Research on the premotor symptoms of Parkinson's disease: clinical and etiological implications.
BACKGROUND
The etiology and natural history of Parkinson's disease (PD) are not well understood. Some non-motor symptoms such as hyposmia, rapid eye movement sleep behavior disorder, and constipation may develop during the prodromal stage of PD and precede PD diagnosis by years.


OBJECTIVE
We examined the promise and pitfalls of research on premotor symptoms of PD and developed priorities and strategies to understand their clinical and etiological implications.


METHODS
This review was based on a workshop, Parkinson's Disease Premotor Symptom Symposium, held 7-8 June 2012 at the National Institute of Environmental Health Sciences in Research Triangle Park, North Carolina.


CONCLUSIONS
Research on premotor symptoms of PD may offer an excellent opportunity to characterize high-risk populations and to better understand PD etiology. Such research may lead to evaluation of novel etiological hypotheses such as the possibility that environmental toxicants or viruses may initiate PD pathogenesis in the gastrointestinal tract or olfactory bulb. At present, our understanding of premotor symptoms of PD is in its infancy and faces many obstacles. These symptoms are often not specific to PD and have low positive predictive value for early PD diagnosis. Further, the pathological bases and biological mechanisms of these premotor symptoms and their relevance to PD pathogenesis are poorly understood.


CONCLUSIONS
This is an emerging research area with important data gaps to be filled. Future research is needed to understand the prevalence of multiple premotor symptoms and their etiological relevance to PD. Animal experiments and mechanistic studies will further understanding of the biology of these premotor symptoms and test novel etiological hypothesis.
National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, Research Triangle Park, North Carolina, USA.
Honglei
H
Chen
Edward A
EA
Burton
G Webster
GW
Ross
Xuemei
X
Huang
Rodolfo
R
Savica
Robert D
RD
Abbott
Alberto
A
Ascherio
John N
JN
Caviness
Xiang
X
Gao
Kimberly A
KA
Gray
Jau-Shyong
JS
Hong
Freya
F
Kamel
Danna
D
Jennings
Annette
A
Kirshner
Cindy
C
Lawler
Rui
R
Liu
Gary W
GW
Miller
Robert
R
Nussbaum
Shyamal D
SD
Peddada
Amy Comstock
AC
Rick
Beate
B
Ritz
Andrew D
AD
Siderowf
Caroline M
CM
Tanner
Alexander I
AI
Tröster
Jing
J
Zhang
D000377:Agnosia / Q000503:physiopathology; D003248:Constipation / Q000503:physiopathology; D018450:Disease Progression; D006801:Humans; D010300:Parkinson Disease / Q000209:etiology* / Q000503:physiopathology*; D062706:Prodromal Symptoms; D020187:REM Sleep Behavior Disorder / Q000503:physiopathology; D012106:Research