Sleep in Parkinson's disease: A comparison of actigraphy and subjective measures

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. Thirty non-demented individuals with PD and 14 normal control participants (NC) were included. Sleep was measured using 24-h 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.     

A comparison of clinical and objective measures of freezing of gait in Parkinson's disease

Freezing of gait, a paroxysmal motor block, is common in the latter stages of Parkinson's disease. The current 'gold standard' of assessing the severity of freezing is based on clinical identification (by up to 3 raters) of the number of episodes from video. The aims of this study were to systematically assess this 'gold standard' across multiple Parkinson's disease centers, and to compare these clinical ratings with objective measures derived from lower limb acceleration data. Video recordings were acquired during a timed up-and-go task from 10 Parkinson's disease patients (with a clinical history of freezing) in the 'off' state. Patients were instrumented with accelerometers on the lateral aspect of each shank. Ten experienced clinicians were recruited from four Parkinson's disease centers to independently assess the videos for number and duration of freezing events. The reliability of clinical video assessment for number of freezing events was moderate (intraclass correlation coefficient 0.63). Percent time frozen (cumulative duration of freezing episodes/total duration of the walking task) demonstrated stronger agreement between raters (0.73). Agreement of accelerometry-derived measures of freezing severity with mean clinician ratings was strong for number of episodes (0.78) and very strong for percent time frozen (0.93). The results demonstrate the viability of objective measures of freezing, and that percent time frozen is a more reliable metric of severity than number of freezing events for both clinical and objective measures. The large variability between clinicians suggests that caution should be used when comparing subjective ratings across centers.     

Sleep and fatigue in Parkinson's disease

Sleep disorders and fatigue are common problems in Parkinson's disease (PD). Although they frequently appear together, they are often distinct symptoms that must be understood separately. Fatigue has been reported to be the most bothersome aspect of PD in about one-third of patients, yet it is poorly understood and not clearly treatable. Sleep disorders, while more common, are less bothersome to the patients and often responsive to therapy. An overview of sleep disorders in PD and an approach to therapy will also be outlined. The little that is known about fatigue in PD will be reviewed.     

Exacerbated physical fatigue and mental fatigue in Parkinson's disease.

OBJECTIVE: To characterize fatigue in Parkinson's disease (PD). BACKGROUND: Fatigue is a recognized problem in PD. Fatigue can be in the physical realm or in the mental realm. Fatigue has not been characterized in PD. METHODS: We characterized fatigue in 39 PD patients and 32 age-matched normal controls using five questionnaires: A. The Multidimensional Fatigue Inventory (MFI), which measures five dimensions of fatigue independently including general fatigue, physical fatigue, reduced motivation, reduced activity, and mental fatigue. B. The Fatigue Severity Inventory (FSI), which quantifies fatigue in general. C. The Profile of Mood States (POMS), which assesses six subjective subscales: tension-anxiety, depression-dejection, anger-hostility, fatigue-inertia, vigor-activity, and confusion-bewilderment. D. Center for Epidemiological Studies-Depression Scale (CES-D). E. Visual Analog linear scale of energy (VA-E). RESULTS: PD patients scored higher in all of the five dimensions of fatigue in the MFI including general fatigue, physical fatigue, reduced motivation, reduced activity, and mental fatigue (P < 0.001 except for mental fatigue P = 0.005). The severity of physical fatigue did not correlate with that of mental fatigue. PD patients scored higher on the FSI, POMS, CES-D, and scored lower on the VA-E. The scores in the FSI correlated with general fatigue, physical fatigue, reduced activity, and reduced motivation but not with mental fatigue in the MFI. Depression correlated with all dimensions of fatigue except physical fatigue in the MFI. Disease severity, as measured by Modified Hoehn and Yahr staging, did not correlate with any of the measures. CONCLUSIONS: PD patients have increased physical fatigue and mental fatigue compared to normals. Physical fatigue and mental fatigue are independent symptoms in PD that need to be assessed and treated separately.     

Speech-related fatigue and fatigability in Parkinson's disease

This study tested the assumption that speech is more susceptible to fatigue than normal in persons with dysarthria. After 1?h of speech-like exercises, participants with Parkinson's disease (PD) were expected to report increased perceptions of fatigue and demonstrate fatigability by producing less precise speech with corresponding acoustic changes compared to neurologically normal participants. Twelve adults with idiopathic PD and 13 neurologically normal adults produced sentences with multiple lingual targets before and after six 10-min blocks of fast syllable or word productions. Both groups reported increasing self-perceived fatigue over time, but trained listeners failed to detect systematic differences in articulatory precision or speech naturalness between sentences produced before and after speech-related exercises. Similarly, few systematic acoustic differences occurred. These findings do not support the hypothesis that dysarthric speakers are particularly susceptible to speech-related fatigue; instead, speech articulation generally appears to be resistant to fatigue induced by an hour of moderate functional exercises.     

A comparative study of physical performance measures in Parkinson's disease

The objective of this study is to compare physical performance measures for their ability to discriminate between levels of disability and disease severity in Parkinson's disease (PD). Disability in PD is commonly assessed by patient self‐report, which may be limited by patient insight. Methods: Seventy‐nine patients with PD were tested with seven performance measures: Physical Performance Test (PPT), modified Physical Performance Test (mPPT), Short Physical Performance Battery (SPPB), Performance Test of Activities of Daily Living (PADL), Berg Balance Scale (BBS), Timed Up and Go (TUG), and Functional Reach (FR). These measures were compared with patient‐reported disability on the Older Americans Resource and Services Disability subscale (OARS) and disease severity on the Unified Parkinson's Disease Rating Scale (UPDRS). The performance measures were more sensitive to levels of disease severity than disability. Four measures discriminated across quartiles of disability (PPT, mPPT, BBS, TUG: P < 0.05), whereas all seven measures discriminated across quartiles of the Total UPDRS (PPT, mPPT, BBS, TUG, FR: P < 0.01; SPPB, PADL: P < 0.05). However, no measure consistently discriminated between subgroups with a range of early and advanced disease severity. The seven physical performance measures showed different profiles of strengths and weaknesses in assessing disability and disease severity. The results of this study will facilitate choosing performance measures for clinical care and clinical trials in PD. © 2008 Movement Disorder Society     

Clinical measures of progression in Parkinson's disease

Despite all recent advances in symptomatic therapy Parkinson's disease (PD) continues to be a relentlessly progressive neurodegenerative disorder. Therefore therapies that will slow or hold disease progression are a major medical unmet need in PD. Clinical measures of disease progression that have been used in disease modification trials so far have focused on indices of progression of cardinal motor features like bradykinesia, rigidity, and tremor as captured by the UPDRS and the emerging need for effective dopaminergic symptomatic therapy. Progression of global disability in PD, however, is driven by additional factors beyond progressive nigrostriatal denervation leading to increasing severity of cardinal motor features. Progressive pathology in extranigral sites in the brain or peripheral autonomic nervous system contribute to poorly levodopa responsive motor symptoms like postural instability, freezing and falls or nonmotor symptoms. In addition treatment‐induced motor complications also impact on PD disability. Although it is widely accepted that clinical progression of PD is multidimensional and in addition includes effects of aging, there is no consensus how to best implement more clinically meaningful endpoints for disease progression trials that would reflect these complex interactions impacting on the evolution of global disability in PD. There is an urgent need for biomarkers for disease progression that would faithfully reflect advancing neurodegeneration and resulted clinical disability in PD and that could be used in shorter term clinical trials testing putative disease modifying agents. © 2009 Movement Disorder Society     

Pathophysiology of pain and fatigue in Parkinson's disease

In Parkinson's disease (PD), nigral degeneration determines an altered neuronal ouput from the subthalamic nucleus and globus pallidus, and as a consequence functional changes in the motor circuits linking basal ganglia to the motor cortical areas. Movement slowness, rigidity and tremor are among the principal motor symptoms of PD. Studies of movement execution have shown that PD patients have difficulty in performing simultaneous and sequential movements. In executing sequential movements the abnormalities of PD patients worsen as the sequence progresses. This phenomenon, called sequential effect, may be one of the mechanisms underlying the fatigue of PD patients. Cortical deafferentation is thought to be responsible for the motor disturbances of PD and studies using transcranial magnetic stimulation showed that in PD patients there are abnormalities in cortical plasticity and in cortical connectivity. Sensorimotor integration refers to the processes that link sensory input to motor output to produce appropriate voluntary movements. Sensory information is important for motor preparation and execution in parkinsonian patients, and PD patients have greater difficulty in performing movements when no external cues are provided. Investigating the role of sensory information, several studies provided evidence that PD patients have numerous somatosensory deficits, including tactile temporal discrimination threshold. Neurophysiological testing in PD has also found altered central somatosensory processing. Finally PD patients may experience painful sensations after the onset of the disease and various evidence suggests an abnormal nociceptive input processing in the central nervous system that might predispose PD patients to developing pain.     

Clinical management of pain and fatigue in Parkinson's disease

Pain and fatigue are part of the phenomenological spectrum of Parkinson's disease (PD). These non-motor symptoms can be as troublesome as motor symptoms, impact activities of daily living, and are often underdiagnosed. The recognition of pain and fatigue requires a high degree of clinical suspicion and is facilitated by the use of specific questionnaires and ancillary tests. This workup is highly valuable particularly considering that pain and fatigue in PD may be treatable. We review here the clinical manifestations and management of these non-motor symptoms. Their resolution can be challenging, as there is insufficient evidence concerning effective treatment options.     

A comparison of cerebral glucose metabolism in Parkinson's disease, Parkinson's disease dementia and dementia with Lewy bodies

Parkinson's disease dementia (PDD) and dementia with Lewy bodies (DLB) share many similar aspects, and making a clinical diagnosis of one disorder over the other relies heavily on an arbitrary criterion, so-called 1-year rule. This study was designed to search for any difference of metabolic patterns in these two disorders using F-18 fluorodeoxyglucose (FDG) positron emission tomography (PET) images.
We enrolled 16 patients with PD, 13 patients with PDD, and seven patients with DLB. FDG PET was performed, and images were reconstructed by iterative reconstruction using the computed tomography (CT) images, and were normalized to a standard template. Statistical comparison between groups were performed on a voxel-by-voxel basis using t -statistics (two-sample t -test).
Compared with the patients with PD, both PDD and DLB patients showed similar patterns of decreased metabolism in bilateral inferior and medial frontal lobes, and right parietal lobe ( P _uncorrected < 0.001). In a direct comparison, DLB patients had significant metabolic decrease ( p _uncorrected < 0.005) in the anterior cingulate compared with those with PDD. These findings support the concept that PDD and DLB have similar underlying neurobiological characteristics, and that they can be regarded as a spectrum of Lewy body disorders.     

A comparison of dopamine agonists and catechol-O-methyltransferase inhibitors in Parkinson's disease

To compare the efficacy and tolerability of three dopamine agonists--pergolide (PRG), pramipexole (PRX), and ropinirole (ROP)-and two catechol-O-methyltranferase (COMT) inhibitors-tolcapone (TOL) and entacapone (ENT)-as add-on therapies to levodopa (L-Dopa) in Parkinson's disease, we analyzed randomized, double-blind, placebo-controlled, multicenter studies. To our knowledge, they had not yet been evaluated in comparison with each other. Statistical analyses used odds ratios, numbers needed to harm, and Fisher's inverse chi2 method. Seven studies meeting the inclusion criteria included treatment of 1,756 patients. The common efficacy measures were the reduction of L-Dopa dose and "off' duration. The reported reduction in L-Dopa dose was significant for all drugs in relation to placebo, but was most significant for PRX and ENT (p < 0.0001). The most significant reduction in "off' duration was with PRG, PRX, and ENT (p < 0.001). The common tolerability measures were the percentage of patients withdrawn because of side effects, because of any reason, and because of the development of dyskinesias. Ropinirole, PRX, and ENT caused fewer withdrawals related to side effects. Pergolide was better than other analyzed drugs concerning withdrawals for any reason. All drugs caused more dyskinesias than placebo (p < 0.0001), with overlapping confidence intervals, except for TOL 600 mg, which caused more dyskinesias than dopamine agonists and ENT. Pramipexole and ENT had the best efficacy and tolerability profile in this analysis.     

Sensitive measures of executive dysfunction in non-demented Parkinson's disease

BackgroundWe examined the sensitivity of different executive function measures for detecting deficits in Parkinson's disease patients without dementia.MethodsTwenty-one non-demented PD subjects and 21 neurologically healthy controls were administered widely used clinical executive functioning measures as well as the NIH EXAMINER battery, which produces Cognitive Control, Working Memory, and Verbal Fluency scores, along with an overall Executive Composite score, using psychometrically matched scales.ResultsNo significant differences between groups were observed on widely used clinical measures. The PD patients scored lower than controls on the EXAMINER Executive Composite, Cognitive Control, and Working Memory Scores.ConclusionsThe NIH EXAMINER Executive Composite and Cognitive Control Scores are sensitive measures of executive dysfunction in non-demented PD, and may be more sensitive than several widely used measures. Results highlight the importance of careful test selection when evaluating for mild cognitive impairment in PD.     

The modified bradykinesia rating scale for Parkinson's disease: Reliability and comparison with kinematic measures

Bradykinesia encompasses slowness, decreased movement amplitude, and dysrhythmia. Unified Parkinson's Disease Rating Scale–based bradykinesia‐related items require that clinicians condense abnormalities in speed, amplitude, fatiguing, hesitations, and arrests into a single score. The objective of this study was to evaluate the reliability of a modified bradykinesia rating scale, which separately assesses speed, amplitude, and rhythm and its correlation with kinematic measures from motion sensors. Fifty patients with Parkinson's disease performed Unified Parkinson's Disease Rating Scale–directed finger tapping, hand grasping, and pronation–supination while wearing motion sensors. Videos were rated blindly and independently by 4 clinicians. The modified bradykinesia rating scale and Unified Parkinson's Disease Rating Scale demonstrated similar inter‐ and intrarater reliability. Raters placed greater weight on amplitude than on speed or rhythm when assigning a Unified Parkinson's Disease Rating Scale score. Modified bradykinesia rating scale scores for speed, amplitude, and rhythm correlated highly with quantitative kinematic variables. The modified bradykinesia rating scale separately captures bradykinesia components with interrater and intrarater reliability similar to that of the Unified Parkinson's Disease Rating Scale. Kinematic sensors can accurately quantify speed, amplitude, and rhythm to aid in the development and evaluation of novel therapies in Parkinson's disease. © 2011 Movement Disorder Society     

Sleep, excessive daytime sleepiness and fatigue in Parkinson's disease

Summary The objective of this questionnaire-based survey was to evaluate the prevalence and causes of sleep disturbances in 90 nondepressive patients with Parkinson's disease (PD) and 71 age-matched healthy subjects. We also assessed the prevalence and characteristics of excessive daytime sleepiness (both groups) and excessive fatigue (PD patients).A high prevalence of sleep disturbances in PD patients was found; this is to a large extent probably the result of aging. As compared with controls, patients had a more severely disturbed sleep maintenance because of nycturia, pain, stiffness, and problems with turning in bed. The prevalence of excessive dreaming is similar in both groups, but altered dream experiences almost exclusively occurred in PD.Patients rated themselves more often to be morning-types than controls. This finding may account for the reported adaptation effects in experimental settings and the reduced REM latency in PD patients.The prevalence of daytime sleepiness was similar in both groups. Excessive daytime sleepiness showed a clear diurnal pattern with a peak in the early afternoon. As for excessive fatigue, the majority of the patients did not report a preferential time for this symptom. Our findings further argue against an association of fatigue with any circadian factor, and instead suggest a relationship with the motor deficits of PD.     

Fatigue in Japanese patients with Parkinson's disease: A study using Parkinson fatigue scale

The objective of this multicenter cross‐sectional study was to determine the prevalence of fatigue and factors contributing to it in a large sample of Japanese patients with Parkinson's disease (PD). We used the 16‐item Parkinson Fatigue Scale (PFS‐16), which was designed to assess fatigue exclusively associated with PD. We carried out this study using PFS‐16, the Unified Parkinson's Disease Rating Scale, Zung's Self‐Rating Depression Scale, Parkinson's Disease Sleep Scale (PDSS), and the PD quality of life (QOL) scale (PDQ‐39) by interview using questionnaires and physical examination by neurologists in 361 nondemented PD patients. Fatigue (an average PFS score of 3.3 or greater) was revealed in 151 patients (41.8%). Multiple logistic regression analysis indicated that the significant independent variables related to the presence of fatigue were the scores of PDSS and PDQ‐39. Depression score was not a significant contributing factor. Our study revealed that the prevalence of fatigue in Japanese PD patients is as high as that in Western countries, and that fatigue is a relatively independent symptom, although sleep disturbance may be associated with fatigue. Since fatigue is significantly related to QOL reduction, therapeutic interventions including treatment of sleep disturbance are important. © 2009 Movement Disorder Society     

A comparison of treatment thresholds in two large Parkinson's disease clinical trial cohorts

Deprenyl and Tocopherol Antioxidative Therapy of Parkinsonism (DATATOP) and Parkinson Research Examination of CEP‐1347 Trial (PRECEPT) were two clinical trials of potential disease‐modifying agents for Parkinson's disease that used the time to reaching disability sufficient to require dopaminergic therapy as the primary endpoint. To compare the thresholds for initiating dopaminergic treatment for Parkinson's disease between the two studies, conducted fifteen years apart. Baseline and 12‐month endpoint characteristics for subjects in the placebo arms of the two studies were compared. DATATOP placebo subjects had slightly higher total Unified Parkinson's Disease Rating Scale (UPDRS) scores at baseline than PRECEPT placebo subjects (26.1 vs. 23.6, P = 0.03). Time to endpoint was not significantly different. Mean total UPDRS scores at endpoint among those subjects reaching endpoint by 12 months were 48.4 in DATATOP and 37.5 in PRECEPT (P < 0.0001). Baseline disease severity and time to disability requiring dopaminergic therapy were similar in the DATATOP and PRECEPT trials. The threshold for starting dopaminergic treatment was lower in PRECEPT than in the earlier DATATOP study. This may relate to changes in philosophies with respect to starting treatment for Parkinson's disease, but the factors underlying this change remain to be elucidated. © 2009 Movement Disorder Society