How specific are non-motor symptoms in the prodrome of Parkinson's disease compared to other movement disorders?

The clinical diagnosis of Parkinson's disease (PD) based on motor signs is often preceded by several non-motor symptoms that can indicate early prodromal neurodegenerative processes. Such prodromal symptoms can aid the early detection of PD, but their specificity for prodromal PD in comparison to prodromes of other movement disorders is still largely unclear. We here aim to give a first insight into the published evidence of prodromal non-motor symptoms in PD, dementia with Lewy bodies (DLB), multiple system atrophy (MSA), Huntington's disease (HD), progressive supranuclear palsy (PSP) and spinocerebellar ataxia (SCA). REM-sleep behavior disorder (RBD) and autonomic dysfunction have been observed in the prodromes of PD, MSA, DLB and SCA. Depression and cognitive decline have been reported for prodromal PD, DLB, HD, SCA, and PSP. Olfactory loss has only been described in prodromal PD/DLB. However, estimating the specificity of prodromal non-motor symptoms in PD is so far complicated by scarce prospective evidence and study limitations. Information on marker specificity is a prerequisite for an accurate early (differential) diagnosis of prodromal diseases, as well as specific recruitment for targeted neuroprotective interventions. We here would like to raise awareness of these issues and encourage further prospective research of prodromal non-motor symptoms in neurodegenerative movement disorders and other diseases.