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 [123I][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 [123I][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.

Cognition in individuals at risk for Parkinson's: Parkinson associated risk syndrome (PARS) study findings

“…In the general population, an association between DAT binding and cognitive function was demonstrated in 12 individuals without PD, 35 and in a cohort of 491 PD patients, de novo at baseline, lower baseline striatal DAT binding was associated with global cognitive decline over a 22-month period. 36 Conversely, cognitive reductions in prodromal PD may be partially mediated by early extrastriatal disease pathology or nondopaminergic systems. This is supported by animal data; in a mouse model of PD, cognitive dysfunction (abnormalities in spatial learning and novel object recognition) was noted preceding motor abnormalities and before loss of dopaminergic neurons was expected.…”

A Comprehensive View of the Neurotoxicity Mechanisms of Cocaine and Ethanol

“…Several studies have shown that DA at high concentrations may participate in neurodegenerative processes, such as in Parkinson's disease (Ahlskog 2007;Ravina et al 2012). Although cocaine is able to inhibit the reuptake of DA, noradrenaline and serotonin, its powerful effect is believed to ensue from its actions on the dopamine transporter (DAT) in neuron terminals, causing an increase of the concentration and of the intensity of action of DA at the postsynaptic receptors ( Fig.…”

The Semicolon Sign: Dopamine Transporter Imaging Artifact from Head Tilt

“…to aid in the diagnosis of Parkinson disease and other Parkinsonian syndromes such as Lewy body dementia and progressive supranuclear palsy (1,2). DAT imaging is special among clinical nuclear medicine scans in that the already small caudate and putamen, with average volumes of 3.4 and 4.3 cm 3 , respectively (3), are presented in multiple thin axial cuts.…”