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

SummaryBackgroundSerial dopamine transporter (DAT) imaging in patients with Parkinson's disease (PD) and other synucleinopathies 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.MethodsIn a prospective study, 20 patients with IRBD (mean age 70·55 years [SD 6·02]) underwent serial DAT imaging with 123I-2β-carbomethoxy-3β-(4-iodophenyl)-N-(3-fluoropropyl)-nortropane (123I-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 123I-FP-CIT uptake between patients and controls in each striatal region and rates of decline were assessed by use of multivariate ANOVA (MANOVA).FindingsCompared with controls, patients had significantly reduced mean 123I-FP-CIT binding in all four striatal regions at baseline and after 3 years. Striatal 123I-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 123I-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 nucleus, and 7·14% (2·74 to 11·56) in the right caudate nucleus. After adjustment for the baseline 123I-FP-CIT uptake ratios, the decline in 123I-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 nucleus (8·07%, 1·44 to 14·70), but not in the right caudate nucleus (4·16%, −3·00 to 11·34). At the 3-year assessment, three patients were diagnosed with PD. These patients had the lowest 123I-FP-CIT uptake at baseline and a mean reduction in 123I-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.InterpretationIn patients with IRBD, serial 123I-FP-CIT SPECT shows decline in striatal tracer uptake that reflects progressive nigrostriatal dopaminergic dysfunction. Serial 123I-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.FundingFondo de Investigaciones Sanitarias of Spain.