Parkinson's disease (PD) is a common progressive neurological disorder and is composed of motor and non-motor symptoms. Sleep disturbances are frequent problems for patients with PD. The relationship between sleep disturbances with Hoehn and Yahr (H&Y) staging have been demonstrated. However, the relationship between sleep disorders and H&Y is still unclear in patients with PD without dementia in Chinese PD patients. In this study, we interviewed 487 non-demented PD patients of Chinese Han descents by H&Y classification. We found that night sleep quality was significantly associated with the severity of PD (P = 0.008). Panic disorder severity scale (PDSS) total scores were correlated with PD non-motor symptoms scale (PDNMS) scores (r = -0.528, P < 0.001), the Hamilton depression scale (HAMD) scores (r = -0.545, P < 0.001) and the Hamilton anxiety scale (HAMA) scores (r = -0.498, P < 0.001). Our results indicated that sleep quality deteriorated with the advancing of PD in Chinese non-demented patients with PD. Depression and anxiety may partly explain sleep disturbances in non-demented patients with PD.
sleep quality; depression; anxiety; Parkinson disease; non-demented
Background: No formal instruments are available for quantifying sleep problems in Parkinson's disease.
Objective: To develop a new sleep scale to quantify the various aspects of nocturnal sleep problems in Parkinson's disease, which may occur in up to 96% of affected individuals.
Methods: Employing a multidisciplinary team approach, a visual analogue scale was devised addressing 15 commonly reported symptoms associated with sleep disturbance in Parkinson's disease—the Parkinson's disease sleep scale (PDSS). In all, 143 patients with Parkinson's disease completed the PDSS, covering the entire spectrum of disease from newly diagnosed to advanced stage. As controls, 137 age healthy matched subjects also completed the scale. Test–retest reliability was assessed in a subgroup of subjects. The Epworth sleepiness scale was also satisfactorily completed by 103 of the patients with Parkinson's disease.
Results: PDSS scores in the Parkinson group were significantly different from the healthy controls. Patients with advanced Parkinson's disease had impaired scores compared with early/moderate disease. Individual items of the scale showed good discriminatory power between Parkinson's disease and healthy controls. Relevant items of the PDSS correlated with excessive daytime sleepiness. The scale showed robust test–retest reliability.
Conclusions: This appears to be the first description of a simple bedside screening instrument for evaluation of sleep disturbances in Parkinson's disease. A combination of subitems may help identify specific aspects of sleep disturbance, which in turn may help target treatment.
As one of the most frequent symptoms, measurement of fatigue is an issue of interest in Parkinson's disease (PD). The fatigue severity scale (FSS) is one of the recommended questionnaires for this purpose. The aim of our study was to evaluate psychometric properties of the Persian version of the FSS (FSS-Per) to assess fatigue in PD patients. Ninety nondemented idiopathic Parkinson's disease (IPD) patients were consecutively recruited from an outpatient referral movement disorder clinic. In addition to the disease severity scales, the FSS-Per was used for fatigue measurement. The internal consistency coefficient was larger than 0.8 for all of the items with a total Cronbach's alpha of 0.96 (95% CI: 0.95–0.97). The FSS-Per score correlated with the UPDRS score (r = 0.55, P < 0.001) and the “Hoehn and Yahr” (HY) stage (r = 0.48, P < 0.001). The total score of the FSS-Per significantly discriminated IPD patients with more severe disability (HY stage > 2) versus those with less severe disease (HY stage ≤2) (AUC = 0.81 (95% CI: 0.72–0.90)). The FSS-Per fulfilled a high internal consistency and construct validity to measure the severity of fatigue in Iranian IPD patients. These acceptable psychometric properties were reproducible in subgroups of IPD patients regarding different levels of education, disease severity, sex and age groups.
Nonmotor symptoms (NMS) like neuropsychiatric symptoms, sleep disturbances or autonomic symptoms are a common feature of Parkinson's disease (PD). To explore the existence of groups of NMS and to relate them to PD characteristics, 71 idiopathic non-demented PD out-patients were recruited. Sleep was evaluated by the PD Sleep Scale (PDSS). Several neuropsychiatric, gastrointestinal and urogenital symptoms were obtained from the NMSQuest. Sialorrhea or dysphagia severity was obtained from the Unified PD Rating Scale activities of daily living section. MADRS depression scale was also administered. Exploratory factor analysis revealed the presence of 5 factors, explaining 70% of variance. The first factor included PDSS measurement of sleep quality, nocturnal restlessness, off-related problems and daytime somnolence; the second factor included nocturia (PDSS) and nocturnal activity; the third one included gastrointestinal and genitourinary symptoms; the forth one included nocturnal psychosis (PDSS), sialorrhea and dysphagia (UPDRS); and the last one included the MADRS score as well as neuropsychiatric symptoms. Sleep disorders correlated with presence of wearing-off, nocturia with age >69 years, and nocturnal psychosis with levodopa equivalent dose or UPDRS II score. Neuropsychiatric symptoms correlated with UPDRS II+III score and non-tricyclic antidepressants. These results support the occurrence of significant NMS grouping in PD patients.
To investigate clinical features, iron metabolism and neuroinflammation in Parkinson’s disease (PD) patients with sleep disorders (SD).
211 PD patients were evaluated by Pittsburgh Sleep Quality Index (PSQI) and a body of scales for motor symptoms and non-motor symptoms. 94 blood and 38 cerebral spinal fluid (CSF) samples were collected and iron and its metabolism-relating proteins, neuroinflammatory factors were detected and analyzed.
136 cases (64.5%) of PD patients were accompanied by SD. Factor with the highest score in PSQI was daytime dysfunction. Depression, restless leg syndrome, autonomic symptoms and fatigue contributed 68.6% of the variance of PSQI score. Transferrin level in serum and tumor necrosis factor–α level in CSF decreased, and the levels of iron, transferrin, lactoferrin and prostaglandin E2 in CSF increased in PD patients with SD compared with those without SD. In CSF, prostaglandin E2 level was positively correlated with the levels of transferrin and lactoferrin, and tumor necrosis factor–α level was negatively correlated with the levels of iron, transferrin and lactoferrin in CSF.
Depression, restless leg syndrome, autonomic disorders and fatigue are the important contributors for the poor sleep in PD patients. Abnormal iron metabolism may cause excessive iron deposition in brain and be related to SD in PD patients through dual potential mechanisms, including neuroinflammation by activating microglia and neurotoxicity by targeting neurons. Hence, inhibition of iron deposition-related neuroinflammation and neurotoxicity may cast a new light for drug development for SD in PD patients.
The aim of this study was to compare the results of the day-to-day self-evaluation of sleep quality by sleep logs with Parkinson’s disease sleep scale (PDSS) in Parkinson’s disease (PD) patients. Actigraphy was used as an independent analysis of nighttime activity interfering with sleep. A total of 71 idiopathic PD patients and 21 age- and sex-matched normal individuals lacking any type of sleep disturbance were recruited. Sleep was evaluated by PDSS, 7-d sleep log and actigraphy. Sleep logs and PDSS showed reduced sleep quality and daytime somnolence scores in moderate/severe PD patients as compared to healthy controls. Significant correlations were found between sleep quality in sleep logs and all domains of PDSS sleep quality, except for the presence of nocturia, which correlated with nocturnal activity. PD severity and depression were the only predictors of reduced sleep quality. The retrospective and day-to-day sleep self-evaluations were coincident. Reduced sleep quality was related to increased PD severity and depression scores.
Sleep logs; Parkinson’s disease; Actigraphy; Sleep disorders; Sleep evaluation
This study aimed to evaluate the effects of add-on Yang-Xue-Qing-Nao granules (YXQN) on sleep dysfunction in patients with Parkinson’s disease (PD).
PD participants fitted with an actigraph took either YXQN or placebo granules in a randomized manner for 12 weeks while maintaining other anti-parkinsonism medications (e.g., dopaminergic agent, dopamine agonist) unchanged. Additional participants without sleep disturbance or PD served as controls. The changes in detrended fluctuation analysis (DFA) of physical activity with respect to diurnal activity (DA), evening activity (EA), nocturnal activity (NA), Parkinson’s disease sleep scale (PDSS) score and unified Parkinson’s disease rating scale (UPDRS) score were evaluated every 4 weeks during the 12-week YXQN intervention period and again at week 16.
A total of 61 (placebo group, n = 30; YXQN group, n = 31) idiopathic PD participants with sleep dysfunction (mean age ± standard deviation, 63.4 ± 8.6 years; mean duration of illness, 5.8 ± 6.6 years) completed the study. Significant improvements in EA (p = 0.033, 0.037 and 0.029), DA (p = 0.041, 0.038 and 0.027) and PDSS score (p = 0.034, 0.028 and 0.029) were observed in the YXQN group at weeks 8 and 12, and maintained until week 16, respectively.
YXQN improved the DFA parameters, and PDSS and UPDRS scores in PD participants.
Parkinson's disease (PD) is a progressive neurodegenerative disorder causing motor and non-motor symptoms. The latter are common and include autonomic dysfunction, cognitive impairment, and sleep difficulties. Many of the non-motor aspects of PD such as sleep disturbance are more common and significantly affect the day-to-day activities of patients and their quality of life. The most important aim of this study was to evaluate the sleep quality in patients with PD.
This case-control study was performed on patients with PD referred to the Neurology Clinic of our teaching hospital in 2011. Thirty-four patients with PD and 34 healthy people as control group were enrolled in this study. Sleep quality of patients and control was evaluated by Parkinson's disease sleep scale (PDSS) questionnaire. PDSS is a reliable and valid tool to measure sleep disorders in PD.
The mean total PDSS score in patient group was 55.29 (SD = 26.92) indicating moderate to severe sleep disturbances whereas, the mean total score in control group was 20.34 (SD = 10.65). Difference between the two groups’ mean scores was significant (P < 0.05).
Our study demonstrated that patients with PD experienced poorer nocturnal sleep quality than the control group.
Parkinson's disease; Parkinson's disease sleep scale; sleep disturbances; sleep quality
Drooling as symptom of Parkinson’s disease (PD) has thus far been poorly defined. This uncertainty is reflected by high variations in published prevalence rates. The aim of this study was to investigate the prevalence of saliva loss versus accumulation of saliva as a possible preliminary stage, and diurnal drooling versus nocturnal drooling. In addition, we evaluated the association between drooling severity and the severity of facial and oral motor disorders. We collected age, disease duration, UPDRS III and Hoehn & Yahr stage from 104 consecutive outpatients with PD. Diurnal and nocturnal drooling was evaluated with a validated questionnaire (ROMP-saliva). A speech pathologist, blinded for drooling severity, rated facial expression, involuntary mouth opening and difficulty with nose breathing and also interviewed patients about sleeping position and nose-breathing during the night. Thirty patients (29%) had no complaints with saliva control (‘non-droolers’), 45 patients (43%) experienced accumulation of saliva or only nocturnal drooling (‘pre-droolers’), and 29 (28%) had diurnal drooling (24 of which also drooled during the night; ‘droolers’). The droolers had longer disease duration (10 vs. 7 years, p = 0.01) and drooling was independently associated with involuntary mouth opening (OR = 2.0; 95% CI 1.02–3.99) and swallowing complaints (OR = 1.2; 95% CI 1.03–1.31). Diurnal drooling—defined as dribbling of saliva while awake—is present in about 28% of PD patients. This is less than usually reported. Diurnal drooling typically appeared later in the disease course. The association with oral motor behavior should encourage the development of behavioral treatment approaches.
Parkinson’s disease; Diurnal drooling; Nocturnal drooling
In a multinational, double-blind, placebo-controlled trial (NCT00474058), 287 subjects with Parkinson's disease (PD) and unsatisfactory early-morning motor symptom control were randomized 2:1 to receive rotigotine (2–16 mg/24 hr [n = 190]) or placebo (n = 97). Treatment was titrated to optimal dose over 1–8 weeks with subsequent dose maintenance for 4 weeks. Early-morning motor function and nocturnal sleep disturbance were assessed as coprimary efficacy endpoints using the Unified Parkinson's Disease Rating Scale (UPDRS) Part III (Motor Examination) measured in the early morning prior to any medication intake and the modified Parkinson's Disease Sleep Scale (PDSS-2) (mean change from baseline to end of maintenance [EOM], last observation carried forward). At EOM, mean UPDRS Part III score had decreased by −7.0 points with rotigotine (from a baseline of 29.6 [standard deviation (SD) 12.3] and by −3.9 points with placebo (baseline 32.0 [13.3]). Mean PDSS-2 total score had decreased by −5.9 points with rotigotine (from a baseline of 19.3 [SD 9.3]) and by −1.9 points with placebo (baseline 20.5 [10.4]). This represented a significantly greater improvement with rotigotine compared with placebo on both the UPDRS Part III (treatment difference: −3.55 [95% confidence interval (CI) −5.37, −1.73]; P = 0.0002) and PDSS-2 (treatment difference: −4.26 [95% CI −6.08, −2.45]; P < 0.0001). The most frequently reported adverse events were nausea (placebo, 9%; rotigotine, 21%), application site reactions (placebo, 4%; rotigotine, 15%), and dizziness (placebo, 6%; rotigotine 10%). Twenty-four-hour transdermal delivery of rotigotine to PD patients with early-morning motor dysfunction resulted in significant benefits in control of both motor function and nocturnal sleep disturbances. © 2010 Movement Disorder Society
dopamine agonist; rotigotine; transdermal; motor function; sleep; quality of life
Fatigue is a common complaint in Parkinson disease (PD). We investigated fatigue in a cohort of previously untreated patients with early PD enrolled in the Earlier vs Later Levodopa (ELLDOPA) clinical trial.
A total of 361 patients were enrolled in the randomized, double-blind, placebo-controlled ELLDOPA trial and assigned to receive placebo or carbidopa-levodopa 37.5/150 mg, 75/300 mg, or 150/600 mg daily for 40 weeks, followed by a 2-week medication washout period. Subjects who scored >4 on the Fatigue Severity Scale were classified as fatigued. PD severity was assessed using the Unified Parkinson's Disease Rating Scale (UPDRS), Hoehn-Yahr scale, and Schwab-England Activities of Daily Living Scale. A subgroup of subjects underwent [123I]-β-CIT SPECT to measure striatal dopamine transporter density.
Of the 349 ELLDOPA subjects who completed fatigue measures, 128 were classified as fatigued at baseline. The fatigued group was significantly more impaired neurologically (UPDRS, all subscales and Hoehn and Yahr staging) and functionally (Schwab-England Scale) but no significant differences were observed in β-CIT measurements between the two groups. Analysis of covariance showed a greater increase in fatigue score from baseline to the end of the 2-week washout in the placebo group (0.75 points) than in the three groups receiving levodopa (increases of 0.30 [150 mg/day], 0.36 [300 mg/day], and 0.33 [600 mg/day]; p = 0.03 for heterogeneity).
Fatigue is a frequent symptom in early, untreated, non-depressed patients with Parkinson disease (PD), affecting over 1/3 of the patients in this cohort at baseline and 50% by week 42. Fatigue was associated with the severity of PD, and progressed less in patients treated with levodopa.
= Earlier vs Later Levodopa;
= Fatigue Severity Scale;
= Hamilton Depression Scale;
= Parkinson disease;
= Unified Parkinson's Disease Rating Scale.
Motor impairments are the prerequisite for the diagnosis in Parkinson's disease (PD). The cardinal symptoms (bradykinesia, rigor, tremor, and postural instability) are used for disease staging and assessment of progression. They serve as primary outcome measures for clinical studies aiming at symptomatic and disease modifying interventions. One major caveat of clinical scores such as the Unified Parkinson Disease Rating Scale (UPDRS) or Hoehn&Yahr (H&Y) staging is its rater and time-of-assessment dependency. Thus, we aimed to objectively and automatically classify specific stages and motor signs in PD using a mobile, biosensor based Embedded Gait Analysis using Intelligent Technology (eGaIT). eGaIT consist of accelerometers and gyroscopes attached to shoes that record motion signals during standardized gait and leg function. From sensor signals 694 features were calculated and pattern recognition algorithms were applied to classify PD, H&Y stages, and motor signs correlating to the UPDRS-III motor score in a training cohort of 50 PD patients and 42 age matched controls. Classification results were confirmed in a second independent validation cohort (42 patients, 39 controls). eGaIT was able to successfully distinguish PD patients from controls with an overall classification rate of 81%. Classification accuracy increased with higher levels of motor impairment (91% for more severely affected patients) or more advanced stages of PD (91% for H&Y III patients compared to controls), supporting the PD-specific type of analysis by eGaIT. In addition, eGaIT was able to classify different H&Y stages, or different levels of motor impairment (UPDRS-III). In conclusion, eGaIT as an unbiased, mobile, and automated assessment tool is able to identify PD patients and characterize their motor impairment. It may serve as a complementary mean for the daily clinical workup and support therapeutic decisions throughout the course of the disease.
Objective: To measure the effect of deep brain stimulation (DBS) of the subthalamic nucleus in patients with advanced Parkinson's disease.
Design: Open label follow up using blinded ratings of videotaped neurological examinations.
Patients: 30 patients with advanced Parkinson's disease (19 male, 11 female; mean age 58.8 years; mean disease duration 12.8 years), complicated by intractable wearing off motor fluctuations and dopaminergic dyskinesias.
Main outcome measures: Unified Parkinson's disease rating scale (UPDRS), part III (motor), score at one year, from blinded reviews of videotaped neurological examinations. Secondary outcomes included the other UPDRS subscales, Hoehn and Yahr scale, activities of daily living (ADL) scale, mini-mental state examination (MMSE), estimates of motor fluctuations and dyskinesia severity, drug intake, and patient satisfaction questionnaire.
Results: Subthalamic nucleus stimulation was associated with a 29.5% reduction in motor scores at one year (p<0.0001). The only important predictors of improvement in UPDRS part III motor scores were the baseline response to dopaminergic drugs (p = 0.015) and the presence of tremor (p = 0.027). Hoehn and Yahr scores and ADL scores in the "on" and "off" states did not change, nor did the mean MMSE score. Weight gain occurred in the year after surgery, from (mean) 75.8 kg to 78.5 kg (p = 0.028). Duration of daily wearing off episodes was reduced by 69%. Dyskinesia severity was reduced by 60%. Drug requirements (in levodopa equivalents) declined by 30%.
Conclusions: The 30% improvement in UPDRS motor scores was a more modest result than previously reported. DBS did not improve functional capacity independent of drug use. Its chief benefits were reduction in wearing off duration and dyskinesia severity.
Objectives: To evaluate the reliability and validity of the Short Parkinson's Evaluation Scale (SPES)/SCales for Outcomes in Parkinson's disease (SCOPA)—a short scale developed to assess motor function in patients with Parkinson's disease (PD).
Methods: Eighty five patients with PD were assessed with the SPES/SCOPA, Unified Parkinson's Disease Rating Scale (UPDRS), Hoehn and Yahr (H&Y) scale, and Schwab and England (S&E) scale. Thirty four patients were examined twice by two different assessors who were blinded to each other's scores and test executions. Additionally, six items of the motor section of the SPES/SCOPA were assessed in nine patients and recorded on videotape to evaluate inter-rater and intra-rater reliability.
Results: The reproducibility of the sum scores in the clinical assessments was high for all subscales of the SPES/SCOPA. Inter-rater reliability coefficients for individual items ranged from 0.27–0.83 in the motor impairment section, from 0.58–0.82 in the activities of daily living section, and from 0.65–0.92 in the motor complications section. Inter-rater reliability of the motor items in the video assessments ranged from 0.70–0.87 and intra-rater reliability ranged from 0.81–0.95. The correlation between related subscales of the SPES/SCOPA and UPDRS were all higher than 0.85, and both scales revealed similar correlations with other measures of disease severity. The mean time to complete the scales differed significantly (p<0.001) and measured 8.1 (SD 1.9) minutes for the SPES/SCOPA and 15.6 (SD 3.6) minutes for the UPDRS.
Conclusion: The SPES/SCOPA is a short, reliable, and valid scale that can adequately be used in both research and clinical practice.
The aim of this study was to investigate the clinical heterogeneity of Parkinson’s disease (PD) among a cohort of Chinese patients in early stages. Clinical data on demographics, motor variables, motor phenotypes, disease progression, global cognitive function, depression, apathy, sleep quality, constipation, fatigue, and L-dopa complications were collected from 138 Chinese PD subjects in early stages (Hoehn and Yahr stages 1–3). The PD subject subtypes were classified using k-means cluster analysis according to the clinical data from five to three-cluster consecutively. Kappa statistical analysis was performed to evaluate the consistency among different subtype solutions. The cluster analysis indicated four main subtypes: the non-tremor dominant subtype (NTD, n=28, 20.3%), rapid disease progression subtype (RDP, n=7, 5.1%), young-onset subtype (YO, n=50, 36.2%), and tremor dominant subtype (TD, n=53, 38.4%). Overall, 78.3% (108/138) of subjects were always classified between the same three groups (52 always in TD, 7 in RDP, and 49 in NTD), and 98.6% (136/138) between five- and four-cluster solutions. However, subjects classified as NTD in the four-cluster analysis were dispersed into different subtypes in the three-cluster analysis, with low concordance between four- and three-cluster solutions (kappa value=−0.139, P=0.001). This study defines clinical heterogeneity of PD patients in early stages using a data-driven approach. The subtypes generated by the four-cluster solution appear to exhibit ideal internal cohesion and external isolation.
Parkinson’s disease; Heterogeneity; Subtype; Cluster analysis
Sleep disorders occur commonly in Parkinson’s disease (PD), and reduce quality of life. Sleep-related problems in PD include insomnia, restless legs syndrome, rapid eye movement sleep behavior disorder, sleep apnea, parasomnias, excessive daytime sleepiness, and sleep attacks. This article reviews sleep disorders and their treatment in PD.
insomnia; restless legs syndrome; sleep apnea
The 39-item Parkinson’s Disease Questionnaire (PDQ-39) has been tested in many languages, but not in Chinese mainland. We aimed to assess the Chinese (mainland) version of the PDQ-39. Seventy-one subjects with Parkinson’s disease (PD) completed the PDQ-39 and the Medical Outcomes Study 36-item Short Form Health Survey (SF-36). All subjects were retested with the PDQ-39 a week later. The united Parkinson’s disease rating scale (UPDRS) and the Hoehn and Yahr (H & Y) scale were also used to evaluate the subjects. Reliability was assessed by Cronbach’s α and intra-class correlation coefficient (ICC). Validity was examined in terms of agreement with SF-36, UPDRS, and H & Y scales. The Chinese (mainland) version of the PDQ-39 demonstrated acceptable reliability (Cronbach’s α: 0.84–0.88; ICC: 0.56–0.82). The item-total correlations (0.33–0.88) and scaling success rates (77.56%) indicated satisfactory convergent and discriminant validity of the PDQ-39 items. The correlations between related constructs of the PDQ-39 and UPDRS (r=0.44–0.68) and between those of the PDQ-39 and SF-36 (r=(−0.46)–(−0.69)) were all statistically significant (P<0.01). Except for stigma, cognitions, and bodily discomfort, all other dimensions of the PDQ-39 significantly discriminated patients at different H & Y stages indicated by the H & Y scale. Although our observations indicate that some problematic subscales of this version of the PDQ-39 could be improved upon, this study suggests acceptable reliability and validity of the Chinese (mainland) version of the PDQ-39.
39-item Parkinson’s Disease Questionnaire (PDQ-39); Quality of life; Validity; Reliability
To compare verbal fluency among Alzheimer's disease, Parkinson's disease, and major depression and to assess the sociodemographic and clinical factors associated with the disease severity.
Patients from an outpatient university center with a clinical diagnosis of Alzheimer's disease, Parkinson's disease or major depression were studied. Severity was staged using the Hoehn & Yahr scale, the Hamilton Depression scale and the Clinical Dementia Rating for Parkinson's disease, major depression, and Alzheimer's disease, respectively. All subjects were tested with the Mini-Mental State Examination, the digit span test, and the verbal fluency test (animals).
We fit four types of regression models for the count variable: Poisson model, negative binomial model, zero-inflated Poisson model, and zero-inflated negative binomial model.
The mean digit span and verbal fluency scores were lower in patients with Alzheimer's disease (n = 34) than in patients with major depression (n = 52) or Parkinson's disease (n = 17) (p<0.001). The average number of words listed was much lower for Alzheimer's disease patients (7.2 words) compared to the patients presenting with major depression (14.6 words) or Parkinson's disease (15.7 words) (KW test = 32.4; p<0.01). Major depression and Parkinson's disease groups listed 44% (ROM = 1.44) and 48% (ROM = 1.48) more words, respectively, compared to those patients with Alzheimer's disease; these results were independent of age, education, disease severity and attention. Independently of diagnosis, age, and education, severe disease showed a 26% (ROM = 0.74) reduction in the number of words listed when compared to mild cases.
Verbal fluency provides a better characterization of Alzheimer's disease, major depression, and Parkinson's disease, even at later stages.
Verbal fluency; cognition; diagnosis; neuropsychology
PINK1 loss-of-function causes recessive, early-onset parkinsonism. In Tunisia there is a high rate of consanguineous marriage but PINK1 carrier frequency and disease prevalence have yet to be assessed.
The frequency of PINK1 mutations in familial parkinsonism, community-based patients with idiopathic Parkinson disease (PD) (non-familial PD), and control subjects was determined. Demographic and clinical characteristics of individuals with PINK1 homozygous or heterozygous variants, or without PINK1 mutations, were compared.
A total of 92 kindreds (with 208 affected and 340 unaffected subjects), 240 nonfamilial PD, and 368 control participants were recruited from the Institut National de Neurologie, Tunis. Clinical examinations included Hoehn &Yahr, UPDRS, and Epworth scales. PINK1 sequencing and dosage analysis was performed in familial index patients, the variants identified screened in all subjects. Parkin and LRRK2 genes were also examined.
Four PINK1 homozygous mutations, three novel (Q129X, Q129fsX157, G440E, and one previously reported; Q456X), segregate with parkinsonism in 46 individuals in 14 of 92 families (15%). Six of 240 patients with nonfamilial PD were found with either homozygous Q456X or Q129X (2.5%) substitutions. In patients with familial disease, PINK1 homozygotes were younger at disease onset (36 ± 12 years) than noncarriers (57 ± 15 years) and more often had an akinetic-rigid presentation at examination and slow progression.
Segregation of PINK1 mutations with parkinsonism within families, and frequency estimates within population controls, suggested only four PINK1 mutations were pathogenic. Several PINK1 sequence variants are potentially benign and there was no evidence that PINK1 heterozygosity increases susceptibility to idiopathic Parkinson disease.
= age at onset;
= case report forms;
= essential tremor;
= Parkinson disease;
= Unified Parkinson's Disease Rating Scale.
the factors that determine quality of life (QoL) in patients with
idiopathic Parkinson's disease in a population based sample. Quality
of life (QoL) is increasingly recognised as a critical measure in
health care as it incorporates the patients' own perspective of their health.
with Parkinson's disease seen in a
population based study on the prevalence of parkinsonism were asked to
complete a disease-specific QoL questionnaire (PDQ-39) and the Beck
depression inventory. A structured questionnaire interview and a
complete neurological examination, including the Hoehn and Yahr scale, the Schwab and England disability scale, the motor part of the unified
Parkinson's disease rating scale (UPDRS part III), and the mini mental
state examination were performed by a neurologist on the same day.
rate was 78%. The factor most closely associated with QoL was the
presence of depression, but disability, as measured by the Schwab and
England scale, postural instability, and cognitive impairment
additionally contributed to poor QoL. Although the UPDRS part III
correlated significantly with QoL scores, it did not contribute
substantially to predicting their variance once depression, disability,
and postural instability had been taken into account. In addition,
patients with akinetic rigid Parkinson's
disease had worse QoL scores than those with tremor dominant disease,
mainly due to impairment of axial features.
disability, postural instability, and cognitive impairment have the
greatest influence on QoL in Parkinson's
disease. The improvement of these features should therefore become an
important target in the treatment of the disease.
are common problems affecting the quality life
of Parkinson's disease (PD) patients and are
often underestimated. The causes of sleep
disturbances are multifactorial and include
nocturnal motor disturbances, nocturia,
depressive symptoms, and medication use.
Comorbidity of PD with sleep apnea syndrome,
restless legs syndrome, rapid eye movement sleep
behavior disorder, or circadian cycle disruption
also results in impaired sleep. In addition, the
involvement of serotoninergic, noradrenergic,
and cholinergic neurons in the brainstem as a
disease-related change contributes to impaired
sleep structures. Excessive daytime sleepiness
is not only secondary to nocturnal disturbances
or dopaminergic medication but may also be due
to independent mechanisms related to impairments
in ascending arousal system and the orexin
system. Notably, several recent lines of
evidence suggest a strong link between rapid eye
movement sleep behavior disorder and the risk of
neurodegenerative diseases such as PD. In the
present paper, we review the current literature
concerning sleep disorders in PD.
Though infections are associated with psychotic symptoms, whether or not subclinical inflammation is associated with hallucinations is not known in Parkinson’s disease (PD).
To investigate the association of illusions/hallucinations and plasma CRP levels in PD patients without symptomatic infections.
PD patients not diagnosed as having infections were assessed for illusions and hallucinations using the Parkinson Psychosis Questionnaire (PPQ). It comprises four-domain questions: PPQ-A for sleep problems, PPQ-B for hallucinations/illusions, PPQ-C for delusions, and PPQ-D for disorientation. Assigning patients with ≥1 points in the PPQ-B score to be cases and others as controls, the association of hallucinations/illusions and clinical features (age, sex, duration of PD, Unified Parkinson’s Disease Rating Scale part 3 (UPDRS-3), Mini-Mental State Examination (MMSE) score, sleep disturbance (PPQ-A score) as well as daily doses of L-Dopa, dopamine agonists, amantadine, and selegiline) were analyzed using a case–control design.
A total of 111 patients were examined and plasma CRP levels were <0.1–6.0 mg/L. Hallucinations or illusions were detected in 28 (25.2%). There were significant differences in age, UPDRS-3 score, MMSE score, PPQ-A, daily doses of L-Dopa and dopamine agonists and plasma CRP levels between cases and controls. A multivariate logistic regression model revealed that UPDRS-3 scores and plasma CRP levels were significantly associated with hallucinations/illusions with an adjusted odds ratio of 1.96 (95% confidence interval (CI) 1.20–3.20) per 10 points and 1.57 (95% confidence interval 1.13–2.16) per two-fold, respectively. Dividing patients into thirds by CRP levels (≤0.2, 0.3–0.6, ≥0.7 mg/L), the prevalence of hallucinations/illusions was 13.2%, 21.6%, and 41.7%, in the bottom-, middle-, and top-thirds, respectively (for trend p = 0.012).
Subclinical elevation of plasma CRP levels was associated with hallucinations or illusions after adjustment for motor disability, suggesting that subclinical elevations of CRP levels might be an independent risk for hallucinations/illusions.
Pulmonary thromboembolism is a common cause of death in patients with autopsy-confirmed Parkinsonism. This study investigated the incidence of leg deep vein thrombosis in Parkinson’s disease and relationships between deep vein thrombosis and clinical/laboratory findings, including postural abnormalities as assessed by photographic measurements.
This cross-sectional study assessed the presence of deep vein thrombosis using bilateral leg Doppler ultrasonography in 114 asymptomatic outpatients with Parkinson’s disease.
Deep vein thrombosis was detected in 23 patients (20%) with Parkinson’s disease. Deep vein thrombosis was located in the distal portion in 18 patients and in the proximal portion in 5 patients. No significant differences in age, sex, body mass index, disease duration, Hoehn-Yahr stage, anti-Parkinson’s drugs, or daily levodopa-equivalent dose were seen between deep vein thrombosis-positive and -negative groups. Univariate analysis for developing deep vein thrombosis in patients with Parkinson’s disease identified the following markers: long-term wheelchair use, bent knee, bent spine, and D-dimer elevation. Bending angles were significantly greater in the deep vein thrombosis-positive group at the knee and spine than in the deep vein thrombosis-negative group. Half of Parkinson’s disease patients with camptocormia had deep vein thrombosis. Among diabetes mellitus cases, long-term wheelchair use, bent knee over 15°, camptocormia, D-dimer elevation, the more risk markers were associated with a higher incidence of DVT. The presence of risk markers contributed to the development of deep vein thrombosis. On multivariate logistic regression analysis, a bent knee posture was strongly associated with an increased risk of deep vein thrombosis.
Presence of leg deep vein thrombosis correlated with postural abnormalities in Parkinson’s disease. We recommend non-invasive ultrasonographic screening for leg deep vein thrombosis in these high-risk patients with Parkinson’s disease.
Falls are a major source of disability in Parkinson's disease. Risk factors for falling in Parkinson's disease remain unclear. To determine the relevant risk factors for falling in Parkinson's disease, we screened 160 consecutive patients with Parkinson's disease for falls and assessed 40 variables. A comparison between fallers and nonfallers was performed using statistical univariate analyses, followed by bivariate and multivariate logistic regression, receiver-operating characteristics analysis, and Kaplan-Meier curves. 38.8% of patients experienced falls since the onset of Parkinson's disease (recurrent in 67%). Tinetti Balance score and Hoehn and Yahr staging were the best independent variables associated with falls. The Tinetti Balance test predicted falls with 71% sensitivity and 79% specificity and Hoehn and Yahr staging with 77% sensitivity and 71% specificity. The risk of falls increased exponentially with age, especially from 70 years onward. Patients aged >70 years at the onset of Parkinson's disease experienced falls significantly earlier than younger patients.
Sleep disturbances are common in Parkinson's disease (PD). Actigraphy has emerged as an alternative to polysomnography to measure sleep, raising the question of its ability to capture sleep quality in PD patients. Our aim was to compare self-report data with actigraphic data and to examine associations with clinical variables. Thirty non-demented individuals with PD and 14 normal control participants (NC) were included. Sleep was measured using 24-hour wrist actigraphy over a seven-day period, during which time participants kept a sleep diary. Subjective sleep and arousal questionnaires included the Parkinson's Disease Sleep Scale, and Epworth Sleepiness Scale. Patients with PD presented with more sleep problems than NC. In NC, none of the actigraphic sleep variables were related to any of the self-report measures of sleep. In PD, scores on subjective sleep measures correlated with actigraphy-derived estimates of sleep quality. Our results suggest that actigraphy is an appropriate method of measuring sleep quality in PD.
Parkinson's disease; sleep; actigraphy; subjective sleep ratings