MRI.