Defining at‐risk populations for Parkinson's disease: Lessons from ongoing studies

Abstract

It is currently widely acknowledged that the natural history of PD includes a preclinical phase, and there are increasing efforts to identify markers that would allow the identification of individuals at risk for PD. Here, we discuss the issues related to defining at-risk populations for PD and review findings of current population-based cohorts that have reported potential biomarkers for PD, such as the Honolulu-Asia Aging Study (HAAS) and the PRIPS (Prospective Validation of Risk factors for the development of Parkinson Syndromes) study. We also discuss enriched risk cohorts designed to evaluate specificity and predictive value of markers exemplified by the PARS (Parkinson Associated Risk Study) and the TREND (Tübinger evaluation of Risk factors for the Early detection of NeuroDegeneration) study. Although there is still a long way to go, studies designed according to these concepts might eventually provide sufficient data to form the basis for future screening programs for PD risk to be applied at a population level.

The Parkinson's progression markers initiative (PPMI) – establishing a PD biomarker cohort

“…Furthermore, testing for depression, anxiety, and autonomic function demonstrate impairment in PD compared to HC subjects. These findings are consistent with the notion that PD results in widespread nervous system dysfunction even early in the disease course and potentially prior to motor dysfunction 43, 44, 45, 46…”

Expression of prion protein in the cerebrospinal fluid of patients with Parkinson’s disease complicated with rapid eye movement sleep behavior disorder

“…The progress of the illness may not conform to the previously observed course of PD, and periodical revision is highly recommended (Kalia and Lang, 2015). For the reasons described above, accurate early diagnosis is of critical importance (Braak et al, 2003;Tolosa et al, 2009;Berg et al, 2012).…”

“…Consistent with our finding, other studies have identified an increased incidence of neurodegenerative diseases in RBD patients with disease progression. For example, the risk of developing into neurodegenerative diseases in idiopathic RBD patients is approximately 18% within 5 years and approximately 41% within 10 years, and most of those patients will develop PD or dementia with Lewy bodies (Doty et al, 1988;Hughes et al, 1992;Braak et al, 2003;Tolosa et al, 2009;Berg et al, 2012). Therefore, the occurrence of primary RBD in aged people may be related to synuclein disease.…”

“…As PD progresses, dementia, depression, and anxiety are commonly observed (Berg et al, 2015). Non-motor disorders, such as cognition and sleeping disorders, which severely compromise a patient's quality of life, also occur (Doty et al, 1988;Braak et al, 2003;Berg et al, 2012). To date, no effective treatment for PD has been developed, and initial therapy usually depends on the use of the anti-PD medication levodopa, which gradually becomes ineffective after the application of dopamine agonists (Kalia and Lang, 2015).…”

Biomarkers of Parkinson's disease: recent insights, current challenges, and future prospects

“…[10][11][12] The occurrence of NMS during the premotor phase reflects the widespread neurochemical and neuroanatomical changes that occur throughout the course of PD, with involvement of not only the dopaminergic nigrostriatal system but also serotonergic and noradrenergic brain stem areas, cholinergic frontal and brain stem regions. 13 However, each of these clinical biomarkers has poor predictive value when considered individually.…”