Update on New Prodromal Cohort Added to PPMI

This March, the Parkinson?s Progression Markers Initiative (PPMI) will launch a new study arm to enroll and follow a prodromal Parkinson?s disease (PD) cohort.   Defining a pre-diagnostic or prodromal phase for PD presents both an immediate challenge ? how to reliably identify individuals during this prodromal period at high risk to phenoconvert to PD ? and an eventual opportunity:  can we ultimately treat these individuals at high risk for PD prior to the onset of symptoms of disease to prevent or delay the development of manifest PD? It is hoped that this additional cohort will provide researchers with the opportunity to examine biomarker progression prior to the onset of motor symptoms.  The PPMI study has built a robust infrastructure of 24 sites (22 of which will participate in the prodromal cohort) and eight cores with well-defined processes to ensure standardization across sites that will be to support the prodromal Parkinson cohort.


As scientists have long recognized, PD has a prolonged pre-diagnostic period during which nigral dopamine degeneration and likely brainstem and olfactory bulb pathology has occurred several years in advance of typical motor symptoms. Numerous studies have demonstrated that at clinical diagnosis of PD, a 40-60% loss of dopaminergic neurons has already occurred during a prodromal period estimated to be 5-15 years in duration.

Several lines of evidence suggest that dopaminergic imaging can reliably identify subjects with a reduction in dopamine transporter density during this prodromal phase of their disease. Early non-motor symptoms like olfactory loss, autonomic dysfunction, sleep disturbance, cognitive and behavioral impairment may also occur prior to typical PD motor symptoms, reflecting early brainstem or extra-nigral pathology. Recent understanding of both these early non-motor manifestations and the molecular genetics of PD have provided several specific strategies to identify those individuals without typical PD motor symptoms, but at increased risk to develop PD. Several proof of concept studies have demonstrated that enriching a population for PD risk by combining non-motor symptoms (olfaction or REM Sleep Behavior Disorder (RBD)) or genetic risk (LRRK2 will be the focus for this study) with dopamine transporter imaging (DAT) may successfully identify individuals at high risk to phenoconvert to manifest PD.

Study Design:

Subjects with either hyposmia (< 10th percentile by age and gender), RBD (defined by Polysomnography (PSG) criteria) and/or LRRK2 mutation who also have a dopamine transporter deficit based on brain imaging are at high risk to phenoconvert to motor PD within two years. Approximately 100 individuals with hyposmia, RBD or LRRK2 with a dopamine transporter deficit will be enrolled. Subjects will be followed for four years and will follow the same schedule of events as is outlined for PD subjects in the study. Based on preliminary data we anticipate that approximately 30% of prodromal subjects may develop motor PD within 2 years.

To review the full details on the study design for this new cohort, review the updated protocol.

Study Recruitment:

All subjects enrolled in this arm of PPMI will be age 60 and above, enriching for age which is perhaps the greatest risk factor for PD. None of these subjects will have PD. Specific recruitment tactics for the previously mentioned risk factors include:

Hyposmia: PPMI seeks 20,000 people to take a smell survey and then be smell tested using the UPSIT to determine their ability to smell. Those scored as being less than the 10th percentile will be invited to consent for the study.

RBD: Individuals with a diagnosis of RBD through a polysomnogram will be recruited through sleep centers at select PPMI sites and invited to consent for the study. To learn more visit www.michaeljfox.org/ppmi/sleep.

LRRK2: People who are 60 or older who do not have PD and know they have a LRRK2 mutation will be invited to participate. Genetic Counseling and testing will be available to those who are able to travel to the Boca Raton area and who are of Eastern European (Ashkenazi) Jewish descent. To learn more visit www.michaeljfox.org/ppmi/genetics.

Recruitment for the study is expected to begin in March 2013. As PPMI continues to expand, opportunities for additional new cohorts could inevitably follow. With the initial investment of time, money, and expertise already made, the Steering Committee will continue to consider new populations that can be incorporated into the initiative to deepen our understanding and move the field forward.