Objective: We sought to examine which demographic, genetic, and clinical characteristics in

Parkinson’s disease (PD) are associated with differences in levodopa equivalent daily dose

(LEDD) at five years.

Background: PD is marked by considerable heterogeneity in clinical presentation, progression

rate, and treatment response. This variability complicates the development of effective treatment

strategies. Understanding PD’s heterogeneous nature may improve treatment efforts and quality

of life.

Method: This study utilized data from the Parkinson’s Progression Markers Initiative (PPMI)

study. An input-cluster analysis was performed on PD patients based on sex, age group, genetic

status, comorbidities, race, tremor status, and body mass index. In addition, separate clustering

was conducted based on genetic status and alpha-synuclein seeding assay (SAA) status.

Regarding outcome, LEDD clusters were defined based on 100 mg increments in LEDD.

Results: A total of 278 PD patients met the inclusion criteria and had five years of follow-up

data available. Cluster analysis based on input variables identified 157 distinct patient groups

(group size ranging from 1 to 10 individuals), while outcome-based analysis revealed 19 distinct

clusters (group size ranging from 1 to 38 individuals). The largest input cluster, comprising 10

patients, was distributed across six different outcome clusters with LEDD ranging from 100 mg

to 1000 mg [figure-1]. Furthermore, separate clustering based exclusively on genetic and SAA

status resulted in 4 clusters with sizes of 3, 142, 33, and 100, which were dispersed into 3, 16,13,

and 17 distinct outcome groups, respectively [figure-2].

Conclusion: These findings underscore the extensive heterogeneity in PD, as demonstrated by

the wide dispersion of patients across distinct input and outcome clusters. The significant

variation in LEDD requirements at five years suggests that patient-specific factors play a crucial

role in treatment response, highlighting the need for personalized medicine approaches to

optimize therapeutic interventions.

Figure-1

Figure-2

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MDS Abstracts - https://www.mdsabstracts.org/abstract/unraveling-parkinsons-disease-heterogeneity-variability-in-dopaminergic-medication-response-over-five-years-a-cluster-analysis-of-ppmi-data/