Table 4. . Clinical biomarkers.

Clinical finding	Assessment	Potential uses	Limitations	Study (year)	Ref.
Hyposmia	UPSIT	Enrichment of presymptomatic cohort; may be useful for PD risk	Not specific to PD	Xiao et al. (2014) Nalls et al. (2015)	[24,25]
RBD	RBD screening questionnaire	Enrichment of presymptomatic cohort; may be useful for PD risk score	Not specific to PD, long delay between RBD symptoms and PD symptoms. comparatively low sensitivity/specificity	Iranzo et al. (2006)	[26]
	Polysomnogram	Enrichment of presymptomatic cohort; may be useful for PD risk score	Not specific to PD, long delay between RBD symptoms and PD symptoms	Iranzo et al. (2006)	[26]
Motor symptoms	UKBB	Diagnostic criteria	Approximately 10% misdiagnosis; not progression marker, some criteria need revision†	Hughes et al. (1992)	[27]
	MDS diagnostic criteria	Updated diagnostic criteria	Not progression marker	Postuma et al. (2015)	[28]
	MDS-UPDRS III	Progression, evaluation of change after therapeutic intervention	Scores vary with levodopa-induced motor fluctuations and amount	Goetz et al. (2008)	[29]
Cognitive	MoCA	Global cognitive screening; diagnostic for cognitive changes; monitoring progression	Minimal testing per domain; not specific to PD	Dalrymple-Alford (2010)	[30]
	SCOPA-COG	Global cognitive screening; diagnostic for cognitive changes; monitoring progression	Minimal testing per domain	Marinus et al. (2003)	[31]
Psychiatric symptomatology	HAM-A/HAM-D	Global screening tool; diagnostic criteria for anxiety or depression, monitoring progression and treatment response	Npt specific to PD, numerous somatic questions that overlap with PD symptoms; time consuming to administer	Hamilton (1959) Forjaz et al. (2013) Hamilton (1976)	[32] [33] [34]
	Parkinsons Anxiety Scale	Specific to PD, observer or patient-rated scale, diagnostic criteria for anxiety	Not as widely used, not validated for PD anxiety disease progression	Leentjens et al. (2014)	[35]
Fatigue	Epworth Sleepiness Scale	Global screening tool; diagnostic criteria for extreme sleepiness and monitor disease progression	Not specific to PD; does not refer to etiology of fatigue	Johns MW (1991)	[36]
Patient-reported outcomes	PDQ-39	Specific to PD, widely used and patient self-administered, progression monitor for overall quality of life	Difficult to determine index score without specific calculations	Jenkinson et al. (1997)	[37]

^†List represents markers with high certainty or potentially high effect sizes developed by PDBP investigators; it does not presume to represent the entire literature.

UKBB exclusion criteria for diagnosis of PD includes a family history of PD.

HAM-A/HAM-D: Hamilton Anxiety Rating Scale/Hamilton Depression Rating Scale; MDS: Movement Disorder Society; MDS-UPDRS: Movement Disorder Society-Unified Parkinson's Disease Rating Scale; MoCA: Montreal Cognitive Assessment; PDQ-39: Parkinson's Disease Questionnaire; RBD: REM behavior disorder; SCOPA-COG: Scales for Outcomes in Parkinson's Disease-Cognitive; UKBB UK Brain Bank; UPSIT: University of Pennsylvania Smell Inventory Test.