title: Serial dopamine transporter imaging of nigrostriatal function in patients with idiopathic rapid-eye-movement sleep behaviour disorder: a prospective study.
abstract: BACKGROUND
  Serial 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.
  
  
  METHODS
  In a prospective study, 20 patients with IRBD (mean age 70·55 years [SD 6·02]) underwent serial DAT imaging with (123)I-2β-carbomethoxy-3β-(4-iodophenyl)-N-(3-fluoropropyl)-nortropane ((123)I-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 (123)I-FP-CIT uptake between patients and controls in each striatal region and rates of decline were assessed by use of multivariate ANOVA (MANOVA).
  
  
  RESULTS
  Compared with controls, patients had significantly reduced mean (123)I-FP-CIT binding in all four striatal regions at baseline and after 3 years. Striatal (123)I-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 (123)I-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 (123)I-FP-CIT uptake ratios, the decline in (123)I-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 (123)I-FP-CIT uptake at baseline and a mean reduction in (123)I-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.
  
  
  CONCLUSIONS
  In patients with IRBD, serial (123)I-FP-CIT SPECT shows decline in striatal tracer uptake that reflects progressive nigrostriatal dopaminergic dysfunction. Serial (123)I-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.
  
  
  BACKGROUND
  Fondo de Investigaciones Sanitarias of Spain.
authors.affiliation: Neurology Service, Hospital Clinic, Barcelona, Spain. airanzo@clinic.ub.es
authors.forename: Alex
authors.initials: A
authors.lastname: Iranzo
authors.forename: Francesc
authors.initials: F
authors.lastname: Valldeoriola
authors.forename: Francisco
authors.initials: F
authors.lastname: Lomeña
authors.forename: José Luis
authors.initials: JL
authors.lastname: Molinuevo
authors.forename: Mónica
authors.initials: M
authors.lastname: Serradell
authors.forename: Manel
authors.initials: M
authors.lastname: Salamero
authors.forename: Albert
authors.initials: A
authors.lastname: Cot
authors.forename: Domènec
authors.initials: D
authors.lastname: Ros
authors.forename: Javier
authors.initials: J
authors.lastname: Pavía
authors.forename: Joan
authors.initials: J
authors.lastname: Santamaria
authors.forename: Eduardo
authors.initials: E
authors.lastname: Tolosa
mesh_terms: D000368:Aged; D015331:Cohort Studies; D003342:Corpus Striatum / Q000000981:diagnostic imaging* / Q000378:metabolism; D050483:Dopamine Plasma Membrane Transport Proteins / Q000378:metabolism; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D020187:REM Sleep Behavior Disorder / Q000000981:diagnostic imaging* / Q000378:metabolism; D013378:Substantia Nigra / Q000000981:diagnostic imaging* / Q000378:metabolism; D013997:Time Factors; D015899:Tomography, Emission-Computed, Single-Photon / Q000379:methods
chemical_list: D050483:Dopamine Plasma Membrane Transport Proteins