Predictors of fatigue severity in early,de novo Parkinson disease patients: A 1-year longitudinal study

IntroductionFatigue is one of the most common and disabling nonmotor symptom in Parkinson's disease (PD). The aim of the present study was to investigate the 1-year course of fatigue in a consecutive sample of de novo drug-naïve patients with PD, and at systematically searching for baseline motor and nonmotor predictors associated with fatigue severity over time.MethodsFifty-five consecutive de novo PD patients (age: 64.71 ± 7.74 years) underwent a comprehensive examination, including Parkinson Fatigue Scale, Epworth Sleepiness Scale, Parkinson's Disease Sleep Scale, Beck Depression Inventory, Parkinson's Anxiety Scale, Apathy Evaluation Scale, and an extensive neuropsychological evaluation. Bivariate and multiple regression analyses were performed to identify baseline predictors independently related to fatigue severity at 1-year follow-up.ResultsPrevalence rate of fatigue (defined by PFS cut-off) increased from 22% at baseline to 38% at 1-year follow-up. A similar increase in prevalence was observed for excessive daytime sleepiness, and apathy. Among patients with fatigue at baseline, 91% had fatigue at follow-up too (i.e., persistent fatigue). Multivariate regression analysis identified fatigue (p < 0.01), daytime sleepiness (p < 0.01), and emotional apathy (p < 0.01) as the main baseline variables significantly predicting fatigue severity at 1-year follow-up.ConclusionIn early PD, fatigue increases and persists over time, and its severity is related to higher baseline levels of fatigue, excessive daytime sleepiness, and emotional apathy. These results warrant to monitor fatigue since the early stage of disease, and suggest that treating excessive daytime sleepiness and emotional apathy might prevent its worsening.     

Relationships among cognitive impairment,sleep, and fatigue in Parkinson's disease using the MDS-UPDRS

BackgroundNon-motor complications of Parkinson's disease (PD), specifically cognitive impairment, sleep disturbances, and fatigue, are recognized as important contributors to poor patient outcomes and quality of life. How sleep problems and fatigue interrelate and impact cognitive function, however, has not systematically been investigated across the stages of PD. The aim of our study was to investigate the relationships among cognitive impairment, night-time sleep problems, daytime sleepiness, and fatigue across all severities of PD.MethodsWe examined these non-motor problems using the Movement Disorder Society-Sponsored Revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS) in a study of 1319 PD patients drawn from three large cohort studies: the Parkinson's Progressive Markers Initiative, the Rush University PD Cognitive-Behavioral-Imaging study, and the Movement Disorder Society-Unified Parkinson's Disease Rating Scale Clinimetric testing program study, which spanned the gamut of disease, from early to advanced PD. Generalized linear mixed models with logit linking functions and covariates including study cohort, age, PD duration, and presence/absence of PD medications were used to examine relationships between these three non-motor symptoms and cognitive impairment.ResultsOf these three frequent, and often inter-twined, non-motor complications, greater daytime sleepiness and fatigue were associated with worse cognitive impairment across the full spectrum of PD (F[16,1158] = 2.40 and F[16,1158] = 3.45 respectively, p's < 0.0005), but an association with night-time sleep was not detected (p = 0.83).ConclusionsGiven this association of daytime sleepiness and fatigue with cognitive impairment, clinical monitoring for these problems should be considered across all points in the PD spectrum, from early to more advanced disease.     

Apathy in drug-naïve patients with Parkinson's disease

ObjectiveThe aim of this study is to explore the prevalence and clinical correlates of apathy in early-stage Parkinson's disease (PD) from a cohort of Chinese patients.MethodsA cross-sectional analysis of 133 treatment-naive PD patients was conducted. Each subject was categorized as PD with or without apathy using the Lille Apathy Rating Scale (LARS).ResultsOf 133 patients, 30 PD patients (22.56%) reported apathy, of whom 23 (17.29%) did not have concomitant depression. The stepwise binary logistic regression model indicated that the lower Frontal assessment battery (FAB) score (OR = 0.623, 95% CI = 0.466–0.834, P = 0.001), the higher sleep/fatigue score from the Non-Motor Symptoms Scale (NMSS) (OR = 1.171, 95% CI = 1.071–1.279, P = 0.001), the higher Hamilton Depression Rating Scale including 24 items (HAMD-24) score (OR = 1.112, 95% CI = 1.005–1.230, P = 0.039) and the higher Unified Parkinson's Disease Rating Scale (UPDRS) part III score (OR = 1.119, 95% CI = 1.045–1.198, P = 0.001) were associated with apathy. No significant associations were found between apathy and other parameters such as age, sex distribution, disease duration, anxiety, Fatigue Severity Scale (FSS) score, Montreal Cognitive Assessment (MOCA) score and remaining domain scores for NMSS.ConclusionsApathy is not rare (22.56%) in Chinese treatment-naïve PD patients. Apathy in PD is not only related to the severity of motor symptoms of the disease but also to some non-motor symptoms, such as executive dysfunction, depression and sleep disturbances.     

Comparison of sleep and other non-motor symptoms between SWEDDs patients and de novo Parkinson's disease patients

BackgroundSWEDDs (Scans Without Evidence of Dopaminergic Deficits) was defined from a series of pharmaceutical trials on Parkinson's disease (PD). Non-motor features including sleep-related problems are common even in early-stage PD patients; however, little is known about the burden of the non-motor symptoms in SWEDDs patients.MethodsThe Non-motor Symptoms Assessment Scale (NMSS), revised version of the Parkinson's Disease Sleep Scale (PDSS-2), Epworth Sleepiness Scale (ESS), and EuroQol 5-Dimension (EQ-5D) were applied to evaluate 17 SWEDDs patients and 28 de novo PD patients. The presence of clinically probable rapid eye movement sleep behavior disorder (cpRBD) was assessed using the International Classification of Sleep Disorders-Revised (ICSD-R) criteria.ResultsThe total NMSS score for the SWEDDs group was significantly lower than for the de novo PD group (p = 0.032). The most distinct difference was in taste or smell change (p < 0.000). Prevalence of cpRBD was higher in de novo PD patients than in SWEDDs patients (p = 0.030), though no significant differences in the PDSS-2 total score (p = 0.496) or the ESS score (p = 0.517) were found. The SWEDDs patients did not significantly differ from the de novo PD patients with regard to quality of life, as measured by the EQ-5D index score (p = 0.177).ConclusionsThe patients with SWEDDs have less non-motor problems than newly diagnosed untreated PD patients. Given the difficulty distinguishing between SWEDDs and early PD, identifying some of non-motor symptoms, such as RBD or olfactory impairment, could aid clinicians in their work.     

Rotigotine and specific non-motor symptoms of Parkinson's disease: Post hoc analysis of RECOVER

BackgroundNon-motor symptoms of Parkinson's disease (PD) represent major causes of morbidity. RECOVER, a randomized controlled trial of rotigotine transdermal system, was the first prospective controlled trial to use the Non-Motor Symptoms Scale (NMSS) as an exploratory outcome for assessment of treatment effects on non-motor symptoms in PD. Rotigotine improved NMSS total score compared with placebo, and the “Sleep/fatigue” and “Mood/apathy” domains. This post hoc analysis further characterizes the effects of rotigotine on sleep/fatigue and mood/apathy.MethodsPatients with PD and unsatisfactory early-morning motor impairment were randomized to transdermal patches of rotigotine (2–16 mg/24 h) or placebo. Treatment was titrated to optimal dose over 1–8 weeks, maintained for 4 weeks. The NMSS was assessed at baseline and end of treatment. Post hoc analyses are presented for individual items of the “Sleep/fatigue” and “Mood/apathy” domains. The interpretation of p-values is considered exploratory in nature.ResultsOf 287 patients randomized, NMSS data were available for 267 patients (178 rotigotine, 89 placebo). Within the “Sleep/fatigue” domain there was a significant difference, in favor of rotigotine, in change from baseline score in 1 of 5 items: “fatigue (tiredness) or lack of energy” (ANCOVA, p < 0.0001). Within the “Mood/apathy” domain, there were significant differences in favor of rotigotine in 4 of 7 items: “lost interest in surroundings” (p < 0.0001), “lost interest in doing things” (p < 0.0001), “seems sad or depressed” (p < 0.01), and “difficulty experiencing pleasure” (p < 0.05).ConclusionsRotigotine transdermal system may improve non-motor symptoms such as fatigue, symptoms of depression, anhedonia, and apathy in patients with PD; further prospective controlled studies are required to confirm this post hoc analysis.     

What determines resilience in patients with Parkinson's disease?

ObjectiveTo investigate the relationship of resilience to disease severity, disability, quality of life (QoL) and non-motor symptoms in Parkinson's disease (PD). A secondary objective was to investigate whether resilience is distinct from other personality domains in PD.BackgroundResilience is the ability to reestablish emotional equilibrium in the face of adversity. It may play a pivotal role in disability and quality of life and has not been studied in PD.Methods83 PD patients (Age 66.3 ± 10.6, Total Unified Parkinson's Disease Rating Scale (T-UPDRS) 36.9 ± 17.8) completed the Resilience Scale 15 (RS-15). Scales measuring disability, mental and physical health-related QoL, non-motor symptoms (depression, anxiety, somatization, apathy, fatigue), and personality domains were completed. Pearson's correlations were analyzed between these scales and the RS-15.ResultsGreater resilience correlated with less disability (r = ?.30, p = .01), and better physical and mental QoL (r = .31, p < .01; r = .29, p = .01), but not with PD severity (T-UPDRS, r = ?.17, p > .05). Among non-motor symptoms and personality domains, resilience strongly correlated with less apathy (r = ?.66), less depression (r = ?.49), and more optimism (r = .54, all p < .001). Moderate correlations were seen between more resilience, reduced fatigue (r = ?.40) and anxiety (r = ?.34; both p < .001).ConclusionsResilience correlated with less disability and better QoL but not with PD severity. Resilience was also highly associated with both non-motor symptoms (less apathy, depression, fatigue) and a personality domain (more optimism). The role of resilience in helping patients adapt to living with symptoms of chronic disease may explain its lack of correlation with PD severity.     

The relation of testosterone levels with fatigue and apathy in Parkinson's disease

Objective

Fatigue and apathy are frequent in patients with Parkinson's disease (PD). Testosterone deficiency in male patients may contribute in development of fatigue and apathy as well. We investigated whether a possible relation exists between serum testosterone levels, fatigue and apathy in male PD patients.

Materials and methods

We included 29 non-demented and non-depressed PD patients and 30 age- and sex-matched healthy subjects. Fatigue Severity Scale (FSS) and Apathy Evaluation Scale (AES-C) were used for the evaluations. In PD patients and healthy subjects, a relationship between FSS, AES-C scores and plasma testosterone levels were assessed. In addition, a correlation between FSS, AES-C and Unified Parkinson's Disease Rating Scale was investigated in PD group.

Results

The mean scores of FSS and AES-C were significantly higher in PD patients than those of the control group. The Unified Parkinson's Disease Rating Scale (UPDRS) scores were significantly correlated with FSS and AES-C scores. Mean free testosterone level was significantly lower in PD patients than controls (p = 0.008). f-Testosterone levels of PD patients were not correlated with FSS or AES-C scores.

Conclusion

Apathy and fatigue are frequent in PD and show significant correlation with the severity of the disease. f-Testosterone levels are not related with apathy or fatigue in male PD patients and the role of testosterone in the pathophysiology of these non-motor symptoms is still controversial.     

Levodopa-carbidopa intestinal gel in advanced Parkinson's: Final results of the GLORIA registry

IntroductionThis registry evaluated the 24-month safety and efficacy of levodopa-carbidopa intestinal gel (LCIG) treatment in advanced Parkinson's disease (PD) patients under routine clinical care.MethodsMotor fluctuations, dyskinesia, non-motor symptoms, quality of life, and safety were evaluated. Observations were fully prospective for treatment-naïve patients (60% of patients) and partially retrospective for patients with ≤12 months of pre-treatment with LCIG (40% of patients). Hours of “On” and “Off” time were assessed with a modified version of the Unified Parkinson's Disease Rating Scale part IV items 32 and 39.ResultsOverall, 375 patients were enrolled by 75 movement disorder centers in 18 countries and 258 patients completed the registry. At 24 months LCIG treatment led to significant reductions from baseline in “Off” time (hours/day) (mean ± SD = −4.1 ± 3.5, P < 0.001), “On” time with dyskinesia (hours/day) (−1.1 ± 4.8, P = 0.006), Non-Motor Symptom Scale total (−16.7 ± 43.2, P < 0.001) and individual domains scores, and Parkinson's Disease Questionnaire-8 item total score (−7.1 ± 21.0, P < 0.001). Adverse events deemed to have a possible/probable causal relationship to treatment drug/device were reported in 194 (54%) patients; the most frequently reported were decreased weight (6.7%), device related infections (5.9%), device dislocations (4.8%), device issues (4.8%), and polyneuropathy (4.5%).ConclusionsLCIG treatment led to sustained improvements in motor fluctuations, non-motor symptoms particularly sleep/fatigue, mood/cognition and gastrointestinal domains, as well as quality of life in advanced PD patients over 24 months. Safety events were consistent with the established safety profile of LCIG.     

Subjective cognitive Complaints in early Parkinson's disease patients with normal cognition are associated with affective symptoms

IntroductionSubjective cognitive complaints (SCC) and affective symptoms are highly prevalent in Parkinson's Disease (PD). In early PD, SCC prevalence and its affective correlates, using recommended Movement Disorders Society (MDS) Level II Criteria to define the underlying cognitive impairment, has not been previously explored.MethodsWe recruited 121 participants with early PD from two tertiary hospitals in Singapore. The presence of SCC was defined using a Non-Motor Symptoms Scale Domain-5 Score ≥1. Comprehensive neuropsychological testing was conducted with Mild Cognitive Impairment (PD-MCI) defined using recommended MDS Level II Criteria. Affective symptoms were assessed using the Hospital Anxiety Depression Scale (HADS), Geriatric Depression Scale (GDS) and Apathy Scale (AS). Analysis using multivariable linear regression model was performed.ResultsIn our early PD cohort, SCC prevalence independent of underlying cognitive status was 38.8%. Prevalence of SCC in cognitively impaired and cognitively normal participants was 10.7% and 28.1% respectively (р = 0.241). In cognitively normal PD participants, multivariable linear regression analysis revealed that SCC was significantly associated with anxiety (β = 0.28, 95% CI = 0.09–0.79, p = 0.014), depression (β = 0.31, 95% CI = 0.10–0.59, p = 0.006) and apathy (β = 0.32, 95% CI = 1.15–5.98, p = 0.004). Such an association was not found in cognitively impaired PD participants.ConclusionSCC is highly prevalent even in early PD. Its implications in early PD differ depending on underlying cognitive status. SCC in cognitively impaired participants underestimates the true prevalence of PD-MCI. In contrast, SCC in cognitively normal participants is suggestive of an underlying affective disorder.     

Apathy dimensions in Parkinson's disease

Objective

Apathy is a prominent and disabling symptom in Parkinson's disease (PD) and is a multidimensional behaviour, but which dimensions are specifically affected is unclear. Therefore, the aim of this preliminary study was to determine the psychometric properties of the Dimensional Apathy Scale (DAS) and explore the multidimensional profile of apathy in PD patients.

Methods

Thirty‐four PD patients, with 30 of their informants/carers, and 34 healthy controls, with 30 of their informants, completed the DAS, Apathy Evaluation Scale and the Geriatric Depression Scale Short Form. Motor staging and independent living status were recorded.

Results

Comparative group analyses revealed that PD patients were significantly more apathetic on self‐rated executive (p = 0.01) and initiation (p = 0.03) dimensions than controls, where only executive apathy was significantly higher in ratings of patients' informants/carers compared with controls' informants (p = 0.02). A third of patients were impaired on at least one apathy dimension. Additionally, patients with apathy tended to have more impaired activities of daily living, while none of the apathy dimensions related to motor disability.

Conclusion

Our findings show the DAS is a valid and reliable multidimensional apathy tool for use in PD. PD is characterised by an executive apathy profile as determined by informants/carers, although patients described both executive and initiation apathy. This indicates a lack of motivation for planning, organisation and attention and lack of initiation of thoughts or behaviours. Further research is needed to determine the cognitive underpinnings of this emerging apathy profile and the clinical impact in PD. Copyright © 2017 John Wiley & Sons, Ltd.     

Dissociations among daytime sleepiness,nighttime sleep,and cognitive status in Parkinson's disease

BackgroundDaytime and nighttime sleep disturbances and cognitive impairment occur frequently in Parkinson's disease (PD), but little is known about the interdependence of these non-motor complications. Thus, we examined the relationships among excessive daytime sleepiness, nighttime sleep quality and cognitive impairment in PD, including severity and specific cognitive deficits.MethodsNinety-three PD patients underwent clinical and neuropsychological evaluations including the Epworth Sleepiness Scale (ESS) and Pittsburgh Sleep Quality Index (PSQI). Patients were classified as having normal cognition (PD-NC), mild cognitive impairment (PD-MCI), or dementia (PDD) using recently proposed Movement Disorder Society PD-MCI and PDD criteria. Relationships between the sleep and cognitive measures and PD cognitive groups were examined.ResultsThe PD cohort included PD-NC (n = 28), PD-MCI (n = 40), and PDD (n = 25) patients. ESS scores, as a measure of daytime sleepiness, were significantly worse (p = 0.005) in cognitively impaired PD patients, particularly PDD patients. ESS scores correlated significantly with Mini-Mental State Examination scores and also with cognitive domain scores for attention/working memory, executive function, memory, and visuospatial function. In contrast, PSQI scores, as a measure of nighttime sleep quality, neither differed among cognitive groups nor correlated with any cognitive measures.ConclusionsDaytime sleepiness in PD, but not nighttime sleep problems, is associated with cognitive impairment in PD, especially in the setting of dementia, and attention/working memory, executive function, memory, and visuospatial deficits. The presence of nighttime sleep problems is pervasive across the PD cognitive spectrum, from normal cognition to dementia, and is not independently associated with cognitive impairment or deficits in cognitive domains.     

Are the EEG microstates correlated with motor and non-motor parameters in patients with Parkinson's disease?

ObjectivesThis study compared electroencephalography microstates (EEG-MS) of patients with Parkinson's disease (PD) to healthy controls and correlated EEG-MS with motor and non-motor aspects of PD.MethodsThis cross-sectional exploratory study was conducted with patients with PD (n = 10) and healthy controls (n = 10) matched by sex and age. We recorded EEG-MS using 32 channels during eyes‐closed and eyes‐open conditions and analyzed the four classic EEG-MS maps (A, B, C, D). Clinical information (e.g., disease duration, medications, levodopa equivalent daily dose), motor (Movement Disorder Society - Unified Parkinson Disease Rating Scale II and III, Timed Up and Go simple and dual-task, and Mini-Balance Evaluation Systems Test) and non-motor aspects (Mini-Mental State Exam [MMSE], verbal fluency, Hospital Anxiety and Depression Scale, and Parkinson's Disease Questionnaire-39 [PDQ-39]) were assessed in the PD group. Mann-Whitney U test was used to compare groups, and Spearman's correlation coefficient to analyze the correlations between coverage of EEG-MS and clinical aspects of PD.ResultsThe PD group showed a shorter duration of EEG-MS C in the eyes-closed condition than the control group. We observed correlations (rho = 0.64 to 0.82) between EEG-MS B, C, and D and non-motor aspects of PD (MMSE, verbal fluency, PDQ-39, and levodopa equivalent daily dose).ConclusionAlterations in EEG-MS and correlations between topographies and cognitive aspects, quality of life, and medication dose indicate that EEG could be used as a PD biomarker. Future studies should investigate these associations using a longitudinal design.     

High-Frequency Repetitive Transcranial Magnetic Stimulation over the Primary Foot Motor Area in Parkinson's Disease

BackgroundRepetitive transcranial magnetic stimulation (rTMS) has been reported to be clinically effective for treating motor symptoms in Parkinson's disease (PD). Few studies have been performed reporting the effects of rTMS on non-motor symptoms such as depression and apathy in PD.ObjectiveWe assessed the effects of high-frequency (HF) rTMS over the primary motor (M1) foot area on motor symptoms, depression and apathy scales, and sensory symptoms in PD.MethodsWe investigated the efficacy of 3 consecutive days of HF-rTMS over the M1 foot area in 21 patients with PD using a randomized, double-blind cross-over trial compared with sham stimulation. Motor effects were evaluated using the Unified Parkinson's Disease Rating Scale part III (UPDRS-III), the self-assessment motor score, the visual analog scale (VAS), the 10-m walking test, and finger tapping. Non-motor effects were analyzed using the Montgomery Asberg Depression Rating Scale, the Apathy Scale, and quantitative sensory testing.ResultsHF-rTMS significantly improved UPDRS-III (P < 0.001), VAS (P < 0.001), the walking test (P = 0.014), self-assessment motor score (P = 0.010), and finger tapping measurement (P < 0.05) compared to sham stimulation. In contrast, no significant improvement was observed in depression and apathy scales. Consecutive days of rTMS did not significantly increase the improvement in motor symptoms. There were no adverse effects following rTMS on patients with PD.ConclusionsWe confirmed that HF-rTMS over the M1 foot area significantly improved motor symptoms in patients with PD. In addition, daily repeated stimulation was not significantly more effective than a single session of stimulation, but may be effective for maintaining the improvement in motor symptoms in patients with PD.     

Is serum uric acid related to non-motor symptoms in de-novo Parkinson's disease patients?

BackgroundLow serum uric acid (UA) has been consistently shown to be associated with increased risk of Parkinson's disease (PD), and to predict faster motor and cognitive decline in established PD. The aim of the present study is to evaluate the relationship between serum UA and non-motor symptoms (NMS) in de novo PD.MethodsSerum UA was measured in consecutively recruited, early drug-naïve PD patients. Exclusion criteria were: treatment with UA modifying drugs; current smoking status; metabolic or cardiac morbidity. All patients completed the NMS Questionnaire (NMSQuest). The relationship between UA levels and NMSQuest domains was explored by logistic regression, subsequently adjusted for age, gender, disease duration (months since reported motor onset) UPDRS part III, H&Y scale, and MMSE. Regression analysis studied the overall relationship between UA levels and total NMS score, and was subsequently adjusted for age, gender, disease duration UPDRS part III, H&Y scale and MMSE.ResultsEighty PD patients were recruited. At logistic regression, higher UA levels were related to lower involvement of Attention/Memory (p = 0.004), Cardiovascular (0.009) and Sleep (p = 0.028) domains of NMSQuest. UA levels showed a significant negative correlation with total NMSQuest score at regression analysis (p = 0.001; Adjusted R-squared = 0.319).DiscussionThe present study investigated, for the first time, the relationship between NMSQuest and UA in de novo PD. Lower UA was related to higher NMSQuest total score and in particular to Attention/Memory, Cardiovascular and Sleep domains. Thus, UA seems to be a major candidate to be a valuable biomarker of such early features of PD as NMS.     

Relationship between sleep disorders and other non-motor symptoms in Parkinson's disease

BackgroundThe association between sleep disorders and other non-motor symptoms (NMS) in Parkinson's disease (PD) has been scarcely investigated.ObjectiveTo describe the prevalence of insomnia and hypersomnia in PD and analyze their relationship with other NMS.MethodsCross-sectional, multicenter study including 388 PD patients evaluated with Hoehn and Yahr, Clinical Impression of Severity Index for PD, Scales for Outcomes in Parkinson's Disease (SCOPA)-Sleep(S), SCOPA-Cognition, SCOPA-Psychiatric Complications, SCOPA-Autonomic, Hospital Anxiety and Depression Scale, and fatigue and pain visual analogue scales. Spearman correlation coefficients, Mann–Whitney test and multiple linear regression analysis were applied.ResultsMean age (54% male) was 65.9 ± 11.2 years old, with disease duration of 8.1 ± 6.0 years and median HY = 2 (range: 1–5). Mean SCOPA-S nocturnal sleep (NS) was 5.4 ± 4.0 (range: 0–15), daytime sleepiness (DS) was 3.76 ± 3.04 (range: 0–15). Most of the sample declared nocturnal or daytime sleep problems (87.4%). Weak-to-moderate correlations were found between sleep disturbances and other NMS (range: 0.14–0.37). SCOPA-S subscales showed higher scores with the presence of most other NMS such as psychiatric complications and autonomic dysfunctions (p < 0.05). Regression models showed that fatigue, depression, urinary, cardiovascular, and thermoregulatory dysfunctions were significant determinants of SCOPA-NS score (variance: 23%); cognitive impairment, urinary, cardiovascular, and pupillomotor disorders influenced SCOPA-DS score (variance: 14%).ConclusionsInsomnia and daytime sleepiness are extremely prevalent in PD. Depression, fatigue, cognitive impairment, cardiovascular, urinary and thermoregulatory dysfunctions may contribute to insomnia/hypersomnia. This is the first clinical study to relate cardiovascular and thermoregulatory dysfunctions with sleep in PD.     

Cognitive impairment is associated with Hoehn and Yahr stages in early,de novo Parkinson disease patients

IntroductionThe relationship between motor impairment and cognitive deterioration has long been described in Parkinson's disease (PD). The aim of the study was to compare cognitive performance of de novo PD patients in relation to the motor impairment severity according to Hoehn and Yahr (HY) stages.MethodsForty de novo PD patients at HY stage I and 40 patients at HY stage II completed a standardized neuropsychological battery. A multivariate analysis of covariance was used to compare cognitive performance between HY groups. Odds ratios (ORs) were employed to explore the risk of cognitive impairment between HY stages. Finally, the prevalence of mild cognitive impairment (MCI) was estimated for patients in HY stage I and II.ResultsPatients at HY stage I obtained better scores on neuropsychological tests than patients at HY stage II (p = 0.001). Univariate analysis of covariance revealed significant differences between HY stages on Rey's auditory verbal learning test -immediate recall (p < 0.0001), 10 points Clock Drawing Test (p = 0.002), and Rey-Osterrieth Complex Figure Test -copy (p < 0.0001). ORs of having cognitive impairment were greater for HY stage II than stage I group. MCI occurred in 7.5% of patients in HY stage I, and in 42.5% of patients in HY stage II.ConclusionIn de novo PD patients, the severity of motor impairment at the diagnosis is associated to cognitive deficits and higher risk of MCI.     

Sleep and impulsivity in Parkinson's disease

BackgroundImpulsive behavior and poor sleep are important non-motor features of Parkinson's disease (PD) that negatively impact the quality of life of patients and their families. Previous research suggests a higher level of sleep complaints in PD patients who demonstrate impulsive behaviors, but the nature of the sleep disturbances has yet to be comprehensively tested.MethodsConsecutive idiopathic PD patients (N = 143) completed the Minnesota Impulse Disorder Interview and a sleep questionnaire that assessed sleep efficiency, excessive daytime sleepiness, restless legs symptoms, snoring, dreams/nightmares, and nocturia. Patients were also given a Unified Parkinson's Disease Rating Scale motor examination and they completed cognitive testing.ResultsImpulsive PD patients endorsed more sleep complaints than non-impulsive PD patients. The group difference was primarily attributable to poor sleep efficiency (e.g., greater nocturnal awakenings), p < .01, and greater daytime sleepiness, p < .01, in the impulsive PD patients. Interestingly, restless legs symptoms were also greater in the impulsive PD patients, p < .05. The results could not be explained by medications or disease severity.ConclusionsPoor sleep efficiency, restless legs symptoms, and increased daytime sleepiness are associated with impulsivity in PD. Longitudinal studies are needed to determine whether sleep disturbances precede impulsivity in PD.     

Gender and onset age-related features of non-motor symptoms of patients with Parkinson's disease – A study from Southwest China

BackgroundNon-motor symptom (NMS) differences between male Parkinson's disease (PD) and female PD, and between early-onset PD (EOPD) and late-onset PD (LOPD) in Chinese populations remain largely unknown.MethodsA total of 522 PD patients from Southwest China were included. Patients were assessed using the Non-Motor Symptom Scale (NMSS) and Unified PD Rating Scale (UPDRS).ResultsMore NMS and significantly higher NMSS score were found in LOPD patients than in EOPD patients (9.3 ± 5.9 vs. 7.7 ± 5.6, P = 0.005; 37.4 ± 32.2 vs. 30.5 ± 28.9, P = 0.018), while no such differences were found between male and female patients. The NMS of gastrointestinal and urinary domains were more common in LOPD patients than in EOPD patients, whereas sexual dysfunction was more common in EOPD than in LOPD. The sleep/fatigue domain, the mood/apathy domain and “pain” symptoms were more prevalent and severe in female patients than in male patients while urinary symptoms were more common and severe in male patients. Significant positive correlations were observed between disease duration, Hoehn & Yahr stage, UPDRS Ⅲ, and NMSS score in the total sample, subgroups of both male and female patients as well as both EOPD and LOPD patients.ConclusionsNMS are common in the Chinese PD population. LOPD patients are likely to present with more and severe NMS than EOPD patients. Males are subjected to urinary symptoms and females are subjected to mood/apathy, sleep and pain symptoms.     

Long-term effect of bilateral STN-DBS on non-motor symptoms in Parkinson's disease: A four-year observational,prospective study

BackgroundSeveral studies have shown beneficial effects of bilateral stimulation of the subthalamic nucleus (STN-DBS) on motor as well as on non-motor symptoms (NMS) up to 36 months post-surgery in advanced Parkinson's disease (PD) patients. We set to explore the long-term effect of STN-DBS on NMS in a four-year follow-up, prospective, observational study.MethodsForty patients were enrolled and assessed at baseline. Twenty-eight were followed-up at 6, 12, 24, 36 and 48 months after the operation. The effect of post-operative time on NMS was analyzed by six-level repeated measures ANOVA. In a post-hoc analysis the follow-up scores were compared to baseline using a paired t-test.ResultsThe following scores stayed improved up to 24 months after surgery, presented as baseline/24 months, p-value (t-test): total Non-Motor Symptoms Scale score (54.0 ± 5.6/44.9 ± 5.0, p = 0.029), Hamilton Anxiety Scale (14.3 ± 1.3/11.3 ± 1.2, p = 0.019) and PDQ39 (53.4 ± 4.5/40.2 ± 2.9, p = 0.012). PD Sleep Scale 2 remained improved throughout the study (17.4 ± 2.0/12.8 ± 1.3 at 48 months, p = 0.032), while Beck Depression Inventory only at six months post-surgery (9.5 ± 1.2/6.7 ± 0.7 at 6 months, p = 0.006). Montreal Cognitive Assessment remained stable up to 24 months and then declined at 36 months (26.3 ± 0.5/25.4 ± 0.5 at 36 months, p = 0.003), Starkstein Apathy Scale deteriorated throughout the study (7.6 ± 0.7/12.7 ± 0.9 at 48 months, p = 0.006).ConclusionsWe observed beneficial effect of STN-DBS in several but not all domains of NMS at least up to 24 months post-op in advanced PD. Further long-term studies on larger cohorts of PD patients and longer follow-up need to be conducted to better understand the long-term effect of STN-DBS on NMS.     

Cognitive correlates of visual hallucinations in non-demented Parkinson's disease patients

BackgroundVisual hallucinations (VH) in Parkinson's disease (PD) are associated with PD dementia and have been related to cognitive impairments in non-demented PD patients. Reports on the specific cognitive domains affected are conflicting. The aim of the present study was to investigate the presence of specific cognitive impairments in non-demented PD patients with VH, compared to those without VH.MethodsWe compared the clinical characteristics and neuropsychological test scores of 31 non-demented PD patients with VH with those of 31 PD patients without VH that were carefully matched for sex, age, disease duration and educational level. Several non-motor symptoms, including depression, anxiety and sleep disturbances, were also taken into account, as these may influence cognitive performance.ResultsThe PD with VH group performed significantly worse on the Trail Making Test part A (p = 0.01) and the Rey Auditory Verbal Learning Test, immediate recall (p = 0.01). In addition, PD patients with VH were more anxious, more depressed and reported more sleep disturbances. Verbal learning scores were not associated with levels of anxiety, depression or sleep disruption, whereas worse Trail Making Test A performance was associated with concomitant sleep disturbances.ConclusionsIn non-demented PD patients, the presence of VH is associated with a cognitive profile characterized by impairments in verbal learning and probably attention. Since these cognitive functions are believed to be non-dopaminergic mediated functions, the present results support the hypothesis that multiple neurotransmitter systems, other than dopamine, contribute to the pathophysiology of VH in PD.