Longitudinal Changes in Dopamine Transporter Predict Neurodegenerative Risk in iRBD

Baseline and long-term monitoring of changes in the dopamine transporter (DAT) availability may help identify patients with idiopathic rapid-eye-movement sleep behavior disorder (iRBD) who are at high risk of conversion to neurodegenerative diseases, according to study results published in Neurology.

Previous studies have indicated that iRBD is a powerful prodromal marker of Parkinson disease (PD). Study researchers therefore sought to investigate the relationship between longitudinal changes in DAT availability and prodromal markers in iRBD.

In this prospective study, South Korean researchers enrolled 31 patients with drug-naïve PD, 39 patients with iRBD, and 19 healthy patients as controls. They recorded age, sex, and RBD duration at baseline. Participants underwent olfaction and neuropsychological evaluation, and study researchers assessed their PD motor and non-motor symptoms using the Movement Disorders Society revised-Unified PD Rating Scale. Participants also underwent F-FP-CIT PET scans every 2 years. In addition, the study researchers also assessed longitudinal changes in DAT availability using a principal component analysis of tracer uptakes in bilateral striatum.

No differences were found between the groups in terms of sex and age at baseline. In the patients with iRBD, 10 patients converted to neurodegenerative disease during a mean follow-up period of 3.22 years. The calculated phenoconversion rates at 2 and 5 years were 14.7% and 36.6%, respectively. The estimated annual conversion rate for this cohort was 7.32%.

The DAT pattern of patients with iRBD and baseline hyposmia, constipation, and mild parkinsonian signs distributed toward a PD pattern that distinguished them from patients in the healthy control group. Additionally, during follow-up, the DAT pattern over time moved toward PD patterns in some patients with iRBD in the healthy control pattern. In these patients, hyposmia at baseline represented the only biomarker associated with this change.

The PD-pattern of DAT at baseline predicted approximately 58 percent of disease converters (hazard ratio [HR], 4.95; 95% CI, 1.16-21.08). A combination of both hyposmia as well as baseline PD pattern of DAT predicted up to 67 percent of conversion (HR, 7.89; 95% CI, 1.85-33.69). A significantly lower percentage of hyposmia was observed in nonconverters (29.4%) who completed follow up compared with converters (P =.0044).

According to the study researchers, findings from this study indicate “hyposmia should be considered as a unique clinical marker reflecting the baseline status of neurodegeneration, and prediction of upcoming rapid DAT decline and phenoconversion to neurodegenerative diseases” in patients with iRBD.

Reference

Shin JH, Lee JY, Kim YK, et al. Longitudinal change in dopamine transporter availability in idiopathic REM sleep behavior disorder. Neurology. Published online September 28, 2020. doi:10.1212/WNL.0000000000010942