Table 1.

A summary of studies that have attempted to define advanced PD or late stage PD and provide treatment guidelines

Reference	Type of study	Population base	Outcome
Hely et al. (2005)	Follow up of a cohort recruited to Bromocriptine vs low dose levodopa study	130 patients with 52 surviving at 15 years	At 15 or more years falls, autonomic disturbance, neuropsychiatric symptoms, and dementia cause disability Motor fluctuations and dyskinesias while common are less disabling
Hely et al. (2008)	Follow up of a cohort recruited to Bromocriptine vs low dose levodopa study With 50 age and gender matched controls	30 surviving patients at 20 years FU	83% had dementia along with excessive daytime sleepiness 70%, falls 87%, freezing 81%, symptomatic postural hypotension 48%, urinary incontinence in 71%, hallucinations in 74%
Coelho et al. (2010)	Cross-sectional analysis of an international (Spain-Portugal) out patient cohort	50 PD patients in HY stages 4–5 (late stage) UPDRS, nonmotor fluctuation, cognition and quality of life assessments	Motor and nonmotor (mainly non-levodopa responsive symptoms) were prevalent and the main cause of disability. 50%, however, were considered to be non-demented
Antonini et al. (2015)	Delphi panel—based on consensus	a group of approximately 20 EU neurologists, using 2 rounds of data collection via an online survey and a single in-person meeting	Dementia, hallucinations, psychosis, nonmotor fluctuations, and nighttime sleep disturbances flagged as important potential hallmarks of advanced PD with functional consequences of falls, dependency and risk of pneumonia
Cilia et al. (2015)	Retrospective, cross-sectional study and longitudinal study	Patients with disease duration ≥ 20 years	Older age at onset and longer disease duration independently associated with a higher prevalence of major motor and nonmotor milestones of disease Mortality associated with male gender, older age, dysphagia, orthostatic hypotension, postural instability, fractures and institutionalisation
Odin et al. (2015)	International expert recommendations for the management of PD refractory to oral/transdermal therapies	Collection and consensus of opinions on structured questions from 103 experts from 13 countries overseen by an International Steering Committee (ISC) with 13 movement disorder specialists	Patients requiring levodopa > 5 times daily with severe, troublesome ‘off’ periods (> 1–2 h/day) despite optimal oral/transdermal levodopa or non-levodopa-based therapies considered for advanced therapies even if disease duration is < 4 years Cognitive decline related to nonmotor fluctuations is an indication for device-aided therapies
Luquin et al. (2017)	CEPA Study—a 3-round Delphi study	Including neurologists in Spain and using a Delphi system identification and quantification of clinical variables that characterize patients with APD	Motor syndrome and sleep problems rated as key issues severe dysphagia, recurrent falls, and dementia
Hassan et al. (2015)	International, multicentre National Parkinson’s Foundation Quality Improvement Initiative (NPF-QII) study database used to identify PD-20 subjects	187 PD-20 subjects (55% men) (4% of all NPF-QII participants)	(75%) had 20-25 years of PD duration, longest duration being 49 years. PD-20 subjects reflect an elite group of PD survivors with early onset disease and relatively mild cognitive disability despite long disease duration