Journal of Parkinson's Disease - Volume 5, issue 1

Authors: Caviness, John N. | Hentz, Joseph G. | Belden, Christine M. | Shill, Holly A. | Driver-Dunckley, Erika D. | Sabbagh, Marwan N. | Powell, Jessica J. | Adler, Charles H.

Article Type: Research Article

Abstract: Background: QEEG could provide physiological biomarkers for changes over time in Parkinson's disease (PD) cognitive decline if they track with longitudinal neuropsychological performance. Objective: Our aim was to correlate longitudinal changes in frequency domain quantitative electroencephalography (QEEG) measures with change in neuropsychological performance testing in PD. Methods: 71 PD subjects, not demented at baseline, were studied from the Arizona Study of Aging and Neurodegenerative Disorders cohort. Baseline and follow-up digital EEG from PD subjects were analyzed for QEEG measures of background rhythm frequency and global relative power in delta (2.5–4 Hz), theta (4–8 Hz), alpha (8–13 Hz), and beta (13–30 …Hz) bands. Baseline and subsequent evaluation included Mini Mental Status Examination and five other neuropsychological tests that load on cognitive domains known to decline in PD. Pearson coefficient was used to assess correlations. Multiple linear regression modeling was used to assess the effect of variable combinations of QEEG and other measures, including age and PD duration. Results: Changes in delta bandpower showed the highest and most consistent pattern of correlations with longitudinal changes in neuropsychological testing. The highest correlation was between delta bandpower increase and decline in the Rey Auditory-Verbal Learning Test (−0.59:p < 0.001). Delta bandpower was also increased in the incident dementia group compared to non-dementia at followup. Conclusions: 1) Longitudinal change in the QEEG frequency domain measure of delta bandpower correlated best with longitudinal neuropsychological performance change in PD; 2) These results constitute preliminary evidence that delta bandpower may be a suitable biomarker for evaluating PD cognitive deterioration longitudinally. Show more

Keywords: Parkinson's disease, dementia, electroencephalography, biological markers

DOI: 10.3233/JPD-140480

Citation: Journal of Parkinson's Disease, vol. 5, no. 1, pp. 117-124, 2015

Authors: Lin, Tanya P. | Rigby, Heather | Adler, Jennifer S. | Hentz, Joseph G. | Balcer, Laura J. | Galetta, Steven L. | Devick, Steve | Cronin, Richard | Adler, Charles H.

Article Type: Research Article

Abstract: Background: Low-contrast vision is thought to be reduced in Parkinson's disease (PD). This may have a direct impact on quality of life such as driving, using tools, finding objects, and mobility in low-light condition. Low-contrast letter acuity testing has been successful in assessing low-contrast vision in multiple sclerosis. We report the use of a new iPad application to measure low-contrast acuity in patients with PD. Objective: To evaluate low- and high-contrast letter acuity in PD patients and controls using a variable contrast acuity eye chart developed for the Apple iPad. Methods: Thirty-two PD and 71 control subjects were studied. Subjects …viewed the Variable Contrast Acuity Chart on an iPad with both eyes open at two distances (40 cm and 2 m) and at high contrast (black and white visual acuity) and 2.5% low contrast. Acuity scores for the two groups were compared. Results: PD patients had significantly lower scores (indicating worse vision) for 2.5% low contrast at both distances and for high contrast at 2 m (p < 0.003) compared to controls. No significant difference was found between the two groups for high contrast at 40 cm (p = 0.12). Conclusions: Parkinson's disease patients have reduced low and high contrast acuity compared to controls. An iPad app, as used in this study, could serve as a quick screening tool to complement more formal testing of patients with PD and other neurologic disorders. Show more

Keywords: Parkinson's disease, vision, contrast sensitivity, visual acuity

DOI: 10.3233/JPD-140470

Citation: Journal of Parkinson's Disease, vol. 5, no. 1, pp. 125-130, 2015

Authors: Duncan, Ryan P. | Leddy, Abigail L. | Cavanaugh, James T. | Dibble, Leland E. | Ellis, Terry D. | Ford, Matthew P. | Foreman, K. Bo | Earhart, Gammon M.

Article Type: Research Article

Abstract: Background: The natural progression of balance decline in individuals with Parkinson disease (PD) is not well understood. Objectives: We aimed to: 1) compare the utility of three standardized clinical measures for detecting balance decline over 1-year, 2) identify components of balance susceptible to decline, and 3) identify factors useful for predicting future balance decline. Methods: Eighty people with PD (59% male; mean age 68.2 ± 9.3; Hoehn & Yahr range I–IV) completed Balance Evaluation Systems Test (BESTest), Mini-BESTest, and Berg Balance Scale (BBS) assessments. Baseline predictor variables included the MDS-UPDRS III sub-score, presence of freezing, 6-month fall history, age, gender, …and physical activity. Balance and MDS-UPDRS III assessments were repeated at 6 (n = 51) and 12 months (n = 44). Results: BESTest and Mini-BESTest score declined over 6 and 12 months (P < 0.01). Postural responses, stability limits, and sensory orientation were most susceptible to decline. BBS score did not change (P > 0.01). MDS-UPDRS III score was unchanged over 6 months (P > 0.01), but declined over 12 months (P < 0.01). Change in BESTest score over 6 months was related to baseline MDS-UPDRS III, H&Y, freezing, and fall history (P < 0.05). Change in BESTest score over 12 months was related to baseline MDS-UPDRS III and freezing (P < 0.05). Change in Mini-BESTest over 12 months was related to baseline MDS-UPDRS III and age (P < 0.05). Conclusions: The BESTest and Mini-BESTest were responsive to balance decline in individuals with PD and helped to identify decline in underlying balance components. Disease severity and freezing most consistently predicted balance decline in persons with PD. Show more

Keywords: Parkinson disease, postural balance, outcome assessment, physical therapy, rehabilitation

DOI: 10.3233/JPD-140478

Citation: Journal of Parkinson's Disease, vol. 5, no. 1, pp. 131-139, 2015

Authors: Sterling, Nicholas W. | Cusumano, Joseph P. | Shaham, Noam | Piazza, Stephen J. | Liu, Guodong | Kong, Lan | Du, Guangwei | Lewis, Mechelle M. | Huang, Xuemei

Article Type: Research Article

Abstract: Background: Reduced arm swing amplitude, symmetry, and coordination during gait have been reported in Parkinson's disease (PD), but the relationship between dopaminergic depletion and these upper limb gait changes remains unclear. Objective: We aimed to investigate the effects of dopaminergic drugs on arm swing velocity, symmetry, and coordination in PD. Methods: Forearm angular velocity was recorded in 16 PD and 17 control subjects (Controls) during free walking trials. Angular velocity amplitude of each arm, arm swing asymmetry, and maximum cross-correlation were compared between control and PD groups, and between OFF- and ON-medication states among PD subjects. Results: Compared to Controls, …PD subjects in the OFF-medication state exhibited lower angular velocity amplitude of the slower- (p = 0.0018), but not faster- (p = 0.2801) swinging arm. In addition, PD subjects demonstrated increased arm swing asymmetry (p = 0.0046) and lower maximum cross-correlation (p = 0.0026). Following dopaminergic treatment, angular velocity amplitude increased in the slower- (p = 0.0182), but not faster- (p = 0.2312) swinging arm among PD subjects. Furthermore, arm swing asymmetry decreased (p = 0.0386), whereas maximum cross-correlation showed no change (p = 0.7436). Pre-drug angular velocity amplitude of the slower-swinging arm was correlated inversely with the change in arm swing asymmetry (R = −0.73824, p = 0.0011). Conclusions: This study provides quantitative evidence that reduced arm swing and symmetry in PD can be modulated by dopaminergic replacement. The lack of modulations of bilateral arm coordination suggests that additional neurotransmitters may also be involved in arm swing changes in PD. Further studies are warranted to investigate the longitudinal trajectory of arm swing dynamics throughout PD progression. Show more

Keywords: Arm swing, dopamine, Parkinson's disease, locomotion, asymmetry, gait

DOI: 10.3233/JPD-140447

Citation: Journal of Parkinson's Disease, vol. 5, no. 1, pp. 141-150, 2015

Authors: Tramontana, Michael G. | Molinari, Anna L. | Konrad, Peter E. | Davis, Thomas L. | Wylie, Scott A. | Neimat, Joseph S. | May, Alexandra T. | Phibbs, Fenna T. | Hedera, Peter | Gill, Chandler E. | Salomon, Ronald M. | Wang, Lily | Song, Yanna | Charles, David

Article Type: Research Article

Abstract: Background: Deep brain stimulation (DBS) is an effective treatment for patients with advanced Parkinson's disease (PD) and motor symptom complications. Recently, attention has been focused on whether offering DBS earlier in the course of PD is beneficial. Objective: The purpose of this study was to determine the effects of DBS on neuropsychological functioning in subjects with early stage PD. Methods: Thirty subjects with early PD (Hoehn & Yahr Stage II off medication) were randomized to optimal drug therapy (ODT) (n = 15) or bilateral subthalamic nucleus (STN) DBS+ODT (n = 15) after completing an expanded informed consent process specially designed …for the study and administered by a medical ethicist and the study team. Comprehensive neuropsychological testing was completed in the treatment-withdrawn state at baseline and at 12 month and 24 month follow-ups. Results: Two serious adverse events occurred in the DBS+ODT group. One subject experienced a stroke and another developed infected hardware that contributed to specific declines in cognitive functioning. However, compared to the ODT group, the remaining subjects in the DBS+ODT group exhibited modest reductions on a few measures of attention, executive function, and word fluency at 12 months. These differences were largely diminished at 24 months, especially when those with the adverse events were excluded. Conclusions: The results of this trial provide novel data regarding the effects of DBS on cognitive function in early PD. We believe that the findings and insights from this trial can help guide the safety analysis and risk-benefit evaluations in future discussions of DBS in early stage PD. Show more

Keywords: Parkinson's disease, deep brain stimulation, subthalamic nucleus, neuropsychological tests

DOI: 10.3233/JPD-140448

Citation: Journal of Parkinson's Disease, vol. 5, no. 1, pp. 151-163, 2015

Authors: Slevin, John T. | Fernandez, Hubert H. | Zadikoff, Cindy | Hall, Coleen | Eaton, Susan | Dubow, Jordan | Chatamra, Krai | Benesh, Janet

Article Type: Research Article

Abstract: Background: Levodopa-carbidopa intestinal gel (LCIG) is delivered continuously via intrajejunal percutaneous gastrostomy tube. Objective: To examine long-term safety, efficacy and quality of life of LCIG in an open-label extension study. Methods: Patients received 52 weeks of open-label LCIG treatment following a 12-week double-blind, double-dummy trial in which they were randomized to either LCIG or immediate-release oral levodopa-carbidopa. Patient cohort designation was by receipt of LCIG in the preceding trial randomization (continuing-LCIG vs. LCIG-naïve patients). Results: Sixty-two of 66 subjects in the double-blind proceeded to the open-label extension. Most subjects (95%) reported ≥1 adverse event (AE); only 3 subjects (4.8%) discontinued …due to AEs. AE incidence declined gradually over 52 weeks. Serious AEs were reported by 23%. LCIG-naïve patients (N = 29) showed a decrease in “Off” time and an increase in “On” time without troublesome dyskinesia (change from baseline to final visit in mean [SD] hours = −2.34 [2.78] P < 0.001 and 2.19 [3.70] P = 0.005, respectively), while continuing-LCIG patients (N = 33) showed sustained “Off” time duration and further improvement in “On” time without troublesome dyskinesia (−0.42 [2.67] P = 0.377 and 1.00 [2.58] P = 0.036, respectively). The majority of patients in both groups (LCIG-naïve, continuing-LCIG, respectively) were rated ‘Much Improved’ or ‘Very Much Improved’ at final visit on the Clinical Global Impression-Improvement scale (69.0%, 69.7%). Conclusions: Continuing-LCIG patients continued to derive benefit from LCIG while the magnitude of improvement among LCIG-naïve patients was similar to that observed for patients on LCIG in the preceding double-blind study. The overall AE profile was consistent with previous phase 3 clinical trials involving the LCIG system. Show more

Keywords: Parkinson's disease, levodopa-carbidopa intestinal gel, motor fluctuations, percutaneous endoscopic gastrostomy, clinical trial

DOI: 10.3233/JPD-140456

Citation: Journal of Parkinson's Disease, vol. 5, no. 1, pp. 165-174, 2015

Authors: Abbott, Sarah K. | Jenner, Andrew M. | Spiro, Adena S. | Batterham, Marijka | Halliday, Glenda M. | Garner, Brett

Article Type: Research Article

Abstract: Background: Oxidative stress contributes to Parkinson's disease (PD) etiology. Although previous studies have focused on sources of free radical formation in brain regions affected by PD, less is known regarding changes in lipid composition and the implications for susceptibility to peroxidation. Objective: To assess fatty acid profiles from control and PD tissues that are susceptible to PD pathology but devoid of severe destruction. Methods: We used gas chromatography methods to assess fatty acid profiles from control (n = 10) and PD (n = 9) postmortem tissues. We focused on the anterior cingulate cortex (ACC), a region that accumulates alpha-synuclein, but …does not undergo severe destruction, and compared this to the occipital cortex, a region that is pathologically spared. Results: Our data indicate a significant 33% increase in the proportion of polyunsaturated fatty acids (mol%) present in the PD ACC as compared to control ACC. Increases in highly unsaturated 22:5n-6 and 22:6n-3 fatty acids were particularly pronounced (109% and 73%, respectively). Calculation of a peroxidation index (accounting for total fatty acyl double bounds) indicated a 44% increase in susceptibility of the PD ACC to lipid peroxidation compared to control ACC. Such differences were not detected in the occipital cortex from the same donors. Assessment of F2 -isprostane levels confirmed that PD tissue lipids were more oxidized than controls. Conclusions: The global composition of fatty acids in the PD ACC is altered in a way that increases susceptibility to peroxidation in a region-specific manner. This has important implications for PD, supporting the oxidative stress hypothesis of PD pathogenesis. Show more

Keywords: Parkinson's disease, fatty acids, lipid peroxidation, F2-isoprostanes, oxidative stress, postmortem tissue analysis

DOI: 10.3233/JPD-140479

Citation: Journal of Parkinson's Disease, vol. 5, no. 1, pp. 175-185, 2015

Authors: Serrano, J. Artur | Larsen, Frank | Isaacs, Tom | Matthews, Helen | Duffen, Joy | Riggare, Sara | Capitanio, Fulvio | Ferreira, Joaquim J. | Domingos, Josefa | Maetzler, Walter | Graessner, Holm | SENSE-PARK Consortium

Article Type: Research Article

Abstract: Background: There is a growing interest in the objective assessment of health related outcomes using technology providing quality measurements to be applied not only in daily clinical practice, but also in scientific research. Differences in the understandings of the condition and the terminology used between people with Parkinson's (PwPs), clinicians and technical developers may influence the progress of a participatory design process. Objective: This paper reports on a participatory design process to achieve a consensus among PwPs, clinicians and technologists over the selection of a set of symptomatic domains to be continuously assessed, in order to provide results relevant to …both PwPs and clinicians. Methods: The methods used were a Web based user survey, end-user focus groups, ranking by combined methods, a Delphi process performed among clinicians and scientists, and prioritization of the results in a concertation workshop for PwPs, clinicians and technologists. Results: The following symptomatic domains were commonly agreed by PwPs and clinicians to be of central importance in a system of continuous assessment: hypokinesia/bradykinesia, tremor, sway, gait, sleep and cognition. This list satisfied both the needs of the PwPs and the concerns of the clinicians regarding the means of advancing new strategies in assessment and interventions in PD. Conclusions: A participatory design strategy allowed the definition of a consensual list of symptomatic domains. Both the strategy and the achieved results may be of relevance for similar interdisciplinary approaches in the field of PD using a participatory design involving patients, clinicians and technologists. Show more

Keywords: Parkinson's Disease (PD), People with Parkinson's (PwPs), participatory design, assessment strategies, biomarkers, chronic disease management, combined methods, degenerative disease, diagnostic markers, focus group, symptomatic domain, monitoring

DOI: 10.3233/JPD-140472

Citation: Journal of Parkinson's Disease, vol. 5, no. 1, pp. 187-196, 2015