Objective: The aim of this systematic review was to analyze the available literature and evaluate the efficacy of DaT-SPECT for the prediction of PD phenoconversion in populations exhibiting two prominent prodromal findings: REM Behavior Disorder (RBD) and hyposmia.

Background: Parkinson’s Disease (PD) often has a prodromal period which can be characterized by a variety of motor and non-motor findings. In instances of clinical ambiguity regarding diagnosis, Dopamine transporter (DaT) single-photon emission tomography (SPECT) has become a crucial tool to differentiate PD from other parkinsonian syndromes, although its utility as a predictive tool in the absence of significant clinical findings is still unclear.

Method: A PubMed search identified longitudinal studies of polysomnography-confirmed idiopathic/isolated RBD with baseline dopamine-transporter imaging (DaT-SPECT or DaT-PET) and reported phenoconversion to PD or related synucleinopathy (DLB/MSA/PD dementia). Titles/abstracts and full texts were screened, and data were extracted for cohort size, design, follow-up duration, DaT abnormality definition, phenoconversion frequency, and (when available) conversion stratified by baseline scan status. When 2×2 outcome data were available, risk ratios (RR) for phenoconversion (abnormal vs normal baseline DaT) were pooled using a random-effects model.

Results: Six longitudinal studies met inclusion criteria (n = 625), including four prospective and two retrospective cohorts. Among studies reporting baseline scan status (3/6), baseline DaT abnormalities were present in 52.4% (86/164). Follow-up ranged 2.2–9.9 years. Overall phenoconversion to PD/synucleinopathy occurred in 39.0% (244/625). Two studies provided usable stratified (abnormal vs normal) outcomes: phenoconversion was 54.3% (19/35) with abnormal baseline DaT versus 11.9% (5/42) with normal baseline scans, corresponding to a pooled RR 4.32 (95% CI 1.32–14.11). Pooled analysis was limited by heterogeneous DaT abnormality definitions and inconsistent methodology of outcome reporting.

Conclusion: In established RBD, an abnormal dopaminergic scan substantially increases the likelihood of future PD/synucleinopathy phenoconversion. Standardized DaT abnormality thresholds and harmonized longitudinal reporting are needed to strengthen pooled estimates and translation into established clinical utility.

References: Palermo G, Ceravolo R. Molecular Imaging of the Dopamine Transporter. Cells. 2019;8(8):872. doi:10.3390/cells8080872

Poewe W. Non-motor symptoms in Parkinson’s disease. Eur J Neurol. 2008;15 Suppl 1:14-20. doi:10.1111/j.1468-1331.2008.02056.x

Poewe W, Seppi K, Tanner CM, et al. Parkinson disease. Nat Rev Dis Primer. 2017;3:17013. doi:10.1038/nrdp.2017.13

St Louis EK, Boeve AR, Boeve BF. REM Sleep Behavior Disorder in Parkinson’s Disease and Other Synucleinopathies. Mov Disord. 2017;32(5):645-658. doi:10.1002/mds.27018

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