Pauline Anderson

June 29, 2017

AMSTERDAM — Patients with Parkinson's disease (PD) who are deep sleepers, defined as getting more slow-wave sleep, have slower progression of their disease compared to light sleepers, new research suggests.

If that's the case, enhancing deep sleep may be a treatment target in PD patients, said Simon Schreiner, MD, Department of Neurology, University of Zurich, Switzerland.

"The association we found between slow-wave sleep and PD progression was very robust," said Dr Schreiner. "It indicates that higher slow-wave sleep predicts a slower progression of axial symptoms as well as gait and postural function in patients with Parkinson's disease."

He presented his study here at the Congress of the European Academy of Neurology (EAN) 2017.

Sleep disturbances are common in PD. It's believed that the underlying neurodegeneration affects the brain system that regulates the sleep-wake cycle, said Dr Schreiner.

However, there's growing evidence of a bidirectional relationship: that sleep disturbances also influence neurodegeneration as well as the other way around, he said.

Very Relevant

"This is very relevant," said Dr Schreiner. "If this is true, this could lead to a vicious cycle resulting in accelerated neurodegeneration due to sleep disturbances. On the other hand, this could offer treatment possibilities aimed at sleep enhancement."

Experts believe that deep sleep (slow-wave sleep) is the most restorative type of sleep. It may have a positive influence on neurodegeneration by promoting clearance of toxins, such as β-amyloid and possibly α-synuclein (a presynaptic neuronal protein linked to PD) from the brain.

Dr Schreiner and his colleagues conducted a retrospective analysis of 131 consecutive patients with PD (mean age, 62.6 years; 34% female), who were seen at their movement disorders outpatient clinic. All the patients had undergone polysomnography.

The mean disease duration of these patients was 5.2 years. The median time between baseline and polysomnography was 3 months.

Researchers collected clinical data at two time points: baseline and a follow-up at least 2 years later. During these examinations, investigators obtained Unified Parkinson's Disease Rating Scale (UPDRS) scores. They also looked at an index of seven UPDRS 3 symptoms (the UPDRS progression factor), which, according to Dr Schreiner, best indicates PD progression. 

These seven symptoms are speech, hypomimia, arise from chair, posture, gait, postural stability, and body bradykinesia.

To quantify deep sleep, investigators used a measure called slow-wave energy (SWE). "This measure represents the depth and duration of slow-wave sleep," said Dr Schreiner.

He noted that the study sample represented "a real-life-scenario cohort" in that the patients were receiving "best medical treatment at each time point."

Over a mean observation time of about 5 years, the levodopa equivalent dose was significantly increased, as were the UPDRS 3 score and the "progression factor."

"As expected, there was a progression of PD," said Dr Schreiner.

The researchers split the sample into deep sleepers (high SWE) and light sleepers (low SWE). The groups were similar in terms of age, disease duration, and clinical subtypes (tremor, akinetic-rigid, mixed). "I think this is important when you compare these two groups," said Dr Schreiner.

However, he noted that there were significantly more female deep sleepers. "This makes a lot of sense because women are known to be deeper sleepers than men."

At baseline, there were no statistically significant differences between the groups for UPDRS score or for levodopa equivalent dose. However, at follow-up, the deep sleepers had a significantly lower UPDRS score (P < .001) and significantly less levodopa equivalent dose (P = .04).

For the UPDRS progression factor, there were no differences between the groups at baseline, but there were "marked differences" with "much higher scores" for the light sleepers compared with the deep sleepers (P < .001) at follow-up.

"In clinical terms, the progression was much faster in the group of light sleepers compared to the group of deep sleepers," he said.

This finding was confirmed by a "very strongly significant interaction" of the high and low SWE measure with time, he added.

Novel Finding

An "obvious" limitation of the study was its retrospective design, although the associations that were uncovered were "very robust," said Dr Schreiner.

And although the finding is novel, he added, it needs to be replicated, "ideally in a prospective manner."  

Future studies should address whether slow-wave sleep may be progression marker of PD and whether it has a direct or indirect effect on the disease course, he added.

Asked about medications interfering with sleep quality, Dr Schreiner said he and his colleagues attempted to control for this. Dopamine agonists, in particular, are known to affect slow-wave sleep, he said.

"We included these medications as control variables and didn't really see an effect."

If deep sleep does slow disease progression, session co-chair Alberto Albanese, MD, professor, neurology, Institute of Neurology, Catholic University of the Sacred Heart, Milan, Italy, wanted to know what difference this would make per year on the UPDRS.

Dr Schreiner noted that in the study, the difference for the UPDRS total sum score "was not that pronounced, but it was still there."

However, for the progression index — the seven symptoms — "there was a very strong progression in the one group and not so much progression in the other group," he said.

One delegate noted that there is no real agreement concerning the use of the "UPDRS progression factor."

Dr Schreiner has disclosed no relevant financial relationships.

Congress of the European Academy of Neurology (EAN) 2017. Abstract O3207. Presented June 26, 2017.

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