Objective: To compare disease progression events between GBA PD and iPD using the Parkinson’s Progression Markers Initiative (PPMI) database

Background: GBA PD patients exhibit more rapid progression in motor symptoms and cognitive abilities(1). Qualitative research in people with GBA PD identified domains of motor, cognitive/psychiatric, and other non-motor symptoms, as well as proximal motor functioning limitations and distal impacts[2]. The MDS-UPDRS Part II captures the majority of motor function symptoms and limitations considered most important to patients. In the cognitive/psychiatric domain, memory loss including word finding difficulties, and attentional impairment were considered the most important. PPMI is a longitudinal, observational, multi-center study designed to collect comprehensive clinical and biological participant data at ~50 sites worldwide. It represents the largest dataset containing both GBA PD and iPD.

Method: Using PPMI data, we selected GBA PD participants (n=75) with H&Y ≤2 and disease duration ≤5 years. iPD participants were matched using propensity score matching (age, sex, disease duration, H&Y, and baseline scores for MoCA and MDS-UPDRS). Worsening of motor function was defined as the time to an increase of ≥2 points in MDS-UPDRS II [3], with no reduction in MDS-UPDRS III score. Worsening of cognition was defined as the time to worsening by 1 standard deviation (SD) in at least 2 of 5 selected cognitive outcomes (HLVT-TR, HVLT-DR, LNS, semantic fluency and SDMT)[4]. Cox proportional hazards regression was used to compare the time to worsening between GBA PD and iPD over the first 7 years of follow-up in the selected patient cohorts.

Results: Time to worsening of motor function (HR=0.62; 95% CL=0.42 to 0.92) and cognitive abilities (HR=0.23; 95% CL=0.08 to 0.55) was shorter in GBA PD compared with iPD.

Conclusion: Motor function and cognitive abilities decline more rapidly in GBA PD compared with iPD participants, including in time-to-event outcomes that can be used in clinical trials. It remains critical to measure and find treatments for rapidly progressing motor and cognitive decline in GBA PD patients.

Progression of Motor Function

Worsening of Cognition

References: 1. Brockmann K, Srulijes K, Pflederer S, Hauser AK, Schulte C, Maetzler W, Gasser T, Berg D. GBA-associated Parkinson’s disease: reduced survival and more rapid progression in a prospective longitudinal study. Mov Disord. 2015 Mar;30(3):407-11. doi: 10.1002/mds.26071. Epub 2014 Dec 1. PMID: 25448271.
2. Bonner N, Bozzi S, Morgan L, Mason B, Peterschmitt MJ, Fischer TZ, Arbuckle R, Reaney M. Patients’ experiences of Parkinson’s disease: a qualitative study in glucocerebrosidase and idiopathic Parkinson’s disease. J Patient Rep Outcomes. 2020 Aug 5;4(1):65. doi: 10.1186/s41687-020-00230-9. PMID: 32757092; PMCID: PMC7406609.
3. Horváth K, Aschermann Z, Kovács M, Makkos A, Harmat M, Janszky J, Komoly S, Karádi K, Kovács N. Minimal clinically important differences for the experiences of daily living parts of movement disorder society-sponsored unified Parkinson’s disease rating scale. Mov Disord. 2017 May;32(5):789-793. doi: 10.1002/mds.26960. Epub 2017 Feb 20. PMID: 28218413.
4. Litvan I, Goldman JG, Tröster AI, Schmand BA, Weintraub D, Petersen RC, Mollenhauer B, Adler CH, Marder K, Williams-Gray CH, Aarsland D, Kulisevsky J, Rodriguez-Oroz MC, Burn DJ, Barker RA, Emre M. Diagnostic criteria for mild cognitive impairment in Parkinson’s disease: Movement Disorder Society Task Force guidelines. Mov Disord. 2012 Mar;27(3):349-56. doi: 10.1002/mds.24893. Epub 2012 Jan 24. PMID: 22275317; PMCID: PMC3641655.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/decline-in-motor-function-and-cognitive-abilities-in-gba-pd-compared-to-idiopathic-pd-ipd/