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Background: The relation between dementia with Lewy bodies (DLB) and Parkinson's disease with dementia (PDD) is unknown. Objectives: To compare the cognitive profiles of patients with DLB and PDD, and [...]

Objectives: To examine the development of nocturnal sleeping problems in patients with Parkinson's disease (PD) over an 8-year period and to study the clinical and demographic correlates of insomnia.Methods: 231 patients were included in a population-based prevalence study in 1993, and re-examined in 1997 and 2001. At all study visits, we applied semi-structured interviews to obtain information on clinical and demographic data, as well as on nocturnal sleeping problems. Standardised rating scales of parkinsonism, depression and cognitive impairment were used. The relationship between insomnia and demographic and clinical variables was analysed using population-averaged logistic regression models for correlated data. 231 patients were included at baseline, 142 were available for re-evaluation in 1997 and 89 patients in 2001.Results: Most nocturnal sleeping problems varied little in prevalence over time, whereas problems related to turning in bed and vivid dreaming or nightmares increased. Insomnia was present in 54-60% of the patients at each of the three study visits and varied considerably in individual patients over time. The presence of insomnia was closely related to disease duration, higher Montgomery-Asberg Depression Rating Scale scores and female sex.Conclusion: Insomnia is a highly frequent complaint in patients with PD. It fluctuates over time in individual patients, and its origin seems to be multifactorial. Physicians should be aware of the high prevalence of insomnia in patients with PD and should examine their patients for a possible coexisting depression. [ABSTRACT FROM AUTHOR]

Background: Dementia is common in Parkinson's disease, but the underlying brain pathology is not yet fully understood.Aim: To examine the changes in the brain of patients with Parkinson's disease with mild cognitive impairment (MCI) and dementia, using structural magnetic resonance imaging.Methods: Using voxel-based morphometry, the grey matter atrophy on brain images of patients with Parkinson's disease and dementia (PDD; n = 16) and Parkinson's disease without dementia (PDND; n = 20), and healthy elderly subjects (n = 20) was studied. In the PDND group, 12 subjects had normal cognitive status and 8 had MCI. Standardised rating scales for motor, cognitive and psychiatric symptoms were used.Results: Widespread areas of cortical atrophy were found in patients with PDD compared with normal controls (in both temporal and frontal lobes and in the left parietal lobe). Grey matter reductions were found in frontal, parietal, limbic and temporal lobes in patients with PDD compared with those with PDND. In patients with PDND with MCI, areas of reduced grey matter in the left frontal and both temporal lobes were found.Conclusion: These findings show that dementia in Parkinson's disease is associated with structural neocortical changes in the brain, and that cognitive impairment in patients with PDND may be associated with structural changes in the brain. Further studies with larger groups of patients are needed to confirm these findings. [ABSTRACT FROM AUTHOR]

Objectives: To examine the change over time in health related quality of life (HRQL) in a community based cohort of patients with Parkinson's disease.Methods: One hundred and eleven patients were evaluated for HRQL in 1993 and then again in a follow up study 4 years later. The patients included in the study in 1993 were derived from a prevalence study of patients with Parkinson's disease in the county of Rogaland, Norway. The HRQL was measured by the Nottingham health profile (NHP). At both evaluations clinical and demographic variables were determined during semistructured interviews and by clinical examinations by a neurologist.Results: During the 4 year follow up period there was a significant increase in NHP scores, reflecting a decreased HRQL, in the dimensions of physical mobility, emotional reactions, pain, and social isolation. In the same time period mean total NHP score increased from 120.0 (SD 102.6) to 176.0 (SD 119.4) (p<0.01). There were no clinical or demographic factors found in 1993 that identified patients at higher risk for developing decreased HRQL. Increased UPDRS score (unified Parkinson's disease rating scale) and Hoehn and Yahr stage during the 4 year study period correlated with increased NHP scores. Even though there was no increase in depressive symptoms or self reported insomnia, these symptoms, together with lower Schwab and England score, were the most important factors for a poor HRQL in 1997.Conclusions: Parkinson's disease has a substantial impact on HRQL. Despite modern care, we found a significantly increased distress during the 4 year follow up period. Increased parkinsonism, measured by UPDRS and Hoehn and Yahr stage, correlated with increased stress, not only in the dimension of physical mobility, but also in the areas of pain, social isolation, and emotional reactions. In addition to the clinical examination, HRQL scoring provides valuable information on the total health burden of Parkinson's disease in both cross sectional and longitudinal evaluations, and contributes to a more comprehensive picture of the total disease impact. [ABSTRACT FROM AUTHOR]

Aims: Veno-arterial extracorporeal membrane oxygenation (VA-ECMO) with profound left ventricular (LV) failure is associated with inadequate LV emptying. To unload the LV, VA-ECMO can be combined with Impella CP (ECMELLA). We hypothesized that ECMELLA improves cardiac energetics compared with VA-ECMO in a porcine model of cardiogenic shock (CS)., Methods and Results: Land-race pigs (weight 70 kg) were instrumented, including a LV conductance catheter and a carotid artery Doppler flow probe. CS was induced with embolization in the left main coronary artery. CS was defined as reduction of ≥50% in cardiac output or mixed oxygen saturation (SvO 2 ) or a SvO 2  < 30%. At CS VA-ECMO was initiated and embolization was continued until arterial pulse pressure was <10 mmHg. At this point, Impella CP was placed in the ECMELLA arm. Support was maintained for 4 h. CS was induced in 15 pigs (VA-ECMO n = 7, ECMELLA n = 8). At time of CS MAP was <45 mmHg in both groups, with no difference at 4 h (VA-ECMO 64 mmHg ± 11 vs. ECMELLA 55 mmHg ± 21, P = 0.08). Carotid blood flow and arterial lactate increased from CS and was similar in VA-ECMO and ECMELLA [239 mL/min ± 97 vs. 213 mL/min ± 133 (P = 0.6) and 5.2 ± 3.3 vs. 4.2 ± 2.9 mmol/ (P = 0.5)]. Pressure-volume area (PVA) was significantly higher with VA-ECMO compared with ECMELLA (9567 ± 1733 vs. 6921 ± 5036 mmHg × mL/min × 10 -3 , P = 0.014). Total diureses was found to be lower in VA-ECMO compared with ECMELLA [248 mL (179-930) vs. 506 mL (418-2190); P = 0.005]., Conclusions: In a porcine model of CS, we found lower PVA, with the ECMELLA configuration compared with VA-ECMO, indicating better cardiac energetics without compromising systemic perfusion., (© 2024 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Background: The relationship between speckle tracking assessed global longitudinal strain (GLS) and Doppler-based echocardiography with basic physiological markers of cardiac function derived from pressure-volume loops is poorly elucidated., Objective: We aimed to describe the association between LS and Doppler-based echocardiography and direct measurements of central haemodynamic parameters from conductance catheter-based pressure-volume loops in an animal model with increasing left ventricular (LV) dysfunction., Methods: 12 Danish landrace female pigs (75-80 kg) were used. All instrumentations were performed percutaneously, including the conductance catheter in the LV. Progressive LV dysfunction was induced by embolisation through the left main coronary artery with microspheres every 3 min until a >50% reduction in cardiac output (CO) or mixed venous saturation (SvO 2 ), compared with baseline, or SvO 2 <30%. Echocardiography was performed at baseline and 90 s after each injection., Results: With progressive LV dysfunction, mean CO decreased from 5.6±0.9 L/min to 2.1±0.9 L/min, and mean SvO 2 deteriorated from 61.1±7.9% to 35.3±6.1%. Mean LS and LV outflow tract velocity time integral (LVOT VTI) declined from -13.8±3.0% to -6.1±2.0% and 16.9±2.6 cm to 7.8±1.8 cm, respectively. LS and LVOT VTI showed the strongest correlation to stroke work in unadjusted linear regression (r 2 =0.53 and r 2 =0.49, respectively). LS correlated significantly with stroke volume, end-systolic elastance, systolic blood pressure, ventriculo-arterial coupling and arterial elastance., Conclusion: In an animal model of acute progressive LV dysfunction, echocardiographic and conductance catheter-based measurements changed significantly. LS and LVOT VTI displayed the earliest and the largest alterations with increased myocardial damage and both correlated strongest with stroke work., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: In selected cases of cardiogenic shock, veno-arterial extracorporeal membrane oxygenation (V-A ECMO) is combined with trans valvular micro axial flow pumps (ECMELLA). Observational studies indicate that ECMELLA may reduce mortality but exposing the patient to two advanced mechanical support devices may affect the early inflammatory response. We aimed to explore inflammatory biomarkers in a porcine cardiogenic shock model managed with V-A ECMO or ECMELLA., Methods: Fourteen landrace pigs had acute myocardial infarction-induced cardiogenic shock with minimal arterial pulsatility by microsphere embolization and were afterwards managed 1:1 with either V-A ECMO or ECMELLA for 4 h. Serial blood samples were drawn hourly and analyzed for serum concentrations of interleukin 6 (IL-6), IL-8, tumor necrosis factor alpha, and serum amyloid A (SAA)., Results: An increase in IL-6, IL-8, and SAA levels was observed during the experiment for both groups. At 2-4 h of support, IL-6 levels were higher in ECMELLA compared to V-A ECMO animals (difference: 1416 pg/ml, 1278 pg/ml, and 1030 pg/ml). SAA levels were higher in ECMELLA animals after 3 and 4 h of support (difference: 401 ng/ml and 524 ng/ml) and a significant treatment-by-time effect of ECMELLA on SAA was identified (p = 0.04). No statistical significant between-group differences were observed in carotid artery blood flow, urine output, and lactate levels., Conclusions: Left ventricular unloading with Impella during V-A ECMO resulted in a more extensive inflammatory reaction despite similar end-organ perfusion., (© 2024. The Author(s).)

Objective: To explore if pregnant women with pelvic girdle pain (PGP), subgrouped following the results from two clinical tests with high validity and reliability, differ in demographic characteristics and weekly amount of days with bothersome symptoms through the second half of pregnancy., Design: A prospective longitudinal cohort study., Participants: Pregnant women with pelvic and lumbopelvic pain due for their second-trimester routine ultrasound examination., Setting: Obstetric outpatient clinic at Stavanger University Hospital, Norway., Methods: Women reporting pelvic and lumbopelvic pain completed a questionnaire on demographic and clinical features. They were clinically examined following a test procedure recommended in the European guidelines for the diagnosis and treatment of PGP. Women without pain symptoms completed a questionnaire on demographic data. All women were followed weekly through an SMS-Track survey until delivery., Primary and Secondary Outcome Measures: The outcome measures were the results from clinical diagnostic tests for PGP and the number of days per week with bothersome pelvic pain., Results: 503 women participated. 42% (212/503) reported pain in the lumbopelvic region and 39% (196/503) fulfilled the criteria for a probable PGP diagnosis. 27% (137/503) reported both the posterior pelvic pain provocation (P4) and the active straight leg raise (ASLR) tests positive at baseline in week 18, revealing 7.55 (95% CI 5.54 to 10.29) times higher mean number of days with bothersome pelvic pain compared with women with both tests negative. They presented the highest scores for workload, depressed mood, pain level, body mass index, Oswestry Disability Index and the number of previous pregnancies. Exercising regularly before and during pregnancy was more common in women with negative tests., Conclusion: If both P4 and ASLR tests were positive mid-pregnancy, a persistent bothersome pelvic pain of more than 5 days per week throughout the remainder of pregnancy could be predicted. Increased individual control over work situation and an active lifestyle, including regular exercise before and during pregnancy, may serve as a PGP prophylactic., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2018. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Fine-needle aspiration (FNA) is a cornerstone in diagnosing thyroid nodules. For decades, Danish FNA has been categorised into the groups: "FNA not performed", "Inadequate", "Cystic", "Inconclusive", "Benign", "Suspicious", "Malignant" and "Information missing". Internationally, The Bethesda Classification System (TBCS) is increasingly accepted, especially owing to a detailed specification of FNA suspicious for malignancy. The Danish "Suspicious" group is very broad and includes atypia, follicular neoplasia and FNA suspicious of other malignancies. The purpose of this study was to apply TBCS to the Danish "Suspicious" FNA group and to estimate the frequency of malignancy in the individual Bethesda groups (BG)., Methods: This descriptive study is based on a prospective cohort from the THYKIR database. It includes 479 patients with a "Suspicious" FNA and surgical treatment in The Region of Southern Denmark from 2001 to 2013. Based on pathology records, FNA was classified according to the TBCS. Malignancy was determined by the histological diagnosis from the THYKIR database., Results: The Danish "Suspicious" group was allocated to the BG I, II, III, IV, V and VI with a malignancy risk of 36.4%, 13.3%, 17.2%, 16.1%, 55.3% and 88.2%, respectively., Conclusions: The Danish "Suspicious" group contains a broad spectrum of BG with varying malignancy risk. The results indicate a need for standardisation of the Danish FNA classification. A national introduction of the TBCS might secure an international and comparable standard., Funding: none., Trial Registration: not relevant., (Articles published in the Danish Medical Journal are “open access”. This means that the articles are distributed under the terms of the Creative Commons Attribution Non-commercial License, which permits any non-commercial use, distribution, and reproduction in any medium, provided the original author(s) and source are credited.)

DJ-1 is an oxidation sensitive protein encoded by the PARK7 gene. Mutations in PARK7 are a rare cause of familial recessive Parkinson's disease (PD), but growing evidence suggests involvement of DJ-1 in idiopathic PD. The key clinical features of PD, rigidity and bradykinesia, result from neurotransmitter imbalance, particularly the catecholamines dopamine (DA) and noradrenaline. We report in human brain and human SH-SY5Y neuroblastoma cell lines that DJ-1 predominantly forms high molecular weight (HMW) complexes that included RNA metabolism proteins hnRNPA1 and PABP1 and the glycolysis enzyme GAPDH. In cell culture models the oxidation status of DJ-1 determined the specific complex composition. RNA sequencing indicated that oxidative changes to DJ-1 were concomitant with changes in mRNA transcripts mainly involved in catecholamine metabolism. Importantly, loss of DJ-1 function upon knock down (KD) or expression of the PD associated form L166P resulted in the absence of HMW DJ-1 complexes. In the KD model, the absence of DJ-1 complexes was accompanied by impairment in catecholamine homeostasis, with significant increases in intracellular DA and noraderenaline levels. These changes in catecholamines could be rescued by re-expression of DJ-1. This catecholamine imbalance may contribute to the particular vulnerability of dopaminergic and noradrenergic neurons to neurodegeneration in PARK7-related PD. Notably, oxidised DJ-1 was significantly decreased in idiopathic PD brain, suggesting altered complex function may also play a role in the more common sporadic form of the disease., (© The Author 2017. Published by Oxford University Press.)

Background: The aim of this study was to investigate the outcome of chiropractic management for a subgroup of pregnant women with dominating one-sided pelvic girdle pain (PGP)., Methods: The study population was recruited from a prospective longitudinal cohort study of pregnant women. Women reporting pelvic pain (PP), and who were diagnosed with dominating one-sided PGP after a clinical examination, were invited to participate in the intervention study. Recruitment took place either at 18 weeks, or after an SMS-tracking up to week 29. The women were randomized into a treatment group or a control group. The treatment group received chiropractic treatment individualized to each woman with regards to treatment modality and number of treatments. The control group was asked to return to conventional primary health care. The primary outcome measure was new occurrence of full time and/or graded sick leave due to PP and/or low back pain. Secondary outcome measures were self-reported PP, physical disability and general health status. Proportion of women reporting new occurrence of sick leave were compared using Chi squared tests. Differences in secondary outcome measures were estimated using linear regression analyses., Results: Fifty-Six women were recruited, and 28 of them were randomized into the treatment group, and 28 into the control group. There was no statistically significant difference in sick leave, PP, disability or general health status between the two groups during pregnancy or after delivery., Conclusion: The study did not demonstrate superiority of chiropractic management over conventional care for dominating one-sided PGP during pregnancy. However, the analyses revealed wide confidence intervals containing both positive and negative clinically relevant effects., Trial Registration: The study was registered in ClinicalTrials.gov ( NCT01098136 ; 22/03/2010).

Background: Flight related low back pain (LBP) among helicopter pilots is frequent and may influence flight performance. Prolonged confined sitting during flights seems to weaken lumbar trunk (LT) muscles with associated secondary transient pain. Aim of the study was to investigate if structured training could improve muscular function and thus improve LBP related to flying., Methods: 39 helicopter pilots (35 men and 4 women), who reported flying related LBP on at least 1 of 3 missions last month, were allocated to two training programs over a 3-month period. Program A consisted of 10 exercises recommended for general LBP. Program B consisted of 4 exercises designed specifically to improve LT muscular endurance. The pilots were examined before and after the training using questionnaires for pain, function, quality of health and tests of LT muscular endurance as well as ultrasound measurements of the contractility of the lumbar multifidus muscle (LMM)., Results: Approximately half of the participants performed the training per-protocol. Participants in this subset group had comparable baseline characteristics as the total study sample. Pre and post analysis of all pilots included, showed participants had marked improvement in endurance and contractility of the LMM following training. Similarly, participants had improvement in function and quality of health. Participants in program B had significant improvement in pain, function and quality of health., Conclusions: This study indicates that participants who performed a three months exercise program had improved muscle endurance at the end of the program. The helicopter pilots also experienced improved function and quality of health., Trial Registration: Identifier: NCT01788111 Registration date; February 5th, 2013, verified April 2016.

Introduction: Fine-needle aspiration biopsy (FNAB) is the cornerstone of thyroid nodule evaluation. In most cases, FNAB can discriminate between benign and malignant disease. In other cases, it is only indicative of malignancy and the results are considered "suspicious". In Denmark, thyroid FNAB results are categorised into six groups: "inadequate", "cystic", "inconclusive", "benign", "suspicious" and "malignant". The risk of malignancy in the Danish "suspicious" group is of interest for patients as well as doctors participating in the diagnosis and treatment. The Danish Thyroid Surgery Database (THYKIR) registers preoperative thyroid FNAB and final histology. The aim of this study was to assess the malignancy risk among patients with a suspicious thyroid FNAB according to the Danish criteria and to identify possible predictors of malignant histology., Methods: A prospective cohort counting 483 patients with a "suspicious" thyroid FNAB who had been treated surgically in The Region of Southern Denmark in the 2001-2013 period was retrieved from the THYKIR database., Results: The risk of malignancy in the Danish thyroid FNAB "suspicious" group is 22%. Serum thyroid-stimulating hormone outside the normal range and vocal cord palsy may be patient-related predictors of malignancy., Conclusion: Awaiting the introduction of reliable tools for preoperative evaluation, the current practice with histo-logical clarification of the "suspicious" thyroid FNAB seems justified., Funding: none., Trial Registration: not relevant.

Increased somatic mitochondrial DNA (mtDNA) mutagenesis causes premature aging in mice, and mtDNA damage accumulates in the human brain with aging and neurodegenerative disorders such as Parkinson disease (PD). Here, we study the complete spectrum of mtDNA changes, including deletions, copy-number variation and point mutations, in single neurons from the dopaminergic substantia nigra and other brain areas of individuals with Parkinson disease and neurologically healthy controls. We show that in dopaminergic substantia nigra neurons of healthy individuals, mtDNA copy number increases with age, maintaining the pool of wild-type mtDNA population in spite of accumulating deletions. This upregulation fails to occur in individuals with Parkinson disease, however, resulting in depletion of the wild-type mtDNA population. By contrast, neuronal mtDNA point mutational load is not increased in Parkinson disease. Our findings suggest that dysregulation of mtDNA homeostasis is a key process in the pathogenesis of neuronal loss in Parkinson disease.

This study aimed to identify a PD-specific MRI pattern using combined diffusion tensor imaging (DTI) and arterial spin labeling (ASL) to discriminate patients with early PD from healthy subjects and evaluate disease status. Twenty-one early and 22 mid-late PD patients, and 22 healthy, age/gender-matched controls underwent 3-T MRI with apparent diffusion coefficient (ADC), fractional anisotropy (FA), fiber number (FN) and cerebral blood flow (CBF) measurements. We found that compared with healthy subjects, there was a profound reduction in FN passing through the SN in PD. FA in the SN and CBF in the caudate nucleus were inversely correlated with motor dysfunction. A negative correlation was observed between FA in the hippocampus (Hip) and the NMSS-Mood score, whereas CBF in the Hip and the prefrontal cortex(PFC) correlated with declined cognition. Stratified five-fold cross-validation identified FA in the SN(FA-SNAv), CBF in the PFC(CBF-PFCAv) and FA in the parietal white matter(FA-PWMAv), and the combination of these measurements offered relatively high accuracy (AUC 0.975, 90% sensitivity and 100% specificity) in distinguishing those with early PD from healthy subjects. We demonstrate that the decreased FNs through SN in combination with changes in FA-SNAv, CBF-PFCAv and FA-PWMAv values might serve as potential markers of early-stage PD.

The last decade has experienced the emergence of microRNAs as a key molecular tool for the diagnosis and prognosis of human diseases. Although the focus has mostly been on cancer, neurodegenerative diseases present an exciting, yet less explored, platform for microRNA research. Several studies have highlighted the significance of microRNAs in neurogenesis and neurodegeneration, and pre-clinical studies have shown the potential of microRNAs as biomarkers. Despite this, no bona fide microRNAs have been identified as true diagnostic or prognostic biomarkers for neurodegenerative disease. This is mainly due to the lack of precisely defined patient cohorts and the variability within and between individual cohorts. However, the discovery that microRNAs exist as stable molecules at detectable levels in body fluids has opened up new avenues for microRNAs as potential biomarker candidates. Furthermore, technological developments in microRNA biology have contributed to the possible design of microRNA-mediated disease intervention strategies. The combination of these advancements, with the availability of well-defined longitudinal patient cohort, promises to not only assist in developing invaluable diagnostic tools for clinicians, but also to increase our overall understanding of the underlying heterogeneity of neurodegenerative diseases. In this review, we present a comprehensive overview of the existing knowledge of microRNAs in neurodegeneration and provide a perspective of the applicability of microRNAs as a basis for future therapeutic intervention strategies.

Background. Loss of independence is considered an important outcome measure in Parkinson's disease (PD), but tools to assess dependency have not been tested in PD. Methods. In this study of 158 PD patients, we examined the two most widely used scales and cut-offs for dependency evaluation in PD, the Hoehn and Yahr (HY) stage > 3 and the Schwab and England (SE) scale score < 80%, against a standardized clinical interview assessing dependency in activities of daily living (ADL). We also examined the performance of the generic Barthel ADL index. In addition, we determined whether alternative cut-offs improved the utility of these tools. Results. Compared to clinical interview as gold standard, HY stage > 3 had 21% sensitivity and 98% specificity in detecting dependency in ADL. Corresponding figures for SE score < 80% were 55% and 92%, respectively. Using alternative cut-off values improved the overall diagnostic accuracy only slightly. Barthel ADL index had 67% sensitivity and 78% specificity in detecting dependency at its optimal cut-off value. Conclusion. Both the disease-specific HY staging and SE scale and the generic Barthel ADL index are suboptimal tools for assessing independence loss in PD. Clinical interview should be the assessment of choice in studies of dependency.

An 88-year-old woman with a clinical diagnosis of Alzheimer's disease and advanced dementia, was evaluated with standard MRI of the brain as well as Susceptibility Weighted Imaging (SWI) with the MRI. SWI revealed more extensive brain microhemorrhages than standard MRI techniques, allowing the radiologic diagnosis of cerebral amyloid angiopathy. SWI shows promise as a more sensitive diagnostic tool than standard brain MRI for the evaluation of patients with dementia.

MicroRNAs are key regulators associated with numerous diseases. In HEK293 cells, miR-153-3p and miR-205-5p down-regulate alpha-synuclein (SNCA) and Leucine-rich repeat kinase 2 (LRRK2), two key proteins involved in Parkinson's disease (PD). We have used two-dimensional gel electrophoresis (2D-PAGE) coupled to mass spectrometry (MS) to identify a spectrum of miR-153-3p and miR-205-5p targets in neuronal SH-SY5Y cells. We overexpressed and inhibited both microRNAs in SH-SY5Y cells and through comparative proteomics profiling we quantified ~240 protein spots from each analysis. Combined, thirty-three protein spots were identified showing significant (p-value < 0.05) changes in abundance. Modulation of miR-153-3p resulted in seven up-regulated proteins and eight down-regulated proteins. miR-205 modulation resulted in twelve up-regulated proteins and six down-regulated proteins. Several of the proteins are associated with neuronal processes, including peroxiredoxin-2 and -4, cofilin-1, prefoldin 2, alpha-enolase, human nucleoside diphosphate kinase B (Nm23) and 14-3-3 protein epsilon. Many of the differentially expressed proteins are involved in diverse pathways including metabolism, neurotrophin signaling, actin cytoskeletal regulation, HIF-1 signaling and the proteasome indicating that miR-153-3p and miR-205-5p are involved in the regulation of a wide variety of biological processes in neuroblastoma cells.

Background: The incidence of pelvic girdle pain (PGP) in pregnancy is wide ranged depending on definition, the utilised diagnostic means, and the design of the studies. PGP during pregnancy has negative effects on activities of daily living and causes long sick leave, which makes it a major public health issue. Our objectives were to explore the frequency of sick leave in pregnancy due to PGP, assess the relationship between different types of pain-related activities of daily living, examine physical workload, type of work in relation to sick leave, and to explore factors that make women less likely to take sick leave for PGP., Methods: All women giving birth at the maternity ward of Stavanger University Hospital, Norway, were asked to participate and complete a questionnaire on demographic features, PGP, pain-related activities of daily living, sick leave in general and for PGP, frequency of exercising before and during pregnancy. Drawings of pelvic girdle and low back area were used for the localization of pain. PGP intensity was then rated retrospectively on a numerical rating scale. Non-parametric tests, multinomial logistic regression and sequential linear regression analysis were used in the statistical analysis., Results: PGP is a frequent and major cause of sick leave during pregnancy among Norwegian women, which is also reflected in activities of daily living as measured with scores on all Oswestry disability index items. In the multivariate analysis of factors related to sick leave and PGP we found that work satisfaction, problems with lifting and sleeping, and pain intensity were risk factors for sick leave. In addition, women with longer education, higher work satisfaction and fewer problems with sitting, walking and standing, were less likely to take sick leave in pregnancy, despite the same pain intensity as women being on sick leave., Conclusions: A coping factor in pregnant women with PGP was discovered, most likely dependant on education, associated with work situation and/or work posture, which decreases sick leave. We recommend these issues to be further examined in a prospective longitudinal study since it may have important implications for sick leave frequency during pregnancy.

The PARK16 locus, spanning five genes on chromosome 1, was among the first genetic regions to show genome-wide association in Parkinson's disease (PD). Subsequent investigations have found variability in PARK16 top-hits and association patterns across populations, and the implicated genes and mechanisms are currently unclear. In the present study, we aimed to explore the contribution of PARK16 variability to PD risk in a Scandinavian population. We genotyped 17 single-nucleotide polymorphisms in a case-control sample set of 2570 individuals from Norway and Sweden to fine map the locus. Targeted resequencing of the full coding regions of SLC45A3, NUCKS1, RAB7L1, SLC41A1 and PM20D1 was performed in DNA pools from a subset of 387 patient samples. We find evidence for an association with PD for rs1775143 as well as a haplotype located around the 5' region of RAB7L1, implicating variants which are not in high linkage disequilibrium with the strongest signal from a recent large meta-analysis in Caucasians. We also provide suggestive support for epistasis between RAB7L1 and LRRK2 as previously hypothesized by others. Comparing our results with previous work, allelic heterogeneity at PARK16 appears likely, and further studies are warranted to disentangle the complex patterns of association and pinpoint the functionally relevant variants.

Background. Parkinson's disease (PD) and Alzheimer's disease (AD) share pathological features, including amyloid-beta pathology. Amyloid-beta peptide is generated by sequential proteolysis of amyloid precursor protein (APP), and genetic variations in the processing pathway genes have been found to increase the risk of AD; however, the contribution in PD is unknown. Methods. The aim of this study was to investigate whether candidate polymorphisms in five genes (ADAM10, BACE1, BACE2, PSEN2, and CLU) involved in the APP processing pathway affect PD risk in a population-based cohort of patients with incident PD and control subjects from the Norwegian ParkWest study. Results. We found an association of rs638405 in BACE1 with increased risk of PD, thus providing a novel link, at the genetic level, between amyloid-beta pathology and PD.

Mutations in DJ-1 are a cause of recessive, early-onset Parkinson's disease (PD). Although oxidative stress and mitochondrial integrity have been implicated in PD, it is largely unknown why neurons degenerate. DJ-1 is involved in oxidative stress-mediated responses and in mitochondrial maintenance; however, its specific function remains vague. Here we show that DJ-1 exhibits neuronal dynamic intracellular trafficking, with dimeric/monomeric cycling modulated by the oxidative environment. We demonstrate that oxidative stress enhances monomerization of wild-type cytosolic DJ-1, leading to nuclear recruitment. The pathogenic DJ-1/E163K variant is unable to homodimerize but is retained in the cytosol upon wild-type DJ-1 heterodimerization. We found that this wild-type/pathogenic heterodimer is disrupted by oxidative stress, leading to DJ-1/E163K mitochondrial translocation. We further demonstrated that endogenously expressed wild-type DJ-1 is imported into neuronal nuclei as a monomer and that nucleo-cytoplasmic transport is oxidative stress mediated. We identified a novel proline-tyrosine nuclear localization signal (PY-NLS) in DJ-1, and we found that nuclear monomeric DJ-1 import is mediated by an oxidative stress-dependent interaction with karyopherin β2. Our study provides evidence that oxidative stress-mediated intracellular trafficking of DJ-1, mediated by dynamic DJ-1 dimeric/monomeric cycling, is implicated in PD pathogenesis., (Copyright © 2014, American Society for Microbiology. All Rights Reserved.)

Background: Parkinson's disease (PD) is the second most common neurodegenerative movement disorder, caused by preferential dopaminergic neuronal cell death in the substantia nigra, a process also influenced by oxidative stress. L-3,4-dihydroxyphenylalanine (L-DOPA) represents the main treatment route for motor symptoms associated with PD however, its exact mode of action remains unclear. A spectrum of conflicting data suggests that L-DOPA may damage dopaminergic neurons due to oxidative stress whilst other data suggest that L-DOPA itself may induce low levels of oxidative stress, which in turn stimulates endogenous antioxidant mechanisms and neuroprotection., Results: In this study we performed a two-dimensional gel electrophoresis (2DE)-based proteomic study to gain further insight into the mechanism by which L-DOPA can influence the toxic effects of H2O2 in neuronal cells. We observed that oxidative stress affects metabolic pathways as well as cytoskeletal integrity and that neuronal cells respond to oxidative conditions by enhancing numerous survival pathways. Our study underlines the complex nature of L-DOPA in PD and sheds light on the interplay between oxidative stress and L-DOPA., Conclusions: Oxidative stress changes neuronal metabolic routes and affects cytoskeletal integrity. Further, L-DOPA appears to reverse some H2O2-mediated effects evident at both the proteome and cellular level.

Mutations in HTRA2/Omi/PARK13 have been implicated in Parkinson disease (PD). PARK13 is a neuroprotective serine protease; however, little is known about how PARK13 confers stress protection and which protein targets are directly affected by PARK13. We have reported that Arabidopsis thaliana represents a complementary PD model, and here we demonstrate that AtPARK13, similar to human PARK13 (hPARK13), is a mitochondrial protease. We show that the expression/accumulation of AtPARK13 transcripts are induced by heat stress but not by other stress conditions, including oxidative stress and metals. Our data show that elevated levels of AtPARK13 confer thermotolerance in A. thaliana. Increased temperatures accelerate protein unfolding, and we demonstrate that although AtPARK13 can act on native protein substrates, unfolded proteins represent better AtPARK13 substrates. The results further show that AtPARK13 and hPARK13 can degrade the PD proteins α-synuclein (SNCA) and DJ-1/PARK7 directly, without autophagy involvement, and that misfolded SNCA and DJ-1 represent better substrates than their native counterparts. Comparative proteomic profiling revealed AtPARK13-mediated proteome changes, and we identified four proteins that show altered abundance in response to AtPARK13 overexpression and elevated temperatures. Our study not only suggests that AtPARK13 confers thermotolerance by degrading misfolded protein targets, but it also provides new insight into possible roles of this protease in neurodegeneration., (© 2014 by The American Society for Biochemistry and Molecular Biology, Inc.)

Progressive neurodegenerative diseases are among the most frequently occurring aging-associated human pathologies. In a screen for Caenorhabditis elegans mutant animals that lack their normal complement of dopaminergic neurons, we identified two strains with progressive loss of dopaminergic neurons during postembryonic life. Through whole-genome sequencing we show that both strains harbor dominant (d), gain-of-function mutations in the Transient Receptor Potential (TRP) mechanosensory channel trp-4, a member of the invertebrate and vertebrate TRPN-type of the TRP family channels. Gain-of-function mutations in TRP channels have not been previously implicated in dopaminergic neuronal degeneration. We show that trp-4(d) induces cell death in dopamine neurons through a defined, calcium-related downstream pathway.

Background: Chronic obstructive pulmonary disease (COPD) is a major cause of acute hospital admissions. The main object of our study was to evaluate the effects of telemedicine video-consultation (TVC) on the frequency of hospital re-admissions due to COPD exacerbations. Our secondary aim was to assess the impact of TVC on the length of re-admission stays within 6 and 12 months follow up after TVC. Patient satisfaction was also evaluated., Methods: The study was a retrospective observational study of COPD patients who after hospital discharge or during outpatient treatment for acute COPD exacerbations, were monitored for 2 weeks by TVC at home by a specialist nurse at the hospital during a pilot project period. Retrospectively, we compared the frequencies (chi-square test) and durations of hospital re-admissions (paired t-test) due to COPD exacerbations within 6 and 12 months follow up after TVC to comparable events 6 and 12 months prior to TVC., Results: Among 99 patients followed for 6 months after TVC, 56 were followed for totally 12 months. The number of patients re-admitted and the number of re-admissions due to COPD exacerbations were not reduced within 6 or 12 months post-TVC, as compared to 6 and 12 months pre-TVC.The mean length of re-admission stays within 12 months post-TVC was markedly reduced as compared to pre-TVC. Patients hospitalised the last 6 and 12 months pre-TVC, had significantly shorter re-admission stays, p = 0.033 and p = 0.001, respectively. Patient satisfaction was high., Conclusion: Despite the failure to demonstrate reduced frequency of re-admissions within 6 and 12 months post-TVC, the re-admission length within 12 months post-TVC was markedly reduced as compared to pre-TVC. The patient satisfaction was high. Future prospective, randomised, controlled trials must be performed before TVC can be recommended in COPD management.

The progressive loss of motor control due to reduction of dopamine-producing neurons in the substantia nigra pars compacta and decreased striatal dopamine levels are the classically described features of Parkinson disease (PD). Neuronal damage also progresses to other regions of the brain, and additional non-motor dysfunctions are common. Accumulation of environmental toxins, such as pesticides and metals, are suggested risk factors for the development of typical late onset PD, although genetic factors seem to be substantial in early onset cases. Mutations of DJ-1 are known to cause a form of recessive early onset Parkinson disease, highlighting an important functional role for DJ-1 in early disease prevention. This study identifies human DJ-1 as a metal-binding protein able to evidently bind copper as well as toxic mercury ions in vitro. The study further characterizes the cytoprotective function of DJ-1 and PD-mutated variants of DJ-1 with respect to induced metal cytotoxicity. The results show that expression of DJ-1 enhances the cells' protective mechanisms against induced metal toxicity and that this protection is lost for DJ-1 PD mutations A104T and D149A. The study also shows that oxidation site-mutated DJ-1 C106A retains its ability to protect cells. We also show that concomitant addition of dopamine exposure sensitizes cells to metal-induced cytotoxicity. We also confirm that redox-active dopamine adducts enhance metal-catalyzed oxidation of intracellular proteins in vivo by use of live cell imaging of redox-sensitive S3roGFP. The study indicates that even a small genetic alteration can sensitize cells to metal-induced cell death, a finding that may revive the interest in exogenous factors in the etiology of PD.

Purpose: To estimate the incidence of sudden unexpected death in epilepsy (SUDEP) in Rogaland County, Norway, in the period August 1 1995-July 31 2005, and to investigate whether use of lamotrigine (LTG) was associated with increased risk in female patients or other subgroups., Methods: SUDEP victims were identified from autopsy reports and data from the Norwegian Cause of Death Registry. In all cases where SUDEP was considered as a possible cause of death, the hospital records were also reviewed. For each deceased, at least three living patients with epilepsy were randomly selected as controls. The market share in defined daily doses was collected for each year to estimate the number of patient-years at risk on each antiepileptic drug., Key Findings: We identified 26 cases of SUDEP: 16 definite, 3 probable, and 7 possible; 15 patients were female and 11 were male. Of these, 10 patients (38.5%) were treated with LTG: 9 of these patients were female. The incidence of SUDEP was estimated as 1.0 per 1,000 patient-years when all cases were included, and 0.7 per 1,000 patient-years for definite and probable SUDEP. Seven of 12 (58.3%) of female patients with definite and probable SUDEP and 10 of 41 (24.4%) of controls matched on age and gender were on LTG (p = 0.038). The incidence of definite and probable SUDEP in women on LTG, was estimated as 2.5 per 1,000 patient-years and 0.5 per 1,000 patient-years in female who were not taking LTG (p = 0.007)., Significance: The incidence of SUDEP was significantly higher among female patients with epilepsy who were being treated with LTG than among female patients with epilepsy who were not taking LTG, and a significantly higher proportion of female SUDEP cases than controls were taking LTG. Our findings may have implications for treatment of epilepsy in female patients., (Wiley Periodicals, Inc. © 2011 International League Against Epilepsy.)

Mutations in the DJ-1 gene (also known as PARK7) cause inherited Parkinson's disease, which is characterized by neuronal death. Although DJ-1 is thought to be an antioxidant protein, the underlying mechanism by which loss of DJ-1 function contributes to cell death is unclear. Human DJ-1 and its Arabidopsis thaliana homologue, AtDJ-1a, are evolutionarily conserved proteins, indicating a universal function. To gain further knowledge of the molecular features associated with DJ-1 dysfunction, we have characterized AtDJ-1a. We show that AtDJ-1a levels are responsive to stress treatment and that AtDJ-1a loss of function results in accelerated cell death in aging plants. By contrast, transgenic plants with elevated AtDJ-1a levels have increased protection against environmental stress conditions, such as strong light, H(2)O(2), methyl viologen and copper sulfate. We further identify superoxide dismutase 1 (SOD1) and glutathione peroxidase 2 (GPX2) as interaction partners of both AtDJ-1a and human DJ-1, and show that this interaction results in AtDJ-1a- and DJ-1-mediated cytosolic SOD1 activation in a copper-dependent fashion. Our data have highlighted a conserved molecular mechanism for DJ-1 and revealed a new protein player in the oxidative stress response of plants.

Background: Early Parkinson's disease is dominated by a motor syndrome called parkinsonism, but as the disease develops motor complications and non-motor problems may occur as well. This paper describes how to diagnose Parkinson's disease and the various motor complications and gives recommendations on how to treat the symptoms in these patients., Material and Methods: The paper builds on international evidence-based publications and the Norwegian guidelines for treatment of Parkinson's disease., Results and Interpretation: Motor symptoms such as tremor at rest, akinesia, rigidity and postural instability are the cardinal signs in Parkinson's disease. After diagnosing a patient with the disease we recommend to start with selegiline as a disease-modifying treatment strategy. When symptoms lead to functional impairment, symptomatic treatment should be started in addition. Dopamine agonists are primarily recommended in younger patients and levodopa in the older ones. When the patients develop motor complications it is important to first thoroughly evaluate the problems to arrive at the best possible treatment strategy. If a sufficient response is not obtained both deep brain stimulation and treatment with continuous delivery of medication should be considered.

Background: A variety of neuropsychiatric symptoms commonly occur in Parkinson's disease. Extensive research the last 10 years has provided new knowledge in the field., Material and Methods: This review is based on literature retrieved from a Medline search and own research and clinical experience., Results and Interpretation: Neuropsychiatric symptoms occur in the majority of patients with Parkinson's disease, and are associated with impaired quality of life for patients and relatives, additional deterioration of function and increased use of health resources. Medical and surgical therapies can induce or worsen such symptoms. Cognitive impairment and dementia are among the most common and severe complications to Parkinson's disease. No disease-modifying treatment is available, but rivastigmine was effective in one large randomised trial. Visual hallucinations are common and often persistent, but can be treated with klozapin if reducing the number and dose of antiparkinson agents are not helpful. Depression occurs frequently, usually mild, but there is little evidence of treatment efficacy. Apathy, anxiety and sleep disturbances are additional commonly occurring neuropsychiatric symptoms. Neuropsychiatric symptoms are so frequent in Parkinson's disease that they should be considered an integral part of the disease; it is important that clinicians are aware of these symptoms.

Background: We studied the level of distress in caregivers of patients with recently diagnosed multiple sclerosis (MS), and their relation to clinical characteristics., Methods: Caregivers of patients with MS and Parkinson's disease completed measures of distress and quality of life. MS patients underwent neurological, neuropsychiatric and neuropsychological examinations. Multivariate regression analyses were used to explore the relationship between patient variables and caregiver distress., Results: Caregivers of patients with MS experienced high levels of distress and reduced quality of life related to caregiving. The level of distress was similar to that reported by elderly spouses of patients with longstanding Parkinson's disease. Psychiatric symptoms and cognitive impairment in patients with MS were associated with caregiver's distress and quality of life, even after controlling for level of disability (all p values <0.01). Patients' physical impairment was associated with caregiver distress, but not with caregiver quality of life., Conclusion: Caregivers of patients with MS experience high levels of distress and reduced quality of life. Psychiatric symptoms and cognitive impairment contributed significantly to caregiver distress, over and above the effect of disability due to neurological symptoms.

Background: Parkinson's disease (PD) is the second most common neurodegenerative disorder. Recently, mutations in the PINK1 (PARK6) gene were shown to rarely cause autosomal-recessively transmitted, early-onset parkinsonism. In order to evaluate whether PINK1 contributes to the risk of common late-onset PD we analysed PINK1 sequence variations. A German (85 patients) and a Norwegian cohort (90 patients) suffering from late-onset PD were screened for mutations and single nucleotide polymorphisms (SNPs) in the PINK1 gene. Both cohorts consist of well-characterized patients presenting a positive family history of PD in approximately 17%. Investigations were performed by single strand conformation polymorphism (SSCP), denaturating high performance liquid chromatography (DHPLC) and sequencing analyses. SNP frequencies were compared by the chi2 test., Results: Several common SNPs were identified in our cohorts, including a recently identified coding variant (Q115L) in exon 1. Genotyping of the Q115L variation did not reveal significant frequency differences between patients and controls. Pathogenic mutations in the PINK1 gene were not identified, neither in the German nor in the Norwegian cohort., Conclusion: Sequence variation in the PINK1 gene appears to play a marginal quantitative role in the pathogenesis of the late-onset form of PD, in German and Norwegian cohorts, if at all.

Background: Studies have shown that diagnosing and treating patients with parkinsonism in nursing homes could be improved. Parkinson's disease is the most important cause of parkinsonism., Materials and Methods: The data for this article have been obtained through a literature search and by research in our own centre., Results and Interpretation: Parkinsonism is a frequent cause of functional impairment among the elderly. The diagnosis is based on an evaluation of the four cardinal signs of parkinsonism (resting tremor, akinesia, rigidity, and postural abnormalities). Parkinsonism may be caused by Parkinson's disease, symptomatic parkinsonism, pseudoparkinsonism or be a part of the presentation of other neurodegenerative diseases. A systematic examination for suspected parkinsonism followed by an evaluation of causes of parkinsonism will improve the diagnostic quality in nursing homes. Patients with Parkinson's disease have motor as well as non-motor problems, hence management should focus on all aspects of the symptoms experienced by these patients, not only the motor symptoms. Several investigations have shown that non-motor problems may detract more from the quality of life than the motor symptoms. 5% of all residents in nursing homes in Norway have Parkinson's disease; 20% of them are unrecognised by the medical staff. Intervention in nursing homes from physicians with more knowledge on parkinsonism has been shown to improve diagnostic accuracy as well as management.

Objective: To study the safety and efficacy of the cholinesterase inhibitor donepezil in patients with Parkinson's disease (PD) and cognitive impairment., Methods: This was a double blind, randomised and placebo controlled, crossover study in which 14 patients with PD and cognitive impairment received donepezil (5 or 10 mg per day) or matching placebo during two sequential periods lasting 10 weeks each. The primary outcome measures were the mini mental state examination (MMSE) score, the clinician's interview based impression of change plus caregiver input (CIBIC+) score, and the motor subscale of the unified Parkinson's disease rating scale (UPDRS)., Results: Two patients on donepezil (14%) dropped out after one and four weeks of the first treatment period because of peripheral cholinergic side effects, otherwise the adverse effects were few and not severe. Carryover or residual effects were not observed. Parkinsonism did not increase during donepezil treatment. After 10 weeks of treatment, the mean MMSE score was increased by 2.1(SD 2.7) points on donepezil and 0.3 (SD 3.2) points on placebo, and the CIBIC+ score was 3.3 (SD 0.9) on donepezil and 4.1 (SD 0.8) on placebo. Statistical analysis of the repeated measurements and crossover study design showed significant effects of donepezil compared with placebo for MMSE (p=0.013) and CIBIC+ (p=0.034). Five (42%) patients on donepezil and two (17%) on placebo were rated as improved on the basis of the CIBIC+ score., Conclusions: Donepezil improves cognition, and seems to be well tolerated and not to worsen parkinsonism in patients with cognitive impairment.

Objectives: Disturbances of cognition and emotion are common in patients with Parkinson's disease. Most previous studies of psychopathology in Parkinson's disease have focused on a single psychiatric diagnosis or condition. The objective of this study was to describe the range of neuropsychiatric symptoms in a representative sample of patients with Parkinson's disease., Methods: The sample of 139 patients was drawn from an epidemiological study of Parkinson's disease in Rogaland county, Norway, and represented 93% of those who had survived during the 4 years since the initial assessment. The diagnosis of Parkinson's disease was based on published criteria. Neuropsychiatric symptoms were assessed using the neuropsychiatric inventory, a caregiver based structured interview, which assesses severity and frequency of 10 psychiatric symptoms present during the past month., Results: At least one psychiatric symptom was reported in 61% of the sample. The most common behaviours were depression (38%) and hallucinations (27%), and the least common symptoms were euphoria and disinhibition. The highest mean scores were found for depression, apathy, and hallucinations. Factor analysis showed that hallucinations, delusions, and irritability clustered into one factor, and apathy and anxiety constituted another factor. Psychiatric symptoms were more common among patients living in nursing homes compared with home dwelling patients, and correlated with stage of disease and cognitive impairment, but not with age or duration of disease. No relation to left or right sided parkinsonism was found., Conclusion: This study emphasises the importance of psychiatric symptoms in Parkinson's disease, which were present in most patients. Clinicians should focus on the emotional and cognitive disturbances in addition to the motor manifestations of the disease.

Objectives: To identify the clinical and demographic factors that are associated with a poor quality of life in patients with Parkinson's disease., Methods: 233 of a total of 245 patients identified in a community based study in a Norwegian county participated in the study. Quality of life was measured by the Nottingham Health Profile (NHP). The results were compared with those in 100 healthy elderly people. Clinical and demographic variables were determined during a semistructured interview and by clinical examination by a neurologist. Multiple regression analyses were used to determine which variables were associated with higher distress scores., Results: Patients with Parkinson's disease had higher distress scores than the healthy elderly people for all the NHP dimensions. The variables that most strongly predicted a high total NHP score were depressive symptoms, self reported insomnia, and a low degree of independence, measured by the Schwab and England scale. Severity of parkinsonism contributed, but to a lesser extent. Nearly half the patients with Parkinson's disease reported lack of energy, compared with a fifth of the control group. Severity of depressive symptoms and a higher score on the UPDRS motor subscale only partly accounted for this finding. Only 30% of the variation in NHP energy score was explained by the predictive variables identified in this study., Conclusions: Parkinson's disease has a substantial impact on health related quality of life. Depressive symptoms and sleep disorders correlated strongly with high distress scores. Patients with Parkinson's disease should be examined for both conditions, which require treatment. Low energy was commonly reported and may be a separate entity of Parkinson's disease.

Objective: To examine the extent of under-diagnosis and overdiagnosis of Parkinson's disease and to determine quality of treatment in a defined population., Design: Clinical evaluation of an elderly population., Setting: 40 Norwegian nursing homes., Subjects: 3322 residents of nursing homes, of whom 500 were selected by nursing staff for evaluation on the basis of a structured information programme on Parkinson's disease and 269 were examined in detail by neurologists., Main Outcome Measures: Patients' scores on clinical rating scales, diagnosis of parkinsonism, and effect of changing drug treatment., Results: 169 (5.1%) patients were found to have clinical idiopathic Parkinson's disease, 31 of whom had not had the disease diagnosed previously. In addition, 31 patients without the disease were taking antiparkinsonian drugs unnecessarily. Eighty patients were judged to be receiving "optimal" treatment. In the remaining 58, the treatment was changed, and 36 patients showed a definite functional improvement after a 12 week observation period., Conclusions: The quality of life of many elderly patients with Parkinson's disease could be improved by increasing medical and neurological services.