Major advances in Parkinson's disease over the past two decades and future research directions

Developments in levodopa formulations and the standardisation of deep brain stimulation (DBS) substantially improved clinical management of patients with Parkinson's disease before the turn of the century. As a result of these developments, Parkinson's disease has become a chronic disorder and it is associated with a plethora of non-motor disabling complications. Cognitive impairment is now a major complication of Parkinson's disease. 1 Hely MA Reid WGJ Adena MA Halliday GM Morris JGL The Sydney multicenter study of Parkinson's disease: the inevitability of dementia at 20 years. Mov Disord. 2008; 23: 837-844 Crossref PubMed Scopus (1510) Google Scholar Patients gradually develop from being cognitively normal, to having mild cognitive impairment and then dementia as part of a continuum of progressive pathological changes in the brain, including misfolded protein deposition and neuronal loss. 2 Halliday GM Leverenz JB Schneider JS Adler CH The neurobiological basis of cognitive impairment in Parkinson's disease. Mov Disord. 2014; 29: 634-650 Crossref PubMed Scopus (231) Google Scholar Gait dysfunction, leading to an inability to walk, is another major complication associated with long-term disease progression. Moreover, dysautonomia (eg, urinary dysfunction, constipation, and blood pressure dysregulation) can affect quality of life. These and other manifestations mean that Parkinson's disease is now a chronic multisystem disorder (figure).