To determine nonmotor signs (NMS) and evaluate the utility of several diagnostic tools in patients with de novo Parkinson disease (PD).
This is a large single-center study of the DeNoPa cohort, ...including frequency-matched healthy controls. This study covers motor signs, NMS, and a combination of diagnostic tests including olfactory testing, transcranial sonography of substantia nigra (TCS), and polysomnography (PSG). We report the frequency and characteristics of NMS and the outcomes of nonmotor tests at the time of diagnosis.
Cross-sectional analyses of baseline investigations identified significant differences in the NMS Questionnaire (NMSQuest) and the Scopa-AUT Gastrointestinal score in 159 drug-naïve PD patients vs 110 controls. In addition, patients with PD showed reduced olfactory function, hyperechogenicity on TCS, and higher frequency of REM sleep behavior disorder (RBD). In exploring predictive markers, we found that the combination of several investigations, i.e., the NMSQuest, Scopa-AUT Gastrointestinal score, and Smell Identification Test reached an area under the receiver operating characteristic curve (AUC) of 0.913 (95% confidence interval CI 0.878-0.948). With the addition of serum cholesterol and mean heart rate values, the AUC value reached 0.919 (95% CI 886-0.953); when TCS and PSG were added, the AUC increased to 0.963 (95% CI 0.943-0.982).
We show feasibility and utility of standardized data acquisition in a large, single-center cohort of patients with de novo PD and matched healthy controls. The baseline results from our prospective investigations reached a value of >0.9 sensitivity and specificity for biological markers when we added routine laboratory investigations and quantified nonmotor features including sleep.
Abstract
Study Objectives
Patients diagnosed with isolated rapid eye movement (REM) sleep behavior disorder (iRBD) and Parkinson’s disease (PD) have altered sleep stability reflecting ...neurodegeneration in brainstem structures. We hypothesize that neurodegeneration alters the expression of cortical arousals in sleep.
Methods
We analyzed polysomnography data recorded from 88 healthy controls (HC), 22 iRBD patients, 82 de novo PD patients without RBD, and 32 with RBD (PD + RBD). These patients were also investigated at a 2-year follow-up. Arousals were analyzed using a previously validated automatic system, which used a central electroencephalography lead, electrooculography, and chin electromyography. Multiple linear regression models were fitted to compare group differences at baseline and change to follow-up for arousal index (ArI), shifts in electroencephalographic signals associated with arousals, and arousal chin muscle tone. The regression models were adjusted for known covariates affecting the nature of arousal.
Results
In comparison to HC, patients with iRBD and PD + RBD showed increased ArI during REM sleep and their arousals showed a significantly lower shift in α-band power at arousals and a higher muscle tone during arousals. In comparison to HC, the PD patients were characterized by a decreased ArI in non-REM (NREM) sleep at baseline. ArI during NREM sleep decreased further at the 2-year follow-up, although not significantly.
Conclusions
Patients with PD and iRBD present with abnormal arousal characteristics as scored by an automated method. These abnormalities are likely to be caused by neurodegeneration of the reticular activation system due to alpha-synuclein aggregation.
This was a longitudinal single-center cohort study to comprehensively explore multimodal progression markers for Parkinson disease (PD) in patients with recently diagnosed PD (n = 123) and ...age-matched, neurologically healthy controls (HC; n = 106).
Thirty tests at baseline and after 24 months covered nonmotor symptoms (NMS), cognitive function, and REM sleep behavior disorder (RBD) by polysomnography (PSG), voxel-based morphometry (VBM) of the brain by MRI, and CSF markers. Linear mixed-effect models were used to estimate differences of rates of change and to provide standardized effect sizes (d) with 95% confidence intervals (CI).
A composite panel of 10 informative markers was identified. Significant relative worsening (PD vs HC) was seen with the following markers: the Unified Parkinson's Disease Rating Scale I (d 0.39; CI 0.09-0.70), the Autonomic Scale for Outcomes in Parkinson's Disease (d 0.25; CI 0.06-0.46), the Epworth Sleepiness Scale (d 0.47; CI 0.24-0.71), the RBD Screening Questionnaire (d 0.44; CI 0.25-0.64), and RBD by PSG (d 0.37; CI 0.19-0.55) as well as VBM units of cortical gray matter (d -0.2; CI -0.3 to -0.09) and hippocampus (d -0.15; CI -0.27 to -0.03). Markers with a relative improvement included the Nonmotor Symptom (Severity) Scale (d -0.19; CI -0.36 to -0.02) and 2 depression scales (Beck Depression Inventory d -0.18; CI -0.36 to 0; Montgomery-Åsberg Depression Rating Scale d -0.26; CI -0.47 to -0.04). Unexpectedly, cognitive measures and select laboratory markers were not significantly changed in PD vs HC participants.
Current CSF biomarkers and cognitive scales do not represent useful progression markers. However, sleep and imaging measures, and to some extent NMS, assessed using adequate scales, may be more informative markers to quantify progression.
Objectives
Rapid eye movement (REM) sleep behavior disorder (RBD) is proposed as an early diagnostic marker in Parkinson's disease (PD). We investigated the frequency of RBD during the progression of ...PD in the advanced stages and identified potential risk factors for developing RBD earlier or later.
Patients and Methods
We performed a retrospective analysis and determined the frequency of RBD in all PD in‐patients (Hoehn and Yahr stages ≥3) with motor fluctuations who had undergone video‐polysomnography (vPSG) for a sleep complaint or daytime sleepiness. To correct for selection bias, we analyzed the prevalence of RBD in PD patients from the DeNoPa cohort. PD patients with RBD were compared with PD without RBD. To identify potential risk factors, we performed multiple regression modeling.
Results
A total of 504 PD patients had vPSG. 37 were excluded due to missing REM or artifacts during REM. RBD was present in 406/467 (86.9%) PD patients. PD + RBD patients were older than PDnonRBD (69 ± 7.7 vs. 64 ± 9.2 years, P < 0.01), were more likely to have postural instability 234 (59.1%) vs. 19 (33.9%), P < 0.01, and were treated more often with antidepressants (other than SSRIs) 141 (34.7%) vs. 7 (13%), P < 0.01. Multiple regression modeling identified predictors of RBD with an AUC of 0.78.
Conclusion
The prevalence of RBD in patients with advanced PD is high and increases with disease severity, motor deficits, postural instability, orthostatic symptoms, and age. This suggests RBD is a progression marker of PD in patients with sleep complaints.
Highlights • Validation of the RBD screening questionnaire (RBDSQ) in 2 patient samples with Parkinson's disease. • The diagnostic value of the RBDSQ differed substantially between both samples. • ...The main difference was the individual's awareness on RBD. • This critical finding deserves clarification before use in epidemiological studies is recommended.
Background
Rapid eye movement (REM) sleep behavior disorder (RBD) is associated with neurodegenerative diseases; however, few longitudinal studies assess the individual evolution of RBD and REM sleep ...without atonia (RWA) in Parkinson's disease (PD).
Objectives
We aimed to evaluate RBD and RWA changes over time as well as potentially influential factors.
Methods
RBD and RWA were analyzed using video‐supported polysomnography (vPSG) in initially de novo PD patients at baseline and every 2 years for a total of 6 years. The influence of time, age, sex, levodopa equivalent daily dose (LEDD), unified Parkinson's disease rating scale (UPDRS) sum scores, benzodiazepine intake, Mini‐Mental State Examination (MMSE) total scores, and dyskinesia on RWA were investigated using mixed‐effect models to account for intra‐individual correlations.
Results
After 6 years, vPSG data were available from 98 of the initial 159 de novo PD patients. RBD prevalence increased from 25% at baseline to 52%. Of the 31 PD patients with RBD and valid vPSGs at all time‐points, RWA increased from an average of 19% at baseline to 41% at 6‐year follow‐up modeled to grow by 29.7% every 2 years (P < 0.001). Time was an independent factor (P < 0.001) for RWA increase. Age was an independent factor influencing RWA increase (P = 0.04). Sex, LEDD, UPDRS sum scores, benzodiazepines, MMSE total scores, and dyskinesia did not have any significant influence.
Conclusions
RBD and RWA increased significantly over time in PD; time and age were independent factors in a prospective cohort. RBD and RWA can be considered PD progression markers.
PDF
