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Purpose The purpose of this study was to investigate the subjective recovery from pregnancy-related pelvic girdle pain (PGP) during the first 6 weeks after delivery and to detect possible risk factors for a poor recovery. Methods The participants were included in this study at the routine ultrasound examination at 18 weeks of pregnancy. The women received a weekly SMS with the question “How many days during the last week has your PGP been bothersome?” The SMS-track from the final 10 weeks of pregnancy and first 6 weeks after delivery were assessed and sorted, based on individual graphs. A total of 130 women who reported PGP during pregnancy and met for clinical examination 6 weeks after delivery were included in the study. Results In all, 83% of the women experienced substantial recovery from severe or moderate PGP within 6 weeks after delivery. Of these, 44% reported a substantial recovery already within 2 weeks after delivery. More multiparous women, women reporting PGP the year before pregnancy, and women with high pain intensity during pregnancy had a poor recovery. Conclusions The prognosis following PGP in pregnancy is good and the majority of women recovered substantially from severe and moderate pregnancy-related PGP within 6 weeks after delivery. For many women, a subjective substantial recovery occurred within 2 weeks after delivery. Predictors for a poor recovery were multiparity, PGP the year before pregnancy and a high pain intensity during pregnancy. Graphic abstract These slides can be retrieved under Electronic Supplementary Material.

Introduction Both polymorphisms and mutations in glucocerebrosidase ( GBA ) may influence the development of dementia in patients with Parkinson's disease. Methods Four hundred forty-two patients and 419 controls were followed for 7 years. Dementia was diagnosed using established criteria. Participants were analyzed for GBA genetic variants, including E326K, T369M, and L444P. Associations between GBA carrier status and dementia were assessed with Cox survival analysis. Results A total of 12.0% of patients with Parkinson's disease carried a GBA variant, and nearly half (22/53) of them progressed to dementia during follow-up. Carriers of deleterious GBA mutations (adjusted hazard ratio 3.81, 95% confidence interval 1.35 to 10.72; P = .011) or polymorphisms (adjusted hazard ratio 1.79; 95% confidence interval 1.07 to 3.00; P = .028) progressed to dementia more rapidly than noncarriers. Discussion GBA variants are of great clinical relevance for the development of dementia in Parkinson's disease, especially due to the relatively higher frequency of these alleles compared with other risk alleles.

Depression is common in patients with Parkinson disease and causes suffering and increased caregiver burden. A better understanding of depressive symptoms in Parkinson disease, their progression, and risk factors may, therefore, benefit management of these patients. The present study included 187 drug-naïve patients with incident PD and 166 controls from the population-based Norwegian ParkWest project. Depressive symptoms were examined with the Montgomery and Aasberg Depression Rating Scale (MADRS) at time of diagnosis and inclusion in the study and after 1, 3, 5, and 7 years of follow-up. Associations between MADRS scores and risk factors were assessed using generalized estimating equations (GEE). The mean MADRS score from all 823 examinations during the study period was 4.2 in patients and 1.3 in 732 examinations among controls. Among controls, the occurrence of depressive symptoms was also lower and rather stable during follow-up, while in patients, we observed a decrease from time of diagnosis and until the 1-year visit, followed by a steady increase in these symptoms over time. Factors associated with higher MADRS score in the multivariable model were female sex, being dependent, higher pain score, higher Unified PD Rating Scale (UPDRS) motor score, and lower Mini-Mental State Examination (MMSE) score. The results from this study underscore the importance and frequency of depressive symptoms in patients with early PD. Furthermore, risk factors that may be considered PD-nonspecific are associated with depressive symptoms as are factors that reflect the progression of PD.

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). 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. 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. 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. The study was registered in ClinicalTrials.gov ( NCT01098136 ; 22/03/2010).

Background Impulsive and compulsive behaviors (ICBs) are frequent in Parkinson's disease (PD), but data from population-based cohorts is lacking. Objectives To determine the frequency and associated demographic, clinical, neuropsychiatric and cognitive features of ICBs in a population-based PD cohort. Methods This cross-sectional study included 125 patients with PD and 159 age- and gender-matched normal controls recruited from the Norwegian ParkWest study. Participants underwent comprehensive neurological, neuropsychiatric and neuropsychological assessments. ICBs were assessed using the Questionnaire for Impulsive-Compulsive Disorders in PD short form. Multiple logistic regression analyses were performed to compare the odds of ICBs between groups and to identify independent correlates of ICBs in PD. Results 30.4% of patients reported at least one ICB, with an odds ratio (OR) of 3.2 (95% confidence interval [CI] 1.8-5.9) compared with controls. Multiple ICBs were experienced by 8.8% of patients vs 1.3% of controls (OR 7.6, 95% CI 1.7-34.8). Compared to controls, the ORs of having an ICB were 7.4 (95% CI 2.6-20.9) in patients taking DA without levodopa, 4.6 (95% CI 2.3-9.3) in those treated with both DA and levodopa, and 1.2 (95% CI 0.5-3.2) in patients using levodopa but not DA. In multivariate models, ICB status in patients was independently associated with DA treatment and depressive symptoms, but not with other dopaminergic medications, motor function, or cognitive performance. Conclusions Patients with PD treated with DA, but not other dopaminergic medications, have increased odds of having ICBs compared with age- and gender-matched controls. This has implications for individualized patient management and follow-up.

Objective:To examine the incidence, progression, and reversion of mild cognitive impairment in patients with Parkinson disease (PD-MCI) over 5 years.Methods:A population-based cohort of patients with incident PD underwent repeated neuropsychological testing of attention, executive function, memory, and visuospatial abilities at baseline (n = 178), 1 year (n = 175), 3 years (n = 163), and 5 years (n = 150). Patients were classified as PD-MCI and diagnosed with dementia according to published criteria.Results:Thirty-six patients (20.2%) fulfilled criteria for PD-MCI at baseline. Among those with normal cognition at baseline (n = 142), the cumulative incidence of PD-MCI was 9.9% after 1 year, 23.2% after 3 years, and 28.9% after 5 years of follow-up. Overall, 39.1% of patients with baseline or incident PD-MCI progressed to dementia during the 5-year study period. The conversion rate to dementia was 59.1% in patients with persistent PD-MCI at 1 year vs 7.2% in those with normal cognition during the first year (adjusted odds ratio 16.6, 95% confidence interval 5.1–54.7, p < 0.001). A total of 27.8% of patients with baseline PD-MCI and 24.2% of those with incident PD-MCI had reverted to normal cognition at study end, but the reversion rate decreased to 9.4% in those with persistent PD-MCI at 2 consecutive visits. Compared with cognitively normal patients, PD-MCI reverters within the first 3 years of follow-up were at increased risk of subsequently developing dementia (adjusted odds ratio 10.7, 95% confidence interval 1.5–78.5, p = 0.019).Conclusions:Early PD-MCI, regardless of persistence or reversion to normal cognition, has prognostic value for predicting dementia in patients with PD.

The objective of this study is to examine the frequency, development, concomitants, and risk factors of falls in a population-based incident Parkinson’s disease (PD) cohort. One hundred eighty-one drug-naive patients with incident PD and 173 normal controls recruited from the Norwegian ParkWest study were prospectively monitored over 7 years. Information on falls was obtained biannually from patients, and at baseline and after 1, 3, 5, and 7 years of follow-up in control subjects. Generalized estimating equation models for correlated data were applied to investigate concomitant features of falls and risk factors for incident falls during 7 years of follow-up in PD. Overall, 64.1% of patients reported falling during the study period. The 7-year cumulative incidence of falls in non-falling patients at baseline (n = 153) was 57.5%, with a relative risk to controls of at least 3.1 (95% confidence interval 1.5–6.3; p

Objective:To examine the development of factors associated with insomnia in a cohort of originally drug-naive patients with incident Parkinson disease (PD) during the first 5 years after diagnosis.Methods:One hundred eighty-two drug-naive patients with PD derived from a population-based incident cohort and 202 control participants were assessed for insomnia before treatment initiation and were repeatedly examined after 1, 3, and 5 years. Insomnia was diagnosed according to the Stavanger Sleepiness Questionnaire. The Parkinson's Disease Sleep Scale was used to differentiate sleep initiation problems from problems of sleep maintenance. Generalized estimating equation models were applied for statistical measures.Results:The prevalence of insomnia in general was not higher in patients with PD compared to controls at the 5-year follow-up. There were changes in the prevalence of the different insomnia subtypes over the 5-year follow-up. The prevalence of solitary problems in sleep maintenance increased from 31% (n = 18) in the drug-naive patients at baseline to 49% (n = 29) after 1 year and were associated with the use of dopamine agonists and higher Montgomery-Åsberg Depression Rating Scale scores. The prevalence of solitary sleep initiation problems decreased continuously from 21% (n = 12) at baseline to 7.4% (n = 4) after 5 years; these were associated with less daytime sleepiness.Conclusions:The prevalence rates of the different insomnia subtypes changed notably in patients with early PD. The frequency of sleep maintenance problems increased, and these problems were associated with dopamine agonist use and depressive symptoms, while the total number of patients with insomnia remained stable. Our findings reflect the need for early individual assessments of insomnia subtypes and raise the possibility of intervention to reduce these symptoms in patients with early PD.

Parkinson's disease and other synucleinopathies are characterized by the presence of intra-neuronal protein aggregates enriched in the presynaptic protein α-synuclein. α-synuclein is considered an intrinsically disordered 14 kDa monomer, and although poorly understood, its transition to higher-order multimeric species may play central roles in healthy neurons and during Parkinson's disease pathogenesis. In this study, we demonstrate that α-synuclein exists as defined, subcellular-specific species that change characteristics in response to oxidative stress in neuroblastoma cells and in response to Parkinson's disease pathogenesis in human cerebellum and frontal cortex. We further show that the phosphorylation patterns of different α-synuclein species are subcellular specific and dependent on the oxidative environment. Using high-performance liquid chromatography and mass spectrometry, we identify a Parkinson's disease enriched, cytosolic ~36-kDa α-synuclein species which can be recapitulated in Parkinson's disease model neuroblastoma cells. The characterization of subcellular-specific α-synuclein features in neurodegeneration will allow for the identification of neurotoxic α-synuclein species, which represent prime targets to reduce α-synuclein pathogenicity.

Background Familial aggregation has been described in PD of both early and late onset, but has not been studied in a true population-based sample. Moreover, little is known about its association with disease progression and endophenotypes. Objectives The objectives of this work were to determine familial aggregation of idiopathic PD in a population-based cohort and study the association with clinical endophenotypes and disease progression. Methods We examined family history data from the Norwegian ParkWest study, a well-characterized, population-based cohort of incident PD patients and age-matched healthy controls. Family data were collected at baseline with a simplified questionnaire (192 cases and 193 controls) and after 3 years of longitudinal follow-up using an extended questionnaire (172 cases and 171 controls). Results Compared to the controls, the PD patients had an increased relative risk of having a first-degree relative with PD when using the extended questionnaire (relative risk = 1.988; P = 0.036), but not when using the simplified questionnaire (relative risk = 1.453; P = 0.224). There was no significant difference in age of onset or motor subtype (P = 0.801). However, cases with a family history of PD had reduced progression over 7 years as measured by UPDRS II (P = 0.008) and smaller rate of decrease of MMSE (P = 0.046). Conclusions Our findings confirm familial aggregation in a population-based cohort of idiopathic PD. Moreover, we show that positive family history of PD in patients is associated with a slower progression of PD symptoms and cognitive decline. © 2016 International Parkinson and Movement Disorder Society

Introduction As current clinical diagnostic protocols for Parkinson's disease (PD) may be prone to inaccuracies there is a need to identify and validate molecular biomarkers, such as circulating microRNAs, which will complement current practices and increase diagnostic accuracy. This study identifies, verifies and validates combinatory serum microRNA signatures as diagnostic classifiers of PD across different patient cohorts. Methods 370 PD (drug naive) and control serum samples from the Norwegian ParkWest study were used for identification and verification of differential microRNA levels in PD which were validated in a blind study using 64 NY Parkinsonism in UMea (NYPUM) study serum samples and tested for specificity in 48 Dementia Study of Western Norway (DemWest) study Alzheimer's disease (AD) serum samples using miRNA-microarrays, and quantitative (q) RT-PCR. Proteomic approaches identified potential molecular targets for these microRNAs. Results Using Affymetrix GeneChip® miRNA 4.0 arrays and qRT-PCR we comprehensively analyzed serum microRNA levels and found that the microRNA (PARKmiR)-combinations, hsa-miR-335-5p/hsa-miR-3613-3p (95% CI, 0.87–0.94), hsa-miR-335-5p/hsa-miR-6865-3p (95% CI, 0.87–0.93), and miR-335-5p/miR-3613-3p/miR-6865-3p (95% CI, 0.87–0.94) show a high degree of discriminatory accuracy (AUC 0.9–1.0). The PARKmiR signatures were validated in an independent PD cohort (AUC ≤ 0.71) and analysis in AD serum samples showed PARKmiR signature specificity to PD. Proteomic analyses showed that the PARKmiRs regulate key PD-associated proteins, including alpha-synuclein and Leucine Rich Repeat Kinase 2. Conclusions Our study has identified and validated unique miRNA serum signatures that represent PD classifiers, which may complement and increase the accuracy of current diagnostic protocols.

Background and purpose Fatigue is a common and disabling non-motor symptom in Parkinson's disease (PD). The pathogenesis is unknown, and the treatment options are limited. The aim of the present study was to investigate the development of fatigue during the first year after diagnosis. Methods The study design was a prospective, controlled population-based longitudinal cohort study, comprising 181 de novo, drug-naive patients with PD and 162 control participants. PD was diagnosed according to the Gelb criteria. Fatigue was assessed by the Fatigue Severity Scale (FSS). Both groups were assessed for fatigue at baseline and after 1 year. Results Patients reported more fatigue than the control subjects at baseline and at the 1-year follow-up evaluation. The FSS scores in the patient group improved from a mean score of 4.4 (SD 1.6) to 4.0 (SD 1.6). Patients with fatigue at baseline received higher doses of dopaminergic medication during follow-up. Patients who received dopamine agonists improved slightly more than patients who received levodopa. A regression analysis did not show a correlation between an improvement in fatigue and a change in disease severity, depressive symptoms, sleep problems, apathy or cognitive impairment. Conclusion Fatigue is a common symptom in PD, also in early, untreated patients. During the first year of observation, an improvement in the fatigue scores was found. The improvement could not be attributed to a change in disease severity or depressive symptoms. The results indicate a better effect of dopamine agonists than of levodopa. This may have implications for treatment in patients with PD-associated fatigue.

Background: Abnormal α-synuclein aggregation and deposition is the pathological hallmark of Parkinson’s disease (PD) and dementia with Lewy bodies (DLB), but is also found in Alzheimer disease (AD). Therefore, there is a gaining interest in α-synuclein in cerebrospinal fluid (CSF) as potential biomarker for these neurodegenerative diseases. To broaden the available choices of α-synuclein measurement in CSF, we developed and validated a new assay for detecting total α-synuclein. Methods: This novel ELISA uses commercially available antibodies and is based on electrochemiluminescence technology. The assay protocol is straightforward, with short and simple incubation steps, and requires only small amounts of CSF. We validated this assay for precision, parallelism, dilution linearity, specificity, and spike recovery. We further compared it to the newly validated α-synuclein assay from BioLegend by analyzing a set of 50 CSF samples with both assays. Results: The new assay quantifies α-synuclein in CSF with a lower limit of detection of 36.3 pg/mL and shows no cross-reactivity with human β- and γ-synuclein. Results of dilution linearity, parallelism, spike recovery, and precision classify this assay as well suited for α-synuclein detection in human CSF samples. Conclusions: We present a novel assay based on freely available components to quantify total α-synuclein in CSF as an additional method for α-synuclein as a biomarker in neurodegenerative diseases. The assay convinces with its simple and convenient protocol paired with high sensitivity.

Although mutations in the leucine-rich repeat kinase 2 (LRRK2) gene are the most common cause of genetic Parkinson's disease, their function is largely unknown. LRRK2 is pleiotropic in nature, shown to be involved in neurodegeneration and in more peripheral processes, including kidney functions, in rats and mice. Recent studies in zebrafish have shown conflicting evidence that removal of the LRRK2 WD40 domain may or may not affect dopaminergic neurons and/or locomotion. This study shows that ∼50% LRRK2 knockdown in zebrafish causes not only neuronal loss but also developmental perturbations such as axis curvature defects, ocular abnormalities, and edema in the eyes, lens, and otic vesicles. We further show that LRRK2 knockdown results in significant neuronal loss, including a reduction of dopaminergic neurons. Immunofluorescence demonstrates that endogenous LRRK2 is expressed in the lens, brain, heart, spinal cord, and kidney (pronephros), which mirror the LRRK2 morphant phenotypes observed. LRRK2 knockdown results further in the concomitant upregulation of β-synuclein, PARK13, and SOD1 and causes β-synuclein aggregation in the diencephalon, midbrain, hindbrain, and postoptic commissure. LRRK2 knockdown causes mislocalization of the Na(+) /K(+) ATPase protein in the pronephric ducts, suggesting that the edema might be linked to renal malfunction and that LRRK2 might be associated with pronephric duct epithelial cell differentiation. Combined, our study shows that LRRK2 has multifaceted roles in zebrafish and that zebrafish represent a complementary model to further our understanding of this central protein. © 2016 Wiley Periodicals, Inc.

Stroke is one of the leading causes of mortality worldwide. Understanding the risk factors associated with stroke mortality is important to improve patient management. Few studies have examined long-term mortality and its associated predictive risk factors.We examined long-term mortality in 1137 patients with acute stroke and compared it to a geographically age- and sex-matched, stroke-free control group. We followed the stroke patients for as long as 16.4 years. In 1018 of these patients we assessed the effect of demographic, clinical, and hematological factors on mortality.At the end of the study period, 51.7% of the patients and 32.7% of the stroke-free control individuals had died (hazard ratio 2.2, confidence interval 1.9-2.5, P .001). A total of 72.5% of the patients and 53% of the controls with 12 years' follow-up (n = 570) had died (P .001). Regression analyses indicate that, in addition to known risk factors such as age, diabetes, and stroke severity, both low cholesterol (P .001) and hemoglobin (P .002), hyperhomocysteinemia (P = .005), and elevated serum creatinine (P .001) at index stroke are associated with increased long-term mortality.Stroke patients surviving the first year after stroke have a markedly increased mortality rate as seen in long-term follow-up. Furthermore, the results from this study indicate that changes in creatinine, homocysteine, and hemoglobin should be followed more carefully as standard practice after acute stroke.

Motor complications may become major challenges in the management of patients with Parkinson's disease. In this study, we sought to determine the incidence, risk factors, evolution, and treatment of motor fluctuations and dyskinesias in a population-representative, incident Parkinson's disease cohort.In this prospective population-based 5-year longitudinal study, we followed 189 incident and initially drug-naïve Parkinson's disease patients biannually for detailed examination of dyskinesias and motor fluctuations as defined by the Unified Parkinson's disease Rating Scale. We performed Kaplan-Meier survival and Cox regression analyses to assess cumulative incidence and risk factors of these motor complications.The 5-year cumulative incidence of motor complications was 52.4%. Motor fluctuations occurred in 42.9% and dyskinesias in 24.3%. Besides higher motor severity predicting both motor fluctuations (p = 0.016) and dyskinesias (p0.001), lower age at diagnosis predicted motor fluctuations (p = 0.001), whereas female gender predicted dyskinesias (p = 0.001). Actual levodopa dose at onset of motor fluctuations (p = 0.037) or dyskinesias (p0.001) rather than initial treatment with levodopa (p0.1) independently predicted development of motor complications. Motor fluctuations reversed in 37% and dyskinesias in 49% of patients on oral treatment and remained generally mild in those with persistent complications. No patients received device-aided therapies during the study.More than 50% in the general Parkinson's disease population develop motor complications within 5 years of diagnosis. However, they remain mild in the vast majority and are reversible in a substantial proportion of patients.

Neuronal cell death, in neurodegenerative disorders, is mediated through a spectrum of biological processes. Excessive amounts of free radicals, such as reactive oxygen species (ROS), has detrimental effects on neurons leading to cell damage via peroxidation of unsaturated fatty acids in the cell membrane. Edaravone (3-methyl-1-phenyl-2-pyrazolin-5-one) has been used for neurological recovery in several countries, including Japan and China, and it has been suggested that Edaravone may have cytoprotective effects in neurodegeneration. Edaravone protects nerve cells in the brain by reducing ROS and inhibiting apoptosis. To gain further insight into the cytoprotective effects of Edaravone against oxidative stress condition we have performed comparative two-dimensional gel electrophoresis (2DE)-based proteomic analyses on SH-SY5Y neuroblastoma cells exposed to oxidative stress and in combination with Edaravone. We showed that Edaravone can reverse the cytotoxic effects of H2O2 through its specific mechanism. We observed that oxidative stress changes metabolic pathways and cytoskeletal integrity. Edaravone seems to reverse the H2O2-mediated effects at both the cellular and protein level via induction of Peroxiredoxin-2.

Objective The aim of this study was to provide information on the occurrence of spinal pain, i.e., low back and neck pain, among commercial helicopter pilots, along with possible associations between pain and anthropometric and demographic factors and flying exposure. Methods Data were collected through a subjective and retrospective survey among all the 313 (294 men, 19 women) full-time pilots employed by two helicopter companies. A questionnaire was used to assess the extent of spinal complaints in a transient and recurrent pain pattern along with information on physical activities, occupational flying experience, and airframes. Results The survey had 207 responders (194 men, 13 women). The pilots had extensive flying experience. Spinal pain was reported by 67%. Flying-related transient pain was reported among 50%, whereas recurrent spinal pain, not necessarily associated with flying, was reported by 52%. Women experienced more pain, but sample size prevented further conclusions. Male pilots reporting any spinal pain flew significantly more hours last year (median 500 h, IQR 400-650) versus men with no pain (median 445 h, IQR 300-550). Male pilots with transient or recurrent spinal pain did not differ from nonaffected male colleagues in the measured parameters. Conclusion Spinal pain is a frequent problem among male and female commercial helicopter pilots. For men, no significant associations were revealed for transient or recurrent spinal pain with age, flying experience in years, total hours, annual flying time, type of aircraft, or anthropometric factors except for any spinal pain related to hours flown in the last year.

ObjectiveTo 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.DesignA prospective longitudinal cohort study.ParticipantsPregnant women with pelvic and lumbopelvic pain due for their second-trimester routine ultrasound examination.SettingObstetric outpatient clinic at Stavanger University Hospital, Norway.MethodsWomen 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 measuresThe outcome measures were the results from clinical diagnostic tests for PGP and the number of days per week with bothersome pelvic pain.Results503 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.ConclusionIf 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.

Objective The purpose of this study was to investigate the feasibility of conducting a study examining the influence of individualized rehabilitation and chiropractic treatment, compared with individualized rehabilitation alone, in women with persistent dominating 1-sided pelvic girdle pain (PGP) 3 to 6 months after delivery. Methods Women were recruited from an outpatient clinic at Stavanger University Hospital, Norway and in a private chiropractic clinic in Stavanger. Those with persistent, dominating 1-sided PGP were included in this pilot study. Those who met inclusion criteria were randomized into 2 groups, one group received individualized rehabilitation and chiropractic treatment and the other group women received individualized rehabilitation alone. Treatment was measured for 20 weeks. Results Of 330 consenting women who were recruited who reported pelvic pain during pregnancy, 68 reported PGP or low back pain, and 63 consented to fill in a questionnaire. Forty-seven women underwent a clinical examination 3 to 6 months after delivery. During the examination, the women were diagnosed into subgroups for PGP. After exclusion of the women with low back pain only, a total of 13 women were diagnosed with dominating 1-sided PGP and thus included in this study. Six were randomized to the individualized rehabilitation and chiropractic treatment group and 5 to the individualized rehabilitation alone group. After 20 weeks of intervention, both groups reported improvement in disability and pain, but not in general health status. No serious or long-lasting adverse events were registered after treatment or training. Conclusion We found that a study of this nature is feasible. However, the conditions of patient recruitment need to be considered carefully. We learned that a trial to investigate the effect of chiropractic treatment for PGP pain should include all subgroups of PGP to reach an acceptable sample size.

Parkinson's disease is a chronic, progressive neurodegenerative disorder with increased prevalence in the aging population. It is estimated that approximately 1.5 million individuals in the US alone suffer from Parkinson's disease and with the extension of life expectancy this number is expected to rise dramatically within the next twenty-five years. The majority of Parkinson's disease cases are sporadic. But mutations in genes such as α-synuclein, Parkin, PINK1, DJ-1 and LRRK2, have been conclusively associated with both early- and late-onset of the disease. Although the genetics of Parkinson's disease is starting to become unraveled, the interplay between genetic and environmental factors is largely unknown as are the underlying mechanisms that trigger the disease as the brain ages. The risk of Parkinson's disease increases dramatically in individuals over the age of 60 and it is estimated that more than 1% of all seniors have some form of the condition. In this review, we will highlight some of the central proteins associated with Parkinson's disease and how they may be linked to processes and factors associated with age.

Objective: To examine the frequency, development, and risk factors of excessive daytime sleepiness (EDS) in a cohort of originally drug-naive patients with incident Parkinson disease (PD) during the first 5 years after diagnosis. Methods: One hundred fifty-three drug-naive patients with early PD derived from a population-based incident cohort and 169 control participants were assessed for EDS and reevaluated after 1, 3, and 5 years on medication. EDS was diagnosed according to the Epworth Sleepiness Scale. Cutoff score above 10 was applied. Generalized estimating equation models for correlated data were used to examine associated and risk factors for EDS. Results: Patients reported EDS more often than control participants at the time of diagnosis and during follow-up. The frequency of EDS in PD increased from 11.8% at baseline to 23.4% after 5 years. Associated factors were male sex, the use of dopamine agonists, and higher Montgomery-Asberg Depression Rating Scale and Unified Parkinson9s Disease Rating Scale–activities of daily living scores. Main risk factor for developing EDS was an increased Epworth Sleepiness Scale score at baseline. Conclusion: EDS is more frequent in PD even before treatment initiation compared with control participants and increases in occurrence with disease progression. The main risk factor for developing EDS with time is an early predisposition for sleepiness. In addition, the use of dopamine agonists was associated with the development of EDS. These findings necessitate caution in patients with PD and early increased sleep propensity and when using dopamine agonists.

Citrus peel is the preferred raw material for pectin production, mainly due to its high pectin content but also due to the gelling capabilities. Especially the high galacturonic acid content and the high degree of methyl esterification make it an attractive starting material for further modification. Until now the presence of rhamnogalacturonan-I (RG-I) in commercial pectin has received less attention due to its relatively low abundance. Using a gentle industrial extraction process we discovered a slightly higher composition in neutral sugars of RG-I. In particular, the arabinose concentration in mildly extracted pectin was higher compared to conventionally extracted pectin. The use of enzymes specific for either arabinan or galactan allowed assessing the implications of varying neutral sugar composition on the gelling capabilities of pectin. A comparison between untreated and debranched pectin revealed a significant decrease in both gelling temperature (up to 20 °C) and gel strength (up to 38%), following the specific reduction in neutral sugars concentration. Coil-overlap and entanglement effects were analysed to further understand the impact of RG-I side chains on polymer rheology.

Persistent pelvic girdle pain (PGP) after delivery is considered uncommon. The aim of this study was to assess the frequency of persistent PGP after delivery in an unselected population, its influence on the women’s daily life, and potential risk factors. The study population was drawn from a previous retrospective study of pelvic pain (PP) during pregnancy. The women were followed until 3–6 months after delivery in a prospective cohort study. All women were contacted by telephone and those with persistent PP were invited to fill in questionnaires and undergo a clinical examination. 68 of 330 women reported persistent pain in the pelvic area 3–6 months after delivery. 47 underwent a clinical examination, after which 36 women were diagnosed with either PGP alone (n = 25), or PGP combined with low back pain (LBP) (n = 11). Affected women reported a poor subjective health status, but the pain did not have a major impact on their daily life activities. Women with 3 independent risk factors: age ≥30 years, a moderate or high Oswestry Disability Index in pregnancy, and combined PP and LBP during pregnancy, had a 27-fold increased risk for persistent PGP compared with women without these risk factors. 16 % of women that reported PP during pregnancy were found to have persistent PGP 3–6 months after the delivery. Women with risk factors for persistent PGP should be identified while pregnant, and offered a follow-up examination 3 months after delivery.

Introduction Freezing of gait (FOG) is a potentially disabling motor problem in Parkinson's disease (PD) with uncertain etiology. Longitudinal studies of FOG in PD are scarce. We determined the prevalence, incidence, and associated clinical risk factors and concomitants of FOG during prospective long-term follow-up of a population-based PD cohort. Methods A community-based prevalent cohort of 232 PD patients was followed prospectively over 12 years. Reassessments were conducted at 4 and 8 years, and then annually. FOG, as well as severity of parkinsonism, motor complications, and psychotic symptoms were assessed by the Unified PD Rating Scale, and cognitive impairment by the Mini-Mental State Examination. Generalized estimating equations were applied to investigate baseline risk factors and concomitants of FOG over time. Results The point prevalence of FOG at baseline was 27% (95% confidence interval (95%-CI) 22–33%). By study end, 63% (95%-CI 56–69%) of patients had developed FOG. The incidence rate of FOG was 124.2 (95%-CI 101.5–152.1) per 1000 person-years. Motor fluctuations (odds ratio (OR) 3.45; p = 0.036) and higher levodopa dose (OR 1.30/100 mg, p = 0.009) at baseline were independent risk factors of incident FOG. Prevalent FOG over time was additionally associated with features thought to reflect extrastrial, non-dopaminergic pathologies, including PIGD (postural instability/gait difficulty, OR 6.30/10 points, p Conclusion These findings demonstrate that FOG affects the majority of patients in the general PD population and provide support to the hypothesis that alterations in both basal ganglia and extrastriatal brain areas are involved in the pathogenesis of FOG in PD.

Background Prospective long-term studies of falls in Parkinson's disease (PD) are scarce. Objective To examine the development of falls over 8 years in a population-based cohort of ambulatory patients with PD, and to investigate predictors of future falls in non-fallers at baseline. Methods All patients were examined at baseline and after 4 and 8 years, including the UPDRS, MMSE, Montgomery and Aaberg Depression Rating Scale, Functional Comorbidity Index, and a clinical dementia interview. Logistic regression models were applied to investigate baseline risk factors for future falls. A total of 211 patients were included at baseline, whereas 121 and 64 were re-examined at 4 and 8 years, respectively. Results The prevalence of falls increased from 41% (87 of 211) at baseline to 72% (46 of 64) after 8 years of prospective follow-up (disease duration 16.2 ± 4.8 years). Forty-seven non-falling patients at baseline completed all study visits, of these 68% (n = 32) changed fall status during follow-up. Predictive variables for current falling after 4 years were rare or occasional freezing of gait (OR 6.6, 95% CI 1.2–36.9), higher levodopa equivalent doses and more severe speech and axial impairment (both OR 1.3, 95% CI 1.0–1.7) in non-fallers at baseline. Higher baseline age was the only risk factor for current falling after 8 years. Conclusions Nearly ¾ of the PD cohort reported falling after 8 years of follow-up. Disease-specific gait and axial impairments were the major risk factors for future falls in non-fallers at baseline. This has implications for patient education and management.

Objectives Stroke is one of the leading causes for nursing home placement (NHP). We have studied the prognosis and risk factors regarding NHP for stroke patients initially discharged to their homes. Materials and methods All stroke patients in the municipality of Stavanger, Norway, between January 1, 1996, and March 31, 2004, were included and followed until death or May 31, 2012. Time intervals for NHP and death were compared to an age- and sex-matched, stroke-free control cohort. Logistic regression analysis was used to assess risk factors for NHP. Results A total of 452 patients were included. A total of 48 patients (10.6%) were directly placed in a nursing home, while 401 patients (88.7%) were discharged to their homes; 180 patients (44.7%) directly and 221 patients (55.3%) after temporary rehabilitation. Of the patients discharged to their homes, 29.7% needed NHP at a later time point as compared to 19.9% of the controls (P

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. Correction: Dominik Piston, Lydia Alvarez-Erviti, Vikas Bansal, Daniela Gargano, Zhi Yao, Gyorgy Szabadkai, Mark Odell, M Rhyan Puno, Benny Björkblom, Jodi Maple-Grødem, Peter Breuer, Oliver Kaut, Jan Petter Larsen, Stefan Bonn, Simon Geir Møller, Ullrich Wüllner, Anthony H V Schapira, Matthew E Gegg. DJ-1 is a redox sensitive adapter protein for high molecular weight complexes involved in regulation of catecholamine homeostasis. Human Molecular Genetics. Volume 27, Issue 3, 1 February 2018, Pages 576. DOI: 10.1093/hmg/ddx425

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. Electronic supplementary material The online version of this article (doi:10.1186/s12891-017-1631-0) contains supplementary material, which is available to authorized users.

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.

Background Parkinson's disease is a progressive movement disorder recognized by motor symptoms which frequently are measured and longitudinally monitored using the Unified Parkinson Disease Rating Scale (UPDRS). The factor structure of the UPDRS has yet not been analyzed in early PD. Methods A population-based cohort of patients with PD was investigated at the time of diagnosis, one year and three years later. The factor structure of the motor section of the UPDRS was explored using Principal Component Analysis (PCA). Results We found that the factor structure, the interrelatedness among variables, is different in the first year from diagnosis compared to later stages, but evolves at three years to resemble the factor structure reported for more advanced PD. The only consistent factor throughout the observation period was an axial factor. Conclusion The factor structure differs in early versus more advanced PD, but resembles the factor structure of more advanced PD after three years. This is likely due to a higher proportion of subjects with unilateral motor symptoms in early stages of PD together with a changing distribution of motor symptoms with further disease progression. Initiation of PD medication did not alter the factor structure in early PD. The axial factor was the most consistent factor in early PD and could be the most appropriate factor to monitor progression across the earliest stages of PD.

Parkinson's disease (PD) is a progressive and irreversible neurodegenerative disorder coupled to selective degeneration of dopamine-producing neurons in the substantia nigra. The majority of PD incidents are sporadic, but monogenic cases account for 5-10% of cases. Mutations in PINK1 cause autosomal recessive forms of early-onset PD, and PINK1 stimulates Omi/HtrA2/PARK13 protease activity when both proteins act as neuroprotective components in the same stress pathway. Studies on PINK1 and PARK13 have concentrated on phosphorylation-dependent PINK1-mediated activation of PARK13 and mitochondrial functions, because both proteins are classically viewed as mitochondrial. Although PARK13-mediated protective mechanisms are at least in part regulated by PINK1, little is known concerning how these two proteins are regulated in different subcellular compartments or, indeed, the influence of PARK13 on PINK1 characteristics. We show that PARK13 localizes to a variety of subcellular locations in neuronal cells and that PINK1, although more restrictive, also localizes to locations other than those previously reported. We demonstrate that PARK13 accumulation leads to a concomitant accumulation of PINK1 and that the increase in PINK1 levels is compartmental specific, indicating a correlative relationship between the two proteins. Moreover, we show that PARK13 and PINK1 protein levels accumulate in response to H2 O2 and L-DOPA treatments in a subcellular fashion and that both proteins show relocation to the cytoskeleton in response to H2 O2 . This H2 O2 -mediated relocation is abolished by PARK13 overexpression. This study shows that PARK13 and PINK1 are subcellular-specific, but dynamic, proteins with a reciprocal molecular relationship providing new insight into the complexity of PD.

Progressive neurodegenerative diseases are among the most frequently occurring aging-associated human pathologies. In a screen forCaenorhabditis elegansmutant 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 channeltrp-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 thattrp-4(d)induces cell death in dopamine neurons through a defined, calcium-related downstream pathway.

To identify MRI biomarkers associated with long-term disability progression in patients with multiple sclerosis (MS), and to define the rate of evolution of global, tissue-specific and regional atrophy in patients with MS over long-term.MRI of the brain and clinical neurological assessment was performed in 81 patients at time of first visit and after 5 and 10 years of follow-up. MRI was acquired on 1.5 T scanners. T1-lesion and T2-lesion volumes (LVs) were calculated. Global and tissue-specific atrophy changes were longitudinally assessed, using a direct measurement approach, by calculating percentage volume changes between different time points. Regional tissue volumes for the subcortical deep grey matter (SDGM) structures were also obtained. Disability progression was defined as an increase in Expanded Disability Status Scale of ≥ 1.0 compared to baseline at 5-year and 10-year follow-up.Over 5 years, patients with disability progression showed significantly increased loss of whole brain (-3.8% vs -2.0%, p0.001), cortical (-3.4% vs -1.8%, p=0.009) and putamen volume changes (-10.6% vs -3.8%, p=0.003) compared to patients with no disability progression. No significant change in white matter (WM) volume was observed when comparing progressing and non-progressing patients. Over 10 years, there was a trend for greater decrease in whole brain volume (-5.5% vs -3.7%, p=0.015) in the progressing patients. No significant changes in LV measures were detected between the patients with and without disability progression.This long-term study shows that whole brain, cortical and putamen atrophy occurs throughout the 10-year follow-up of this MS cohort and is more pronounced in the group that showed disability progression at 5, but not at 10 years of follow-up. Overall, GM atrophy showed better association with disease progression than WM atrophy over 5-year and 10-year follow-up.

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., Accumulated damage to mitochondrial DNA (mtDNA) occurs during the ageing process and neurodegenerative disease. Here, the authors show that mtDNA copy number increases in an age-dependent manner in substantia nigra of healthy individuals, but not in individuals with Parkinson disease.

Recent advances within the field of proteomics, including both upstream and downstream protocols, have fuelled a transition from simple protein identification to functional analysis. A battery of proteomics approaches is now being employed for the analysis of protein expression levels, the monitoring of cellular activities and for gaining an increased understanding into biochemical pathways. Combined, these approaches are changing the way we study disease by allowing accurate and targeted, large scale protein analysis, which will provide invaluable insight into disease pathogenesis. Neurodegenerative disorders, including Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), amyotrophic lateral sclerosis (ALS), prion disease, and other diseases that affect the neuromuscular system, are a leading cause of disability in the aging population. There are no effective intervention strategies for these disorders and diagnosis is challenging as it relies primarily on clinical symptomatic features, which often overlap at early stages of disease. There is, therefore, an urgent need to develop reliable biomarkers to improve early and specific diagnosis, to track disease progression, to measure molecular responses towards treatment regimes and ultimately devise new therapeutic strategies. To accomplish this, a better understanding of disease mechanisms is needed. In this review we summarize recent advances in the field of proteomics applicable to neurodegenerative disorders, and how these advances are fueling our understanding, diagnosis, and treatment of these complex disorders.

Background The relative impact of motor- and non-motor symptoms on health-related quality of life in early Parkinson's disease is poorly documented. Methods 188 patients with incident Parkinson's disease from a population-based study were examined at the time of diagnosis, before initiation of dopaminergic treatment, with follow-up of 166 patients three years later. Health-related quality of life was assessed by the 36-item Short-form Health Survey (SF-36). Motor and non-motor variables were derived from the Unified Parkinson's disease rating scale and other established scales. Results Multiple regression analyses showed that the non-motor symptoms strongest associated with reduced SF-36 scores at diagnosis and three years later were depression, fatigue and sensory complaints. The motor symptoms most related to impaired SF-36 scores were problems with gait and activities of daily living that cover personal needs. The variance of SF-36 mental summary scores was much better explained by non-motor vs. motor symptoms, both at baseline ( R 2 = 0.384 vs. 0.095) and 3 years later ( R 2 = 0.441 vs. 0.195). Also SF-36 physical summary scores were better explained by non-motor vs. motor symptoms with R 2 = 0.372 vs. 0.322 at baseline and R 2 = 0.468 vs. 0.315 after 3 years. Conclusion In early PD, including the phase before dopaminergic treatment is initiated, non-motor symptoms are more important for reduced health-related quality of life than motor symptoms. Fatigue, depression, sensory complaints and gait disturbances emerge as the most relevant symptoms and should be given corresponding attention in the management of patients with early PD.

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.

ParkWest is a large Norwegian multicenter study of newly diagnosed drug-naive subjects with Parkinson's disease (PD). Cognitively normal PD subjects (PDCN) and PD subjects with mild cognitive impairment (PDMCI) from this cohort have significant hippocampal atrophy and ventricular enlargement, compared to normal controls. Here, we aimed to investigate whether the same structural changes are associated with cerebrospinal fluid (CSF) levels of amyloid beta (Aβ)38 , Aβ40 , Aβ42 , total tau (t-tau), and phosphorylated tau (p-tau). We performed three-dimensional radial distance analyses of the hippocampi and lateral ventricles using the MRI data from ParkWest subjects who provided CSF at baseline. Our sample consisted of 73 PDCN and 18 PDMCI subjects. We found significant associations between levels of all three CSF Aβ analytes and t-tau and lateral ventricular enlargement in the pooled sample. In the PDCN sample, all three amyloid analytes showed significant associations with the radial distance of the occipital and frontal horns of the lateral ventricles. CSF Aβ38 and Aβ42 showed negative associations, with enlargement in occipital and frontal horns of the lateral ventricles in the pooled sample, and a negative association with the occipital horns in PDMCI. CSF Aβ levels in early PD correlate with ventricular enlargement, previously associated with PD dementia. Therefore, CSF and MRI markers may help identify PD patients at high risk for developing cognitive decline and dementia in the course of their illness. Contrary to Alzheimer's disease, we found no associations between CSF t-tau and p-tau and hippocampal atrophy.

Objectives There are limited data on treatment effect in early and drug-naive Parkinson's disease (PD) outside of clinical trials. We sought to review the treatment effects on motor symptoms in early, unselected PD patients. Methods We included 183 drug-naive patients from a longitudinal cohort (The Norwegian ParkWest study). At the time of diagnosis, motor symptoms were assessed and rated. Treatment was unrestricted, aimed at treating each patient optimally. Patients were reassessed after 12 months, and then grouped according to treatment: No dopaminergic treatment (NDT), dopamine agonists (DA) or levodopa. All strategies could be combined with monoamine oxidase B inhibitors. Results In general, the chosen treatment was coherent with current practice. During follow-up, patients given NDT (n = 40) had unaltered clinical motor symptoms, as opposed to improvement in the DA- and levodopa-treated patients (n = 140). The overall improvement in these two groups was fairly similar, but axial symptoms did not improve in levodopa-treated patients as opposed to the younger DA-treated patients. Conclusions Twelve months after the diagnosis, motor symptoms in approximately one-fifth of PD patients remained clinically stable. Tremor, bradykinesia and rigidity improved in the dopaminergic-treated patients. Axial symptoms were more treatment resistant, and the different symptomatic effects found between treatment strategies may be age related.

PurposeThe reasons why the mortality of patients with epilepsy is significantly increased, even many years after seizure onset, are not fully understood. The aim of this study was to compare the distribution of the causes of death (COD) in an epilepsy population with that in the general population and with previous findings in other epilepsy populations. In addition, we investigated the chronological relationship between the onset of epilepsy and the onset of the diseases leading to death.MethodsThe COD for patients who were registered with a diagnosis of epilepsy at Stavanger University Hospital from August 1 1995–July 31 2005 and died during the same period were obtained from the Norwegian Cause of Death Registry and the hospital records were reviewed. The distribution of the corresponding COD in the general population was obtained from Statistics Norway.ResultsAt least 6.8% (18/266) of the deaths of epilepsy patients were directly related to seizures. Epilepsy patients who had died from brain tumors (n=46) were excluded from further analysis. Of the remaining 220 deceased epilepsy patients, 39 (17.7%) had died from heart disease, compared with 27.8% in the general population (p

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.

Familial aggregation has been described in PD of both early and late onset, but has not been studied in a true population-based sample. Moreover, little is known about its association with disease progression and endophenotypes.The objectives of this work were to determine familial aggregation of idiopathic PD in a population-based cohort and study the association with clinical endophenotypes and disease progression.We examined family history data from the Norwegian ParkWest study, a well-characterized, population-based cohort of incident PD patients and age-matched healthy controls. Family data were collected at baseline with a simplified questionnaire (192 cases and 193 controls) and after 3 years of longitudinal follow-up using an extended questionnaire (172 cases and 171 controls).Compared to the controls, the PD patients had an increased relative risk of having a first-degree relative with PD when using the extended questionnaire (relative risk = 1.988; P = 0.036), but not when using the simplified questionnaire (relative risk = 1.453; P = 0.224). There was no significant difference in age of onset or motor subtype (P = 0.801). However, cases with a family history of PD had reduced progression over 7 years as measured by UPDRS II (P = 0.008) and smaller rate of decrease of MMSE (P = 0.046).Our findings confirm familial aggregation in a population-based cohort of idiopathic PD. Moreover, we show that positive family history of PD in patients is associated with a slower progression of PD symptoms and cognitive decline. © 2016 International Parkinson and Movement Disorder Society.