Early Daytime Sleepiness and Nighttime Slow-wave Sleep Disorganization in Progressive Macaque Model of Parkinson’s Disease

Abstract Parkinsonian patients often experience wake/sleep behavior disturbances, which can appear at an early stage of the disease in a way that is still not fully described. We aimed here at reproducing and characterizing these clinical signs in a progressive non-human primate model of the Parkinson’s disease to better understand the underlying physiopathology and to identify biomarkers of the disease. Three adult non-human primates (macaca fascicularis) were equipped with a polysomnographic telemetry system allowing the characterization of the wake/sleep behavior by long-term neurophysiological recordings and a modified multiple sleep latency test. Experiments were first performed in healthy animals and then during the progressive induction of a parkinsonian syndrome by chronic intramuscular injections of low doses of MPTP. We observed a significant early onset of wake/sleep behavior disturbances, before any motor symptoms, resulting in (i) a disorganization of nighttime sleep with more deep sleep and (ii) a disorganization of daytime naps with an excessive daytime sleepiness characterized by longer duration of naps, which occurred faster. These observations persisted and worsened in stable symptomatic state. In that latter state, we observed persistent excessive daytime sleepiness and more disorganized nighttime sleep architecture and continuity. Interpolating to the human condition, the present study suggests that nighttime and daytime sleep disorders may appear in early stage of the disease. They could thus be used as biomarkers of the disease for early stratification of patients who are at risk of developing Parkinson’s disease.

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Investigation of Nonmotor Symptoms in First-Degree Relatives of Patients with Different Clinical Types of Parkinson’s Disease

Parkinson s Disease ◽

10.1155/2019/1654161 ◽

2019 ◽

Vol 2019 ◽

pp. 1-7 ◽

Cited By ~ 1

Author(s):

Jiang-bing Liu ◽

Jun-ling Leng ◽

Ying-ge Wang ◽

Yu Zhang ◽

Tie-yu Tang ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Cognitive Impairment ◽

Excessive Daytime Sleepiness ◽

Daytime Sleepiness ◽

Late Onset ◽

Severe Depression ◽

Nonmotor Symptoms ◽

Sleep Behavior ◽

First Degree Relatives

Background. Nonmotor symptoms (NMS) are prodromal characteristics of Parkinson’s disease (PD). The first-degree relatives (FDR) of PD patients had a higher risk of PD and also had more NMS. Objective. To delineate NMS in FDR of patients with different clinical types of PD. Methods. A total of 98 PD probands were recruited; 256 siblings of them were enrolled in the FDR group. Various scales were used to assess NMS, including depression, anxiety, cognitive impairment, insomnia, constipation, excessive daytime sleepiness, rapid eye movement sleep behavior disorder (RBD), and restless legs syndrome (RLS). The incidences of NMS were further compared between the FDR groups of PD with different types. Results. The FDR of early-onset PD (EOP) showed a higher incidence of moderate to severe depression (OR = 4.08; 95% CI: 1.12–14.92; P=0.033), anxiety (OR = 4.22; 95% CI: 1.87–9.52; P=0.001), and excessive daytime sleepiness (OR = 3.40; 95% CI: 1.00–11.48; P=0.049) than the FDR of late-onset PD (LOP). It was also found that RBD (OR = 11.65; 95% CI: 3.82–35.54; P<0.001), constipation (OR = 4.94; 95% CI: 1.85–13.21; P=0.001), sleep disorders (OR = 4.51; 95% CI: 1.73–11.78; P=0.002), cognitive impairment (OR = 3.55; 95% CI: 1.62–7.77; P=0.002), and anxiety (OR = 2.49; 95% CI: 1.32–4.71; P=0.005) were more frequent in FDR of tremor-dominant PD (TDP) than in FDR of non-tremor-dominant PD (NTDP). Conclusions. The siblings of patients with EOP and TDP have more NMS, presuming that they have a higher risk in the PD prodromal stage. Whether they have a greater possibility to progress into PD requires further investigation.

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Striatum Shape Hypertrophy in Early Stage Parkinson’s Disease With Excessive Daytime Sleepiness

Frontiers in Neuroscience ◽

10.3389/fnins.2019.01353 ◽

2020 ◽

Vol 13 ◽

Author(s):

Liang Gong ◽

Huaisu Li ◽

Dan Yang ◽

Yinwei Peng ◽

Duan Liu ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Excessive Daytime Sleepiness ◽

Daytime Sleepiness ◽

Early Stage

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Excessive Daytime Sleepiness and REM Sleep Behavior Disorders in Parkinson's Disease: A Narrative Review on Early Intervention With Implications to Neuroprotection

Frontiers in Neurology ◽

10.3389/fneur.2018.00961 ◽

2018 ◽

Vol 9 ◽

Cited By ~ 6

Author(s):

Michaela D. Gjerstad ◽

Guido Alves ◽

Jodi Maple-Grødem

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Early Intervention ◽

Rem Sleep ◽

Excessive Daytime Sleepiness ◽

Behavior Disorders ◽

Daytime Sleepiness ◽

Narrative Review ◽

Sleep Behavior

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Sleep disturbances in newly diagnosed patients with early stages of Parkinson’s disease

Practical medicine ◽

10.32000/2072-1757-2020-5-117-123 ◽

2020 ◽

Vol 18 (5) ◽

pp. 117-123

Author(s):

D. M. KHASANOVA ◽

◽

Z. A. ZALYALOVA ◽

S. E. MUNASIPOVA ◽

◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Excessive Daytime Sleepiness ◽

Daytime Sleepiness ◽

Sleep Disturbances ◽

Control Group ◽

Newly Diagnosed ◽

Falling Asleep ◽

Lack Of Sleep ◽

Nighttime Sleep

According to numerous worldwide studies, patients with Parkinson’s disease (PD) often experience sleep disturbances, the most common of which are insomnia and excessive daytime sleepiness. The purpose of this study was to determine the quantitative and qualitative profile of sleep disorders in patients with the newly diagnosed PD, stages 1 and 2 according to Hoehn and Yahr. The assessment was carried out using the SCOPA-SLEEP scale. The study involved 95 people: 56 patients with a newly diagnosed PD, who had not previously received treatment (main group), and 39 individuals from the control group. Results. The profile of nocturnal sleep disturbances in PD patients was characterized by various symptoms: difficulty falling asleep (62,5%), night awakening (51,8%), long lying awake (57,1%), early awakening (50,0%), feeling lack of sleep (46,4%). In women, irrespective of the form and stage of PD, disturbances in nighttime sleep were found more often. Daytime hypersomnia among healthy volunteers was observed only in 5 participants (12,8%). The profile of daytime hypersomnia in PD patients was diverse: unexpected falling asleep during the day (n = 15, 26,8%), falling asleep in a calm environment (n = 17, 30,4%) or while reading and watching TV (n = 18, 32,1%). Difficulties in maintaining wakefulness during the day were noted by 13 patients (n = 13, 23,2%) with PD, and 4 patients (7,2%) reported difficulties due to excessive daytime sleepiness. Thus, given the prevalence and profile of dyssomnias, sleep disturbances may be an important sign of PD.

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