Objective: Longitudinal evaluation of personalized intervention strategies informed by detailed clinical and laboratory biomarker analysis to reduce relative risk of Parkinson’s disease in first degree relatives.

Background: Preventing PD is a major unmet need. Over the past decade, a multimodal precision medicine approach has been demonstrated to reduce relative risk of cognitive decline in Alzheimer’s disease (1). The Longitudinal Program to Prevent PD (LoPP-PD) was established to provide personalized multidomain precision medicine interventions to at-risk and high-risk first-degree relatives. Due to the heterogeneity of PD, various models of risk stratifying and subtyping disease based on criteria such as phenotype, pathological features, genetics, and other biomarkers have been proposed, but single biomarkers are unlikely to be sufficient to determine risk and clinical trajectory on an individual basis(2).

Method: Eligible participants must be ≥25 years old with a family history of an alpha-synucleinopathy in a first-degree relative. We established detailed, evidence-based risk profiling for motor, cognitive, and other nonmotor risk using combination of symptoms and biomarkers, including phenotypic symptoms, family history, neurologic examination, anthropometric measurements, genetic analysis, fluid biomarkers, neurocognitive testing, and validated clinical scales. Longitudinal monitoring will be informed by adaptive study design, to allow for ongoing refinement of personalized risk reduction strategies.

Results: Enrollment into LoPP-PD is ongoing. The initial cohort is 61% male, mean (SD) age was 54.9 (14.8) years, and 43% meet the criteria for highly probable prodromal PD. Table 1 lists current risk profile domains and validated and exploratory outcome measures.

Conclusion: With increasing prevalence, evidence-based personalized interventions to delay PD in those at higher risk is urgently needed. LoPP-PD will provide clinical evidence and provide rationale for personalized interventions to prevent the onset of motor, cognitive, and other nonmotor symptoms of PD.

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