Sleep Fragmentation as an Important Clinical Characteristic of Sleep Disorders in Parkinson’s Disease: A Preliminary Study

0
0
0

Sleep Fragmentation as an Important Clinical Characteristic of Sleep Disorders in Parkinson’s Disease: A Preliminary Study

Parkinson’s disease (PD), the second most common neurodegenerative disorder globally, is traditionally characterized by motor symptoms such as bradykinesia, rigidity, resting tremor, and postural instability. However, non-motor symptoms, including sleep disturbances, cognitive impairment, and autonomic dysfunction, are increasingly recognized for their substantial impact on patient quality of life. Among these, sleep disorders are particularly prevalent, affecting over 82% of individuals with PD. Despite their high incidence, sleep disorders in PD remain understudied, with unresolved questions regarding their pathophysiology and clinical significance. This study aimed to characterize sleep disorders in PD using polysomnography (PSG), focusing on identifying specific sleep abnormalities and their associations with demographic and clinical parameters.

Background and Rationale

Sleep disorders in PD are multifaceted, encompassing insomnia, REM sleep behavior disorder (RBD), restless legs syndrome, sleep fragmentation (SF), and excessive daytime sleepiness. SF, defined as frequent awakenings during sleep (more than three arousals lasting ≥5 minutes per night), is a common complaint but has not been systematically evaluated as a potential biomarker for PD. Previous studies have highlighted RBD as an early marker of PD, but the role of SF remains unclear. This study posited that SF might serve as a quantifiable marker of PD progression, given its association with neurodegeneration and dopaminergic dysfunction.

Methodology

Participant Recruitment and Clinical Evaluation

The study enrolled 27 PD patients (15 males, 12 females; mean age: 63.9 ± 9.3 years) and 20 age- and gender-matched healthy controls (14 males, 6 females; mean age: 64.2 ± 7.7 years). PD diagnosis adhered to the UK PD Society Brain Bank criteria, excluding secondary Parkinsonism or comorbid psychiatric conditions. Clinical assessments included the Unified Parkinson’s Disease Rating Scale-III (UPDRS-III) for motor severity, Hoehn-Yahr staging, and levodopa equivalent dose (LDE) calculations.

Polysomnography Protocol

Overnight PSG (Cadwell Easy II™) monitored sleep architecture, including electroencephalography (EEG), electromyography (EMG), electrooculography (EOG), respiratory effort, airflow, oxygen saturation, and limb movements. Sleep stages were classified according to the American Academy of Sleep Medicine criteria: wakefulness (Stage W), NREM (N1, N2, N3), and REM sleep. Key parameters analyzed included:

  • Time in Bed (TIB): Total duration from lights-off to lights-on.
  • Total Sleep Time (TST): Cumulative sleep across N1, N2, N3, and REM stages.
  • Sleep Efficiency (SE): Ratio of TST to TIB.
  • Sleep Latency (SL): Time from lights-off to the first N1 stage.
  • REM Sleep Latency (REM-SL): Time from lights-off to the first REM stage.
  • Stage Percentages: N1%, N2%, N3%, and REM% relative to TST.

Statistical Analysis

Data normality was assessed using Shapiro-Wilk tests. Between-group comparisons employed chi-square tests for categorical variables, independent t-tests for normally distributed data, and Mann-Whitney U tests for non-parametric data. Correlations between sleep parameters and clinical variables (age, disease duration, UPDRS-III, Hoehn-Yahr stage, LDE) were analyzed via Pearson’s correlation. Significance was set at P < 0.05.

Key Findings

Sleep Fragmentation Prevalence

SF was significantly more prevalent in PD patients (74.1%) compared to controls (40.0%; P = 0.019). Difficulty falling asleep (25.9% vs. 15.0%) and early awakening (30.0% vs. 20.0%) did not differ significantly between groups. SF in PD showed no correlation with age, disease duration, motor severity, or LDE (P > 0.05), suggesting its independence from traditional progression markers.

PSG Sleep Architecture Alterations

PD patients exhibited marked disruptions in sleep continuity and architecture:

  • Reduced Total Sleep Time and Efficiency: TST was 327.96 ± 105.26 minutes in PD vs. 414.67 ± 78.31 minutes in controls (P = 0.003). SE dropped to 63.26% ± 14.83% in PD vs. 76.8% ± 11.57% in controls (P = 0.001).
  • Impaired Deep Sleep and REM: N3 (slow-wave sleep) duration decreased to 20.00 [39.00] minutes in PD vs. 61.50 [48.87] minutes in controls (P = 0.001). REM sleep duration and percentage (REM%) were halved in PD (32.50 [33.00] minutes; 9.56% ± 6.01%) compared to controls (85.25 [32.12] minutes; 15.50% ± 4.81%; P < 0.001).
  • Prolonged REM Latency: REM-SL increased to 157.89 ± 99.04 minutes in PD vs. 103.47 ± 71.70 minutes in controls (P = 0.034).

Subgroup Analyses

  • Disease Duration: Patients with >5 years of disease had longer SL (41.75 ± 37.26 minutes) than those with ≤5 years (18.94 ± 13.71 minutes; P = 0.030).
  • Motor Subtypes: Akinetic-rigid dominant PD patients showed higher N2% (61.75% ± 18.95%) than postural instability/gait disturbance (PIGD) subtypes (47.50% ± 15.87%; P = 0.037).
  • Hoehn-Yahr Staging: Advanced stages (>2.0) correlated with reduced REM% (r = 0.405, P = 0.036), but no differences in TST or SE were observed between early and advanced stages.

Discussion

SF as a Hallmark of PD Sleep Dysregulation

This study identifies SF as a predominant sleep abnormality in PD, distinct from insomnia or circadian rhythm disturbances. The high SF prevalence (74.1%) aligns with prior reports linking PD to nocturnal motor symptoms (e.g., rigidity, tremors) and non-motor factors (e.g., nocturia, medication side effects). Dopaminergic degeneration in the suprachiasmatic nucleus and brainstem regions may disrupt sleep-wake regulation, contributing to frequent arousals.

Implications of Altered Sleep Architecture

The reduction in N3 and REM sleep underscores the vulnerability of restorative sleep stages in PD. Slow-wave sleep (N3) deficits may exacerbate cognitive decline, while REM suppression could reflect dopaminergic therapy effects or intrinsic neurodegeneration. Prolonged REM latency, a novel finding, suggests dysregulation of cholinergic and monoaminergic pathways involved in REM initiation.

Clinical and Mechanistic Considerations

The lack of correlation between SF and disease duration or severity challenges the notion of SF as a simple progression marker. Instead, SF may arise from heterogeneous mechanisms, including Lewy body pathology in sleep-regulatory centers or comorbid conditions like sleep apnea. The association between akinetic-rigid subtype and elevated N2% warrants further exploration into subtype-specific sleep phenotypes.

Limitations and Future Directions

This preliminary study is limited by its small sample size and single-center design. Longitudinal studies with larger cohorts are needed to validate SF as a PD biomarker and elucidate its temporal relationship with neurodegeneration. Incorporating advanced neuroimaging and molecular biomarkers (e.g., α-synuclein) could clarify the neuroanatomical substrates of SF. Additionally, interventional studies targeting SF may improve sleep quality and slow PD progression.

Conclusion

This study provides robust evidence that sleep fragmentation is a central feature of sleep disorders in PD, detectable via PSG. The distinct alterations in sleep architecture, particularly diminished slow-wave and REM sleep, highlight the need for comprehensive sleep assessments in PD management. While SF shows promise as a quantifiable marker, its pathophysiological and prognostic significance requires further investigation.

doi.org/10.1097/CM9.0000000000000329

Was this helpful?

0 / 0