Caregiver Burden in Late-Stage Parkinsonism and Its Associations

Background: Patients in the late stages of parkinsonism are highly dependent on others in their self-care and activities of daily living. However, few studies have assessed the physical, psychological and social consequences of caring for a person with late-stage parkinsonism. Patients and methods: Five hundred and six patients and their caregivers from the Care of Late Stage Parkinsonism (CLaSP) study were included. Patients’ motor and non-motor symptoms were assessed using the UPDRS and Non-motor symptom scale (NMSS), Neuropsychiatric inventory (NPI-12), and caregivers’ health status using the EQ-5D-3 L. Caregiver burden was assessed by the Zarit Burden Interview (ZBI). Results: The majority of caregivers were the spouse or life partner (71.2%), and were living with the patient at home (67%). Approximately half of caregivers reported anxiety/depression and pain/discomfort (45% and 59% respectively). The factors most strongly associated with caregiver burden were patients’ neuropsychiatric features on the total NPI score (r = 0.38, p < 0.0001), total NMSS score (r = 0.28, p < 0.0001), caring for male patients and patients living at home. Being the spouse, the hours per day assisting and supervising the patient as well as caregivers’ EQ-5D mood and pain scores were also associated with higher ZBI scores (all p < 0.001). Conclusion: The care of patients with late stage parkinsonism is associated with significant caregiver burden, particularly when patients manifest many neuropsychiatric and non-motor features and when caring for a male patient at home

Characteristics of Patients with Late-Stage Parkinsonism who are Nursing Home Residents Compared with those Living at Home

OBJECTIVES: To determine clinical characteristics and treatment complications of patients with late-stage Parkinsonism living in nursing homes compared with those living at home. DESIGN: Cross-sectional analysis. SETTING AND PARTICIPANTS: This study is an analysis of 692 patients with late stage Parkinsonism recruited to an in-depth international study, Care of Late-Stage Parkinsonism (CLaSP). MEASURES: Sociodemographic characteristics were compared between patients who were living in a nursing home (n = 194) and those living at home (n = 498). Clinical assessments included the Unified Parkinson's Disease Rating Scale (UPDRS), the nonmotor symptom scale, the neuropsychiatric inventory, and a structured interview of patients and carers. Predictors of nursing home status were determined in a multivariate analysis. RESULTS: Nursing home placement was strongly associated with more severe cognitive impairment, worse UPDRS motor scores and disability, and with being unmarried and older. Although nursing home residents had significantly higher axial scores, falls were less common. Despite similar levodopa equivalence doses, they had less dyskinesia. Nonmotor symptom burden, particularly delusion, hallucination, and depression scores were higher in nursing home residents, and they were more frequently on psychotropic medication. They had lower rates of dopamine agonist use and lower rates of impulse control disorders. In multivariate analysis, being unmarried, presence of cognitive impairment, worse disease severity as assessed on the UPDRS parts II and III, severity of delusions, and lower rate of dyskinesia were associated with nursing home placement. CONCLUSIONS AND IMPLICATIONS: These clinical characteristics suggest that in patients with Parkinsonsim who are nursing home residents, presence of cognitive impairment and delusions particularly add to the higher overall symptom burden, and more often require specific treatments, including clozapine. Despite similar levodopa equivalent daily dose, motor severity is higher, and dyskinesias, indicative of a response to levodopa, are less common. Falls, however, also occur less commonly, and dopamine agonists are less frequently used, with lower rates of impulse control disorder

The Angiotensin Converting Enzyme Insertion/Deletion polymorphism is not associated with an increased risk of death or bronchopulmonary dysplasia in ventilated very low birth weight infants

BACKGROUND: The ACE gene contains a polymorphism consisting of either the presence (insertion, I) or absence (deletion, D) of a 287 bp alu repeat in intron 16. The D allele is associated with increased ACE activity in both tissue and plasma. The DD genotype is associated with risk of developing ARDS and mortality. The frequency of the D allele is higher in patients with pulmonary fibrosis, sarcoidosis and berylliosis. The role of this polymorphism has not been studied in the development of BPD in the premature newborn. METHODS: ACE I/D genotype was determined in 245 (194 African-American, 47 Caucasian and 4 Hispanic) mechanically ventilated infants weighing less than 1250 grams at birth and compared to outcome (death and/or development of BPD). RESULTS: The incidence of the D allele in the study population was 0.58. Eighty-eight (35.9%) infants were homozygous DD, 107 (43.7%) were heterozygous ID and 50 (20.4%) were homozygous II. There were no significant differences between genotype groups with respect to ethnic origin, birth weight, gestation, or gender. There was no effect of the ACE I/D polymorphism on mortality or development of BPD (O(2 )on 28 days or 36 weeks PCA). Secondary outcomes (intraventricular hemorrhage and periventricular leukomalacia) similarly were not influenced by the ACE ID polymorphism. CONCLUSIONS: The ACE I/D polymorphism does not significantly influence the development of BPD in ventilated infants less than 1250 grams

Feasibility of large-scale deployment of multiple wearable sensors in Parkinson’s disease

Wearable devices can capture objective day-to-day data about Parkinson’s Disease (PD). This study aims to assess the feasibility of implementing wearable technology to collect data from multiple sensors during the daily lives of PD patients. The Parkinson@home study is an observational, two-cohort (North America, NAM; The Netherlands, NL) study. To recruit participants, different strategies were used between sites. Main enrolment criteria were self-reported diagnosis of PD, possession of a smartphone and age ≥18 years. Participants used the Fox Wearable Companion app on a smartwatch and smartphone for a minimum of 6 weeks (NAM) or 13 weeks (NL). Sensor-derived measures estimated information about movement. Additionally, medication intake and symptoms were collected via self-reports in the app. A total of 953 participants were included (NL: 304, NAM: 649). Enrolment rate was 88% in the NL (n = 304) and 51% (n = 649) in NAM. Overall, 84% (n = 805) of participants contributed sensor data. Participants were compliant for 68% (16.3 hours/participant/day) of the study period in NL and for 62% (14.8 hours/participant/day) in NAM. Daily accelerometer data collection decreased 23% in the NL after 13 weeks, and 27% in NAM after 6 weeks. Data contribution was not affected by demographics, clinical characteristics or attitude towards technology, but was by the platform usability score in the NL (χ2 (2) = 32.014, p<0.001), and self-reported depression in NAM (χ2(2) = 6.397, p = .04). The Parkinson@home study shows that it is feasible to collect objective data using multiple wearable sensors in PD during daily life in a large cohort

Design and baseline characteristics of the ParkFit study, a randomized controlled trial evaluating the effectiveness of a multifaceted behavioral program to increase physical activity in Parkinson patients

<p>Abstract</p> <p>Background</p> <p>Many patients with Parkinson's disease (PD) lead a sedentary lifestyle. Promotion of physical activities may beneficially affect the clinical presentation of PD, and perhaps even modify the course of PD. However, because of physical and cognitive impairments, patients with PD require specific support to increase their level of physical activity.</p> <p>Methods</p> <p>We developed the ParkFit Program: a PD-specific and multifaceted behavioral program to promote physical activity. The emphasis is on creating a behavioral change, using a combination of accepted behavioral motivation techniques. In addition, we designed a multicentre randomized clinical trial to investigate whether this ParkFit Program increases physical activity levels over two years in sedentary PD patients. We intended to include 700 sedentary patients. Primary endpoint is the time spent on physical activities per week, which will be measured every six months using an interview-based 7-day recall.</p> <p>Results</p> <p>In total 3453 PD patients were invited to participate. Ultimately, 586 patients - with a mean (SD) age of 64.1 (7.6) years and disease duration of 5.3 (4.5) years - entered the study. Study participants were younger, had a shorter disease duration and were less sedentary compared with eligible PD patients not willing to participate.</p> <p>Discussion</p> <p>The ParkFit trial is expected to yield important new evidence about behavioral interventions to promote physical activity in sedentary patients with PD. The results of the trial are expected in 2012.</p> <p>Trial registration</p> <p><url>http://clinicaltrials.gov</url> (nr NCT00748488).</p

Physical inactivity in Parkinson’s disease

Patients with Parkinson’s disease (PD) are likely to become physically inactive, because of their motor, mental, and emotional symptoms. However, specific studies on physical activity in PD are scarce, and results are conflicting. Here, we quantified daily physical activities in a large cohort of PD patients and another large cohort of matched controls. Moreover, we investigated the influence of disease-related factors on daily physical activities in PD patients. Daily physical activity data of PD patients (n = 699) were collected in the ParkinsonNet trial and of controls (n = 1,959) in the Longitudinal Aging Study Amsterdam (LASA); data were determined using the LAPAQ, a validated physical activity questionnaire. In addition, variables that may affect daily physical activities in PD were recorded, including motor symptoms, depression, disability in daily life, and comorbidity. Patients were physically less active; a reduction of 29% compared to controls (95% CI, 10–44%). Multivariate regression analyses demonstrated that greater disease severity, gait impairment, and greater disability in daily living were associated with less daily physical activity in PD (R2 = 24%). In this large study, we show that PD patients are about one-third less active compared to controls. While disease severity, gait, and disability in daily living predicted part of the inactivity, a portion of the variance remained unexplained, suggesting that additional determinants may also affect daily physical activities in PD. Because physical inactivity has many adverse consequences, work is needed to develop safe and enjoyable exercise programs for patients with PD

Nesfatin-1/NUCB2 as a Potential New Element of Sleep Regulation in Rats.

STUDY OBJECTIVES: Millions suffer from sleep disorders that often accompany severe illnesses such as major depression; a leading psychiatric disorder characterized by appetite and rapid eye movement sleep (REMS) abnormalities. Melanin-concentrating hormone (MCH) and nesfatin-1/NUCB2 (nesfatin) are strongly co - expressed in the hypothalamus and are involved both in food intake regulation and depression. Since MCH was recognized earlier as a hypnogenic factor, we analyzed the potential role of nesfatin on vigilance. DESIGN: We subjected rats to a 72 h-long REMS deprivation using the classic flower pot method, followed by a 3 h-long 'rebound sleep'. Nesfatin mRNA and protein expressions as well as neuronal activity (Fos) were measured by quantitative in situ hybridization technique, ELISA and immunohistochemistry, respectively, in 'deprived' and 'rebound' groups, relative to controls sacrificed at the same time. We also analyzed electroencephalogram of rats treated by intracerebroventricularly administered nesfatin-1, or saline. RESULTS: REMS deprivation downregulated the expression of nesfatin (mRNA and protein), however, enhanced REMS during 'rebound' reversed this to control levels. Additionally, increased transcriptional activity (Fos) was demonstrated in nesfatin neurons during 'rebound'. Centrally administered nesfatin-1 at light on reduced REMS and intermediate stage of sleep, while increased passive wake for several hours and also caused a short-term increase in light slow wave sleep. CONCLUSIONS: The data designate nesfatin as a potential new factor in sleep regulation, which fact can also be relevant in the better understanding of the role of nesfatin in the pathomechanism of depression

RECIST revised: implications for the radiologist. A review article on the modified RECIST guideline

The purpose of this review article is to familiarize radiologists with the recently revised Response Evaluation Criteria in Solid Tumours (RECIST), used in many anticancer drug trials to assess response and progression rate. The most important modifications are: a reduction in the maximum number of target lesions from ten to five, with a maximum of two per organ, with a longest diameter of at least 10 mm; in lymph nodes (LNs) the short axis rather than the long axis should be measured, with normal LN measuring <10 mm, non-target LN ≥10 mm but <15 mm and target LN ≥15 mm; osteolytic lesions with a soft tissue component and cystic tumours may serve as target lesions; an additional requirement for progressive disease (PD) of target lesions is not only a ≥20% increase in the sum of the longest diameter (SLD) from the nadir but also a ≥5 mm absolute increase in the SLD (the other response categories of target lesion are unchanged); PD of non-target lesions can only be applied if the increase in non-target lesions is representative of change in overall tumour burden; detailed imaging guidelines. Alternative response criteria in patients with hepatocellular carcinoma and gastrointestinal stromal tumours are discussed

A Two-Stage Meta-Analysis Identifies Several New Loci for Parkinson's Disease

A previous genome-wide association (GWA) meta-analysis of 12,386 PD cases and 21,026 controls conducted by the International Parkinson's Disease Genomics Consortium (IPDGC) discovered or confirmed 11 Parkinson's disease (PD) loci. This first analysis of the two-stage IPDGC study focused on the set of loci that passed genome-wide significance in the first stage GWA scan. However, the second stage genotyping array, the ImmunoChip, included a larger set of 1,920 SNPs selected on the basis of the GWA analysis. Here, we analyzed this set of 1,920 SNPs, and we identified five additional PD risk loci (combined p<5x10(-10), PARK16/1q32, STX1B/16p11, FGF20/8p22, STBD1/4q21, and GPNMB/7p15). Two of these five loci have been suggested by previous association studies (PARK16/1q32, FGF20/8p22), and this study provides further support for these findings. Using a dataset of post-mortem brain samples assayed for gene expression (n = 399) and methylation (n = 292), we identified methylation and expression changes associated with PD risk variants in PARK16/1q32, GPNMB/7p15, and STX1B/16p11 loci, hence suggesting potential molecular mechanisms and candidate genes at these risk loci

Noisy galvanic vestibular stimulation promotes GABA release in the substantia nigra and improves locomotion in hemiparkinsonian rats

Dopamine related disorders usually respond to dopaminergic drugs, but not all symptoms are equally responsive. In Parkinson’s disease (PD) in particular, axial symptoms resulting in impaired gait and postural control are difficult to treat. Stochastic vestibular stimulation (SVS) has been put forward as a method to improve CNS function in dopamine related disorders, but the mechanisms of action are not well understood. This thesis aimed to investigate the effects of SVS on neuronal brain activity and to evaluate the possible enhancing effect of SVS on motor control in PD and on cognitive functions and motor learning in Attention deficit hyperactivity disorder (ADHD). Behavioural tests were conducted in the 6-OHDA rat model of PD using the accelerating Rotarod and the Montoya skilled reach test to evaluate the effect of SVS on motor control. The effect of SVS on brain activity was assessed using in vivo microdialysis and immunohistochemistry. We evaluated the effect of SVS on postural control and Parkinsonism in patients with PD and the effect of SVS on cognitive function in people with ADHD. The behavioural animal studies indicate that SVS may have an enhancing effect on locomotion, but not skilled forepaw function. SVS increased GABA transmission in the ipsilesional substantia nigra (SN) and may have a rebalancing effect on dysfunctional brain activity. SVS increased c-Fos activity more than levodopa and saline in the vestibular nucleus of all animals. c-Fos expression was also higher in this region in the 6-OHDA lesioned than in shamlesioned animals, supporting the theory that SVS may have larger effects in the dopamine depleted brain. SVS increased c-Fos expression in the habenula nucleus substantially more than levodopa did. Furthermore, SVS and levodopa had similar effects on many brain regions, including the striatum, where saline had no effect. The clinical studies revealed improvement of postural control in PD during SVS. There was a trend towards reduced Parkinsonism during SVS when off levodopa. No substantial effects were found on cognitive performance in ADHD. In PD, SVS may improve motor control by inhibiting the overactive SN, possibly through a non-dopaminergic modulatory pathway involving increased neurotransmission in the habenula nucleus. SVS could be trialled in larger studies to evaluate long-term effects on treatment resistant axial symptoms associated with PD