Participant recruitment and clinical evaluation of PD

The study considered 423 de novo PwP from the PPMI study cohort, out of which successful ‘523’ genotyping was carried out in 368 individuals (see section “TOMM40 ‘523’ alleles and cognitive performance in APOE ε3/ε3 carriers”). Following this, as ‘523’ allele frequencies have been shown to be ethnic-specific⁴⁹ all individuals categorised as Black, Asian, Hispanic/Latino or other were excluded to ensure a more homogenous Caucasian cohort. Data were collected longitudinally from January 2011, with six 12 monthly time points being considered (baseline, 1 year, 2 years, 3 years, 4 years and 5 years). All data pertaining to the PPMI cohort were obtained from the PPMI database (available at http://www.ppmi-info.org/data) on 1st November 2020. For up-to-date information on the study, visit http://www.ppmi-info.org. Inclusion criteria and more specific details of the PPMI study can be found in a previously published communication⁵⁰.

Detailed demographic information was collected from all participants, including age at symptom onset, age at current assessment, disease duration and level of educational attainment. Anti-Parkinsonian medication dosage was obtained from the PPMI database as a total levodopa equivalent daily dose. All subjects were comprehensively evaluated, with motor symptom severity being assessed using the Movement Disorder Society-Unified Parkinson’s Disease Rating Scale) Part III, and disease severity on the Hoehn and Yahr scale⁵¹. The research involving human data was assessed and approved by The University of Western Australia Human Research Ethics Committee (approval number: RA/4/20/4293 and RA/4/20/4470). Written informed consent was obtained from all participants, visit http://www.ppmi-info.org for more information.