PD and HC subjects of similar age and gender from 24 study sites in the US (18), Europe (5) and Australia (1) were enrolled after obtaining informed consent. We acknowledge that the early PD cohort likely includes a small number of subjects with other DAT deficit parkinsonian syndromes such as progressive supranuclear palsy (PSP), multiple system atrophy (MSA) and cortical basal syndrome (CBS), which may be indistinguishable from PD at the earliest stages of disease. At each study visit, the investigators reassess the subject diagnosis to identify any non‐PD subjects.
This study was conducted in accordance with the Declaration of Helsinki and the Good Clinical Practice (GCP) guidelines after approval of the local ethics committees of the participating sites. At enrollment, PD subjects were required to be age 30 years or older, untreated with PD medications (levodopa, dopamine agonists, MAO‐B inhibitors, or amantadine), within 2 years of diagnosis, Hoehn and Yahr <3, and to have either at least two of resting tremor, bradykinesia, or rigidity (must have either resting tremor or bradykinesia) or a single asymmetric resting tremor or asymmetric bradykinesia. All PD subjects underwent dopamine transporter (DAT) imaging with 123I Ioflupane or vesicular monoamine transporter (VMAT‐2) imaging with 18F AV133 (Australia only) and were only eligible if DAT or VMAT‐2 imaging demonstrated dopaminergic deficit consistent with PD in addition to clinical features of the disease. Study investigators evaluated enrolled PD subjects to assess absence of current or imminent (6 months) disability requiring PD medications, though subjects could initiate PD medications at any time after enrollment if the subject or investigator deemed it clinically necessary. Those subjects screened as potential PD subjects who were ineligible due to DAT or VMAT‐2 scans without evidence of dopaminergic deficit (SWEDD) were eligible to be enrolled in a SWEDD cohort.4 HC subjects were required to be age 30 years or older without an active, clinically significant neurological disorder or a first‐degree relative with PD. All enrolled subjects agreed to complete all study evaluations, including lumbar puncture.
PD and SWEDD subjects were excluded if they had a clinical diagnosis of dementia or had taken PD medications within 60 days of baseline or for longer than 60 days in total. HC subjects were excluded if they had a Montreal Cognitive Assessment (MoCA) total score ≤26. All subjects were excluded if they were treated with neuroleptics, metoclopramide, alpha methyldopa, methylphenidate, reserpine, or amphetamine derivative within 6 months or were currently treated with anticoagulants that might preclude safe completion of the lumbar puncture.
This study was conducted in accordance with the Declaration of Helsinki and the Good Clinical Practice (GCP) guidelines after approval of the local ethics committees of the participating sites. At enrollment, PD subjects were required to be age 30 years or older, untreated with PD medications (levodopa, dopamine agonists, MAO‐B inhibitors, or amantadine), within 2 years of diagnosis, Hoehn and Yahr <3, and to have either at least two of resting tremor, bradykinesia, or rigidity (must have either resting tremor or bradykinesia) or a single asymmetric resting tremor or asymmetric bradykinesia. All PD subjects underwent dopamine transporter (DAT) imaging with 123I Ioflupane or vesicular monoamine transporter (VMAT‐2) imaging with 18F AV133 (Australia only) and were only eligible if DAT or VMAT‐2 imaging demonstrated dopaminergic deficit consistent with PD in addition to clinical features of the disease. Study investigators evaluated enrolled PD subjects to assess absence of current or imminent (6 months) disability requiring PD medications, though subjects could initiate PD medications at any time after enrollment if the subject or investigator deemed it clinically necessary. Those subjects screened as potential PD subjects who were ineligible due to DAT or VMAT‐2 scans without evidence of dopaminergic deficit (SWEDD) were eligible to be enrolled in a SWEDD cohort.
PD and SWEDD subjects were excluded if they had a clinical diagnosis of dementia or had taken PD medications within 60 days of baseline or for longer than 60 days in total. HC subjects were excluded if they had a Montreal Cognitive Assessment (MoCA) total score ≤26. All subjects were excluded if they were treated with neuroleptics, metoclopramide, alpha methyldopa, methylphenidate, reserpine, or amphetamine derivative within 6 months or were currently treated with anticoagulants that might preclude safe completion of the lumbar puncture.