Later age at onset in Parkinson's disease over twenty years in an Italian tertiary clinic Gianni Pezzoli a , Catherine Klersy b , Roberto Cilia a , Margherita Canesi a , Anna Lena Zecchinelli a , Claudio Bruno Mariani a , Silvana Tesei a , Giorgio Sacilotto a , Nicoletta Meucci a , Michela Zini a , Ioannis Ugo Isaias a , Claudio Ruffmann a , Michela Barichella a , Erica Cassani a , Stefano Goldwurm a , Emanuele Cereda c, * a Parkinson Institute e Istituti Clinici di Perfezionamento, Milano, Italy b Biometry and Statistics Service, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy c Nutrition and Dietetics Service, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy article info Article history: Received 4 July 2014 Received in revised form 19 August 2014 Accepted 24 August 2014 Keywords: Parkinson's disease Age at onset Epidemiology abstract Background: Age is considered an important risk factor for Parkinson's disease (PD). However, although life-expectancy has increased considerably, incidence rates of PD appeared to be stable over the last two decades. Accordingly, an increase in mean age at onset over time could be expected. We investigated the changes in age at onset in PD over the last two decades. Methods: All consecutive PD patients assessed over a 18-year period (1995e2013) in a single tertiary outpatient clinic were included in the present retrospective cohort study. Results: After adjusting for several confounders (gender, positive family history for PD, education, smoking at onset and past exposure to environmental/occupational pollutants), 5-year cohorts of year of disease onset were associated with increasing age at onset in both prevalent (N ¼ 6996) and incident (N ¼ 4172) cases (for trend, P < 0.001). From 1995e2000 to 2010e2013 there was an increase in predicted age of 4.1 years (95% CI, 3.0e5.2) and 3.9 years (95% CI, 2.7e5.1) in prevalent and incident cases, respectively. However, the change in predicted age at PD onset, across cohorts of year at onset, showed a steeper increase than the corresponding sex and cohort-matched mean age from the official Italian statistics. Conclusions: Over the last two decades, age at onset of PD appeared to shift progressively towards more advanced age. However, sequential, high-quality population-based incidence studies are required. To establish whether there is a trend towards increase in age at onset over and above general population ageing and to assess whether the increase is associated with improved medical and socio-economic conditions. © 2014 Elsevier Ltd. All rights reserved. 1. Introduction Aging is a major risk factor for Parkinson's disease (PD) [1,2]. However, age-related decline in the number of dopaminergic neurons [3] does not appear to fully account for its occurrence. The etiology of PD is not well understood and the hypothesis of a multi- factorial origin (the so-called multiple-hit hypothesis) is supported by findings from several case-control and prospective studies focusing on genetic and environmental factors, lifestyle habits and comorbidities [2,4e8]. Since the last century, living and socio- economic conditions have improved considerably and the in- crease in mean life-expectancy [9] may be a direct consequence. With increasing age, incidence and prevalence of PD would be expected to increase accordingly. However, recent primary care- based analyses have found that incidence rates have been sub- stantially stable over the last two decades [10,11]. To date, there are no studies that have evaluated the trend of the age at onset of Parkinson's disease. Accordingly, we investigated whether age at PD onset has changed over the last two decades in an Italian ter- tiary outpatient clinic. This information may suggest the need of more laborious incidence studies, the results of which could be * Corresponding author. Fondazione IRCCS Policlinico San Matteo, Viale Golgi 19, 27100 Pavia, Italy. Tel.: þ39 0382 501615; fax: þ39 0382 502801. E-mail address: e.cereda@smatteo.pv.it (E. Cereda). Contents lists available at ScienceDirect Parkinsonism and Related Disorders journal homepage: www.elsevier.com/locate/parkreldis http://dx.doi.org/10.1016/j.parkreldis.2014.08.017 1353-8020/© 2014 Elsevier Ltd. All rights reserved. Parkinsonism and Related Disorders 20 (2014) 1181e1185