Study Cohorts

Parkinson’s Progression Markers Initiative (PPMI) Clinical enrolls prodromal, recently diagnosed Parkinson’s participants and healthy controls. This cohort description section covers eligibility criteria at enrollment for PPMI Clinical.

All PPMI participants are also assigned to cohorts and subgroups in an analytic dataset based on a central review of the most recent longitudinal PPMI data.  The analytic cohort reflects new PPMI data that may modify the enrollment cohort designation.  The analytic data set cohort assignments should be used rather than the enrollment cohort assignments for all data analysis.  An Excel file providing definitions for analytic datasets will now be provided with PPMI data downloads. 

Please also note, PPMI began initial recruitment in 2010. After an enrollment hiatus, the study expanded and reinitiated recruitment in 2020. There are some differences in the protocol, eligibility criteria, and schedule of activities between these two phases. All PPMI data has been harmonized in the current data structure. 

See below for the recruitment status of each cohort.

Research Documents and SOPs

Parkinson's Disease

Participants with Parkinson's disease, with and without genetic risk variants.

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Prodromal Cohort

Participants who are at risk of Parkinson’s or another parkinsonism based on clinical features, genetic variants, or other biomarkers.

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Healthy Controls

Participants with no neurologic disorder and no first degree relative with PD.

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Legacy Cohorts

Some initial-phase PPMI cohorts are not restarting recruitment. Their data is available, and some continue study participation.

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Parkinson’s Disease

Participants with early, untreated sporadic Parkinson’s disease or PD with a pathogenic genetic variant(s).

All participants of the PD cohort have a clinical diagnosis of PD and a positive dopamine transporter (DAT) SPECT. The PD cohort is comprised of several subgroups, which include the following key inclusion criteria:

  1. People with untreated PD1:

    The initial phase of PPMI enrolled 423 untreated PD participants. Many of these participants continue in PPMI, and the expansion phase aims to enroll an additional 650 sporadic untreated PD study participants.

  2. People with PD and pathogenic genetic variant(s) in LRRK2, GBA, SNCA

    The initial phase of PPMI enrolled 294 genetic PD participants (across variants). Many of these participants continue in PPMI, and the expansion phase aims to enroll an additional 250 PD participants with pathogenic genetic variants including rare genetic variants such as Parkin, PINK1

    For participants with LRRK2, GBA variants

    Initial Stage Expansion Stage
    Minimum age 18 30
    Years since diagnosis Within 7 years Within 2 years
    Hoehn and Yahr at Baseline I, II, or III I, or II
    Medications for PD Initiated? Allowed Allowed

    For participants with rare genetic variants

    Initial Stage Expansion Stage
    Minimum age 18 30
    Years since diagnosis Within 7 years No Limit
    Hoehn and Yahr at Baseline I, II, or III I, II, or III
    Medications for PD Initiated? Allowed Allowed

Because some PD subjects were enrolled as early as 2010, and have been followed for up to 10 years, most subjects in the initial panel of PD participants are now receiving treatment and have features of established PD such as motor fluctuations and/or dyskinesia.

Footnotes:

  1. A small number of individuals in the PD cohort were initially recruited into the SWEDD cohort of PPMI (link to legacy section), but later on developed PD and are now enrolled in the PD cohort of the study.
  2. In a few instances exceptions were made allowing recruitment of individuals with longer disease duration.

Prodromal Cohort

Participants who are at risk of Parkinson’s based on clinical features, genetic variants, or other biomarkers.

The initial phase of PPMI enrolled 67 prodromal volunteers age 60 or older with REM sleep behavior disorder (RBD), hyposmia with DAT deficit and 445 prodromal volunteers with a genetic risk variant (SNCA, LRRK2, GBA). Many of these participants continue in PPMI, and the expansion phase aims to enroll an additional 2,000 prodromal volunteers.

In the expansion phase, participants in the prodromal cohort are eligible based on a stage risk paradigm with the following sequential criteria:

  1. Age 60 or older
    1. Exception: Age 30 years or older for SNCA or rare genetic variants (e.g., PRKN, PINK1)
  2. No clinical diagnosis of PD or other parkinsonism or of dementia
  3. Presence of risk factors or clinical features related to Parkinson’s disease (PD):
    1. RBD
    2. Known genetic risk variants
    3. First-degree family history of PD
    4. Other known PD risk criteria including those based on questionnaires in PPMI Online
  4. Hyposmia based on UPSIT testing
    1. Exception: Those with SNCA or other rare genetic variants
  5. Positive dopamine transporter (DAT) SPECT on visual inspection
    1. Exception: Some participants without DAT deficit will also be eligible, chosen based on (i) DAT binding that is reduced from age expected but not outside the normal range and/or (ii) individuals with risk factors related to of PD including RBD, LRRK2, GBA, SNCA, or other rare genetic variants. It is estimated that about 25% of eligible participants will not have a DAT deficit.

Note that eligibility and enrollment criteria may change based on findings from this or other studies as the cohort is further enriched for PD risk.

Please see the Protocol on the Research Documents & SOPs page for full inclusion and exclusion criteria.

Related links

Healthy Controls

Participants with no neurologic disorder and no first-degree relative with PD.

At baseline, healthy controls have no current or active clinically significant neurological disorder, no first-degree relative with PD, and normal dopamine transporter (DAT) SPECT imaging by visual inspection.

The initial phase of PPMI recruited 196 control volunteers. Many of these participants continue in PPMI, and the expansion phase aims to recruit an additional 100 healthy controls.

Please see the Protocol on the Research Documents & SOPs page for full inclusion and exclusion criteria. Please make note of differences in inclusion/exclusion criteria for the initial and expansion phases. For example, in the initial phase of recruitment, an exclusion criterion for the healthy control cohort was a Montreal Cognitive Assessment score of ≤26. This criterion is not present in the expansion phase.

Related links

Legacy Cohorts

Two cohorts from the PPMI initial stage will not reopen recruitment in the expansion phase.

  1. The Genetic Registry
    This cohort recruited people with a pathogenic genetic risk variant (LRRK2, GBA, SNCA) either diagnosed Parkinson’s disease (PD) or unaffected. The schedule of activities and duration of follow-up for the Genetic Registry differed from that of the PD and Prodromal Cohorts (see archived Research Documents & SOPs for more details).

    Some Genetic Registry participants were invited to transition to the PD or the Prodromal Cohort. Any transitioned participants will follow the SOA for the active protocol.

Related links
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  1. Scan without dopaminergic deficit (SWEDD)
    This cohort included participants who were clinically diagnosed with PD but had a normal DAT SPECT on visual inspection. A small number of SWEDD individuals continue to participate in longitudinal follow-up.

    In the expansion phase, newly recruited participants will not be eligible if the DAT SPECT is normal (with some exceptions noted in the protocol).

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Resources

Our user guidance resources describe PPMI data, covering variable and schema definitions, values, and more instructional materials.

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The study’s data and biosample collection, storage and analysis methods have become field-wide standards.

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This interactive tool provides an aggregate-level snapshot of PPMI cohort demographics and data collection time points.

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