Continuous intrajejunal infusion of levodopa-carbidopa intestinal gel for patients with advanced Parkinson's disease: a randomised, controlled, double-blind, double-dummy study

Lancet Neurol. 2013 Dec 19. pii: S1474-4422(13)70293-X. doi: 10.1016/S1474-4422(13)70293-X. [Epub ahead of print]

Olanow CW, Kieburtz K, Odin P, Espay AJ, Standaert DG, Fernandez HH, Vanagunas A, Othman AA, Widnell KL, Robieson WZ, Pritchett Y, Chatamra K, Benesh J, Lenz RA, Antonini A; for the LCIG Horizon Study Group.

Abstract

BACKGROUND:

Levodopa is the most effective therapy for Parkinson's disease, but chronic treatment is associated with the development of potentially disabling motor complications. Experimental studies suggest that motor complications are due to non-physiological, intermittent administration of the drug, and can be reduced with continuous delivery. We aimed to assess efficacy and safety of levodopa-carbidopa intestinal gel delivered continuously through an intrajejunal percutaneous tube.

METHODS:

In our 12-week, randomised, double-blind, double-dummy, double-titration trial, we enrolled adults (aged ≥30 years) with advanced Parkinson's disease and motor complications at 26 centres in Germany, New Zealand, and the USA. Eligible participants had jejunal placement of a percutaneous gastrojejunostomy tube, and were then randomly allocated (1:1) to treatment with immediate-release oral levodopa-carbidopa plus placebo intestinal gel infusion or levodopa-carbidopa intestinal gel infusion plus oral placebo. Randomisation was stratified by site, with a mixed block size of 2 or 4. The primary endpoint was change from baseline to final visit in motor off-time. We assessed change in motor on-time without troublesome dyskinesia as a prespecified key secondary outcome. We assessed efficacy in a full-analysis set of participants with data for baseline and at least one post-baseline assessment, and imputed missing data with the last observation carried forward approach. We assessed safety in randomly allocated patients who underwent the percutaneous gastrojejunostomy procedure. This study is registered with ClinicalTrials.gov, numbers NCT00660387 and NCT0357994.

FINDINGS:

From baseline to 12 weeks in the full-analysis set, mean off-time decreased by 4·04 h (SE 0·65) for 35 patients allocated to the levodopa-carbidopa intestinal gel group compared with a decrease of 2·14 h (0·66) for 31 patients allocated to immediate-release oral levodopa-carbidopa (difference -1·91 h [95% CI -3·05 to -0·76]; p=0·0015). Mean on-time without troublesome dyskinesia increased by 4·11 h (SE 0·75) in the intestinal gel group and 2·24 h (0·76) in the immediate-release oral group (difference 1·86 [95% CI 0·56 to 3·17]; p=0·0059). In the safety analyses 35 (95%) of 37 patients allocated to the levodopa-carbidopa intestinal gel group had adverse events (five [14%] serious), as did 34 (100%) of 34 patients allocated to the immediate-release oral levodopa-carbidopa group (seven [21%] serious), mainly associated with the percutaneous gastrojejunostomy tube.

INTERPRETATION:

Continuous delivery of levodopa-carbidopa with an intestinal gel offers a promising option for control of advanced Parkinson's disease with motor complications. Benefits noted with intestinal gel delivery were of a greater magnitude than were those obtained with medical therapies to date, and our study is, to our knowledge, the first demonstration of the benefit of continuous levodopa delivery in a double-blind controlled study.

FUNDING:

AbbVie.

Characterizing mild cognitive impairment in incident Parkinson disease: The ICICLE-PD Study

Neurology. 2013 Dec 20. [Epub ahead of print]

Yarnall AJ, Breen DP, Duncan GW, Khoo TK, Coleman SY, Firbank MJ, Nombela C, Winder-Rhodes S, Evans JR, Rowe JB, Mollenhauer B, Kruse N, Hudson G, Chinnery PF, O'Brien JT, Robbins TW, Wesnes K, Brooks DJ, Barker RA, Burn DJ; On behalf of the ICICLE-PD Study Group.

Author information

From the Institute for Ageing and Health (A.J.Y., G.W.D., M.J.F., D.J.B.), Industrial Statistics Research Unit (S.Y.C.), and Institute of Genetic Medicine (G.H., P.F.C.), Newcastle University; John van Geest Centre for Brain Repair (D.P.B., J.R.E., R.A.B.), Department of Clinical Neurosciences (C.N., S.W.-R., J.B.R.), Behavioural and Clinical Neuroscience Institute (C.N., S.W.-R., J.B.R., T.W.R.), MRC Cognition and Brain Sciences Unit (C.N., S.W.-R., J.B.R.), Departments of Psychiatry (J.T.O.) and Psychology (T.W.R.), University of Cambridge, UK; School of Medicine (T.K.K.), Griffith University, Australia; Paracelsus-Elena-Klinik (B.M.), Kassel, and Göttingen University; Institute for Neuropathology (N.K.), Prion and Dementia Research Unit, University Medical Centre Göttingen, Germany; Centre for Human Psychopharmacology (K.W.), Swinburne University, Melbourne, Australia; and Department of Medicine (D.J.W.), Imperial College London, UK.

Abstract

OBJECTIVE:

To describe the frequency of mild cognitive impairment (MCI) in Parkinson disease (PD) in a cohort of newly diagnosed incident PD cases and the associations with a panel of biomarkers.

METHODS:

Between June 2009 and December 2011, 219 subjects with PD and 99 age-matched controls participated in clinical and neuropsychological assessments as part of a longitudinal observational study. Consenting individuals underwent structural MRI, lumbar puncture, and genotyping for common variants of COMT, MAPT, SNCA, BuChE, EGF, and APOE. PD-MCI was defined with reference to the new Movement Disorder Society criteria.

RESULTS:

The frequency of PD-MCI was 42.5% using level 2 criteria at 1.5 SDs below normative values. Memory impairment was the most common domain affected, with 15.1% impaired at 1.5 SDs. Depression scores were significantly higher in those with PD-MCI than the cognitively normal PD group. A significant correlation was found between visual Pattern Recognition Memory and cerebrospinal β-amyloid 1-42 levels (β standardized coefficient = 0.350; p = 0.008) after controlling for age and education in a linear regression model, with lower β-amyloid 1-42 and 1-40 levels observed in those with PD-MCI. Voxel-based morphometry did not reveal any areas of significant gray matter loss in participants with PD-MCI compared with controls, and no specific genotype was associated with PD-MCI at the 1.5-SD threshold.

CONCLUSIONS:

In a large cohort of newly diagnosed PD participants, PD-MCI is common and significantly correlates with lower cerebrospinal β-amyloid 1-42 and 1-40 levels. Future longitudinal studies should enable us to determine those measures predictive of cognitive decline.

Risk of obstructive sleep apnea in Parkinson's disease: a meta-analysis

PLoS One. 2013 Dec 9;8(12):e82091. doi: 10.1371/journal.pone.0082091.

Zeng J, Wei M, Li T, Chen W, Feng Y, Shi R, Song Y, Zheng W, Ma W.

Author information

Institute of Genetic Engineering, Southern Medical University, Guangzhou, Guangdong, P. R. China.

Sleep Center, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, P. R. China.

Department of Urology, Nanfang hospital, Southern Medical University, Guangzhou, Guangdong. P. R. China.

Abstract

STUDY OBJECTIVES:

Sleep disorders are a common symptom of Parkinson's disease (PD) and they significantly impair the sleep quality of the PD patients. However, there is no conclusive evidence to support the relation between PD and the prevalence of obstructive sleep apnea (OSA). The purpose of this meta-analysis review is to evaluate the association between PD and the prevalence of OSA.

METHODS:

A comprehensive literature search was conducted on PubMed and Embase through July 2013. Only studies that referred to PD and the prevalence of OSA and that met the selection criteria were included in the analysis. The odds ratios (ORs) were used to evaluate the relationship of PD and the prevalence of OSA by the fixed-effect model.

RESULTS:

Five eligible studies were analyzed in this study including 322 cases and 6,361 controls. The pooled-analysis showed the OR to be 0.60 (95% confidence interval (CI): 0.44 to 0.81, P = 0.001) and I(2) = 0.0% (χ(2) = 3.90, P = 0.420) in the fixed-effect model.

CONCLUSIONS:

Although we only included five small sample studies that indicated high homogeneity in the heterogeneity test, the results suggest that there is a significant negative association between PD and the prevalence of OSA; PD patients generally have a reduced prevalence of OSA. According to our analysis, these results are primarily due to the lower BMI of PD patients when compared with the general population controls.

Automatic and objective assessment of alternating tapping performance in Parkinson's disease.

Sensors (Basel). 2013 Dec 9;13(12):16965-84. doi: 10.3390/s131216965.

Memedi M, Khan T, Grenholm P, Nyholm D, Westin J.

Author information

School of Technology and Business Studies, Computer Engineering, Dalarna University, Falun SE-791 88, Sweden.

Abstract

This paper presents the development and evaluation of a method for enabling quantitative and automatic scoring of alternating tapping performance of patients with Parkinson's disease (PD). Ten healthy elderly subjects and 95 patients in different clinical stages of PD have utilized a touch-pad handheld computer to perform alternate tapping tests in their home environments. First, a neurologist used a web-based system to visually assess impairments in four tapping dimensions ('speed', 'accuracy', 'fatigue' and 'arrhythmia') and a global tapping severity (GTS). Second, tapping signals were processed with time series analysis and statistical methods to derive 24 quantitative parameters. Third, principal component analysis was used to reduce the dimensions of these parameters and to obtain scores for the four dimensions. Finally, a logistic regression classifier was trained using a 10-fold stratified cross-validation to map the reduced parameters to the corresponding visually assessed GTS scores. Results showed that the computed scores correlated well to visually assessed scores and were significantly different across Unified Parkinson's Disease Rating Scale scores of upper limb motor performance. In addition, they had good internal consistency, had good ability to discriminate between healthy elderly and patients in different disease stages, had good sensitivity to treatment interventions and could reflect the natural disease progression over time. In conclusion, the automatic method can be useful to objectively assess the tapping performance of PD patients and can be included in telemedicine tools for remote monitoring of tapping.

Inosine to Increase Serum and Cerebrospinal Fluid Urate in Parkinson Disease: A Randomized Clinical Trial

JAMA Neurol. 2013 Dec 23. doi: 10.1001/jamaneurol.2013.5528. [Epub ahead of print]

The Parkinson Study Group SURE-PD Investigators, Schwarzschild MA, Ascherio A, Beal MF, Cudkowicz ME, Curhan GC, Hare JM, Hooper DC, Kieburtz KD, Macklin EA, Oakes D, Rudolph A, Shoulson I, Tennis MK, Espay AJ, Gartner M, Hung A, Bwala G, Lenehan R, Encarnacion E, Ainslie M, Castillo R, Togasaki D, Barles G, Friedman JH, Niles L, Carter JH, Murray M, Goetz CG, Jaglin J, Ahmed A, Russell DS, Cotto C, Goudreau JL, Russell D, Parashos SA, Ede P, Saint-Hilaire MH, Thomas CA, James R, Stacy MA, Johnson J, Gauger L, Antonelle de Marcaida J, Thurlow S, Isaacson SH, Carvajal L, Rao J, Cook M, Hope-Porche C, McClurg L, Grasso DL, Logan R, Orme C, Ross T, Brocht AF, Constantinescu R, Sharma S, Venuto C, Weber J, Eaton K.

Abstract

IMPORTANCE Convergent biological, epidemiological, and clinical data identified urate elevation as a candidate strategy for slowing disability progression in Parkinson disease (PD). OBJECTIVE To determine the safety, tolerability, and urate-elevating capability of the urate precursor inosine in early PD and to assess its suitability and potential design features for a disease-modification trial. DESIGN, SETTING, AND PARTICIPANTS The Safety of Urate Elevation in PD (SURE-PD) study, a randomized, double-blind, placebo-controlled, dose-ranging trial of inosine, enrolled participants from 2009 to 2011 and followed them for up to 25 months at outpatient visits to 17 credentialed clinical study sites of the Parkinson Study Group across the United States. Seventy-five consenting adults (mean age, 62 years; 55% women) with early PD not yet requiring symptomatic treatment and a serum urate concentration less than 6 mg/dL (the approximate population median) were enrolled. INTERVENTIONS Participants were randomized to 1 of 3 treatment arms: placebo or inosine titrated to produce mild (6.1-7.0 mg/dL) or moderate (7.1-8.0 mg/dL) serum urate elevation using 500-mg capsules taken orally up to 2 capsules 3 times per day. They were followed for up to 24 months (median, 18 months) while receiving the study drug plus 1 washout month. MAIN OUTCOMES AND MEASURES The prespecified primary outcomes were absence of unacceptable serious adverse events (safety), continued treatment without adverse event requiring dose reduction (tolerability), and elevation of urate assessed serially in serum and once (at 3 months) in cerebrospinal fluid. RESULTS Serious adverse events (17), including infrequent cardiovascular events, occurred at the same or lower rates in the inosine groups relative to placebo. No participant developed gout and 3 receiving inosine developed symptomatic urolithiasis. Treatment was tolerated by 95% of participants at 6 months, and no participant withdrew because of an adverse event. Serum urate rose by 2.3 and 3.0 mg/dL in the 2 inosine groups (P < .001 for each) vs placebo, and cerebrospinal fluid urate level was greater in both inosine groups (P = .006 and <.001, respectively). Secondary analyses demonstrated nonfutility of inosine treatment for slowing disability. CONCLUSIONS AND RELEVANCE Inosine was generally safe, tolerable, and effective in raising serum and cerebrospinal fluid urate levels in early PD. The findings support advancing to more definitive development of inosine as a potential disease-modifying therapy for PD. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00833690.

Female reproductive factors, menopausal hormone use, and Parkinson's disease

Mov Disord. 2013 Dec 18. doi: 10.1002/mds.25771. [Epub ahead of print]

Liu R, Baird D, Park Y, Freedman ND, Huang X, Hollenbeck A, Blair A, Chen H.

Author information

Epidemiology Branch of the National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina.

Abstract

The objective of this study was to examine the associations of reproductive factors and exogenous hormone use with risk of Parkinson's disease (PD) among postmenopausal women. The study comprised 119,166 postmenopausal women aged 50 to 71 years in the NIH-AARP Diet and Health Study, who completed a baseline questionnaire in 1995-1996 and a follow-up survey in 2004-2006. A total of 410 self-reported PD diagnoses were identified between 1995 and 2006. Multivariate odds ratios (ORs) and 95% confidence intervals (CIs) were derived from logistic regression models. PD risk was not significantly associated with female reproductive factors including age at menarche, age at first live birth, parity, and age at menopause. For example, compared with women with natural menopause at age 50 to 54 years, the ORs were 1.18, (95% CI, 0.78-1.79) for women with natural menopause aged <45, 1.19 (95% CI, 0.88-1.61) for those aged 45 to 49, and 1.33 (95% CI, 0.91-1.93) for those aged 55 or older. We found that oral contraceptive use for ≥10 years (vs. never used) was associated with lower PD risk (OR, 0.59; 95% CI, 0.38-0.92), but shorter use showed no association. Use of menopausal hormone therapy showed inconsistent results. Compared with non-hormone users at baseline, current hormone users for <5 years showed a higher risk of PD (OR, 1.52; 95% CI, 1.11-2.08). However, no associations were observed for past hormone users or current users of ≥5 years. Overall, this large prospective study provides little support for an association between female reproductive factors and PD risk. Our findings on long-term oral contraceptive use and current hormone therapy warrant further investigations. © 2013 International Parkinson and Movement Disorder Society.

Driving errors in Parkinson's disease: moving closer to predicting on-road outcomes

Am J Occup Ther. 2014 Jan-Feb;68(1):77-85. doi: 10.5014/ajot.2014.008698.

Classen S, Brumback B, Monahan M, Malaty II, Rodriguez RL, Okun MS, McFarland NR.

Abstract

Age-related medical conditions such as Parkinson's disease (PD) compromise driver fitness. Results from studies are unclear on the specific driving errors that underlie passing or failing an on-road assessment. In this study, we determined the between-group differences and quantified the on-road driving errors that predicted pass or fail on-road outcomes in 101 drivers with PD (mean age = 69.38 ± 7.43) and 138 healthy control (HC) drivers (mean age = 71.76 ± 5.08). Participants with PD had minor differences in demographics and driving habits and history but made more and different driving errors than HC participants. Drivers with PD failed the on-road test to a greater extent than HC drivers (41% vs. 9%), χ²(1) = 35.54, HC N = 138, PD N = 99, p < .001. The driving errors predicting on-road pass or fail outcomes (95% confidence interval, Nagelkerke R² =.771) were made in visual scanning, signaling, vehicle positioning, speeding (mainly underspeeding, t(61) = 7.004, p < .001, and total errors. Although it is difficult to predict on-road outcomes, this study provides a foundation for doing so.

α-synuclein in the appendiceal mucosa of neurologically intact subjects.

Mov Disord. 2013 Dec 18. doi: 10.1002/mds.25779. [Epub ahead of print]

Gray MT, Munoz DG, Gray DA, Schlossmacher MG, Woulfe JM.

Author information

Centre for Cancer Therapeutics, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada; Department of Pathology and Laboratory Medicine, Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada; Department of Biochemistry, Microbiology and Immunology, Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada.

Abstract

Parkinson's disease is characterized by the pathological aggregation of α-synuclein. The dual-hit hypothesis proposed by Braak implicates the enteric nervous system as an initial site of α-synuclein aggregation with subsequent spread to the central nervous system. Regional variations in the spatial pattern or levels of α-synuclein along the enteric nervous system could have implications for identifying sites of onset of this pathogenic cascade. We performed immunohistochemical staining for α-synuclein on gastrointestinal tissue from patients with no history of neurological disease using the established LB509 antibody and a new clone, MJFR1, characterized for immunohistochemistry here. We demonstrate that the vermiform appendix is particularly enriched in α-synuclein-containing axonal varicosities, concentrated in its mucosal plexus rather than the classical submucosal and myenteric plexuses. Unexpectedly, intralysosomal accumulations of α-synuclein were detected within mucosal macrophages of the appendix. The abundance and accumulation of α-synuclein in the vermiform appendix implicate it as a candidate anatomical locus for the initiation of enteric α-synuclein aggregation and permits the generation of testable hypotheses for Parkinson's disease pathogenesis.

Effect of subthalamic nucleus deep brain stimulation on driving in Parkinson disease

Neurology. 2013 Dec 18. [Epub ahead of print]

Buhmann C, Maintz L, Hierling J, Vettorazzi E, Moll CK, Engel AK, Gerloff C, Hamel W, Zangemeister WH.

Author information

From the Departments of Neurology (C.B., L.M., J.H., C.G., W.H.Z.), Medical Biometry and Epidemiology (E.V.), Neurophysiology and Pathophysiology (C.K.E.M., A.K.E.), and Neurosurgery (W.H.), University Medical Center Hamburg-Eppendorf, Hamburg, Germany.

Abstract

OBJECTIVE:

To examine the influence of subthalamic nucleus (STN) deep brain stimulation (DBS) on driving in patients with Parkinson disease (PD).

METHODS:

Using a driving simulator setup proven to reflect on-road driving, 2 main analyses were performed: 1) comparison of driving performance among 23 patients with deep brain surgery (DBS patients), 21 patients without surgery (no-DBS patients), and 21 controls; and 2) analysis of the effect of stimulation vs levodopa on driving performance. To this end, 3 tests were run in the medicated DBS patient cohort, with 3 different conditions: "stimulation on" (STIM) (equated to daily treatment), "stimulation off" (OFF), and "stimulation off/levodopa" (LD) (dosage aimed at maintaining motor status). Differences in driving times and errors among conditions were analyzed.

RESULTS:

Age and cognitive deficits influenced driving performance negatively. The no-DBS patient group performed worse in driving time and driving errors than controls. DBS patients drove slower than controls and no-DBS patients. Driving safety was comparable to controls but higher than in no-DBS patients. Within the DBS patient group, driving was more accurate with STIM than with LD, although motor effects did not differ. Driving with STIM, but not with LD, was superior to driving in the OFF condition.

CONCLUSION:

DBS of the STN seems to have a beneficial effect on driving ability in patients with PD, potentially because of nonmotor driving-relevant aspects. Our data suggest that driving permission for DBS-treated patients with PD should not be handled more restrictively than permissions for patients with PD in general.

CLASSIFICATION OF EVIDENCE:

This study provides Class IV evidence that STN-DBS in patients with PD is associated with a reduction in driving errors and improvements in driving accuracy in driving simulations.

MIBG myocardial scintigraphy in pre-motor Parkinson's disease: A review

Parkinsonism Relat Disord. 2013 Nov 21. pii: S1353-8020(13)00393-3. doi: 10.1016/j.parkreldis.2013.11.001. [Epub ahead of print]

Sakakibara R, Tateno F, Kishi M, Tsuyusaki Y, Terada H, Inaoka T.

Abstract

OBJECTIVES:

Detecting very early markers of neurodegeneration that predate the diagnosis of idiopathic Parkinson's disease (PD) is a crucial research topic for the development of disease-modifying therapeutic interventions. Recently 123I-metaiodobenzylguanidine (MIBG) myocardial scintigraphy has become widely used for this purpose, since this test shows high sensitivity and specificity in the diagnosis of PD, based on evidence that cardiac sympathetic nerve fibers are affected early and commonly in PD. We reviewed the literature to determine the role of MIBG myocardial scintigraphy for diagnosing pre-motor PD.

METHODS:

We performed a systematic review of the literature to identify the use of MIBG myocardial scintigraphy in relation to the constellation of pre-motor symptoms in PD.

RESULTS:

Mild memory disorder, autonomic failure (constipation and postural hypotension), depression/anxiety, visual hallucination/psychosis (in the elderly), sleep disorder (REM sleep behavior disorder), and impaired olfaction are reported to appear as sole initial symptoms of PD. All clinical features except for impaired olfaction are accompanied by low MIBG uptake, suggestive of very early PD in situ.

CONCLUSION:

Identifying persons with mild memory disorder, constipation/postural hypotension, depression/anxiety, visual hallucination/psychosis (in the elderly), and REM sleep behavior disorder associated with low MIBG uptake may provide a unique opportunity to detect very early PD in situ within a pre-clinical window. Future prospective studies to investigate further the findings of these early cases are warranted.

Substantia nigra in Parkinson's disease: a multimodal MRI comparison between early and advanced stages of the disease.

Neurol Sci. 2013 Dec 11. [Epub ahead of print]

Aquino D, Contarino V, Albanese A, Minati L, Farina L, Grisoli M, Elia A, Bruzzone MG, Chiapparini L.

Author information

Neuroradiology Department, IRCCS Foundation Neurological Institute Carlo Besta, Via Celoria, 11, 20133, Milan, Italy

Abstract

This study focused on the substantia nigra (SN) in Parkinson's disease (PD). We measured its area and volume, mean diffusivity (MD), fractional anisotropy (FA) and iron concentration in early and late PD and correlated the values with clinical scores. Twenty-two early PD (EPD), 20 late PD (LPD) and 20 healthy subjects (age 64.7 ± 4.9, 60.5 ± 6.1, and 61 ± 7.2 years, respectively) underwent 1.5 T MR imaging with double-TI-IR T1-weighted, T2*-weighted and diffusion tensor imaging scans. Relative SN area, MD, FA and R2* were measured in ROIs traced on SN. Correlation with Unified Parkinson Disease Rating Scale (UPDRS) scores was assessed. In LPD, the SN area was significantly reduced with respect to EPD (p = 0.04) and control subjects (p < 0.001). In EPD, the SN area was also significantly smaller than in controls (p = 0.006). Similarly, the SN volume significantly differed between LPD and controls (p = 0.001) and between EPD and LPD (p = 0.049), while no significant differences were found between controls and EPD. Both SN area (r = 0.47, p = 0.004) and volume (r = 0.46, p = 0.005) correlated with UPDRS scores. At 1.5 T, SN morphological measurements were sensitive to early PD changes and able to track the disease progression, while MD and FA measures and relaxometry did not provide significant results.

Assessing plasma levels of selenium, copper, iron and zinc in patients of Parkinson's disease

PLoS One. 2013 Dec 10;8(12):e83060. doi: 10.1371/journal.pone.0083060.

Zhao HW, Lin J, Wang XB, Cheng X, Wang JY, Hu BL, Zhang Y, Zhang X, Zhu JH.

Department of Preventive Medicine, Wenzhou Medical University, Wenzhou, Zhejiang, China.

Abstract

Trace elements have been recognized to play an important role in the development of Parkinson's disease (PD). However, it is difficult to precisely identify the relationship between these elements and the progression of PD because of an insufficient number of patients. In this study, quantifications of selenium (Se), copper (Cu), iron (Fe) and zinc (Zn) by atomic absorption spectrophotometry were performed in plasma from 238 PD patients and 302 controls recruited from eastern China, which is so far the largest cohort of PD patients and controls for measuring plasma levels of these elements. We found that plasma Se and Fe concentrations were significantly increased whereas Cu and Zn concentrations decreased in PD patients as compared with controls. Meanwhile, these four elements displayed differential changes with regard to age. Linear and logistic regression analyses revealed that both Fe and Zn were negatively correlated with age in PD patients. Association analysis suggests that lower plasma Se and Fe levels may reduce the risk for PD, whereas lower plasma Zn is probably a PD risk factor. Finally, a model was generated to predict PD patients based on the plasma concentrations of these four trace elements as well as other features such as sex and age, which achieved an accuracy of 80.97±1.34% using 10-fold cross-validation. In summary, our data provide new insights into the roles of Se, Cu, Fe and Zn in PD progression.

Retinal thinning and correlation with functional disability in patients with Parkinson's disease.

Br J Ophthalmol. 2013 Nov 25. doi: 10.1136/bjophthalmol-2013-304152. [Epub ahead of print]

Satue M, Seral M, Otin S, Alarcia R, Herrero R, Bambo MP, Fuertes MI, Pablo LE, Garcia-Martin E.

Source

Ophthalmology Department, Miguel Servet University Hospital, Zaragoza, Spain.

Abstract

AIMS:

To determine whether there is an association between retinal thinning and functional rating scales in patients with Parkinson's disease (PD).

MATERIALS AND METHODS:

Patients with PD (n=153) and controls (n=242) underwent evaluations of the macula and retinal nerve fibre layer (RNFL) using two new-generation Fourier domain optical coherence tomography (OCT) devices (Cirrus, Carl Zeiss Meditec, Dublin, California, USA; Spectralis, Heidelberg Engineering, Heidelberg, Germany). PD severity was assessed using the Schwab-England Activities of Daily Living scale, the Unified Parkinson Disease Rating Scale, the Hoehn and Yahr (HY) scale. Retinal and RNFL thicknesses were compared between patients and controls. Correlations between structural parameters and the scores of the neurologic scales were evaluated.

RESULTS:

RNFL parameters were significantly reduced in patients with PD, especially when using the Spectralis OCT device. All macular parameters, except for foveal thickness, differed significantly between controls and patients with PD (p<0.001). HY scores were significantly and inversely correlated with all macular parameters when measured with the Spectralis OCT device (p<0.05) and with RNFL thickness when measured with the Cirrus OCT device (nasal quadrant, sectors 2 and 5).

CONCLUSIONS:

The neurodegeneration caused by PD can be detected using Fourier domain OCT. RNFL and macular thicknesses correlate with PD severity.

Early DEtection of wEaring off in Parkinson disease: The DEEP study

Parkinsonism Relat Disord. 2013 Nov 5. pii: S1353-8020(13)00390-8. doi: 10.1016/j.parkreldis.2013.10.027. [Epub ahead of print]

Stocchi F, Antonini A, Barone P, Tinazzi M, Zappia M, Onofrj M, Ruggieri S, Morgante L, Bonuccelli U, Lopiano L, Pramstaller P, Albanese A, Attar M, Posocco V, Colombo D, Abbruzzese G; DEEP study group.

Source

Department of Neurology, Institute of Research and Medical Care, IRCCS San Raffaele, Rome, Italy. Electronic address: fabrizio.stocchi@tin.it.

Abstract

OBJECTIVE:

Assessing the frequency of Wearing-Off (WO) in Parkinson's disease (PD) patients, and its impact on Quality of Life (QoL).

METHODS:

Consecutive ambulatory patients, who were on dopaminergic treatment for ≥1 year, were included in this multicentre, observational cross-sectional study. In a single visit, WO was diagnosed based on neurologist assessment as well as using the validated Italian version of a patient self-rated 19-question Wearing-Off Questionnaire (WOQ-19); WO was defined for scores ≥ 2. QoL was evaluated by the 8-item Parkinson's Disease Questionnaire (PDQ-8).

RESULTS:

617 subjects were included, with a mean anti-Parkinson treatment duration of 6.6 ± 4.6 years, 87.2% were on levodopa treatment. Neurologists identified presence of WO in 351 subjects (56.9%), whereas 415 subjects (67.3%) were identified by the self-administered WOQ-19. In patients with a <2.5 years disease duration, WO was diagnosed in 12 subjects (21.8%) by neurologists and in 23 subjects (41.8%) by the WOQ-19. The most frequent WO symptoms, as identified by WOQ-19, were "slowness of movements" (55.8%) and "reduced dexterity" (48.8%). Younger age, female gender, Unified Parkinson's Disease Rating Scale (UPDRS) part II score and duration of anti-Parkinson treatment were found significantly associated with WO. The number of motor (p < 0.0001) and non-motor (p < 0.0001) WO symptoms correlated with PDQ-8 total score.

CONCLUSIONS:

WO is common already at the early stages of PD and is underestimated by routine neurological clinical evaluation. The number of WO symptoms, both motor and non motor, increases along with disease duration and has a negative impact on patients QoL.

Objective measurement of daytime napping, cognitive dysfunction and subjective sleepiness in Parkinson's disease

PLoS One. 2013 Nov 21;8(11):e81233. doi: 10.1371/journal.pone.0081233.

Bolitho SJ, Naismith SL, Salahuddin P, Terpening Z, Grunstein RR, Lewis SJ.

Source

Parkinson's Disease Clinic, Brain and Mind Research Institute, The University of Sydney, Sydney, New South Wales, Australia.

Abstract

INTRODUCTION:

Sleep-wake disturbances and concomitant cognitive dysfunction in Parkinson's disease (PD) contribute significantly to morbidity in patients and their carers. Subjectively reported daytime sleep disturbance is observed in over half of all patients with PD and has been linked to executive cognitive dysfunction. The current study used daytime actigraphy, a novel objective measure of napping and related this to neuropsychological performance in a sample of PD patients and healthy, age and gender-matched controls. Furthermore this study aimed to identify patients with PD who may benefit from pharmacologic and behavioural intervention to improve these symptoms.

METHODS:

Eighty-five PD patients and 21 healthy, age-matched controls completed 14 days of wrist actigraphy within two weeks of neuropsychological testing. Objective napping measures were derived from actigraphy using a standardised protocol and subjective daytime sleepiness was recorded by the previously validated Epworth Sleepiness Scale.

RESULTS:

Patients with PD had a 225% increase in the mean nap time per day (minutes) as recorded by actigraphy compared to age matched controls (39.2 ± 35.2 vs. 11.5 ± 11.0 minutes respectively, p < 0.001). Significantly, differences in napping duration between patients, as recorded by actigraphy were not distinguished by their ratings on the subjective measurement of excessive daytime sleepiness. Finally, those patients with excessive daytime napping showed greater cognitive deficits in the domains of attention, semantic verbal fluency and processing speed.

CONCLUSION:

This study confirms increased levels of napping in PD, a finding that is concordant with subjective reports. However, subjective self-report measures of excessive daytime sleepiness do not robustly identify excessive napping in PD. Fronto-subcortical cognitive dysfunction was observed in those patients who napped excessively. Furthermore, this study suggests that daytime actigraphy, a non-invasive and inexpensive objective measure of daytime sleep, can identify patients with PD who may benefit from pharmacologic and behavioural interventions to improve these symptoms.