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LOS ANGELES -- Several clinical factors were identified as predictors of neurodegeneration among patients with idiopathic REM sleep behavior disorder (RBD).

While RBD is a known risk factor for several neurological conditions, such as Parkinson's disease and dementia, a study by Ronald Postuma, MD, of Montreal General Hospital in Canada, and colleagues shows the importance of identifying other predictors of neurological decline in order to intervene with neuroprotective therapy.

The study, presented here at the American Academy of Neurology annual meeting, identified several factors tied to a significant increase in conversion from idiopathic RBD to neurodegenerative disease, including dementia or Parkinsonism:

• Abnormal olfaction (HR 2.6, P<0.001)
• Motor symptoms (HR 2.6, P<0.001)
• Subtle motor signs (HR 2.0, P<0.001)
• Abnormal quantitative motor testing (HR 3.5, P<0.001)
• Constipation (HR 1.6, P=0.003)
• Increased REM tone (HR 1.6, P=0.04)
• Abnormal DAT scan (HR 3.2, P<0.001)

The 23-center study included a cohort of 1,130 patients with polysomnographic-proven RBD and no baseline neurodegenerative disease -- assessed via motor, sleep, cognitive, motor, autonomic, and special sensory tests. The patients were followed up annually, for a maximum of 19 years.

The average disease-free follow-up period was approximately 4 years, and the overall risk of neurodegenerative disease conversion was about 6.3% per year, which Postuma noted is similar to that found in previous studies.

"The risk stays constant throughout time," he said.

After 3 years, 12%-18% of the cohort showed conversion to neurodegenerative disease. After 5 years, 24%-36% of the group had disease conversion, while 51%-63% converted after 10 years. Although there was a smaller sample size after a longer duration of follow-up, there was up to a 73% conversion rate after 12 years.

"This is quite striking -- the bottom line is that if you have a patient with polysomnographic-proven RBD in front of you, you are talking to a patient destined to develop a neurodegenerative disease over the next 10 to 12 years," Postuma said.

Several clinical factors were not predictive of disease conversion among these patients: systolic blood pressure drop, depression or anxiety, insomnia, somnolence, urinary or erectile dysfunction, and substantia nigra ultrasound.

Although both abnormal cognition (HR 11.2, P<0.001) and color vision (HR 3.6, P<0.002) were strongly predictive of the development of primary dementia, they were not associated with developing primary Parkinsonism.

The discussant for the study, Aleksandar Videnovic, MD, MSc, of Massachusetts General Hospital in Boston, commented that the lack of a standardized protocol across the multicenter study's sites was the most notable design limitation. In addition, he said, no distinction was made between static versus dynamic biomarkers of neurodegeneration. For example, substantia nigra hyperechogenicity is a stable biomarker and therefore cannot be used to monitor disease progression versus striatal dopamine transporter imaging, which could be useful for RBD-phenotype specific disease progression.

Still, despite these limitations, he called the study of "high significance as it positions the RBD as a very important target for future trials directed at disease modification."

Videnovic also pointed to certain barriers for future research in this area, including difficulty in recruiting a large number of RBD patients, and recommended caution when developing specific inclusion and exclusion criteria and trial endpoints.

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