title: Dopamine transporter imaging is associated with long-term outcomes in Parkinson's disease.
abstract: Dopamine (DA) transporter (DAT) imaging has been studied as a diagnostic tool for degenerative parkinsonism. Our aim was to measure the prognostic value of imaging for motor and nonmotor outcomes in Parkinson's disease (PD). We prospectively evaluated a Parkinson's cohort after enrollment in a de novo clinical trial with a battery of motor (UPDRS), cognitive (Montreal Cognitive Assessment), and behavioral measures. DAT imaging with [(123)I][β]-CIT and single-photon emission computerized tomography (SPECT) was performed at baseline and after 22 months. In total, 491 (91%) of the 537 subjects had evidence of DA deficiency on their baseline scan, consistent with PD, and were included in the analyses. The cohort was followed for 5.5 (0.8) years, with a mean duration of diagnosis of 6.3 (1.2). Lower striatal binding at baseline was independently associated with higher risk for clinical milestones and measures of disease severity, including motor-related disability, falling and postural instability, cognitive impairment, psychosis, and clinically important depressive symptoms. Subjects in the bottom quartile for striatal binding, compared to the top quartile, had an odds ratio (95% confidence interval) of 3.3 (1.7, 6.7) for cognitive impairment and 12.9 (2.6, 62.4) for psychosis. Change from baseline in imaging after 22 months was also independently associated with motor, cognitive, and behavioral outcomes. DAT imaging with [(123)I][β]-CIT and SPECT, shortly after the diagnosis of PD, was independently associated with clinically important long-term motor and nonmotor outcomes. These results should be treated as hypothesis generating and require confirmation.
authors.affiliation: Biogen Idec, Cambridge, Massachusetts 02142, USA. Bernard.ravina@biogenidec.com
authors.forename: Bernard
authors.initials: B
authors.lastname: Ravina
authors.forename: Kenneth
authors.initials: K
authors.lastname: Marek
authors.forename: Shirley
authors.initials: S
authors.lastname: Eberly
authors.forename: David
authors.initials: D
authors.lastname: Oakes
authors.forename: Roger
authors.initials: R
authors.lastname: Kurlan
authors.forename: Alberto
authors.initials: A
authors.lastname: Ascherio
authors.forename: Flint
authors.initials: F
authors.lastname: Beal
authors.forename: James
authors.initials: J
authors.lastname: Beck
authors.forename: Emily
authors.initials: E
authors.lastname: Flagg
authors.forename: Wendy R
authors.initials: WR
authors.lastname: Galpern
authors.forename: Jennifer
authors.initials: J
authors.lastname: Harman
authors.forename: Anthony E
authors.initials: AE
authors.lastname: Lang
authors.forename: Michael
authors.initials: M
authors.lastname: Schwarzschild
authors.forename: Caroline
authors.initials: C
authors.lastname: Tanner
authors.forename: Ira
authors.initials: I
authors.lastname: Shoulson
mesh_terms: D000368:Aged; D003042:Cocaine / Q000031:analogs & derivatives / Q000493:pharmacokinetics; D015331:Cohort Studies; D003342:Corpus Striatum / Q000000981:diagnostic imaging; D050483:Dopamine Plasma Membrane Transport Proteins / Q000378:metabolism*; D005260:Female; D007839:Functional Laterality; D006801:Humans; D016014:Linear Models; D008297:Male; D008609:Mental Status Schedule; D008875:Middle Aged; D010300:Parkinson Disease / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000473:pathology*; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D015899:Tomography, Emission-Computed, Single-Photon / Q000379:methods
chemical_list: D050483:Dopamine Plasma Membrane Transport Proteins; D019275:Radiopharmaceuticals; C069723:2beta-carbomethoxy-3beta-(4-iodophenyl)tropane; D003042:Cocaine