Statistical Models of Parkinson’s Disease Progression: Predictive Validity in a 3-Year Follow-up

Article type: Research Article

Authors: Mendes, Alexandre^{a; b; *} | Gonçalves, Alexandra^{a; b} | Vila-Chã, Nuno^{a; c} | Calejo, Margarida^a | Moreira, Inês^b | Fernandes, Joana^b | Damásio, Joana^a | Teixeira-Pinto, Armando^{c; d; e} | Krack, Paul^{f; g} | Lima, António Bastos^a | Cavaco, Sara^{a; b}

Affiliations: [a] Serviço de Neurologia, Centro Hospitalar do Porto, Porto, Portugal | [b] Unidade Multidisciplinar de Investigação Biomédica, Instituto Ciências Biomédicas Abel Salazar, Universidade do Porto, Porto, Portugal | [c] Faculdade de Medicina da Universidade do Porto, Porto, Portugal | [d] CINTESIS, Faculdade de Medicina da Universidade do Porto, Porto, Portugal | [e] Sydney School of Public Health, University of Sydney, Sydney, Australia | [f] Department of Clinical Neurosciences, Clinic of Neurology, Geneva University Hospital, Geneva, Switzerland | [g] Department of Basic Neurosciences, Medical Faculty, University of Geneva, Geneva, Switzerland

Correspondence: [*] Correspondence to: Alexandre Mendes, Serviço de Neurologia, Hospital de Santo António, Centro Hospitalar do Porto, Largo Prof. Abel Salazar, 4099-001 Porto, Portugal. Tel.: +351 936350136; E-mail: falexandremendes@gmail.com.

Abstract: Background: The rate of Parkinson’s disease (PD) progression varies widely between patients. Current knowledge does not allow to accurately predict the evolution of symptoms in a given individual over time. Objectives: To develop regression-based models of PD progression and to explore its predictive value in a three-year follow-up. Methods: At baseline, 300 consecutive PD patients were assessed using the Unified Parkinson’s Disease Rating Scale (UPDRS) - subscales II and III, Hoehn & Yahr (H&Y) and Schwab and England Independence Scale (S&E); and the Freezing of Gait Questionnaire (FOG-Q). UPDRS-III and H&Y were applied in OFF and ON medication conditions. An axial index was derived from the UPDRS-III. Based on multiple linear regression coefficients, algorithms were developed to adjust test scores to the characteristics of each individual. Sixty-eight patients were reevaluated three years later. Results: In the construction of the models, disease duration, age ≥70, age at disease onset ≥55, tremor as the first symptom alone, and medication description explained between 35% (UPDRS-III in ON) and 57% (axial index in ON) of the variance of test scores. The predictive r2 of the models in a 10-fold cross-validation ranged between 33% (UPDRS-III in ON) and 55% (axial index in ON and S&E in OFF). All measures, except UPDRS-III OFF, H&Y ON, and S&E ON, had moderate/good absolute agreement (intraclass correlation coefficient between 0.60 and 0.72) between baseline and follow-up. Conclusions: A cross-sectional assessment of a PD population allowed the development of models of disease progression, whose predictive value was validated on a three-year longitudinal study.

Keywords: Parkinson disease, disease progression, statistical models, validity of results

DOI: 10.3233/JPD-160877

Journal: Journal of Parkinson's Disease, vol. 6, no. 4, pp. 793-804, 2016