Sleep quality in caregivers of patients with Alzheimer's disease and Parkinson's disease and its relationship to quality of life

ABSTRACT Background: Knowledge about sleep complaints of caregivers of patients with Alzheimer's disease (AD) and Parkinson's disease (PD) is limited, and we lack information about the relationship between caregivers' sleep problems and their quality of life (QoL). Methods: We evaluated subjective sleep quality and its relationship to QoL in a group of 80 caregivers of patients with AD (ADCG, n = 40) and PD (PDCG, n = 40), and in 150 controls. Information about night-time complaints was collected using the Pittsburgh Sleep Quality Index (PSQI). QoL was measured using the McGill QoL Questionnaire. Results: Eighteen ADCG (45%), 22 PDCG (55%), and 45 (30%) controls reported poor sleep quality. Mean global PSQI score of PDCG (6.25 ± 3.9) was not significantly different from that of ADCG (5.8 ± 3.5; p = 0.67). However, both PDCG and ADCG scored significantly higher than control group (4.3 ± 3.1; p < 0.01). ADCG frequently reported difficulties falling asleep (72.5%) and disturbed sleep (100%). PDCG reported reduced subjective sleep quality (80%) and increased sleep disturbances (100%). Poor sleep quality was associated with depressive symptoms and correlated with QoL in caregivers of both groups, particularly the psychological symptoms domain. Conclusions: Among caregivers of patients with AD and PD, poor sleep quality is frequent and significantly linked to QoL and depressive symptoms. Identifying the nature of sleep disturbances not only in patients but also in their caregivers is important as appropriate treatment may lead to a better management of the needs of families coping with these patients.     

Sleep disorders and their determinants in multiple system atrophy

OBJECTIVES: To evaluate the incidence, types, determinants, and consequences of sleep disorders in patients with multiple system atrophy (MSA) and determine whether their characteristics are similar to those of patients with Parkinson's disease (PD). METHODS: Information about sleep disorders was collected using a standardised questionnaire in an unselected group of 57 patients with MSA and in 62 patients with PD matched as a group for age, sex distribution, and disease duration. RESULTS: Seventy percent of patients with MSA complained of sleep disorders compared with 51% of patients with PD (p=0.03). The most commonly reported sleep disorders were sleep fragmentation (52.5%), vocalisation (60%), REM sleep behaviour disorder (47.5%), and nocturnal stridor (19%). Except for sleep fragmentation, the incidence of these disorders was significantly higher than in PD. Sleep problems tended to be associated with more severe motor symptoms, longer disease duration, depression, and longer duration of levodopa treatment. Half of patients with MSA with sleep disorders complained of daytime somnolence compared with 30% of patients with PD. Daytime somnolence was significantly associated with disease severity in MSA. CONCLUSION: This study shows that sleep disorders are more common in patients with MSA than in those with PD after the same duration of the disease, reflecting the more diffuse underlying pathological process in MSA.     

Sleep disorders in Parkinson's disease.

We sought to estimate the frequency and nature of sleep disturbances in Indian Parkinson's disease (PD) patients. One hundred forty nine consecutive PD patients attending the Movement Disorders Clinic of the All India Institute of Medical Sciences, New Delhi, India and 115 age-matched healthy controls participated. After clinical evaluation, sleep assessment was done using a 23-question, validated sleep questionnaire. Mean age of PD patients and the duration of illness were 58.37 (S.D. 10.45) years and 5.7 (S.D. 3.85) years, respectively. The mean age of the controls was 56.50 (S.D. 11.45) years (P > 0.05). Sleep problems were seen in 63 (42%) PD patients compared to 12% of controls. These were: insomnia in 32%, nightmares in 32%, and excessive day time sleepiness in 15% of PD patients as compared with 5%, 5% and 6%, respectively, in controls (P < 0.025). Presence of nightmares was significantly associated with higher Hoehn and Yahr score (P < 0.002), high unified Parkinson's disease rating scale (UPDRS) Part I score (P < 0.000) and levodopa dose (P < 0.025). Excessive daytime sleepiness correlated with higher Hoehn and Yahr stage (P < 0.004), and levodopa dose (P < 0.040). The sleep latency was longer in PD patients as compared to controls (P < 0.000). Multiple logistic regression analysis showed association of sleep disturbances with UPDRS Part III, Schwab and England score, levodopa dose, rigidity score, and bradykinesia score. Sleep problems are much more common in PD patients compared to controls (P < 0.001), and correlate with increased severity of disease.     

Pergolide versus levodopa monotherapy in early Parkinson's disease patients: The PELMOPET study.

Dopamine agonists are used as initial treatment in patients with Parkinson's disease (PD) to reduce incidence and severity of motor complications. This paradigm is based on long-term studies, allowing "rescue" therapy with levodopa. The present strict monotherapy study (PELMOPET, the acronym for the pergolide-versus-L-dopa-monotherapy-and-positron-emission-tomography trial) evaluated the efficacy and safety of pergolide versus levodopa without levodopa "rescue" medication. This multicenter, double-blind, randomized, 3-year trial compared pergolide monotherapy (n=148) with levodopa monotherapy (n=146) in dopamine-naive patients with early PD (Hoehn and Yahr stage 1-2.5). Primary efficacy measures were clinical efficacy, severity and time to onset of motor complications, and disease progression. During the 3 years, severity of motor complications was significantly lower and time to onset of dyskinesia was significantly delayed in the group receiving pergolide (3.23 mg/day) compared with those receiving levodopa (504 mg/day). However, time to onset of motor complications was not longer in patients receiving pergolide after 3 years. Symptomatic relief (assessed by Unified Parkinson's Disease Rating Scale [UPDRS], UPDRS II, and III, Clinical Global Impressions [CGI] severity, and CGI and Patient Global Impressions [PGI] improvement) was significantly greater in patients receiving levodopa. Adverse events led to discontinuation of therapy in 17.6% of pergolide patients and 9.6% of levodopa patients. This is the first study comparing strict monotherapy with a dopamine agonist versus levodopa in previously untreated early PD. In principle, both levodopa and a dopamine agonist such as pergolide seem to be suitable options as initial PD therapy. The choice remains with the treating physician based on the different efficacy and adverse event profiles.     

Sleep disorder related to Parkinson’s disease

Sleep disorders occur in 74–98% of patients with idiopathic Parkinson’s disease (PD), adversely affecting their quality of life. Sleep disruption takes the form of sleep fragmentation with frequent and prolonged awakenings and daytime sleepiness. Nocturia, difficulty in turning over in bed, painful leg cramps, vivid dreams/nightmares, back pain, limb/facial dystonia and leg jerks are the main causes of nocturnal awakening in PD patients. Sleep disturbance gradually worsens with disease progression, suggesting that it is related to the severity of the disease. Sleep disturbances may be generally considered as part of the normal aging process, being more common in the elderly. However, no significant association between sleep disturbances and either age or disease duration was found in a survey of 100 PD patients. Disturbed sleep maintenance in PD patients was more severe than in age-matched controls, and nocturnal awakening was frequently caused by nocturia, pain, stiffness and difficulty in turning over in bed. Sleep disturbance is also a complication of chronic levodopa therapy. Recent data suggest that controlled-release levodopa is less likely to cause nocturnal symptoms than standard levodopa, particularly in mild-to-moderate disease. Depression, which is common in PD patients, contributes to sleep disturbance but has a lesser influence than the disease process itself. Hypnotic and sedative agents, as well as anti-depressants if required, are useful in ameliorating sleep disturbances in PD patients; intranasal desmopressin appears to be effective in reducing nocturia.

     

Increased daytime sleepiness in Parkinson's disease: a questionnaire survey.

We evaluated the frequency and severity of excessive daytime sleepiness in an outpatient population with Parkinson's disease in comparison to age-matched controls and examined its relationship with antiparkinsonian drug therapy and sleep history. Increased daytime sleepiness and involuntary sleep episodes have been described in Parkinson's disease, but the etiology is not completely understood. The Epworth Sleepiness Scale (ESS), a validated questionnaire for daytime sleepiness, was prospectively administered to 99 consecutive outpatients with Parkinson's disease and 44 age-matched controls. In addition, a short sleep-screening questionnaire was used. The ESS revealed significantly increased daytime sleepiness in PD patients compared to controls (7.5 +/- 4.6 vs. 5.8 +/- 3.0, P = 0.013). The ESS score was abnormally high (10 or more) in 33 % of PD patients and 11.4% of controls (P = 0.001). ESS was not different between PD patients on levodopa monotherapy and those on levodopa and dopamine agonists, or between patients taking ergoline or non-ergoline dopamine agonists. In PD patients and in controls, sleepiness was significantly associated with reported heavy snoring. Increased daytime sleepiness is more frequent in patients with PD than in elderly controls. Similar to controls, increased daytime sleepiness in PD patients is correlated with heavy snoring.     

Parkinson's disease and narcolepsy-like symptoms

ObjectiveVarious sleep-related problems, for example, insomnia and symptoms of rapid eye movement behavior disorder (RBD), are common in patients with Parkinson's disease (PD). We studied the prevalence of symptoms of narcolepsy (NARC), hallucinations, and RBD and their association with other symptoms.MethodsAltogether, 1447 randomly selected patients with PD, aged 43–89 years, participated in a questionnaire study. A structured questionnaire with 207 items was based on the Basic Nordic Sleep Questionnaire. Questions on demographics, PD, RBD, and other issues were included.ResultsThe response rate was 59.0%; of these patients, 73% had answered to all questions that were used in the analyses (N = 623). The occurrence of suspected narcolepsy (Ullanlinna Narcolepsy Scale ≥ 14 and Epworth Sleepiness Scale ≥ 11) was observed in 9.3% of the subjects (PD with NARC), RBD (REM Sleep Behavior Disorder Screening Questionnaire ≥ 6) in 39.2% of all patients with PD, and in 62.1% of those with PD and NARC. In patients with PD, hallucinations before going to bed in the evening occurred in 5.8%, hypnagogic hallucinations in 4.0%, hallucinations during night 8.3%, and hypnopompic hallucinations in 3.2%. Cataplexy symptoms occurred in 43.1% of subjects with PD and NARC. In a logistic regression analysis, PD with NARC was associated with RBD, all types of hallucinations, daytime sleepiness, fatigue, insomnia, and intense dreaming also when adjusted for age, sex, disease duration, and levodopa.ConclusionsNarcolepsy-like symptoms may be present in patients with PD. Symptoms of RBD were associated with symptoms of narcolepsy including symptoms of cataplexy.     

Nighttime sleep problems and daytime sleepiness in Parkinson's disease

Our objective is to evaluate nighttime sleep problems (NSP) and daytime sleepiness (DS) in patients with Parkinson's disease (PD) compared to controls, and to assess relations with demographic, disease‐related, and clinical characteristics in patients. NSP and DS were evaluated with the SCOPA‐SLEEP questionnaire in PD patients and controls. In patients, other disease‐related and clinical characteristics were also evaluated. Four hundred twenty PD patients [mean (SD) age 61.1 (11.5) years] and 150 controls [mean (SD) age 60.9 (9.9) years] participated in the study. Compared to controls, a significantly greater proportion of patients had excessive DS (EDS) (43 vs. 10%), excessive NSP (ENSP) (27 vs. 9%), or used sleep medication (17 vs. 12%). Difficulties with falling asleep were similar in both groups. In both patients and controls, women experienced more NSP than men. In patients, depressive symptoms accounted for 21% of NSP variance and was the major contributor to the total explained variance (30%). Furthermore, NSP were related to dopamine‐agonist and levodopa dose, whereas DS was related to age, dopamine‐agonist dose, and disease severity. NSP and DS occur frequently in PD, with EDS being reported more commonly than ENSP. No strong relations were found between DS and demographic or clinical variables. The strong relation between NSP and depressive symptoms in PD calls for future studies to explore the nature of this relation. © 2007 Movement Disorder Society     

Sleepiness in Parkinson's disease: a controlled study.

Sudden-onset sleep episodes while driving have been reported in Parkinson's disease (PD) patients, and termed sleep attacks because they were reported to be irresistible and to occur without warning. We postulate that these episodes are due to excessive daytime sleepiness secondary to the high frequency of sleep disorders in PD patients and the sedative effects of dopaminergic medications. We assessed the frequency and relationship between excess daytime sleepiness and sleep episodes while driving (SE) in patients with PD. We evaluated 101 consecutive PD patients presenting to the Movement Disorder Center at the Mount Sinai School of Medicine using a questionnaire that incorporated a subjective estimate of sleepiness, the Epworth Sleepiness Scale (ESS) and information on disease severity and dopaminergic medications. One hundred age-matched respondents without PD served as a control population. Excess daytime sleepiness was reported in 76% of PD patients compared to 47% of controls (P < 0.05). The mean ESS scores for PD patients was 9.1 +/- 6.1 versus 5.7 +/- 4.4 in controls (P < 0.001). ESS scores > or =10 were observed in 40.6% of PD patients compared to 19% of controls (P < 0.01) and 24% of PD patients had scores > or =15, compared to 5% of controls (P < 0.001). Sleep episodes while driving were experienced by 20.8% of PD drivers compared to 6% of control drivers (P < 0.05). The mean daily levodopa (L-dopa) dose equivalent was 1,142 +/- 858 mg in PD drivers who experienced a SE while driving compared to 626 +/- 667 mg in those who had not (P < 0.05). Similarly, ESS was significantly greater in drivers with a SE than in those without (11.6 +/- 6.4 vs. 8.4 +/- 4.1; P < 0.05). Logistic regression analysis demonstrated that ESS and mean daily L-dopa dose equivalents were predictors of sleep episodes while driving, whereas age, gender, disease severity, and individual dopaminergic agents were not. These findings support the notion that sleep episodes while driving in PD patients are related to excess daytime sleepiness and dopaminergic load. Physicians should advise and treat patients accordingly.     

老年帕金森病患者日间过度思睡的临床调查及相关因素分析

目的了解老年帕金病(PD)患者日间过度思睡(EDS)的临床情况及相关因素。方法收集北京医院老年PD患者80例和年龄、性别相匹配的健康对照者50名,采用爱泼沃斯思睡量表(ESS)评定EDS,简易精神状态量表(MMSE)评定智能状况,比较PD患者和健康对照的EDS情况,同时对PD患者进行改良Webster评分、Hoehn-Yahr(H-Y)分期、Hamilton抑郁和焦虑量表调查,并询问是否具有夜间易醒、疲倦、不宁腿综合征、日间睡眠发作、夜间入睡困难、是否应用多巴受体激动剂及多巴胺药物的用量。根据ESS评分情况将PD患者分为EDS组(ESS≥10)和非EDS组(ESS<10分),并对两组间的上述调查项目进行比较。同时以ESS总分为因变量,以计量资料年龄、Hoehn-Yahr分级、左旋多巴用量、Webster评分、病程、Hamilton抑郁和焦虑评分及睡眠时间为自变量进行多元逐步回归分析,分析ESS评分与以上各因素的相关性。结果 80例PD患者中23例(28.8%)ESS≥10分,健康对照组5名(10.0%)ESS≥10分,两组有差异有统计学意义(χ2=6.40,P=0.01)。EDS组23例(男10例、女13例),年龄(72.26±5.94)岁,日间疲倦18例(78.26%),Hamilton抑郁量表评分(13.57±3.31)分,Hamilton焦虑量表评分(19.13±5.38)分,病程(7.65±4.12)年,非EDS组57例(男40例、女17例),年龄(68.58±5.27)岁,日间疲倦18例(31.58%),Hamilton抑郁量表评分(7.32±2.71)分,Hamilton焦虑量表评分(13.25±5.12)分,病程(5.55±3.40)年,两组间比较有统计学差异(均P<0.05);两组患者Hoe-hn-Yahr分级、改良Webster评分、应用左旋多巴剂量、是否应用多巴受体激动剂、夜间睡眠时间、入睡困难、不宁腿综合征、夜间易醒均无统计学差异(均P>0.05)。多元逐步回归分析结果显示,PD患者年龄和抑郁程度与ESS评分相关(分别回归系数=0.10,标准偏回归系数=0.16,P=0.04;回归系数=0.59,标准偏回归系数=0.66,P=0.00),抑郁程度相关性更强。结论老年PD患者EDS较为常见,可能受年龄和抑郁情绪的影响,但与疾病严重程度可能不存在相关性。     

Relationship between age and subtypes of psychotic symptoms in Parkinson's disease

Abstract Objective Psychotic symptoms (PS) in Parkinson's disease (PD) usually develop as a side effect of the dopaminergic therapy and consist of hallucinations and delusions. We observed that PD patients who developed delusions tend to be younger than those with hallucinations and we aimed to investigate the validity of this observation. Methods The medical records of 127 PD patients with PS were reviewed and 76 patients who were on treatment with dopamine agonists with or without levodopa at the time of developing PS were included. Patients were stratified into 3 groups according to the subtypes of PS: patients with solely hallucinations (n = 46), solely delusions (n = 18), and both types (n = 12). The groups were compared with respect to the age-at-onset of PD and PS, duration of PD, Activities of Daily Living (ADL) and motor subscale scores of Unified PD Rating Scale (UPDRS), and levodopa equivalent dose of the dopaminergic agents administered at the time of PS onset. Results The mean age-atonset of PD and PS was significantly younger (p = 0.0001) in patients with delusions (49 and 55.9 years) than those with hallucinations (61.9 and 68.9 years). The same parameters were also significantly different (p = 0.002 and p = 0.001, respectively) between the groups of patients with concurrent delusions and hallucinations (51.7 and 57.2 years) and those with only hallucinations. ADL and motor subscale scores were higher in patients with hallucinations (p = 0.016 and p = 0.013) compared with those noted in patients with delusions despite similar disease duration. The mean levodopa equivalent doses of the dopaminergic agents administered at the time of onset of PS did not differ between the groups. Conclusion This study supported an association of delusions with younger onset of both PD and psychosis as compared with hallucinations. However, additional factors related to this association remain to be elucidated.     

REM sleep behavior disorder in Japanese patients with Parkinson’s disease: a multicenter study using the REM sleep behavior disorder screening questionnaire

REM sleep behavior disorder (RBD) is known to be observed more frequently in patients with an α-synucleinopathy such as Parkinson's disease (PD) than in the general population. The precise prevalence of RBD in Japanese PD patients is not known. Therefore, we investigated the prevalence and the clinical characteristics of patients with RBD in a large population of Japanese patients with PD. We investigated various clinical features and employed the Japanese version of the RBD screening questionnaire on 469 non-demented Japanese PD patients in this multicenter study. Probable or possible RBD was detected in 146 patients (31.1%) and was significantly associated with longer PD duration, higher Hoehn and Yahr stage, higher Unified Parkinson's Disease Rating Scale part III subscale (7 items), more motor fluctuations, and a higher levodopa-equivalent daily dose (p < 0.01). As to the major autonomic dysfunctions, severe constipation was significantly more frequent in PD patients with RBD than in those without it (p < 0.01). The RBD symptoms of 53 patients (39.0%) preceded the onset of PD motor symptoms. The median interval from the onset of RBD symptoms to PD motor symptoms was 17.5 years, and 3 patients had intervals of over 50 years. This large-scale multicenter study revealed that RBD is a frequent non-motor symptom in Japanese patients with PD, which may precede the onset of motor symptoms. Moreover, RBD that increases with the duration and severity of PD may be associated with autonomic dysfunction.     

Psychiatric comorbidity in a population of Parkinson''s disease patients

Behavioural disturbances are frequently observed in Parkinson's disease (PD), including mood and anxiety disorders. The existence of a comorbidity between such psychiatric disorders in PD patients has been suggested only in a few studies. To assess the prevalence of mood and anxiety disturbances, and the rate of comorbidity of such disorders in PD. Secondary aim was to correlate the prevalence of psychiatric disorders in PD with age, sex, laterality of motor symptomatology, clinical features, severity of disease, age of onset and PD duration, and anti-parkinsonian therapy. Ninety consecutive PD outpatients, and 90 age- and sex-matched controls were included. All PD patients enrolled were non-fluctuating (21 de novo, 69 treated with levodopa or dopamine agonists). PD patients and controls with Mini Mental State Examination score <23 were excluded. Psychiatric diagnosis was performed by semistructured interview according with DSM-IV criteria and the severity of depressive and anxious symptoms was rated with clinical rating scales. Major depression was found in 21.1% PD patients vs. 3.3% controls (P < 0.01, chi-square analysis), dystimia in 18.8% PD patients vs. 4.4% controls (P < 0.05), panic disorders in 30% PD patients vs. 5.5% controls (P < 0.01). No difference in the prevalence of other anxiety disorders was observed between the two groups. The comorbidity of mood and anxiety disorders was found in 19.3% PD patients vs. 8.6% controls (P < 0.01). No correlation was reported between the prevalence of behavioural disturbances and any of the demographic, clinical or pharmacological data taken into account. Our findings might suggest the existence of a wide spectrum of psychiatric disorders in PD ranging from pure depressive disorders, comorbid depressive and anxiety disorders, and pure anxiety disorders, presumably linked to the same neurobiological substrate.     

HLA typing does not predict REM sleep behaviour disorder and hallucinations in Parkinson's disease.

HLA-DR2 haplotype and DQ1 DNA alleles, characterizing 90 to 100% of all narcoleptic patients, were found to be equally distributed in 20 Parkinson's disease (PD) patients with early hallucinations, rapid eye movement (REM) sleep-related behaviour disturbances (RBD), and sleep onset in REM (SOREM), and in 20 PD patients without hallucinations, despite 10 to 15 years of treatment, and no RBD or SOREM.     

Parkinson's disease and sleepiness: an integral part of PD

OBJECTIVE: To investigate the potential causes of excessive daytime sleepiness in patients with PD-poor sleep quality, abnormal sleep-wakefulness control, and treatment with dopaminergic agents. METHODS: The authors performed night-time polysomnography and daytime multiple sleep latency tests in 54 consecutive levodopa-treated patients with PD referred for sleepiness, 27 of whom were also receiving dopaminergic agonists. RESULTS: Sleep latency was 6.3 +/- 0.6 minutes (normal >8 minutes), and the Epworth Sleepiness score was 14.3 +/- 4.1 (normal <10). A narcolepsy-like phenotype (> or = 2 sleep-onset REM periods) was found in 39% of the patients, who were sleepier (4.6 +/- 0.9 minutes) than the other 61% of patients (7.4 +/- 0.7 minutes). Periodic leg movement syndromes were rare (15%, range 16 to 43/h), but obstructive sleep apnea-hypopnea syndromes were frequent (20% of patients had an apnea-hypopnea index >15/h; range 15.1 to 50.0). Severity of sleepiness was weakly correlated with Epworth Sleepiness score (r = -0.34) and daily dose of levodopa (r = 0.30) but not with dopamine-agonist treatment, age, disease duration, parkinsonian motor disability, total sleep time, periodic leg movement, apnea-hypopnea, or arousal indices. CONCLUSIONS: In patients with PD preselected for sleepiness, severity of sleepiness was not dependent on nocturnal sleep abnormalities, motor and cognitive impairment, or antiparkinsonian treatment. The results suggest that sleepiness-sudden onset of sleep-does not result from pharmacotherapy but is related to the pathology of PD.     

Comorbidity of the nonmotor symptoms of Parkinson's disease.

Many patients with Parkinson's disease (PD) have clinically significant anxiety, depression, fatigue, sleep disturbance, or sensory symptoms. The comorbidity of these nonmotor symptoms and their relationship to PD severity has not been extensively evaluated. Ninety- nine nondemented PD patients were evaluated with the following battery of tests: Beck Anxiety Inventory (BAI), Beck Depression Inventory (BDI), Fatigue Severity Scale (FSS), Pittsburgh Sleep Quality Index (PSQI), a sensory symptom questionnaire, Unified Parkinson's Disease Rating Scale (UPDRS), Hoehn & Yahr (H/Y) Stage, and the Schwab & England ADL scale (S/E). The comorbidity of the nonmotor symptoms and their relationship to PD severity was analyzed. Thirty-six percent of the study population had depression (BDI > or =10), 33% had anxiety (BAI > or =10), 40% had fatigue (FSS > 4), 47% had sleep disturbance (PSQI > 5), and 63% reported sensory symptoms. Only 12% of the sample had no nonmotor symptoms. Fifty-nine percent of the patients had two or more nonmotor symptoms, and nearly 25% had four or more. Increased comorbidity was associated with greater PD severity (P < 001). This study reveals that the nonmotor symptoms of PD frequently occur together in the same patients. Increased comorbidity of the five nonmotor symptoms was associated with greater PD severity. These results suggest that recognition of these diverse nonmotor symptoms may be enhanced by looking for others when one nonmotor symptom has been identified.     

Sleep disorders and depression in patients with Parkinson''s disease

OBJECTIVES: Sleep disorders and depression are frequent in patients with Parkinson's disease (PD). However, the exact prevalence and the causality are still unknown. PATIENTS AND METHODS: We interviewed 56 consecutive PD patients and 59 age-matched healthy controls concerning sleep disorders and depression. Sleep Disorders Questionnaire (SDQ) and Zung Depression Scale (ZDS) were used as standardized valid and reliable psychometric tests. RESULTS: Patients with PD had significantly higher values in the clinical-diagnostic scale narcolepsy (P=0.01), correlating with the L-dopa dose (P=0.007). Concerning sleep apnea (P=0.49), psychiatric sleep disorder (P=1.00) and periodic limb movement disorder (P=0.12), no significant difference could be identified. PD patients showed significantly higher depression scores than healthy control subjects (P=0.01), increasing with the duration of PD (P=0.04). CONCLUSION: The significant higher narcolepsy score in PD patients must be seen due to dopaminergic medication and PD-specific neurodegeneration and immobility rather than due to narcolepsy. This leads to the conclusion that extreme caution is advised when carrying out the SDQ and interpreting the results in various persons and patient groups with motor problems. The strong association of depression, disease severity and sleep disorders in PD patients underlines the importance of identifying and treating both conditions in these patients.     

Long term role of pergolide as an adjunct therapy in Parkinson's disease: influence on disability, blood pressure, weight and levodopa syndrome

Pergolide is a dopamine agonist acting on D1 and D2 receptors and has been used as an adjunct therapy with levodopa. We have retrospectively investigated its role over a duration of upto six years in Parkinson's disease (PD) patients to study: (1) its influence on the progression of disability related to PD; (2) effect on blood pressure and weight during the treatment period; (3) whether the use of pergolide has a long term levodopa sparing effect; (4) and how is it tolerated during this period? We studied 43 patients who had been on adjunct therapy with pergolide in addition to levodopa for more than six months. Mean age was 66 years, mean duration of PD prior to adding pergolide was 8 years and final assessment was done after a mean duration of adjunct therapy of 29 (6-72) months. There was no progression of disease disability as assessed on Hoehn and Yahr stage (p=0.09) and Webster score (p=0.20), while there was an improvement in symptom score (p=0.001). There was an insignificant reduction in the dose of levodopa at final assessment from 630 to 535mg (p=0.06). A significant number of patients were able to discontinue taking selegiline (p=0.002). There was no change in the number of patients with hallucinations (p=0.15) and dyskinesia (p=0.09). There was a significant fall in weight (p=0.02), systolic (p=0.023) and diastolic blood pressure (p=0.03). This fall did not correlate with age, dose of pergolide or levodopa or disease severity but was influenced by duration of treatment. Ten patients discontinued pergolide for minor reasons after a mean duration of therapy for 23 months. We conclude that pergolide is a valuable adjunct therapy with levodopa over a duration of upto six years to maintain control of motor symptoms of Parkinson's disease.     

Effects of tolcapone, a catechol-O-methyltransferase inhibitor, on motor symptoms and pharmacokinetics of levodopa in patients with Parkinson's disease

Summary The effects of tolcapone, a catechol-O-methyltransferase inhibitor, on the bioavailability and efficacy of levodopa were evaluated in 12 patients with Parkinson's disease (PD), 8 of whom showed signs of daily motor fluctuations (wearing-off phenomenon). Motor disabilities were assessed in 12 patients at 7 time points before and after the chronic administration of tolcapone using the Unified Parkinson's Disease Rating Scale (UPDRS). The UPDRS score was improved at all points of determination. Eight patients with wearing-off phenomenon on levodopa showed symptomatic improvement on the combination. The area under the curve (AUC) for levodopa increased by 34% (p=0.0059) after the administration of tolcapone. The elimination half-life (T1/2) of levodopa was significantly prolonged by 81% (p=0.0001) after the treatment. The AUC of 3-O-methyldopa, a metabolite of levodopa, was decreased by 79% (p=0.0001) and the Cmax (maximum concentration) was also decreased by 80% after the administration (p=0.0001) of tolcapone. The combination of tolcapone and levodopa was well tolerated. Our findings suggest that tolcapone improves the pharmacokinetics of levodopa in plasma and motor symptoms of fluctuating PD patients. It is suggested that tolcapone may be a useful drug adjunct to levodopa in treating patients with PD with wearing-off phenomena.     

"Panic attacks" in Parkinson's disease

A series of 31 Parkinson's disease (PD) patients suffering from panic attacks (PA), late in the evolution of their disease, was analyzed from a group of 131 levodopa-treated PD patients. We found that many of motor, sensory, and vegetative symptoms, previously described as complicating phenomena in PD, constituted some of the symptoms of panic disorders. Comparing PA series with the series of PD patients who did not complain of PA, we discovered a clear-cut relationship of PA with the presence of standing/gait troubles (p<0.001), depression (p<0.001), and dyskinesias/fluctuations (p<0.001). The patients of the PA series also presented a more precocious age of PD onset, were put on levodopa therapy earlier, and needed to be treated with higher doses of levodopa than the patients without PA. Finally, we hypothesize that PA could be considered to be a sort of abstinence syndrome from levodopa, because they appears mostly (90.3%) in the OFF phase of fluctuations, and are relieved administering new doses of levodopa or dopaminergic agonists. Nevertheless, we suggest PA are not directly related to the pharmacological properties of levodopa, but to alterations of the noradrenergic systems in the CNS.