Conversion to Parkinson Disease in the PARS Hyposmic and Dopamine Transporter-Deficit Prodromal Cohort

This is an exciting study and one of the most eagerly anticipated in the field of prodromal/pre-diagnostic PD... the authors show that the two step screening process works in so far as they can predict a significant proportion of participants that will 'convert' to PD at 4 years of follow-up. However the true screening performance cannot be determined because of big differences in follow up at each stage - we don't know what happens in normosmic participants or those that refused DaTSCAN. 

I am very interested in the proportion at baseline that had subtle motor dysfunction. It seems to offer further support for dispelling the notion of 'pre-motor' and settling on more appropriate terms like pre-diagnostic and prodromal. Motor dysfunction is seen in the PREDICT-PD cohort (http://jnnp.bmj.com/content/88/3/212) and in individuals with iRBD (https://academic.oup.com/brain/article-lookup/doi/10.1093/brain/aws093). Nonetheless it is a huge leap forward in the pre-diagnostic identification of PD...

JAMA Neurol. 2017 Jun 8. doi: 10.1001/jamaneurol.2017.0985. [Epub ahead of print]
Jennings D, Siderowf A, Stern M, Seibyl J, Eberly S, Oakes D, Marek K; PARS Investigators.

http://jamanetwork.com/journals/jamaneurology/article-abstract/2630495

IMPORTANCE: Detecting individuals at risk for Parkinson disease (PD) during the prodromal phase could clarify disease mechanisms and allow for treatment earlier in the disease process to possibly slow or prevent the onset of motor PD.

OBJECTIVE: To determine if the combination of smell identification testing followed by dopamine transporter (DAT) imaging can accurately and efficiently identify individuals from the general population at risk for conversion to a clinical diagnosis of PD.

DESIGN, SETTING, AND PARTICIPANTS: Participants were identified from the community by olfactory testing assessed longitudinally with DAT imaging 2 and 4 years after baseline and by annual clinical follow-up to determine whether they had clinical evidence to establish a PD diagnosis. Participants were contacted by mail and completed olfactory testing at home. Longitudinal follow-up of clinical measures and DAT imaging occurred at specialty centers. There were 203 hyposmic and 100 normosmic participants. A total of 185 hyposmic and 95 normosmic individuals had at least 1 follow-up visit, and 152 hyposmic participants (82.2%) were either observed for 4 years or converted to PD during follow-up.

MAIN OUTCOMES AND MEASURES: Percentage of individuals with hyposmia and a DAT deficit that converted to PD and the change in PD clinical scale scores (Unified Parkinson's Disease Rating Scale) and DAT imaging during 4-year follow-up.

RESULTS: Of 280 total participants, 140 (50.0%) were male, and the mean (SD) age of the cohort was 63 (8.7) years. Among 21 participants with hyposmia and a DAT deficit (65% or less of age-expected lowest putamen binding ratio) at baseline, 14 (67%) converted to PD at 4 years compared with 2 of 22 participants (9%) with a DAT in an indeterminate range (greater than 65%-80%) and 3 of 109 participants (2.8%) with no DAT deficit (greater than 80%) at baseline. Individuals with a baseline DAT deficit experienced a 4-year decline in DAT binding of 20.23% (SD, 15.04%) compared with 3.68% (SD, 18.36%) and 5.45% (SD, 13.58%) for participants with an indeterminate and no DAT deficit, respectively (P = .002). The relative risk of conversion to a diagnosis of PD in hyposmic individuals with a DAT deficit was 17.47 (95% CI, 7.02-43.45) compared with individuals with either indeterminate or no DAT deficit.

CONCLUSIONS AND RELEVANCE: The combination of hyposmia and DAT deficit was highly predictive of conversion to PD within 4 years of clinical follow-up. Individuals with hyposmia and a DAT deficit had a 5% reduction in DAT binding annually, similar to early PD. These results provide a framework for planning disease prevention studies in PD.