By Eleanor McDermid, Senior medwireNews Reporter
Patients with clinical symptoms of early Parkinson’s disease (PD) but no evidence of dopaminergic deficit on brain imaging are unlikely to have the condition, say the PRECEPT Study investigators.
There were 91 (11%) such patients among the 799 participants of the PRECEPT (Parkinson Research Examination of CEP-1347 Trial) Study, a typical proportion for a trial of patients with early PD. At baseline carbomethoxy-3-β-(4-iodophenyl)tropane single-photon emission computed tomography, the lowest putamen dopamine transporter (DAT) density in these patients was greater than 80% of that expected for their age.
By contrast, average putamen DAT density in the other patients was just 41.7% of normal values, and this declined further, by an average of 13.1%, between baseline and follow-up scan at 22 months. In patients without an initial DAT deficit, density declined by just 1.9%, which the researchers say is “consistent with the rate of change previously seen among healthy subjects.”
Clinical findings followed a similar pattern, with total and motor Unified Parkinson’s disease Rating Scale scores increasing by 10.5 and 7.0 points, respectively, in patients with a DAT deficit, compared with 0.5 and –0.4 in those without. Also, 68% of patients with a DAT deficit had started dopamine therapy, compared with 13% of those without.
“While these data are not definitive, they strongly suggest that [patients without a DAT deficit] are unlikely to have idiopathic PD”, write lead study author Kenneth Marek (University of Rochester, New York, USA) and colleagues in Neurology.
At the end of the study, the investigators were asked to provide a probable diagnosis for their patients. More than 96% of patients with an initial DAT deficit retained a diagnosis consistent with PD or a closely related condition. By contrast, 44% of patients without a DAT deficit had switched to a non-PD diagnosis. No single condition predominated, although essential tremor (17% of patients) and non-neurological diagnoses (10%) were most common.
More than half of the patients without an initial DAT deficit retained a PD diagnosis, which the team says “likely reflects the difficulty in revising diagnoses in a clinically variable and slowly progressive illness such as PD.”
However, six of these patients did switch to having an indeterminate or definite DAT deficit by the time of the follow-up scan, “suggesting that these subjects might be on a trajectory of reduced DAT.”
The researchers conclude: “As studies focus on early diagnosis of PD or even premotor diagnosis, the use of imaging in PD clinical studies becomes both more crucial and more complicated.”
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