The relationship between contrast sensitivity, gait, and reading speed in Parkinson's disease

Parkinson's disease (PD) results in reduced walking speed and visual difficulties, including difficulty reading (Davidsdottir, Cronin-Golomb, & Lee, 2005). PD is characterized by a reduction in dopamine, which is instrumental in determining a person's contrast sensitivity (CS). This study assessed the relationship between CS, gait (step length and walking speed), and reading speed in 18 non-demented PD volunteers with normal acuity. We found that CS correlated with walking speed (r = .57, p = .01), step length (r = .53, p = .02), and reading speed (r = .54, p = .02). Visual acuity (which has not been tied to dopamine in the same way) correlated with reading speed (r(s) = -.65, p = .004), but not with gait measures. We also assessed the contribution of age, education, and cognitive status (Shipley Institute of Living Scale) to these variables. We conclude that CS and age both play an important role in determining gait in PD, while reading speed is related to both acuity and CS, but not age.     

Treadmill gait analysis does not detect motor deficits in animal models of Parkinson's disease or amyotrophic lateral sclerosis

Computerized treadmill gait analysis in models of toxicant exposure and neurodegenerative disorders holds much potential for detection and therapeutic intervention in these models, and researchers must validate the technology that assists in that data collection and analysis. The present authors used a commercially available computerized gait analysis system that used (a) a motorized treadmill on retired breeder male C57BL/6J mice, (b) the toxicant-induced (1-methyl-1-, 2-, 3-, 6-tetrahydropyridine) MPTP mouse model of Parkinson's disease (PD), and (c) the superoxide dismutase 1 (SOD1) G93A transgenic mouse model of amyotrophic lateral sclerosis (ALS). The authors compared the detection of deficits by computerized treadmill gait analysis in MPTP-treated mice with inked-paw stride length and correlated these measures to dopamine (DA) loss. The authors found that the computerized treadmill gait analysis system did not distinguish MPTP-treated mice from vehicle controls, despite a nearly 90% deficit of striatal DA. In contrast, decreases in inked-paw stride length correlated strongly with DA losses in these same animals. Computerized treadmill gait analysis could neither reliably distinguish SOD1 G93A mutant mice from controls from 6 to 12 weeks of age nor detect any consistent early motor deficits in these mice. On the basis of the authors' findings, they inferred that computerized gait analysis on a motorized treadmill is not suited to measuring motor deficits in either the MPTP mouse model of PD or the SOD1 G93A mouse model of ALS.     

Everyday tasks impair spatiotemporal variables of gait in older adults with Parkinson's disease

IntroductionAlthough it is known that individuals with Parkinson's disease (PD) have difficulties performing dual-task activities, most of the studies have verified the effect of dual tasks on gait using tasks that are uncommon to perform while walking. However, the realization of tasks involving gait that really represents the daily activities carried out by the participants, allow us to detect real fall risk situations of individuals with PD during their gait.ObjectiveOur aim was to verify the influence of daily-life dual-tasks on gait spatiotemporal variables of the older adults with PD.Methods20 older adults without PD and 20 older adults with PD participated in the study. Gait kinematic was analyzed under three different conditions: walking without dual task, walking carrying bags with weight, and walking talking on the cell phone.ResultsOlder adults with PD presented lower speed (p = .001), cadence (p = .039), and shorter step length (p = .028) than older adults without PD during walking without dual tasks. When walking while carrying bags with weight, older adults with PD had a lower speed (p < .001), cadence (p = .015), shorter step length (p = .008), and greater double support time (p = .021) compared with older adults without PD. During walking while talking on the cell phone, older adults with PD walked with lower speed (p < .001), cadence (p = .013), shorter step length (p = .001) and swing time (p = .013), and increased double support time (p = .008) and support time (p = .014) in relation to older adults without PD.ConclusionDaily-life dual tasks impair the spatiotemporal variables of gait in the older adults with PD, which was most evident during walking talking on the cell phone.     

Investigation of factors impacting mobility and gait in Parkinson disease

Mobility and gait limitations are major issues for people with Parkinson disease (PD). Identification of factors that contribute to these impairments may inform treatment and intervention strategies. In this study we investigated factors that predict mobility and gait impairment in PD. Participants with mild to moderate PD and without dementia (n = 114) were tested in one session ‘off’ medication. Mobility measures included the 6-Minute Walk test and Timed-Up-and-Go. Gait velocity was collected in four conditions: forward preferred speed, forward dual task, forward fast as possible and backward walking. The predictors analyzed were age, gender, disease severity, balance, balance confidence, fall history, self-reported physical activity, and executive function. Multiple regression models were used to assess the relationships between predictors and outcomes. The predictors, in different combinations for each outcome measure, explained 55.7% to 66.9% of variability for mobility and 39.5% to 52.8% for gait velocity. Balance was the most relevant factor (explaining up to 54.1% of variance in mobility and up to 45.6% in gait velocity). Balance confidence contributed to a lesser extent (2.0% to 8.2% of variance) in all models. Age explained a small percentage of variance in mobility and gait velocity (up to 2.9%). Executive function explained 3.0% of variance during forward walking only. The strong predictive relationships between balance deficits and mobility and gait impairment suggest targeting balance deficits may be particularly important for improving mobility and gait in people with PD, regardless of an individual’s age, disease severity, fall history, or other demographic features.     

Kinematic gait parameters for older adults with Parkinson's disease during street crossing simulation

Safe street crossing is important for older adults' social inclusion. We assessed gait kinematic adaptation under different simulated street crossing conditions in older adults with Parkinson's disease (PD) and made comparisons with older adults without PD to understand how PD interferes in outdoor task performance, helping in the development of strategies to reduce road traffic accident risk. In 20 older adults without PD (control group – CG) and 20 with PD (GPD), we assessed usual gait (C1), gait during street crossing simulation (C2), and gait during reduced-time street crossing simulation (C3). Velocity, step length, and step, swing, stance, and double support time were analyzed. Spatiotemporal differences in gait between groups and conditions were analyzed. The GPD walked 16% slower in C1 and 12% slower in C2 and C3 than the CG. GPD also took 11% shorter steps in C1 and 9.5% shorter steps in C2. The double support time was 8.5% greater in C1. In intragroup comparisons, there were significant differences in all gait conditions. The CG showed increased velocity (C2 15% > C1; C3 13% > C2; C3 26% > C1), step length (C2 8% > C1; C3 5% > C2; C3 13% > C1), and swing time (C2 2% > C1; C3 3.7% > C2; C3 6% > C1), and decreased step time (C2 7.5% < C1; C3 8% < C2; C3 15% < C1), stance time (C2 1.3% < C1; C3 2.5% < C2; C3 3.6% < C1), and double support time (C2 6.3% < C1; C3 10.5% < C2; C3 16% < C1). GPD showed increased velocity (C2 19% > C1; C3 13.5% > C2; C3 29.7% > C1), step length, (C2 6% > C1; C3 7% > C2; C3 16% > C1), and swing time (C2 3% > C1; C3 3% > C2; C3 5.5% > C1) and decreased step time (C2 10.3% < C1; C3 7.7% < C2; C3 17% < C1), stance time (C2 1.7% < C1; C3 1.7% < C2; C3 3.4% < C1), and double support time (C2 7% < C1; C3 9.5% < C2; C3 16% < C1). Kinematic changes observed in the intergroup comparison show that participants with PD had lower velocity in all conditions. However, per the intragroup results, both participants with and without PD managed to significantly modify gait variables to attempt to cross the street in the given time. It is necessary to assess whether this increases fall risk by exposing them to road traffic accidents.     

Use of the gait deviation index for the evaluation of patients with Parkinson's disease

The authors aimed to determine whether the Gait Deviation Index (GDI) could be feasible to characterize gait in patients with Parkinson's disease (PD) and evaluate outcomes of levodopa treatment. Twenty-two PD participants were evaluated with clinical examination and 3-D quantitative gait analysis (GDI was calculated from gait analysis) in 2 states (OFF and ON) after taking levodopa. Twenty age-matched healthy participants (CG) were included as controls. The GDI value in the OFF state was 83.4 ± 11.5 (statistically different from CG) while clinical scales demonstrated a moderate-severe gait impairment of these patients. Significant improvements are evident from clinical scores and by GDI values in the ON state. The mean GDI for the ON state (GDI(ON): 87.9 ± 10.4) was significantly higher than in for the OFF state (GDI(OFF): 83.4 ± 11.5), indicating a global gait improvement after the treatment. The results show that GDI has lower value as an indicator of pathology in PD patients than in quantifying the effects of levodopa treatment in PD state.     

Movement parameters that distinguish between voluntary movements and levodopa-induced dyskinesia in Parkinson's disease

It is well known that long-term use of levodopa by patients with Parkinson's disease causes dyskinesia. Several methods have been proposed for the automatic, unsupervised detection and classification of levodopa induced dyskinesia. Recently, we have demonstrated that neural networks are highly successful to detect dyskinesia and to distinguish dyskinesia from voluntary movements. The aim of this study was to use the trained neural networks to extract parameters, which are important to distinguish between dyskinesia and voluntary movements.Thirteen patients were continuously monitored in a home-like situation performing in about 35 daily life tasks for a period of approximately 2.5 h. Behavior of the patients was measured using triaxial accelerometers, which were placed at six different positions of the body. A neural network was trained to assess the severity of dyskinesia. The neural network was able to assess the severity of dyskinesia and could distinguish dyskinesia from voluntary movements in daily life. For the trunk and the leg, the important parameters appeared to be the percentage of time that the trunk or leg was moving and the standard deviation of the segment velocity of the less dyskinetic leg. For the arm, the combination of the percentage of time, that the wrist was moving, and the percentage of time, that a patient was sitting, explained the largest part of the variance of the output. Dyskinesia differs from voluntary movements in the fact that dyskinetic movements tend to have lower frequencies than voluntary movements and in the fact that movements of different body segments are not well coordinated in dyskinesia.     

The effects of nicotine on Parkinson's disease

Post-mortem studies have demonstrated a substantial loss of nicotinic receptors in Parkinson's disease (PD), which may be at least partially responsible for some of the cognitive, motoric, and behavioral deficits seen in this disorder. Epidemiologic studies have suggested that cigarette smoking is a strong negative risk factor for the development of PD. We have previously shown that blockade of central nicotinic receptors produces cognitive impairment in areas of new learning, short-term memory, and psychomotor slowing with increasing dose sensitivity with age and disease. Studies of acute stimulation of nicotinic receptors in Alzheimer's disease with nicotine and the novel agonist ABT-418 in our laboratory and others have shown improvements in several measures of cognitive function. Prior studies of the effects of nicotine in PD have suggested some improvements in clinical symptomatology. We have begun quantitative studies of both acute and chronic nicotine in PD to assess both cognitive and motor effects. Fifteen (15) nondemented subjects (age 66 +/- 5.3; M/F = 11/4) with early to moderate PD (mean Hoehn-Yahr stage = 1.77; MMSE = 28.6) received a dose-ranging study of intravenous nicotine up to 1.25 microg/kg/min, followed by chronic administration of nicotine by transdermal patch with doses ranging up to 14 mg per day for 2 weeks. Testing occurred both during drug administration and up to 2 months after drug cessation to look for prolonged effects. Preliminary analysis shows improvements after acute nicotine in several areas of cognitive performance, particularly measures such as reaction time, central processing speed, and decreased tracking error. Improvements in attention and semantic retrieval were not seen. After chronic nicotine, improvements were seen in several motor measures suggesting improved extrapyramidal functioning. This appeared to be sustained for up to 1 month after drug. The treatment was well tolerated. Nicotinic stimulation may have promise for improving both cognitive and motor aspects of Parkinson's disease.     

Source memory in Parkinson's disease

Three experiments (ns = 14 per group) are reported which investigated the ability of Parkinson patients to remember the characteristics of conditions under which a memory was acquired. In Exp. 1, subjects were required to indicate for each item in a recognition memory test whether it was spoken by Experimenter 1 or by Experimenter 2 (external-external source memory). In Exp. 2, subjects had to indicate for each item whether it was generated by themselves or by the experimenter (internal-external source memory). In Exp. 3, subjects had to judge whether an item was generated by themselves in saying or in thinking (internal-internal source memory). We found that patients with Parkinson's disease were not impaired in the previous two kinds of source memory (Exp. 1 and 2) but were impaired in internal-internal source memory (Exp. 3) relative to the age-matched control groups. In addition, both groups' performance could be improved when given distinctive cues, i.e., perceptual cues in Exp. 1 and different-domain cues in Exp. 2. These results suggest that the availability of cues was critical for Parkinson's disease in source memory. Finally, the result of Exp. 2 also showed generation effects for patients with Parkinson's disease. The generation effect refers to better memory of information by people when they had to produce it, e.g., producing associates to a word, compared with memory of information given to them.     

Impulse-control disorders in Parkinson's disease

Parkinson's disease is a neurodegenerative disorder characterized by bradykinesia, rigidity, postural instability, and resting tremor. Increasingly, Parkinson's disease has been associated with a broad spectrum of non-motor symptoms, such as olfactory loss, sleep disorders, autonomic dysfunction, cognitive impairment, psychosis, depression, anxiety, and apathy. In addition, a minority of Parkinson's disease patients develop compulsive behaviors while receiving dopamine-replacement therapy, including medication hoarding, pathological gambling, binge eating, hyperlibidinous behavior, compulsive shopping, and punding. These behaviors may result in psychosocial impairment for patients and therapeutic challenges for clinicians. This article reviews the anatomic substrates, behavioral spectrum, associated factors, and potential treatments for dopamine-replacement therapy-related compulsions in Parkinson's disease.     

Emotional dysfunction in Parkinson's disease

In addition to motor symptomatology, idiopathic Parkinson's disease is characterized by emotional dysfunction. Depression affects some 30 to 40 percent of Parkinson patients and other psychiatric co-morbidities include anxiety and apathy. Neuropsychological and neuroimaging studies of emotional dysfunction in Parkinson patients suggest abnormalities involving mesolimbic and mesocortical dopaminergic pathways. There is also evidence suggesting that the interaction between serotonin and dopamine systems is important in the understanding and treatment of mood disorders in Parkinson's disease. In this review we discuss the neuropsychiatric abnormalities that accompany Parkinson's disease and describe their neuropsychological, neuropharmacologic, and neuroimaging concomitants.     

Control of saccades in Parkinson's disease

Parkinson's patients (PD) made pro- and antisaccades: In the no-delay condition, the target appeared concurrent with the GO signal. In the delay condition, the target appeared before the signal for movement. Second, we probed spatial working memory in PD. Subjects looked to the remembered locations of sequential targets. In the no-delay prosaccade condition, PD had faster reaction times, made more express saccades, and exhibited hypometria. In the no-delay antisaccade condition, PD had longer reaction times and made more direction errors. In the delay tasks, PD made more direction errors and had more difficulty withholding a movement. PD made more sequencing errors in the spatial working memory task. These findings are consistent with a basal ganglia pathophysiology influencing eye movement processing in the frontal cortex.     

Neuropsychological outcome of GPi pallidotomy and GPi or STN deep brain stimulation in Parkinson's disease

This paper highlights the neuropsychological sequelae of posteroventral pallidotomy (PVP) and deep brain stimulation (DBS) of the subthalamic nucleus (STN) and the internal segment of the globus pallidus (GPi) at 3/6 months postoperatively. Results are based on our extensive experience with PVP and our preliminary observations with DBS. Patients with borderline cognitive or psychiatric functioning risk postoperative decompensation. Nonlateralizing attentional and hemisphere-specific impairments of frontostriatal cognitive functions followed unilateral PVP. "Frontal" behavioral dyscontrol was observed in approximately 25% of patients. Three cases of staged bilateral PVP suggest that premorbid factors may predict outcome, although lesion size and location are also critical. Older patients are at risk for significant cognitive and behavioral decline after bilateral STN DBS, while GPi DBS may be safer.     

Comparison of patients with Parkinson's disease or cerebellar lesions in the production of periodic movements involving event-based or emergent timing

We have hypothesized a distinction between the processes required to control the timing of different classes of periodic movements. In one class, salient events mark successive cycles. For these movements, we hypothesize that the temporal goal is a requisite component of the task representation, what we refer to as event-based timing. In the other class, the successive cycles are produced continuously. For these movements, alternative control strategies can optimize performance, allowing timing to be emergent. In a previous study, patients with cerebellar lesions were found to be selectively impaired on event-based timing tasks; they were unimpaired on a continuously produced task. In the present study, patients with Parkinson's disease were tested on repetitive movement tasks in which timing was either event-based or emergent. Temporal variability on either type of task did not differ between on- and off-medication sessions for the Parkinson's patients nor did patient performance differ from that of controls. These results suggest that the basal ganglia play a minimal role in movement timing and that impairments on event-based timing tasks are specific to cerebellar damage.     

The effect of dopaminergic medication on conflict adaptation in Parkinson's disease

Parkinson's disease (PD) is a neurological disorder associated primarily with motor symptoms such as tremor, slowness of movement, and difficulties with gait and balance. Most patients take dopaminergic medication to improve their motor functions. Previous studies reported indications that such medication can impair higher cognitive functions (cf. dopamine overdose hypothesis). In the present study, we examined the effect of medication status on conflict adaptation. PD patients performed a Stroop task in which we manipulated the proportion of congruent and incongruent items, thereby allowing us to explore conflict adaptation. The use of mouse movements allowed us to examine the action dynamics of conflict adaptation in PD, and their sensitivity to dopaminergic medication. Each patient performed the same task twice: once without making changes to their regular medication regime, and once after overnight withdrawal from their medication. Results showed that medication improved mouse movements and alleviated motor symptoms. Moreover, patients' mouse movements were modulated as a function of the proportion congruency manipulation, revealing conflict adaptation in PD, which was unaffected by medication status. The present study extends earlier work on conflict adaptation in PD where reduced transient (trial-by-trial) conflict adaptation was observed ON compared to OFF medication (Duthoo et al., 2013, Neuropsychology, 27, 556). Our findings suggest that more sustained cognitive control processes may not be sensitive to dopamine overdose effects.     

Ideational fluency in Parkinson's disease.

Recent research on Parkinson's disease (PD) suggests that executive functions are impaired but that visuospatial functions may be spared. This dissociation has been attributed to dysfunction in ascending dopaminergic pathways affecting the prefrontal cortex. We investigated these ideas in a sample of intellectually intact patients with idiopathic, optimally treated PD (N = 20) and in spouse controls (N = 15); the groups were divided into young (age < 60) and old subgroups, each comparable on education, vocabulary level, and Mini-Mental State scores. Six tasks were selected from a set of factor-referenced cognitive tests to measure three abilities: (1) ideational fluency (ability to generate ideas), (2) flexibility of use (ability to shift mental set), and (3) spatial orientation (ability to perceive spatial patterns). PD patients were impaired only on the ideational fluency factor (p = .01). An age-related deficit was seen on the spatial factor (p < .05) with a trend on the flexibility factor (.05 < p < .10). No interactions were significant. The findings suggest that when age and verbal intelligence are controlled, PD patients show no deficit on purely spatial tasks; in contrast, patients seem less able to generate ideas though capable of shifting from one idea to another.     

Sentence processing in Parkinson's disease.

Parkinson's disease (PD) is a neurodegenerative condition that is associated with the depletion of dopamine (DA)-containing neurons in specific brain regions. This article reviews one consequence of this defect-sentence comprehension difficulty in nondemented patients with PD. The first section describes the pattern of cognitive deficits seen in patients with PD, focusing specifically on their difficulties with language processing. Subsequent sections relate the profile of cognitive impairments in PD to studies investigating compromised DA metabolism in fronto-striatal brain regions. The findings suggest that the sentence comprehension deficit in PD is due in large part to limitations in the strategic distribution of cognitive resources such as selective attention that contribute to the processing of complex material. The physiological basis for this deficit appears to be associated with the disruption of a fronto-striatal cerebral network that is compromised following degradation of the DA projection system.     

Noun verb dissociation in Parkinson's disease

A noun/verb dissociation with a relative verb deficit was found in patients affected by Parkinson's disease, even in relatively early stages, when mental deterioration is not severe. This finding is compatible with earlier observations, according to which verbs are dealt with in more anterior regions with respect to nouns. It also supports the speculation that the co-ordination and the manipulation of information associated with a verb world rely on the frontostriatal system.     

Non-motor aspects of Parkinson's disease

Parkinson's disease is primarily considered to be a movement disorder and is defined by its motor signs. Yet, the behavioral manifestations of the disease are often more debilitating than its motor complications. This review will focus on the non-motor aspects of Parkinson's disease, including mood, psychosis, cognitive, sleep, fatigue, apathy, delirium, and repetitive disorders, that may occur. The phenomenology, pathology, and treatment of the behavioral symptoms of Parkinson's disease will be discussed.