Parkinson Disease: Uc EY

Uc EY, Rizzo M. · Department of Neurology, University of Iowa, Carver College of Medicine, 200 Hawkins Drive-2RCP, Iowa City, IA 52242, USA. · Curr Neurol Neurosci Rep. · Pubmed #18713573 No free full text.

Abstract: The proportion of elderly people in the general population is rising, resulting in greater numbers of drivers with neurodegenerative disorders such as Alzheimer's disease and Parkinson's disease. These neurodegenerative disorders impair cognition, visual perception, and motor function, leading to reduced driver fitness and greater crash risk. Yet neither medical diagnosis nor age alone is reliable enough to predict driver safety or crashes or to revoke the driving privileges of these individuals. Driving research utilizes tools such as questionnaires about driving habits and history, driving simulators, standardized road tests utilizing instrumented vehicles, and state driving records. Research challenges include outlining the evolution of driving safety, understanding the mechanisms of driving impairment, and developing a reliable and efficient standardized test battery for prediction of driver safety in neurodegenerative disorders. This information will enable healthcare providers to advise their patients with neurodegenerative disorders with more certainty, affect policy, and help develop rehabilitative measures for driving.

Uc EY, Follett KA. · Department of Neurology, University of Iowa, Iowa City, Iowa 52242, USA. · Semin Neurol. · Pubmed #17390262 No free full text.

Abstract: Deep brain stimulation (DBS) is used for advanced and medically intractable patients with Parkinson's disease (PD), essential tremor (ET), and dystonia who meet strict criteria after a detailed motor, cognitive, and psychiatric evaluation. The potential targets are the ventral intermediate nucleus (VIM) of the thalamus for tremor, the globus pallidus interna (GPI) and the subthalamic nucleus (STN) for PD, and GPI for dystonia. The optimal target for PD has not been determined yet, although STN DBS has been performed more frequently in recent years. The mechanism of DBS effect is believed to be associated with disruption of pathological network activity in the cortico-basal ganglia-thalamic circuits by affecting the firing rates and bursting patterns of neurons and synchronized oscillatory activity of neuronal networks. Good candidates should be free of dementia, major psychiatric disorders, structural brain lesions, and important general medical problems. Although the risk for complications with DBS is less than with lesioning techniques, there is still a small risk for major complications associated with surgery. Bilateral procedures are more likely to cause problems with speech, cognition, and gait.

Uc EY, Rizzo M, Anderson SW, Sparks JD, Rodnitzky RL, Dawson JD. · Department of Neurology, University of Iowa, Carver College of Medicine, Iowa City, IA 52242, USA. · Brain. · Pubmed #17686809 links to  free full text

Abstract: Navigating a new route during automobile driving uses the driver's cognitive resources and has the potential to impair driving ability in people with Parkinson's disease (PD). Our aim was to assess navigation and safety errors during a route following task (RFT) in drivers with the illness. Seventy-seven subjects with mild-moderate PD (median Hoehn-Yahr stage = 2.0) and 152 neurologically normal elderly adults, all active and licensed drivers, were tested with a battery of visual, cognitive and motor tests of abilities. Each driver also performed a RFT administered on the road in an instrumented vehicle. Main outcome variables included: number of incorrect turns, times lost and at-fault safety errors. All group comparisons were adjusted for age, gender, education and familiarity with the region. Drivers with PD performed significantly worse on cognitive, visual and motor tests compared to controls, and took longer to finish the RFT. Higher proportions of these drivers made incorrect turns {53.9% in PD versus 21.1% in controls, Odds Ratio (OR) [95% Confidence Interval (CI)] = 2.8 [1.4, 5.7], P = 0.006}, got lost (15.8% versus 2.0%, OR [95%CI] = 4.7 [1.1, 20.0], P = 0.037), or committed at-fault safety errors (84.2% versus 46.7%, OR [95%CI] = 7.5 [3.3, 17.0], P < 0.001). Within the patient group, the navigational and safety errors were predicted by poor performances on cognitive and visual tests, but not by the severity of motor dysfunction. Drivers with PD made more navigation and safety errors than neurologically normal drivers on a RFT that placed demands on driver memory, attention, executive functions and visual perception. The PD group driver safety was degraded possibly due to an increase in the cognitive load in patients with limited reserves. Navigational errors and lower driver safety were associated more with impairments in cognitive and visual function than the motor severity of their disease in drivers with PD.

Uc EY, Rizzo M, Anderson SW, Sparks JD, Rodnitzky RL, Dawson JD. · Department of Neurology, University of Iowa, Carver College of Medicine, 200 Hawkins Drive-2RCP, Iowa City, IA 52242, USA. · Neurology. · Pubmed #17130409 No free full text.

Abstract: OBJECTIVE: To assess the effects of auditory-verbal distraction on driving performance in Parkinson disease (PD). METHODS: We tested licensed, currently active drivers with mild-to-moderate PD (n = 71) and elderly controls with no neurologic disease (n = 147) on a battery of cognitive, visual, and motor tests. While they drove on a four-lane interstate freeway in an instrumented vehicle, we determined at-fault safety errors and vehicle control measures during a distracter task (Paced Auditory Serial Addition Task [PASAT]) and on an uneventful baseline segment. RESULTS: Compared with controls, drivers with PD committed more errors during both baseline and distraction, and drove slower with higher speed variability during distraction. Although the average effect of distraction on driving performance compared with baseline was not different between the groups, the drivers with PD showed a more heterogeneous response to distraction (p < 0.001): the error count increased in 28.2% of drivers with PD (vs 15.8% in controls), decreased in 16.9% (vs 3.4%), and remained stable in 54.9% (vs 80.8%). The odds of increase in safety errors due to distraction was higher in the PD group even after adjusting for baseline errors, level of engagement in PASAT, sex, and education (odds ratio [95% CI] = 2.62 [1.19 to 5.74], p = 0.016). Decreased performance on tests of cognitive flexibility, verbal memory, postural control, and increased daytime sleepiness predicted worsening of driving performance due to distraction within the PD group. CONCLUSION: The quantitative effect of an auditory-verbal distracter task on driving performance was not significantly different between Parkinson disease (PD) and control groups. However, a significantly larger subset of drivers with PD had worsening of their driving safety errors during distraction. Measures of cognition, motor function, and sleepiness predicted effects of distraction on driving performance within the PD group.

Uc EY, Rizzo M, Anderson SW, Sparks J, Rodnitzky RL, Dawson JD. · Department of Neurology, Carver College of Medicine, University of Iowa, 200 Hawkins Drive-2RCP, Iowa City, IA 52242, USA. · Ann Neurol. · Pubmed #16969860 No free full text.

Abstract: OBJECTIVE: To assess the ability for visual search and recognition of roadside targets and safety errors during a landmark and traffic sign identification task in drivers with Parkinson's disease (PD). METHODS: Seventy-nine drivers with PD and 151 neurologically normal older adults underwent a battery of visual, cognitive, and motor tests. The drivers were asked to report sightings of specific landmarks and traffic signs along a four-lane commercial strip during an experimental drive in an instrumented vehicle. RESULTS: The drivers with PD identified significantly fewer landmarks and traffic signs, and they committed more at-fault safety errors during the task than control subjects, even after adjusting for baseline errors. Within the PD group, the most important predictors of landmark and traffic sign identification rate were performances on Useful Field of View (visual speed of processing and attention) and Complex Figure Test-Copy (visuospatial abilities). Trail Making Test (B-A), a measure of cognitive flexibility independent of motor function, was the only independent predictor of at-fault safety errors in drivers with PD. INTERPRETATION: The cognitive and visual deficits associated with PD resulted in impaired visual search while driving, and the increased cognitive load during this task worsened their driving safety.

Uc EY, Struck LK, Rodnitzky RL, Zimmerman B, Dobson J, Evans WJ. · Department of Neurology, Carver College of Medicine, University of Iowa, Iowa City, Iowa 52242, USA. · Mov Disord. · Pubmed #16534756 No free full text.

Abstract: The objective of this study was to examine the change of body weight (BW) among Parkinson's disease (PD) patients and controls over years and determine the predictors of weight loss among PD patients. Studies on weight loss in PD studies are cross-sectional, have a short follow-up, or lack in clinical detail. We examined the percentage of BW change over years among 49 PD patients and 78 controls. The controls were from another study on longitudinal evolution of BW and body composition in the elderly. We determined the BW, Hoehn and Yahr (HY) stage, and dyskinesia status of 49 consecutive nondemented PD patients with symptom duration of 6.1 +/- 0.7 years (mean +/- SEM) and ascertained their BW at the time of diagnosis and 2.4 +/- 0.2 years before the diagnosis from medical records. We collected data again 7.2 +/- 0.5 years after the first visit. The PD group lost 7.7% +/- 1.5% of BW over the entire symptomatic period (13.1 +/- 0.8 years), while the control group lost only 0.2% +/- 0.7% of BW over 9.9 +/- 0.1 years; weight loss was clinically significant (>5%) in 55.6% of PD patients vs. 20.5% of the controls (both P values < 0.001, adjusted for sex, baseline age, and observation period duration). PD patients lost weight in both the early and advanced phases. While worsening of parkinsonism was the most important factor, age at diagnosis, emergence of visual hallucinations, and possibly dementia were also associated with weight loss. We demonstrated significant weight loss in PD patients compared to controls over approximately 1 decade. Neurodegeneration involving both motor and nonmotor systems may be associated with weight loss in PD.

Uc EY, Rizzo M, Anderson SW, Qian S, Rodnitzky RL, Dawson JD. · Veterans Affairs Medical Center, Department of Neurology, University of Iowa, Iowa City, IA, USA. · Neurology. · Pubmed #16282276 No free full text.

Abstract: OBJECTIVE: To determine the profiles of visual dysfunction and their relationship to motor and cognitive dysfunction and to disability in mild to moderate Parkinson disease (PD) without dementia. METHODS: Seventy-six independently living participants with mild to moderate PD and 161 neurologically normal older adults were studied using a comprehensive battery to assess visual acuity, contrast sensitivity (CS), visual speed of processing and attention, spatial and motion perception, visual and verbal memory, visuoconstructional abilities, executive functions, depression, and motor function. RESULTS: Participants with PD scored significantly worse on all tests of vision and cognition compared with normal elderly persons. Reduced CS contributed to deficits on tests of spatial and motion perception and attention in participants with PD. Impairments in visual attention and spatial perception predicted worse cognitive function. Worse performances on tests of visual speed of processing and attention, spatial and motion perception, visual construction, and executive functions correlated with measures of postural instability and gait difficulty (in the Motor section of the Unified Parkinson's Disease Rating Scale). Impairments in motor function, visual memory, mood, and executive functions predicted worse disability as measured by Schwab-England Activities of Daily Living Scale. CONCLUSIONS: Patients with mild to moderate Parkinson disease showed impaired visual perception and cognition compared with elderly control subjects. Visual dysfunction contributes to parkinsonian disability through its influences on cognition and locomotion.

Uc EY, Lambert CP, Harik SI, Rodnitzky RL, Evans WJ. · Department of Neurology, University of Arkansas for Medical Sciences and Central Arkansas Veterans Healthcare System, Little Rock, AR, USA. · Clin Neuropharmacol. · Pubmed #12897642 No free full text.

Abstract: Animal studies indicate that beta(2)-adrenergic receptor agonists enhance transport of levodopa across the blood-brain barrier. Preliminary studies showed improved response to levodopa in patients with Parkinson disease (PD) who were given albuterol as adjunctive therapy. Beta(2)-adrenergic agonists may offer additional benefits to PD patients via their skeletal muscle anabolic effects, particularly those who experience decreased muscle strength and weight loss. Nondemented, fluctuating PD patients receiving levodopa but not experiencing severe dyskinesias underwent the following tests at baseline and 14 weeks after treatment with albuterol sulfate (4 mg four times a day, orally): Unified Parkinson's Disease Rating Scale motor, tapping, and stand-walk-sit tests every 30 minutes between 8 am and 5 pm; body composition analyses using whole-body plethysmography and computed tomography of the thigh; muscle strength tests; and the Parkinson's Disease Questionnaire (PDQ-39). Results were analyzed using paired t-tests (2 tailed), repeated-measures analysis of variance, and the Wilcoxon signed-rank test. Seven of 8 enrolled patients completed the study; 1 patient withdrew because of headache and anxiety. The area under the curve for all-day UPDRS motor scores improved by 9.8 +/- 9.1% (mean +/- standard deviation; P < 0.05) and tapping improved by 7.6 +/- 8.1% (P < 0.05). The effect was more pronounced when only the response to the first levodopa dose (area under the curve, 8-11 am) was analyzed: 13.0 +/- 9.8% and 9.8 +/- 9.6% respectively. Thigh muscle cross-sectional area increased significantly as measured by computed tomography (5.3 +/- 3.2%, P < 0.01), as did fat-free mass by whole-body plethysmography combined with total-body water determination (9.5 +/- 2.9%, P < 0.05). There was no significant improvement in the stand-walk-sit test, muscle strength tests, other UPDRS sections, daily OFF time, or PDQ-39. Four patients were rated as having a mild global improvement (+1 point) on a -3 to +3-point scale, and 3 of them chose to continue albuterol beyond the termination of the study. The mean heart rate increased from 78.3 +/- 9.3 beats/minute to 85.6 +/- 8.7 beats/minute (P < 0.05). No laboratory abnormalities or electrocardiographic changes were induced by albuterol in any subject. This open-label pilot study suggests that albuterol increases muscle mass and improves the therapeutic response to levodopa in patients with fluctuating PD. A double-blind, placebo-controlled study is needed to confirm the effects and safety profile of beta(2)-agonists in PD.

Uc EY, Dienel GA, Cruz NF, Harik SI. · Department of Neurology, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA. · Mov Disord. · Pubmed #11835439 No free full text.

Abstract: We sought to determine whether beta-adrenergic agonists enhance the brain extraction of L-dopa and L-leucine. Systemic administration of beta-adrenergic agonists increase brain concentrations of L-dopa and other large neutral amino acids (LNAA) in rats and monkeys and may improve symptoms and reduce daily L-dopa requirement in patients with Parkinson's disease. Cerebral blood flow (CBF) using [3H]nicotine and the extraction fraction of 14C-labeled L-dopa or L-leucine were measured simultaneously in various brain regions of conscious rats using the dual-isotope indicator fractionation technique after intraperitoneal administration of isoproterenol (a peripheral nonselective beta-adrenergic agonist), or clenbuterol (a beta2-adrenergic agonist that crosses the blood-brain barrier), or beta-adrenergic agonist preceded by nadolol (a peripheral nonselective beta-adrenergic antagonist), or saline vehicle. Both beta-adrenergic agonists increased regional brain extraction fraction of L-dopa and L-leucine tracers by 35-45%, without altering regional CBF. These changes were accompanied by about a 30% decrease in plasma branched chain LNAA concentrations. Nadolol blocked all these effects. beta-Adrenergic agonists increase the brain extraction of L-dopa and leucine, mainly by peripheral mechanisms that reduce the levels of other competing plasma LNAAs for transport. Thus, beta-adrenergic agonists might be useful in the treatment of patients with Parkinson's disease by enhancing delivery of L-dopa to the brain.