Sleep Benefit May Be Explained by ‘Direct Neurochemical Evidence’

Phenomenon linked to higher levels of dopamine transporter proteins in brain

Marisa Wexler, MS avatar

by Marisa Wexler, MS |

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Sleep benefit — a poorly understood phenomenon where people with Parkinson’s disease have fewer symptoms upon waking up — is associated with higher levels of dopamine transporter proteins in a region of the brain called the putamen, a study shows.

These findings “are meaningful because they provide direct neurochemical evidence to explain the SB [sleep benefit] phenomenon in PD [Parkinson’s disease] patients, a clinical observation first reported over 40 years ago,” researchers wrote.

The study, “Sleep benefit in patients with Parkinson’s disease is associated with the dopamine transporter expression in putamen,” was published in Brain Research.

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Sleep benefit is phenomenon of less-severe symptoms upon waking

Parkinson’s is caused by the death and dysfunction of nerve cells in the brain that make dopamine, a major chemical messenger involved in nerve cell communication. The mainstay of Parkinson’s treatment, levodopa and its derivatives, basically work by giving the brain more materials with which to produce dopamine.

Sleep benefit, affecting as many as half of the people diagnosed with Parkinson’s, is a phenomenon in which patients report less-severe symptoms upon waking after a full night’s sleep. First reported in the 1980s, sleep benefit has since been a puzzle to researchers, as patients generally don’t have medication in their system after a full night’s sleep.

In addition, this phenomenon may even occur after daytime naps for some patients.

To this day, the cause of sleep benefit remains mysterious, but previous studies suggest that Parkinson’s patients with longer disease duration, poor sleep efficiency, and greater motor impairment were more likely to experience sleep benefit. Sleep efficiency is the percentage of time spent asleep while in bed.

Now, a team of researchers at The First Affiliated Hospital of Zhengzhou University, in China, evaluated whether brain levels of dopamine transporter (DAT) — a protein that helps control the release and reuptake of dopamine by nerve cells — were involved in this phenomenon.

The study included 115 people living with Parkinson’s. A total of 61 patients (32 men and 29 women, mean age of 60.3 years) experienced sleep benefit, while the other 54 (26 men and 28 women, mean age 61.9 years) did not.

The two groups were similar in terms of demographic factors including age, sex, and education, and history of smoking; clinical measures of disease severity were also generally comparable.

This is meaningful because it is helpful to discern patients with [sleep benefit] whose symptoms might be alleviated by improving sleep quality rather than increasing the medication dose

However, significantly more patients in the sleep benefit group reported tremor as a main symptom relative to those without sleep benefit. Also, the average levodopa equivalent daily dosing (LEDD), a measure of the total contribution made by each Parkinson’s medication, was significantly lower among patients who experienced sleep benefit.

Most measures of sleep quality did not differ significantly between the two groups, though patients with sleep benefit tended to report higher sleep efficiency on a regular basis and longer sleep duration.

DAT levels were measured using positron emission tomography (PET). DAT-PET scans were successfully completed for 30 patients with sleep benefit and 26 who did not experience sleep benefit. Results showed that DAT levels were significantly higher in several regions of the brain among patients who experienced sleep benefit relative to those who did not.

With these data in hand, the researchers then conducted multivariate statistical analyses, looking across all the data for factors that were significantly associated with sleep benefit.

After adjusting for potential influencing factors, they found that tremor-dominant Parkinson’s, lower LEDD, and a longer sleep duration at night were significantly and independently associated with sleep benefit.

Additionally, higher DAT levels in the putamen — a brain region that’s heavily affected in Parkinson’s disease — were significantly associated with sleep benefit.

These results suggest that sleep benefit in Parkinson’s patients is associated with DAT levels in the putamen. Since DAT helps to regulate dopamine levels, the researchers speculated that brain cells with higher amounts of the protein might be better able to regulate dopamine signaling after sleep, leading to an easing of symptoms.

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Findings may help discern patients whose symptoms may be eased with sleep

To assess whether DAT levels might be used to predict whether a patient will experience sleep benefit, the researchers calculated the area under the receiver operating characteristic curve, or AUC.

This is a statistical test that assesses how well a given measure, in this case DAT levels, can tell the difference between two groups (sleep benefit or not). AUC values can range from 0 to 1, with higher values reflecting a better ability to discriminate.

The AUC for using putamen DAT levels to distinguish between patients with and without sleep benefit was as high as 0.916, suggesting that “the putamen DAT expression level could predict the SB phenomenon in PD patients,” the researchers wrote.

“This is meaningful because it is helpful to discern patients with SB whose symptoms might be alleviated by improving sleep quality rather than increasing the medication dose,” they added.

The team noted that the study was limited by its small size, emphasizing a need for more research to validate these findings. They also stressed that, at present, there are no objective tests that can determine whether or not a patient experiences sleep benefit, so studies rely on subjective patient reports.

“Future studies would also involve collecting more data from a larger number of patients and establishing a clear reference for clinical symptom improvement in patients,” the team wrote.

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