Kate Johnson

June 12, 2014

ST. LOUIS — Patients with idiopathic REM sleep behavior disorders (RBD) and dopamine transporter dysfunctions that can be seen on brain imaging might be at high risk for neurodegenerative disease, according to new research.

"Our study showed a trend toward decreased dopamine transporter density in the brain and parkinsonism in the follow-up data of patients with REM sleep disorder who had no previous evidence of neurodegenerative disease," said Hongyoon Choi, MD, a PhD candidate and researcher in the Department of Molecular Medicine and Biopharmaceutical Sciences at Seoul National University Bundang Hospital in Sungnam, Korea.

Dr. Choi presented the study results here at the Society of Nuclear Medicine and Molecular Imaging 2014 Annual Meeting.

During the 8-year follow-up study, Dr. Choi and colleagues assessed the development of neurodegenerative disease in patients with RBD at baseline. RBD is a well-established risk factor for neurodegenerative disease.

They evaluated 21 consecutive patients (mean age, 65 years) with idiopathic REM sleep disorder, confirmed with video polysomnography, whose main complaint was dream enactment behavior.

At baseline, none of the patients had any parkinsonian features or cognitive dysfunction.

Three hours after receiving an injection of the radiopharmaceutical 123I-FP-CIT, patients underwent single-photon emission tomography (SPECT) scanning to assess baseline dopamine transporter function.

The reduced nigrostriatal uptake seen on imaging in 10 of the 21 patients indicated dopamine transporter dysfunction. This is a finding "that has not previously been reported," said Dr. Choi.

At 8-year follow-up, 7 of the 10 patients had developed neurodegenerative disease; there were 4 cases of Parkinson's disease (with or without cognitive impairment), 1 case of multiple system atrophy, and 2 cases of dementia with Lewy bodies. In addition, 1 of the 10 patients had developed mild parkinsonism; the other 2 had died of unrelated causes.

Baseline scans indicated normal dopamine transportation in 11 of the 21 patients. Scans obtained at 8-year follow-up indicated that 3 of these patients had reduced nigrostriatal uptake and that only 1 of the 11 had developed a neurodegenerative disorder.

"In the future, dopamine transporter imaging could potentially predict development of Parkinson's and other neurodegenerative diseases in patients who have known risk factors, including idiopathic REM behavior disorder," said Dr. Choi.

The link between RBD and the synucleinopathies has been well established, said Bradley Boeve, MD, from the Center for Sleep Medicine at the Mayo Clinic in Rochester, Minnesota. However, the findings support and extend other work that has suggested that "those with idiopathic RBD usually have an underlying neurodegenerative etiology, which is most often a synucleinopathy," he told Medscape Medical News. In addition, "those with idiopathic RBD plus reduced nigrostriatal uptake on 123I-FP-CIT SPECT imaging are at increased risk for developing features of Parkinson's disease, dementia with Lewy bodies, or multiple system atrophy in the next 5 to 15 years."

The challenge lies in predicting the future for those with idiopathic RBD, said Dr. Boeve. "When will future cognitive impairment, parkinsonism, and autonomic dysfunction develop, and which neurodegenerative syndrome will predominate?"

These findings underscore the need for longitudinal comprehensive evaluations of patients with RBD, in which biomarkers such as 123I-FP-CIT SPECT imaging will be key measures, he explained.

"The primary goal for this line of work is to implement disease-modifying strategies to delay the onset of or prevent clinically significant cognitive impairment, parkinsonism, and autonomic dysfunction in those with idiopathic RBD," he said.

Dr. Choi and Dr. Boeve have disclosed no relevant financial relationships.

Society of Nuclear Medicine and Molecular Imaging (SNMMI) 2014 Annual Meeting: Abstract 302, Presented June 10, 2014.


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