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Background: In Parkinson's disease (PD), neurodegenerative changes have been observed in autonomic pathways involving multiple organ systems. We explore pupillary and cardiac autonomic measures as physiological manifestations of PD neurodegeneration.Methods: Pupil measures (pupillary unrest (spontaneous changes of pupil diameter in darkness), constriction velocity and redilation velocity) were assessed in 35 participants (17 PD, 18 controls). Simultaneous cardiac measures (respiratory sinus arrythmia during deep breathing, Valsalva ratio, resting heart rate variability (HRV), orthostatic change in blood pressure and orthostatic change in heart rate) were obtained. Nonparametric statistics were used to compare PD with control participants and to calculate correlation coefficients between pupillary and cardiac measures.Results: Pupillary unrest and orthostatic decreases in systolic blood pressure were greater in PD than controls. Respiratory sinus arrythmia during deep breathing and resting HRV were lower in PD. Among all participants, there was a negative correlation between HRV and redilation velocity and a positive correlation between orthostatic change in heart rate and pupillary unrest. A modifying effect of PD was found on the association between high frequency HRV and pupillary unrest.Conclusions: Results demonstrate simultaneous autonomic dysfunction in both pupillary and cardiac systems in PD. The correlations between pupillary and cardiac measures suggest shared central centers of autonomic integration, while the modifying effect of PD may reflect autonomic effects of PD-related pathology not present in controls. [ABSTRACT FROM AUTHOR]

Objective: Physical therapy, including exercise, improves gait and quality of life in Parkinson's disease (PD). Many programs promoting physical activity have generated significant short-term gains, but adherence has been a problem. A recent evidence-based analysis of clinical trials using physical therapy in PD patients produced four key treatment recommendations: cognitive movement strategies, physical capacity, balance training, and cueing. We have attempted to incorporate all four of these features together through a dance exercise program using the dance videogame "Dance Dance Revolution" (DDR) (Konami Digital Entertainment, El Segundo, CA)., Subjects and Methods: Sixteen medically stable participants with mild to moderate PD were given the opportunity to try DDR with supervision by a research staff member. Feedback about the advantages and disadvantages of DDR as a form of physical activity was elicited through focus groups using the nominal group technique., Results: Of 21 advantages and 17 disadvantages elicited, the most frequently cited advantages were "fun" and "easy to use," followed by "improves balance or coordination," "challenging," and "full body aerobic activity." Common concerns were the distracting or confusing interface, cost, and possible technical issues., Discussion: Interactive dance exercise was appealing to participants with PD and may help promote adherence to physical activity. Concerns regarding familiarity with the technology may be addressed with simplification of the interface or additional training for participants. Results support a larger longitudinal study of DDR in PD.

Background: Arousal symptoms (e.g., sleepiness) are common in Parkinson's disease, and pupillary unrest (spontaneous changes in pupil diameter) is positively associated with sleepiness. We explored pupillary unrest in Parkinson's disease., Methods: Arousal symptoms (Epworth sleepiness scale and sleep/fatigue domain of the nonmotor symptoms scale for Parkinson's disease) and pupillary unrest were assessed in 31 participants (14 patients with Parkinson's disease, 17 controls). Effect sizes and t tests compared patients with Parkinson's disease with control participants. Correlation coefficients were calculated among arousal symptoms, pupillary unrest, and Unified Parkinson Disease Rating Scale Part III. Linear regression was performed with arousal symptoms or pupillary unrest as outcome., Results: Participants with Parkinson's disease reported more arousal symptoms than controls. Pupillary unrest, arousal symptoms, and Unified Parkinson Disease Rating Scale Part III were positively correlated. The association between nonmotor symptoms scale-sleep score and pupillary unrest was higher in participants with Parkinson's disease than controls and higher in those with more Parkinsonian motor signs. Unified Parkinson Disease Rating Scale Part III was positively associated with pupillary unrest., Conclusions: Pupillary unrest correlates with motor and nonmotor features associated with Lewy-related pathology, suggesting it may be a nonmotor marker of progression in Parkinson's disease. © 2011 Movement Disorder Society., (Copyright © 2011 Movement Disorder Society.)

We recently reported findings that loss of cortical acetylcholinesterase (AChE) activity is greater in parkinsonian dementia than in Alzheimer's disease (AD). In this study we determined cognitive correlates of in vivo cortical AChE activity in patients with parkinsonian dementia (PDem, n = 11), Parkinson's disease without dementia (PD, n = 13), and in normal controls (NC, n = 14) using N-[(11)C]methyl-piperidin-4-yl propionate ([(11)C]PMP) AChE positron emission tomography (PET). Cortical AChE activity was significantly reduced in the PDem (-20.9%) and PD (-12.7 %) subjects (P < 0.001) when compared with the control subjects. Analysis of the cognitive data within the patient groups demonstrated that scores on the WAIS-III Digit Span, a test of working memory and attention, had most robust correlation with cortical AChE activity (R = 0.61, p < 0.005). There were also significant correlations between cortical AChE activity and other tests of attentional and executive functions, such as the Trail Making and Stroop Color Word tests. There was no significant correlation between cortical AChE activity and duration of motor disease (R = -0.01, ns) or severity of parkinsonian motor symptoms (R = 0.14, ns). We conclude that cortical cholinergic denervation in PD and parkinsonian dementia is associated with decreased performance on tests of attentional and executive functioning.

Objective: To investigate the relationship between the severity of white matter hyperintensities (WMH) and cortical acetylcholinesterase (AChE) activity in parkinsonian dementia (PDem)., Methods: PDem (n = 11) and control subjects (n = 14) underwent [11C]methyl-4-piperidinyl propionate (11C-PMP) AChE brain positron emission tomography and magnetic resonance (MR) imaging. Presence of WMH on proton density and T2 MR images was scored using a modified version of the semi-quantitative rating scale by Scheltens et al. [J Neurol Sci114 (1993)]., Results: Analysis demonstrated significantly lower mean cortical (11)C-PMP k3 hydrolysis rates in PDem (-19.9%) when compared with control subjects (P < 0.0001). PDem subjects had higher mean severity of WMH (+20.1%) when compared with control subjects (P < 0.05). When WMH severity was entered into the analysis of variance model, there was no significant co-variate effect on cortical AChE activity (F = 0.24, ns)., Conclusions: The concomitant presence of mild to moderate WMH in patients with PDem does not have a significant effect on cortical AChE activity.

Objective: To investigate the relationship between magnetic resonance imaging (MRI) subcortical gray and capsular (SGCH) and white matter hyperintensities (WMH) and cognitive functions in non-demented community dwelling elderly., Methods: The severity of SGCH and WMH on proton density and T2 MR images in 16 subjects was scored using the semi-quantitative rating scale of Scheltens et al. (1993). A limited series of cognitive tests selected a priori were then correlated with severity of SGCH and WMH., Results: Analysis demonstrated that severity of SGCH was inversely related to performance on the Digit Span (R = -0.64, p < 0.01) and the Stroop Color Word Tests (R = -0.64, p < 0.01). Severity of WMH was related to worsening performance on the Trail Making Test (R = 0.67, p < 0.005)., Conclusions: These findings indicate that severity of WMH is negatively related to more pure executive cognitive functions, specifically set shifting, while severity of SGCH is inversely related to more basic functions of attention and working memory., (Copyright 2005 John Wiley & Sons, Ltd.)

We recently reported findings of modest loss of cortical acetylcholinesterase (AChE) activity in patients with overall mild Alzheimer's disease (AD) using N-[11C]methyl-pi-peridin-4-yl propionate ([11C]PMP) AChE positron emission tomography (PET). To determine cognitive correlates of in vivo cortical AChE activity in patients with mild to moderate AD (n=15), and in normal controls (NC, n=12) using [11C]PMP AChE PET imaging. Mean cortical AChE activity in the AD subjects was mildly reduced (-11.1%) compared to the control subjects (P<0.05). Analysis of the cognitive data showed that mean cortical AChE activity was significantly associated with performance on a test of attention and working memory (WAIS-III Digit Span, R=0.46, P=0.01) but not with tests of delayed short or long-term memory functions. Similar findings were present when the analysis was limited to the temporal cortex. Cortical AChE activity is more robustly associated with functions of attention and working memory compared to performance on primary memory tests in AD.

Objectives: To determine in vivo cortical acetylcholinesterase (AChE) activity and cognitive effects in subjects with mild Alzheimer's disease (AD, n = 14) prior to and after 12 weeks of donepezil therapy., Methods: Cognitive and N-[(11)C]methyl-piperidin-4-yl propionate ([(11)C]PMP) AChE positron emission tomography (PET) assessments before and after donepezil therapy., Results: Analysis of the PET data revealed mean (temporal, parietal, and frontal) cortical donepezil induced AChE inhibition of 19.1% (SD 9.4%) (t = -7.9; p<0.0001). Enzyme inhibition was most robust in the anterior cingulate cortex (24.2% (6.9%), t = -14.1; p<0.0001). Donepezil induced cortical inhibition of AChE activity correlated with changes in the Stroop Color Word interference scores (R(2) = 0.59, p<0.01), but not with primary memory test scores. Analysis of the Stroop test data indicated that subjects with AChE inhibition greater than the median value (>22.2%) had improved scores on the Stroop Color Word Test compared with subjects with less inhibition who had stable to worsening scores (t = -2.7; p<0.05)., Conclusions: Donepezil induced inhibition of cortical AChE enzyme activity is modest in patients with mild AD. The degree of cortical enzyme inhibition correlates with changes in executive and attentional functions.

The human postural control system is difficult to quantify since it seems to be subject to both deterministic forces as well as stochastic effects. The attempt made in this paper is to study postural control under quiet stance on the one hand, and by engaging the brain through a fluency test, on the other. A Kistler electronic platform is the vehicle by way of which we gather observations in the form of center of pressure (COP) trajectories. From these two-dimensional trajectories we extract several measures that describe various features of the postural control system. Some of the measures are descriptive, while others incorporate physical forces that enter the process. From these measures we then build predictive models and apply them to a set of patients with Parkinson's disease (PD) and a set of normal control subjects to validate and calibrate them. We further use the measures built out of the center of pressure trajectories to test the significance of the fluency (cognitive-motor dual task) effect on the two groups. The fluency effect is found significant in the parkinsonian group as well as the normal controls. The clinical importance of these findings lies in the fact that the models may be used as a more objective assessment of postural control that may either replace or supplement the more subjective Unified Parkinson's Disease Rating Scale (UPDRS). The models may also be used as an assessment tool for the evaluation of patients subsequent to pharmacological and surgical treatment.

Background: Pathology reports have shown that cholinergic forebrain neuronal losses in parkinsonian dementia (PDem) are equal to or greater than those in Alzheimer disease (AD). We hypothesized that patients with PDem would have cholinergic deficits that were similar to or greater than those of patients with AD., Objective: To determine in vivo cortical acetylcholinesterase (AChE) activity in healthy control subjects and in patients with mild AD, PDem, and Parkinson disease without dementia using AChE positron emission tomography., Setting: University and Veterans' Administration medical center. Design and Patients Group comparison design of patients with AD (n = 12), PDem (n = 14), and Parkinson disease without dementia (n = 11), and controls (n = 10) who underwent AChE imaging between July 1, 2000, and January 31, 2003. Patients with AD and PDem had approximately equal dementia severity., Main Outcome Measures: Cerebral AChE activity., Results: Compared with controls, mean cortical AChE activity was lowest in patients with PDem (-20.0%), followed by patients with Parkinson disease without dementia (-12.9%; P<.001). Mean cortical AChE activity was relatively preserved in patients with AD (-9.1%), except for regionally selective involvement of the lateral temporal cortex (-15%; P<.001)., Conclusion: Reduced cortical AChE activity is more characteristic of patients with PDem than of patients with mild AD.