The Effect of A1- Adrenergic Receptor Antagonist Therapy on Cardiac and Striatal Transporter Uptake in Pre-Motor and Symptomatic Parkinson's Disease
Parkinson's disease (PD) is characterized by many non-motor symptoms that occur several years before the diagnosis, in particular idiopathic REM behavior disorder (iRBD), which is associated with autonomic impairment. The purpose of this study is to investigate the effect of treatment with the selective post-synaptic a1-adrenergic blocker terazosin on 123I-MIBG myocardial uptake in a population of subjects with defined pre-motor PD risks (i.e. hyposmia and RBD) and abnormal baseline 123I-MIBG uptake, with or without 123I-Ioflupane uptake abnormality or PD motor symptoms. Scintigraphic changes will be correlated to motor and non-motor severity of PD, measured by validated clinical scales and cardiac autonomic function tests.
• Male or female of age between 50 and 85 years at time of enrollment.
• Diagnosis of idiopathic REM sleep behavior disorder (iRBD), established either as 'definite RBD' according to the criteria proposed by the International Classification of Sleep Disorders (ICSD)-2 \[AASM, 2005\] or 'probable RBD' following a score of 6 or higher in the RBD questionnaire (RBDSQ) \[Nomura et al, 2011\], with a score of at least 1 in subitems 6.1 to 6.4 of question 6 \[Halsband et al, 2018\].
• At least one of the following:
‣ Diagnosis of hyposmia, established as a University of Pennsylvania Smell Identification Test (UPSIT) score \< 20th percentile for the individual's age group and sex.
⁃ Functional constipation assessed by a scores \> 4 on a questionnaire based on modified ROME IV diagnostic criteria.
⁃ Color vision abnormality, as assessed using HRR Pseudoisochromatic Plates, in the absence of congenital dyschromatopsia
⁃ Symptoms of depression, as assessed by a Beck Depression Inventory (BDI) fast screen score \>3 or concurrent use of antidepressant medications.
• Abnormal 123I-MIBG myocardial scintigraphy, as defined by a Late H/M ratio \< 2.2 and/or a WR \>20%, with normal cardiac ejection fraction (LVEF \>55%).
• Capacity to give informed consent