Moderate Parkinson's Disease Research Articles

Complaints about impairments in executive functions in Parkinson's disease: The association with neuropsychological assessment

Impairments in executive functions are frequently reported in Parkinson's disease (PD). However, little is known about patients' experience regarding these impairments. This knowledge is crucial because if patients do not experience their cognitive impairments they do not report them to their attending neurologist. Consequently, patients might not get appropriate treatment. This study investigated if patients with a mild to moderate PD experience impairments in executive functions in daily life and whether these correspond with impairments as measured in neuropsychological assessments.Forty-three PD patients and 25 healthy participants were included. Groups did not differ in age, sex and education. All participants and their closest relatives completed a standardized questionnaire measuring executive functions in daily life. Furthermore, all participants were assessed with a test battery measuring executive functions.PD patients reported significantly more problems with executive functions in daily life than healthy participants. Furthermore, co-morbid depression had a negative impact on the number of problems with executive functions in daily life as reported by PD patients. The experienced daily life problems in executive functions were not associated with the patients' performance on objective cognitive measures.In conclusion, PD patients were aware of problems with executive functions in daily life and reported considerably more problems than healthy controls. These problems were however not reflected by neuropsychological tests and may indicate a lack of ecological validity of neuropsychological assessment.

The Senior Fitness Test as a functional measure in Parkinson’s disease: A pilot study

ObjectiveThis pilot study aimed to determine if the Senior Fitness Test (SFT) battery can be applied to subjects with Parkinson’s disease (PD) and whether its results can be reliable indicators of disease severity. MethodsThirty people with mild to moderate PD performed the SFT and completed the Parkinson’s Disease Questionnaire (PDQ-39) and the Unified Parkinson’s Disease Rating Scale (UPDRS). To compare the metric properties of the SFT battery with the UPDRS and the PDQ-39, a SFT sum-score was created. ResultsThe tests that compose the SFT were successfully completed by the patients, except for the “Two-Minute Step Test” (2MST), which had to be shortened. We observed a strong correlation among the SFT’s sum-score and the total scores of the PDQ-39 and the UPDRS. Some correlation was also found among the SFT’s sum-score and the analyzed subscales, except for those assessing mental and cognitive levels. ConclusionThe SFT appears to be a useful tool to assess functional fitness in people with PD: it can be carried out in the clinical setting albeit with some minor modifications. However, its validity as an indicator of disease severity remains to be confirmed.

Treadmill training with music cueing: a new approach for Parkinson’s gait facilitation

Background: It has been pointed that cueing techniques may have influence upon gait training in Parkinson’s disease (PD). Objective: Study the effects of music cue on treadmill training in PD patients. Subject and methods: A randomized single-blind controlled trial was conducted. Thirty male PD patients, aged 60 to 80 years with Hoehn and Yahr stage 2-3 were allocated into three groups (each 10 patients). Group A: treadmill with music three days and home walking three days/week, Group B: treadmill three days and home walking three days/week, and Group C: home walking six days/week. Each group received four weeks training followed by selfpractice for other four weeks. Gait performances at pre-program, fourth, and eighth week were compared. Results: The results showed that A, B, and C, stride length gained 12%, 5.2%, and 6.7% (p=0.042), walking-speed gained 8.6%, 6.5%, and -2.4%, six-minute walk distance gained 10.2%, 5.4%, and 2.9%, and Timed Up and Go (TUG) gained 14.2%, 12.5%, and 7.6%. Conclusion: Music cue enhanced gait training in mild to moderate PD patients. Keywords: Cueing technique, music cue, Parkinson’s disease, treadmill training

The role of vision in Parkinson's disease locomotion control: Free walking task

The current study addressed the role of visual information in the control of locomotion in people with Parkinson's disease. Twelve healthy individuals and 12 mild to moderate Parkinson's disease patients were examined while walking at self-selected velocities, under three visual sampling conditions: dynamic (normal lighting), static (static visual samples) and voluntary visual sampling. Subjects wore liquid crystal glasses for visual manipulation. Outcome measures included spatial–temporal parameters, braking and propulsive impulses, number of samples and total duration of voluntary visual samples. Interaction between groups and visual conditions was not observed for kinematic parameters or braking and propulsive impulses. There were no significant differences between groups for voluntary visual sampling variables. These findings suggest that the visual control of locomotion in Parkinson's disease patients was similar to that observed in controls. Furthermore, Parkinson's disease patients were not more dependent on visual information than healthy individuals for the locomotion control.

Impaired economy of gait and decreased six-minute walk distance in Parkinson's disease.

Changes in the biomechanics of gait may alter the energy requirements of walking in Parkinson's Disease (PD). This study investigated economy of gait during submaximal treadmill walking in 79 subjects with mild to moderate PD and the relationship between gait economy and 6-minute walk distance (6 MW). Oxygen consumption (VO2) at the self-selected treadmill walking speed averaged 64% of peak oxygen consumption (VO2 peak). Submaximal VO2 levels exceeded 70% of VO2 peak in 30% of the subjects. Overall the mean submaximal VO2 was 51% higher than VO2 levels expected for the speed and grade consistent with severe impairment in economy of gait. There was an inverse relationship between economy of gait and 6MW (r = −0.31, P < 0.01) and with the self-selected walking speed (r = −0.35, P < 0.01). Thus, the impairment in economy of gait and decreased physiologic reserve result in routine walking being performed at a high percentage of VO2 peak.

Initial neuropsychological impairments in patients with the E46K mutation of the α-synuclein gene (PARK 1)

IntroductionIn 2004 we described the mutation E46K of the α-Synuclein (SNCA). These patients show Parkinson's disease with early cognitive impairment, sleep disorders and autonomic dysfunction. ObjectiveThe main objective is to identify early neuropsychological impairments in patients with the E46K mutation. MethodsThis is a longitudinal neuropsychological study of 4 of the 5 surviving patients with E46K mutation by semi-structured interviews and the following scales: Mattis Dementia Rating Scale (MDRS), semantic and phonemic verbal fluency tests (VFT), Benton Visual Retention Test (BVRT), Stroop Test (STROOP), Clock drawing test (CLOCK), WAIS III Letter and Number sequencing (WAIS III LN), Rey Auditory Verbal Learning Test (RAVLT) and Benton Judgement of Line Orientation Test (BJLOT). Motor status was assessed by UPDRS III. ResultsMotor status: Patients 1, 2 and 3 present mild to moderate Parkinson disease of 7, 8 and 3years of evolution respectively, patient 4 is asymptomatic.Cognitive status: Patient 2 and 3 both refer cognitive decline while patient 1 presents no cognitive complaints, however they all show a progressive cognitive decline across various tasks. Tests of frontal function showed the first alterations in all patients but fluctuate. The first cognitive complaints coincide with deterioration of tasks of posterior cortical basis. Patient 4 presents a normal performance on all tests. Patient 1, 2 and 3 have all presented visual hallucinations. ConclusionsA fluctuating frontal impairment is observed at early stages. Prominent visuospatial alterations and visual hallucinations suggest that posterior cortical dysfunction might be a distinct early feature of the cognitive impairment observed in patients with this mutation.

Postural Sway in Patients with Mild to Moderate Parkinson's Disease

ABSTRACTClinical assessment of postural instability in persons with Parkinson's disease (PD) is done with the retropulsive pull test, but since this test does not assess the underlying causes of postural instability, there is a need for additional assessment tools. The aim of this study was to identify postural sway parameters for use in a multifactorial approach to quantify postural instability. Nineteen adults diagnosed with idiopathic PD, 14 healthy age-matched controls (EH), and 10 healthy young adults (YH) completed the study. Postural parameters were extracted during quiet standing in eyes open (EO) and eyes closed (EC) conditions. Removing visual feedback affected the groups in a similar way. Significant differences between the PD and the two control groups were found in sway path length, area, and ranges in the anterior-posterior (AP) and medial-lateral (ML) directions and the Hurst exponents. PD significantly increased AP sway path length compared with YH and ML sway path length compared with EH. The Hurst exponents in PD were significantly different than in EH. The results suggest that the ML direction is a successful discriminator between PD and age-matched controls and that the interaction between ML and AP directions should be considered in the method used to quantify postural instability.

Reproducibility and Validity of Patient-Rated Assessment of Speech, Swallowing, and Saliva Control in Parkinson's Disease

Kalf JG, Borm GF, de Swart BJ, Bloem BR, Zwarts MJ, Munneke M. Reproducibility and validity of patient-rated assessment of speech, swallowing, and saliva control in Parkinson's disease. Objective To report on the development and psychometric evaluation of the Radboud Oral Motor Inventory for Parkinson's Disease (ROMP), a newly developed patient-rated assessment of speech, swallowing, and saliva control in patients with Parkinson's disease (PD). Design Reliability and validity study. Setting Tertiary-care Parkinson center for multidisciplinary assessment. Participants Consecutive community-dwelling patients with PD (n=129) or atypical parkinsonism (AP; n=49; mean ± SD age, 64±9.8y; mean ± SD disease duration, 7y; median Hoehn and Yahr [HY] stage, 2.5). Interventions Not applicable. Main Outcome Measures To evaluate reproducibility, 60 patients completed the ROMP twice within a mean of 24±12 days. To study validity, another cohort of 118 patients who had completed the ROMP was assessed by both a neurologist (HY stage, Unified Parkinson's Disease Rating Scale III) and speech-language pathologist (severity of dysarthria, dysphagia, drooling) who were blinded to ROMP scores. Results Confirmatory factor analysis identified the 3 a priori–designed ROMP domains of speech, swallowing, and saliva control. Internal consistency was .95 for the total ROMP and .87 to .94 for the 3 domains or subscales. Intraclass correlation coefficients for reproducibility were .94 and .83 to .92 for the subscales. Construct validity was substantial to good with correlations ranging from .36 to .82. The ROMP differentiated significantly ( P<.001) between patients indicated for speech therapy (based on independent assessment) and those who were not and between mild, moderate, and severe PD according to HY stage. Conclusions The ROMP provides a reliable and valid instrument to evaluate patient-perceived problems with speech, swallowing, and saliva control in patients with PD or AP.

Tongue control for swallowing in Parkinson's disease: Effects of age, rate, and stimulus consistency

Patients with Parkinson's disease often suffer from swallowing problems, especially at more advanced stages of the disease. Efficient swallows require well-coordinated tongue movements during bolus flow, but little is known about such movements in Parkinson's disease. The current study presents data on tongue movements for patients with mild to moderate Parkinson's disease (n=10), age-matched adults (n=13), and younger healthy adults (n=15). Participants with Parkinson's disease showed smaller and more variable movements in the horizontal movement plane, indicating that tongue movements are affected in early stages of Parkinson's disease. The small and more variable movements in the horizontal plane of Patients with Parkinson's disease may pose challenges for swallowing liquids efficiently and safely.

Postural preparation prior to stepping in patients with Parkinson's disease

People with Parkinson's disease (PD) frequently have difficulties with generating anticipatory postural adjustments (APAs) for forward propulsion and lateral weight transfer when initiating gait. This impairment has been attributed to deficits in motor planning and preparation. This study examined the preparation of APAs prior to an imperative cue to initiate forward stepping. A startling acoustic stimulus (SAS) was used to probe the state of preparation of the APA in eight PD (off medication) and seven matched control subjects. Subjects performed visually cued trials involving a pre-cue light instructing them to prepare to step, followed 3.5 s later by a go-cue light to rapidly initiate stepping. In random trials, a SAS (124 dB) was presented at -1,500, -1,000, -500, -250, -100, or 0 ms before the go-cue. Subjects also performed self-initiated steps. Ground reaction forces (GRFs), center of pressure (CoP) changes, and electromyographic (EMG) signals were recorded. The SAS triggered APAs in 94 ± 11% (PD) and 96 ± 8% (control) of trials at latencies 89 ± 4 ms (PD) and 97 ± 3 ms (control) earlier than Control trials. The temporal profile of APA preparation was similar between groups. However, peak EMG, GRF, and mediolateral CoP amplitudes were reduced in PD. SAS-evoked APAs at 0 ms matched Control trial APAs and were enhanced compared with self-initiated stepping. These results demonstrate that people with mild to moderate PD can plan and prepare the appropriate APA sequence prior to the expected cue to initiate gait; however, the prepared APAs are underscaled in magnitude.

Oro‐buccal symptoms (dysphagia, dysarthria, and sialorrhea) in patients with Parkinson’s disease: preliminary analysis from the French COPARK cohort

Abnormal oro-buccal functions including dysarthria, sialorrhea and dysphagia commonly affect patients with Parkinson's disease (PD). To estimate the prevalence of such oro-buccal symptoms at baseline in the first 419 patients with PD included in the COPARK cohort and to analyze their correlations with patients' demographics, clinical characteristics, and drugs consumption. Patients were assessed using the Unified PD Rating Scale, the Hospital Anxiety and Depression Scale, and the PDQ-39. Dysarthria, sialorrhea, and dysphagia were defined as UPDRS items 5, 6, or 7 ≥ 1. Dysarthria, sialorrhea, or dysphagia were present in 51%, 37%, or 18% out of the 419 patients, respectively. At least one of these symptom was present in 267/419 patients (65%), whilst a combination of symptoms was present in 136/419 (33%). Logistic regression showed that the presence of each of the three oro-buccal symptoms was significantly correlated with that of the two others. Other correlations included male gender, hallucinations, disease severity, levodopa use and lack of opiates consumption for dysarthria; disease severity, orthostatic hypotension and absence of antidepressants consumption for sialorrhea; female gender, motor fluctuations, and depressive symptoms for dysphagia. None of the three oro-buccal symptoms were associated with a reduced PDQ-39 score. Oro-buccal symptoms were present in two of three patients with moderate PD, the presence of each symptoms being significantly correlated with that of the two others.

Intermittent theta-burst transcranial magnetic stimulation for treatment of Parkinson disease

To investigate the safety and efficacy of intermittent theta-burst stimulation (iTBS) in the treatment of motor symptoms in Parkinson disease (PD). Progression of PD is characterized by the emergence of motor deficits, which eventually respond less to dopaminergic therapy and pose a therapeutic challenge. Repetitive transcranial magnetic stimulation (rTMS) has shown promising results in improving gait, a major cause of disability, and may provide a therapeutic alternative. iTBS is a novel type of rTMS that may be more efficacious than conventional rTMS. In this randomized, double-blind, sham-controlled study, we investigated safety and efficacy of iTBS of the motor and dorsolateral prefrontal cortices in 8 sessions over 2 weeks (evidence Class I). Assessment of safety and clinical efficacy over a 1-month period included timed tests of gait and bradykinesia, Unified Parkinson's Disease Rating Scale (UPDRS), and additional clinical, neuropsychological, and neurophysiologic measures. We investigated 26 patients with mild to moderate PD: 13 received iTBS and 13 sham stimulation. We found beneficial effects of iTBS on mood, but no improvement of gait, bradykinesia, UPDRS, and other measures. EEG/EMG monitoring recorded no pathologic increase of cortical excitability or epileptic activity. Few reported discomfort or pain and one experienced tinnitus during real stimulation. iTBS of the motor and prefrontal cortices appears safe and improves mood, but failed to improve motor performance and functional status in PD. This study provides Class I evidence that iTBS was not effective for gait, upper extremity bradykinesia, or other motor symptoms in PD.

Are the basal ganglia critical in producing redundancy gain effects on simple sensorimotor responses? An investigation on the effects of Parkinson's disease

Redundancy gain (RG) is a well-known effect in the experimental psychology literature which is thought to reflect integration of sensory information. RG is a facilitation in speed of responding on a detection task when two stimuli are presented at once compared to when one stimulus is presented alone. Even though sensorimotor tasks involving integration of sensory information form the basis of a large repertoire of human skilled actions, the neural basis of reliable effects such as RG remains elusive. The present study examines whether the integrity of the basal ganglia system is likely to be critical for RG effects to occur. Based on a thorough analysis of performance on a standard paradigm of RG (and on the related paradigm of crossed-uncrossed differences: CUDs) in patients with mild to moderate Parkinson's disease and matched controls, we found virtually no differences between groups. We conclude that normal RG and CUD effects are not likely to rely critically on the BG.

Significant improvement of motor symptoms by deep brain stimulation of bilateral subthalamic nucleus in patients with moderate or advanced Parkinson's disease

To study the effects of deep brain stimulation (DBS) of bilateral subthalamic nucleus (STN) on the motor and non-motor symptoms in moderate or advanced Parkinson's disease (PD) patients. From August 2006 to January 2010, 21 consecutive PD patients with refractory motor fluctuations or dyskinesia underwent operations at our hospital. All patients were evaluated by unified Parkinson's disease rating scale (UPDRS), Hoehn & Yahr (H&Y) stage, Parkinson's disease questionnaire (PDQ-39), mini mental state examination (MMSE), Parkinson's disease sleep scale-Chinese vision (PDSS-CV), Pittsburgh sleep quality index (PSQI), Hamilton depression rating scale (HAMD) and Hamilton anxiety rating scale (HAMA). And the daily dosage of dopaminergic agents was recorded at 1 week pre-operation and 3, 6 and 12 months post-operation. Ten patients finished a 12-month follow-up. Their motor functions showed significant improvement. And the scores of UPDRS-motor, tremor, rigidity, bradykinesia and axial symptoms reduced significantly in the on-stimulation-off-medication condition and the on-stimulation-on-medication condition vs the on-medication condition pre-operation. And the improvement of tremor was the most pronounced (52.1% and 77.7% respectively). The H&Y stage decreased significantly from 3.2 ± 0.7 to 2.5 ± 0.4 post-operation. The activities of daily living improved while PDQ-39 declined significantly from 56 ± 9 pre-operation to 32 ± 13 at 12 months follow-up. The score changes of MMSE, PDSS-CV, PSQI, HAMA and HAMD were statistically insignificant. The levo-dopa equivalent dose of 1-year post-operation decreased significantly by 49.2% versus that of pre-operation (P < 0.05). Bilateral STN-DBS can significant ameliorate the motor symptoms of moderate or advanced PD patients, reduce the dosage of anti-PD medications and improve the quality of life. This procedure has the advantages of a greater safety, minor side effects and an easy controllability.

The Effects of Tai Chi Based Exercise on Dynamic Postural Control of Parkinson's Disease Patients while Initiating Gait

[Purpose] The purpose of this study was to investigate the effects of Tai Chi (TC) based exercise on dynamic postural control when people with mild or moderate Parkinson's disease (PD) initiate gait. [Subjects] Ten people with PD, who ranged in age from 70 to 84 years, volunteered to participate in a 12-week intervention of TC exercise. [Methods] Participants with PD were tested pre- and post-intervention in a task in which they were instructed to initiate gait from the position of quiet stance. Participants with PD were trained with TC exercise that emphasizes a shift in weight bearing from bilateral to unilateral support, challenging postural stability, three times per week over a period of 12 weeks. Differences between pre- and post-test in COP displacement in the anteroposterior (A-P) and mediolateral (M-L) directions were assessed using two force plates. [Results] After practicing the TC exercise, participants with PD significantly increased A-P and M-L displacement of the COP. [Conclusion] TC exercise increased COP displacement in the A-P and M-L directions, thereby improving participants' ability to generate momentum to initiate gait and maintain lateral stability. The findings of this study support the use of TC exercise as an effective and safe rehabilitation strategy for some individuals with PD.

Impact of external cue validity on driving performance in Parkinson's disease.

This study sought to investigate the impact of external cue validity on simulated driving performance in 19 Parkinson's disease (PD) patients and 19 healthy age-matched controls. Braking points and distance between deceleration point and braking point were analysed for red traffic signals preceded either by Valid Cues (correctly predicting signal), Invalid Cues (incorrectly predicting signal), and No Cues. Results showed that PD drivers braked significantly later and travelled significantly further between deceleration and braking points compared with controls for Invalid and No-Cue conditions. No significant group differences were observed for driving performance in response to Valid Cues. The benefit of Valid Cues relative to Invalid Cues and No Cues was significantly greater for PD drivers compared with controls. Trail Making Test (B-A) scores correlated with driving performance for PDs only. These results highlight the importance of external cues and higher cognitive functioning for driving performance in mild to moderate PD.

Axial rigidity and quality of life in patients with Parkinson’s disease: a preliminary study

Rigidity is a cardinal symptom of Parkinson's disease (PD) and is often clinically assessed by passively flexing and extending a patient's limb. Objective measurements had been employed to examine rigidity in PD subjects, including wrist, elbow, knee and trunk. This study aimed to investigate the relationship between an objective measurement of trunk rigidity and health-related quality of life (HRQoL) and functional status in patients with mild to moderate PD. An isokinetic dynamometer Biodex System 3 was employed to assess trunk rigidity in 36 PD patients. HRQoL was assessed with the EuroQol-5D and Parkinson's Disease Questionnaire-39 items (PDQ-39). Functional status was measured with the Schwab and England scale. Trunk rigidity was correlated with the HRQoL assessed with the mobility, cognition and stigma PDQ-39 domains and the total PDQ-39 scores. No correlations were found among trunk muscle tone assessed with the isokinetic dynamometer and the EuroQoL-5D. Functional status was correlated with the trunk extensors rigidity at all angular velocities. The results from this study suggest that the axial motor impairments impact on QoL and functional status in patients with PD. Further studies are needed with quantitative devices for axial rigidity assessment to determine the relationship between trunk rigidity in PD patients with higher disease severity and HRQoL scales.

Involvement of the cerebellothalamocortical pathway in Parkinson disease

Lesioning or stimulation of the cerebellar thalamus is an established treatment for rest and postural tremors in Parkinson disease (PD). The cerebellothalamocortical (CTC) pathway can be assessed by transcranial magnetic stimulation (TMS) of the cerebellum, which suppresses the contralateral primary motor cortex (M1), a phenomenon termed cerebellar inhibition (CBI). Tremor reset can be used to assess whether the stimulated brain area is involved in the generation or transmission of tremor. We tested whether M1 or cerebellar stimulation can reset PD tremor, and investigated the excitability of the CTC pathway in PD. Ten mild to moderate PD patients in the OFF medication state and 10 healthy controls were studied. Tremor reset was tested with TMS delivered to the cerebellum or M1. CBI was assessed by cerebellar stimulation followed by M1 stimulation at interstimulus intervals of 3 to 8 milliseconds. Subjects were tested both at rest and during arm extension. Rest tremor in PD was reset by M1 stimulation but not by cerebellar stimulation. Postural tremor was reset by both types of stimulation. At rest, CBI was reduced in PD patients compared to controls. Arm extension decreased CBI in controls and turned the inhibition into facilitation in patients. CBI correlated with the degree of tremor reset caused by the cerebellar stimulation. The excitability of CTC pathway is decreased in PD. Rest and postural tremors in PD are mediated by different neuronal pathways, and the CTC pathway is involved in the generation or transmission of postural tremor.

Linguistic complexity, speech production, and comprehension in Parkinson's disease: behavioral and physiological indices.

To investigate the effects of increased syntactic complexity and utterance length demands on speech production and comprehension in individuals with Parkinson's disease (PD) using behavioral and physiological measures. Speech response latency, interarticulatory coordinative consistency, accuracy of speech production, and response latency and accuracy on a receptive language task were analyzed in 16 individuals with PD and 16 matched control participants. Individuals with PD had higher oral motor coordination variability, took a longer time to initiate speech, and made more errors on the speaking task compared with the control group. They also received lower scores on the 2 complex conditions of the receptive language task. Increased length and syntactic complexity negatively affected performance in both groups of speakers. These findings provide a novel window into the speech deficits associated with PD by examining performance on longer, sentence-level utterances in contrast to earlier investigations of single-word or nonword productions. Speech motor control processes and language comprehension were adversely affected in the majority of our participants with mild to moderate PD compared to the control group. Finally, increased syntactic complexity and sentence length affected both the healthy aging and PD groups' speech production performance at the behavioral and kinematic levels.

Step Activity in Persons With Parkinson’s Disease

UPDRS and PDQ-39 are reliable and valid assessments of quality of life and physical function in persons with Parkinson's disease (PD). However, these measures were not designed to track day-to-day or week-to-week changes in community activity in persons with PD. Twelve individuals with PD (stage 1 to 3, Hoehn and Yahr) who were active members of a health and wellness facility were recruited for this study. Investigators collected health history information, asked questions about the amount and frequency of weekly exercise, and assessed motor symptoms and ADL skills using the UPDRS, and provided participants with Step Activity Monitor (SAM). SAM data were collected for a continuous 7-day period. Participants averaged 8996 steps/day, had an average of 322 minutes of step activity per day, but were inactive (minIA) 77% of their time per day. On the days that participants visited the health and wellness facility they took an average of 802 more steps with 12 minutes more activity per day. A SAM can be used to capture activity levels in persons with PD. These pilot data indicate that persons with mild to moderate PD can achieve step activity levels similar to healthy older adults.