Serial dopamine transporter imaging of nigrostriatal function in patients with idiopathic rapid-eye-movement sleep behaviour disorder: a prospective study

Background Serial dopamine transporter (DAT) imaging in patients with Parkinson's disease (PD) and other synudeinopathies shows progressive nigrostriatal dopaminergic dysfunction. Because idiopathic rapid-eye-movement (REM) sleep behaviour disorder (IRBD) can precede the classic symptoms of PD and other synucleinopathies, we postulated that serial DAT imaging in patients with IRBD could be used to detect decline in striatal tracer uptake, indicating progressive nigrostriatal cell degeneration. Methods In a prospective study, 20 patients with IRBD (mean age 70.55 years [SD 6.02]) underwent serial DAT imaging with I-123-2 beta-carbomethoxy-3 beta-(4-iodophenyl)-N-(3-fluoropropyl)-nortropane (I-123-FP-CIT) SPECT at baseline and again after 1.5 years and 3 years; 20 age-matched and sex-matched control participants (69.50 years [6.77]) underwent imaging at baseline and 3 years. The striatum to occipital cortex uptake ratios were calculated for the putamen and caudate nucleus in each hemisphere. In patients, the ratio was judged to be reduced when it was less than two SD of the mean ratio in controls at the same timepoint. Differences in I-123-FP-CIT uptake between patients and controls in each striatal region and rates of decline were assessed by use of multivariate ANOVA (MANOVA). Findings Compared with controls, patients had significantly reduced mean I-123-FP-CIT binding in all four striatal regions at baseline and after 3 years. Striatal I-123-FP-CIT uptake was reduced compared with that in controls in ten patients at baseline and in 13 patients after 3 years. In patients, the mean reduction in I-123-FP-CIT uptake from baseline to 3 years was 19.36% (95% CI 15.14 to 23.59) in the left putamen, 15.57% (10.87 to 20.28) in the right putamen, 10.81% (6.49 to 15.18) in the left caudate nudeus, and 7.14% (2.74 to 11.56) in the right caudate nudeus. After adjustment for the baseline I-123-FP-CIT uptake ratios, the decline in I-123-FP-CIT binding at baseline to 3 years was significantly greater in patients than in controls in the left putamen (9.78% difference between groups, 95% CI 3.22 to 16.32), right putamen (5.43%, 1.99 to 12.86), and left caudate nudeus (8.07%, 1.44 to 14.70), but not in the right caudate nudeus (4.16%, -3.00 to 11.34). At the 3-year assessment, three patients were diagnosed with PD. These patients had the lowest I-123-FP-CIT uptake at baseline and a mean reduction in I-123-FP-CIT uptake at 3 years of 32.81% in the left putamen, 30.40% in the right putamen, 26.51% in the left caudate nucleus, and 23.75% in the right caudate nucleus. Interpretation In patients with IRBD, serial I-123-FP-CIT SPECT shows decline in striatal tracer uptake that reflects progressive nigrostriatal dopaminergic dysfunction. Serial I-123-FP-CIT SPECT can be used to monitor the progression of nigrostriatal deficits in patients with IRBD, and could be useful in studies of potential disease-modifying compounds in these patients. Funding Fondo de Investigaciones Sanitarias of Spain.