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Find video protocols related to scientific articles indexed in Pubmed.
Higher Frequency of Certain Cancers in LRRK2 G2019S Mutation Carriers With Parkinson Disease: A Pooled Analysis.
JAMA Neurol
PUBLISHED: 11-18-2014
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Patients with Parkinson disease (PD) who harbor LRRK2 G2019S mutations may have increased risks of nonskin cancers. However, the results have been inconsistent across studies.
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Interdisciplinary teamwork for the treatment of people with Parkinson's disease and their families.
Curr Neurol Neurosci Rep
PUBLISHED: 09-24-2014
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Parkinson's disease (PD) is a chronic progressive neurodegenerative and multidimensional disease that involves a range of disabling motor and nonmotor symptoms. These symptoms can have a major impact on the quality of life of PD patients. The focus of this article is to stress the importance of the interdisciplinary team intervention approach in the treatment of patients with PD. The team approach uses experts in PD from different health care professions, including a neurologist, a nurse, a speech and language therapist, a physiotherapist, a social worker, a psychiatrist, an occupational therapist, a sexologist, and a dietician. The major aim of the team and of teamwork is to provide professional care in all motor and nonmotor aspects of PD throughout the course of the disease. There are different models of multidisciplinary teams: inpatient facility, community rehabilitation facility, and synchronized multiprofessional treatment in the community. The Tel Aviv Sourasky Medical Center model of interdisciplinary care was designed to create a coordinated multidisciplinary team in the Movement Disorders Unit. The role of each team member and their professional objective are described. Their collaboration is by design a promotion of a team goal for maintaining and enhancing the quality of life of PD patients and their families.
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Gait and balance in Parkinson's disease subtypes: objective measures and classification considerations.
J. Neurol.
PUBLISHED: 08-22-2014
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Parkinson's disease (PD) is often divided into tremor dominant (TD) and postural instability gait difficulty (PIGD) subtypes. However, objective measures of gait (e.g., stride length, variability) and balance have not been well studied in these subtypes. To better understand these motor subtypes, we objectively quantified gait and balance and their behavioral correlates. 110 patients with PD underwent a clinical evaluation and were stratified into PIGD and TD subtypes. Participants walked under single and dual task conditions while wearing a single body-fixed sensor, both "OFF" and "ON" medications and at home for 3 days. We also examined performance-based tests of mobility, balance, and fall risk. Stricter criteria were also applied, dividing the subjects into predominant representative subgroups: p-PIGD and p-TD. Both the PIGD (n = 62) and TD (n = 42) groups and the p-PIGD (n = 31) and p-TD (n = 32) subgroups were similar with respect to basic disease characteristics (e.g., disease duration, p > 0.69). Surprisingly gait speed, stride length, and variability did not differ between the PIGD and TD groups (p > 0.05). In contrast, the p-PIGD group had reduced gait speed (under single and dual task conditions), shorter strides, increased stride variability, and decreased stride regularity (regularity: p-PIGD 0.66 ± 0.10; p-TD 0.74 ± 0.08; p = 0.003). The p-PIGD group also scored worse on performance-based tests, compared to the p-TD. Clinical assessments of the disturbances seen in patients with the PIGD subtype are not consistent with objective measures; overlapping between the groups is seen in many objective features of gait and balance. These findings suggest that the proposed alternate classification scheme may be useful.
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Interest in Genetic Testing in Ashkenazi Jewish Parkinson's Disease Patients and Their Unaffected Relatives.
J Genet Couns
PUBLISHED: 08-17-2014
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Our objective was to explore interest in genetic testing among Ashkenazi Jewish (AJ) Parkinson's Disease (PD) cases and first-degree relatives, as genetic testing for LRRK2 G2019S is widely available. Approximately 18 % of AJ PD cases carry G2019S mutations; penetrance estimations vary between 24 and 100 % by age 80. A Genetic Attitude Questionnaire (GAQ) was administered at two New York sites to PD families unaware of LRRK2 G2019S mutation status. The association of G2019S, age, education, gender and family history of PD with desire for genetic testing (outcome) was modeled using logistic regression. One-hundred eleven PD cases and 77 relatives completed the GAQ. Both PD cases and relatives had excellent PD-specific genetic knowledge. Among PD, 32.6 % "definitely" and 41.1 % "probably" wanted testing, if offered "now." Among relatives, 23.6 % "definitely" and 36.1 % "probably" wanted testing "now." Desire for testing in relatives increased incrementally based on hypothetical risk of PD. The most important reasons for testing in probands and relatives were: if it influenced medication response, identifying no mutation, and early prevention and treatment. In logistic regression, older age was associated with less desire for testing in probands OR?=?0.921 95%CI 0.868-0.977, p?=?0.009. Both probands and relatives express interest in genetic testing, despite no link to current treatment or prevention.
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The Montreal Cognitive Assessment in Cognitively-intact Elderly: A Case for Age-adjusted Cutoffs.
J. Alzheimers Dis.
PUBLISHED: 07-26-2014
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The Montreal Cognitive Assessment (MoCA) is a widely used screening test for evaluation of mild cognitive impairment, with a single cutoff for all ages. We examined whether it is associated with age in a sample of cognitively-intact elderly (CIE). The average MoCA score was negatively correlated with age and was significantly higher for younger than older CIE. Additionally, 42% of the older elderly fell below the proposed mild cognitive impairment cutoff score, although all subjects were CIE. Thus, cognitive abilities captured by the MoCA test decrease with age, even in CIE. Therefore, cutoff scores by age for the MoCA are needed.
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New evidence for gait abnormalities among Parkinson's disease patients who suffer from freezing of gait: insights using a body-fixed sensor worn for 3 days.
J Neural Transm
PUBLISHED: 06-17-2014
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Previous studies conducted in laboratory settings suggest that the gait pattern in between freezing of gait (FOG) episodes is abnormal among patients with Parkinson's disease (PD) who suffer from FOG (i.e., "freezers"), compared to those who do not (i.e., "non-freezers"). We evaluated whether long-term recordings also reveal gait alterations in freezers and if these features were related to freezing severity and its impact on daily function. 72 patients with PD wore a 3-D accelerometer for 3 days. Acceleration-derived gait features included quantity (e.g., the amount of walking) and quality measures (e.g., gait variability). The New FOG-Questionnaire evaluated the subject's perceptions of FOG severity and its impact. Age, gender, and disease duration were similar (p > 0.19) in the 28 freezers and 44 non-freezers. Walking quantity was similar in the two groups, while freezers walked with higher gait variability (i.e., larger anterior-posterior power spectral density width; p = 0.003) and lower gait consistency (i.e., lower vertical stride regularity; p = 0.007). Group differences were observed when comparing the typical (i.e., median), best, and worst performance among the multiple walking bouts measured. Vertical and medio-lateral gait consistency were associated with the impact of FOG on daily living (r < -0.39, p < 0.044). The present findings demonstrate that freezers have altered gait variability and consistency during spontaneous community ambulation, even during optimal performance, and that these measures are associated with the impact of FOG on daily function. Long-term recordings may provide new insights into PD and augment the monitoring of FOG and its response to therapy.
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Genome-wide mapping of IBD segments in an Ashkenazi PD cohort identifies associated haplotypes.
Hum. Mol. Genet.
PUBLISHED: 05-19-2014
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The recent series of large genome-wide association studies in European and Japanese cohorts established that Parkinson disease (PD) has a substantial genetic component. To further investigate the genetic landscape of PD, we performed a genome-wide scan in the largest to date Ashkenazi Jewish cohort of 1130 Parkinson patients and 2611 pooled controls. Motivated by the reduced disease allele heterogeneity and a high degree of identical-by-descent (IBD) haplotype sharing in this founder population, we conducted a haplotype association study based on mapping of shared IBD segments. We observed significant haplotype association signals at three previously implicated Parkinson loci: LRRK2 (OR = 12.05, P = 1.23 × 10(-56)), MAPT (OR = 0.62, P = 1.78 × 10(-11)) and GBA (multiple distinct haplotypes, OR > 8.28, P = 1.13 × 10(-11) and OR = 2.50, P = 1.22 × 10(-9)). In addition, we identified a novel association signal on chr2q14.3 coming from a rare haplotype (OR = 22.58, P = 1.21 × 10(-10)) and replicated it in a secondary cohort of 306 Ashkenazi PD cases and 2583 controls. Our results highlight the power of our haplotype association method, particularly useful in studies of founder populations, and reaffirm the benefits of studying complex diseases in Ashkenazi Jewish cohorts.
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Clinical experience using a 5-week treadmill training program with virtual reality to enhance gait in an ambulatory physical therapy service.
Phys Ther
PUBLISHED: 05-01-2014
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Current literature views safe gait as a complex task, relying on motor and cognitive resources. The use of virtual reality (VR) in gait training offers a multifactorial approach, showing positive effects on mobility, balance, and fall risk in elderly people and individuals with neurological disorders. This form of training has been described as a viable research tool; however, it has not been applied routinely in clinical practice. Recently, VR was used to develop an adjunct training method for use by physical therapists in an ambulatory clinical setting.
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Central nervous system manifestation of IgG4-related disease.
JAMA Neurol
PUBLISHED: 05-01-2014
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IgG4-related disease (IgG4-RD) is characterized by an inflammatory reaction rich in IgG4-positive plasma cells. Head and brain involvement is rare in IgG4-RD, and brain parenchyma involvement has never been reported.
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Effect of rivastigmine on mobility of patients with higher-level gait disorder: a pilot exploratory study.
Drugs R D
PUBLISHED: 04-12-2014
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Higher-level gait disorder (HLGD) in older adults is characterized by postural instability, stepping dysrhythmicity, recurrent falls and progressive immobility. Cognitive impairments are frequently associated with HLGD.
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Automated detection of missteps during community ambulation in patients with Parkinson's disease: a new approach for quantifying fall risk in the community setting.
J Neuroeng Rehabil
PUBLISHED: 03-24-2014
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Falls are a leading cause of morbidity and mortality among older adults and patients with neurological disease like Parkinson's disease (PD). Self-report of missteps, also referred to as near falls, has been related to fall risk in patients with PD. We developed an objective tool for detecting missteps under real-world, daily life conditions to enhance the evaluation of fall risk and applied this new method to 3 day continuous recordings.
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Association between performance on Timed Up and Go subtasks and mild cognitive impairment: further insights into the links between cognitive and motor function.
J Am Geriatr Soc
PUBLISHED: 03-17-2014
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To assess whether different Timed Up and Go (TUG) subtasks are affected differently in older adults with mild cognitive impairment (MCI) and are specific to different cognitive abilities.
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CHRNB3 c.-57A>G functional promoter change affects Parkinson's disease and smoking.
Neurobiol. Aging
PUBLISHED: 03-04-2014
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Cigarette smoking is protective in Parkinson's disease (PD), possibly because of nicotine action on brain nicotinic-acetylcholine receptors. The ?3 nicotinic-acetylcholine receptor subunit (encoded by CHRNB3) is depleted in the striatum of PD patients and associated with nicotine dependence. Herein, the CHRNB3 gene was sequenced, and the c.-57G allele frequency was 0.31 and 0.26 among patients (n = 596) and controls (n = 369), respectively (p = 0.02, odds ratio = 1.33, 95% confidence interval = 1.03-1.73). The c.-57G allele was strongly associated with smoking in patients, as 48.4% of c.-57G carriers compared with 32.6% of noncarriers reported smoking history (p < 0.0001). The transcription factor Oct-1 binding was almost eliminated in lymphoblasts with the c.-57G/G genotype, to only 6.5% percent, and the CHRNB3 promoter activity was reduced in cells with the c.-57G/G genotype by 96%-70%. These findings suggest that the CHRNB3 c.-57A>G alteration affects the promoter activity and is associated with PD and smoking in PD patients. It is therefore possible that nicotine may be valuable for patients who carry this alteration and beneficial in PD only for patients with specific genotypes.
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A motor learning-based intervention to ameliorate freezing of gait in subjects with Parkinson's disease.
J. Neurol.
PUBLISHED: 02-14-2014
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Freezing of gait (FOG) is an episodic gait disturbance that is commonly seen in Parkinson's disease (PD). To date, treatment efficacy is limited. We tested the hypothesis that an intervention that utilizes motor learning provided through intensive cueing can alleviate this symptom. Fifteen subjects with PD suffering from FOG participated in a 6 week progressive motor learning program (three training sessions per week--open trial). A training session included FOG-provoking situations (e.g., turns). Prior to each presumed FOG provocation (e.g., just before a turn), rhythmic auditory stimulation (RAS) was elicited and the subject was trained to walk rhythmically, coordinate left-right stepping and to increase step size, utilizing the RAS cueing. Net training duration increased from week to week and secondary cognitive tasks while walking were added to increase FOG propensity. FOG symptom burden was assessed before, immediately, and 4 weeks after the training period. The mean number of FOG episodes (±SEM) per 10 m of walking in a standardized gait assessment decreased from 0.52 ± 0.29 in the pre-testing to 0.15 ± 0.04 in the post-testing (p < 0.05). The duration of FOG episodes decreased from 4.3 ± 2.1 to 2.6 ± 0.6 s (p < 0.05). Additional measures (e.g., FOG questionnaire, gait speed) varied in their responsiveness to the treatment. These effects were retained 4 weeks after the training. The results of this open label study support the possibility that a motor learning-based intervention is apparently effective in reducing FOG burden, suggesting that RAS can deliver 'anti-FOG' training.
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Inhibition, executive function, and freezing of gait.
J Parkinsons Dis
PUBLISHED: 02-06-2014
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Studies suggest that freezing of gait (FoG) in people with Parkinson's disease (PD) is associated with declines in executive function (EF). However, EF is multi-faceted, including three dissociable components: inhibiting prepotent responses, switching between task sets, and updating working memory.
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Consensus-based clinical practice recommendations for the examination and management of falls in patients with Parkinson's disease.
Parkinsonism Relat. Disord.
PUBLISHED: 02-04-2014
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Falls in Parkinson's disease (PD) are common and frequently devastating. Falls prevention is an urgent priority, but there is no accepted program that specifically addresses the risk profile in PD. Therefore, we aimed to provide consensus-based clinical practice recommendations that systematically address potential fall risk factors in PD. We developed an overview of both generic (age-related) and PD-specific factors. For each factor, we specified: best method of ascertainment; disciplines that should be involved in assessment and treatment; and which interventions could be engaged. Using a web-based tool, we asked 27 clinically active professionals from multiple relevant disciplines to evaluate this overview. The revised version was subsequently reviewed by 12 experts. Risk factors and their associated interventions were included in the final set of recommendations when at least 66% of reviewing experts agreed. These recommendations included 31 risk factors. Nearly all required a multidisciplinary team approach, usually involving a neurologist and PD-nurse specialist. Finally, the expert panel proposed to first identify the specific fall type and to tailor screening and treatment accordingly. A routine evaluation of all risk factors remains reserved for high-risk patients without prior falls, or for patients with seemingly unexplained falls. In conclusion, this project produced a set of consensus-based clinical practice recommendations for the examination and management of falls in PD. These may be used in two ways: for pragmatic use in current clinical practice, pending further evidence; and as the active intervention in clinical trials, aiming to evaluate the effectiveness and cost-effectiveness of large scale implementation.
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A voxel-based morphometry and diffusion tensor imaging analysis of asymptomatic Parkinson's disease-related G2019S LRRK2 mutation carriers.
Mov. Disord.
PUBLISHED: 01-30-2014
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Patients with Parkinson's disease have reduced gray matter volume and fractional anisotropy in both cortical and sub-cortical structures, yet changes in the pre-motor phase of the disease are unknown.
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Increased frontal brain activation during walking while dual tasking: an fNIRS study in healthy young adults.
J Neuroeng Rehabil
PUBLISHED: 01-11-2014
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Accumulating evidence suggests that gait is influenced by higher order cognitive and cortical control mechanisms. Recently, several studies used functional near infrared spectroscopy (fNIRS) to examine brain activity during walking, demonstrating increased oxygenated hemoglobin (HbO2) levels in the frontal cortex during walking while subjects completed a verbal cognitive task. It is, however, still unclear whether this increase in activation was related to verbalization, if the response was specific to gait, or if it would also be observed during standing, a different motor control task. The aim of this study was to investigate whether an increase in frontal activation is specific to dual tasking during walking.
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Objective assessment of fall risk in Parkinson's disease using a body-fixed sensor worn for 3 days.
PLoS ONE
PUBLISHED: 01-01-2014
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Patients with Parkinson's disease (PD) suffer from a high fall risk. Previous approaches for evaluating fall risk are based on self-report or testing at a given time point and may, therefore, be insufficient to optimally capture fall risk. We tested, for the first time, whether metrics derived from 3 day continuous recordings are associated with fall risk in PD.
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Neuroimaging as a window into gait disturbances and freezing of gait in patients with Parkinsons disease.
Curr Neurol Neurosci Rep
PUBLISHED: 10-19-2013
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Neuroimaging has been applied to better understand the neural mechanisms underlying gait disturbances in Parkinsons disease (PD). In the present paper, we review studies that used neuroimaging methods to investigate mobility, walking and freezing of gait (FOG) in PD, focusing on the recent literature. Examination of these studies suggests that gait changes in PD are due to widespread alterations in the structure and function of the brain that go beyond the basal ganglia. For example, cortical structures including the frontal and parietal lobes, the mesencephalic locomotor region and specifically, the pedunculopontine nucleus, all apparently play important roles in the control of gait in PD. Nonetheless, there are some significant inconsistencies across the different studies and many questions remain regarding the precise pathological processes that contribute to gait disturbances, in general, and to FOG, more specifically. A discussion of new insights into the neural mechanisms underlying gait disturbances are presented along with a summary of the disadvantages and limitations of the existing techniques and suggestions for future directions.
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Gray matter atrophy and freezing of gait in Parkinsons disease: Is the evidence black-on-white?
Mov. Disord.
PUBLISHED: 07-31-2013
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The pathophysiology underlying freezing of gait (FOG) in Parkinsons disease (PD) is poorly understood. We tested whether gray matter (GM) atrophy contributes to FOG in PD.
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Elevated titers of anti-thyroperoxidase antibodies in patients with multiple system atrophy: a pilot study.
Clin Neurol Neurosurg
PUBLISHED: 07-28-2013
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Multiple system atrophy (MSA) is a neurodegenerative disease characterized by progressive neuronal loss and alpha-synuclein deposition in oligodendroglial cells in the central nervous system. The cause of MSA remains essentially unknown. A cerebellar syndrome was associated with autoimmune thyroid disease in some cases, apparently not related to MSA and was partially responsive to immunomodulatory therapy.
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Parkinsons disease patients first treated at age 75 years or older: A comparative study.
Parkinsonism Relat. Disord.
PUBLISHED: 06-23-2013
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Parkinsons disease (PD) first diagnosed at older age reportedly has different clinical characteristics and survival rates than when it is first diagnosed at younger age. We compared these features among PD patients who initiated anti-parkinsonian drugs at age 75-85 years (elderly) with those who started treatment at age 50-74 years (younger).
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Does the evaluation of gait quality during daily life provide insight into fall risk? A novel approach using 3-day accelerometer recordings.
Neurorehabil Neural Repair
PUBLISHED: 06-17-2013
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Many approaches are used to evaluate fall risk. While their properties and performance vary, most reflect performance at a specific moment or are based on subjective self-report.
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Identifying axial and cognitive correlates in patients with Parkinsons disease motor subtype using the instrumented Timed Up and Go.
Exp Brain Res
PUBLISHED: 06-13-2013
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Parkinsons disease (PD) is clinically highly heterogeneous, often divided into tremor dominant (TD) and postural instability gait difficulty (PIGD). To better understand these subtypes and to help stratify patients, we applied an objective marker, i.e., an instrumented version of the traditional "Timed Up and Go" test (iTUG). It is not known whether the iTUG is sensitive to PD motor phenotypes or what are its behavioral and cognitive correlates. Subjects performed the iTUG wearing a body-fixed sensor. Subcomponents were studied including walking, transitions and turning. Gait, balance and cognitive function and the associations between iTUG, behavioral and cognitive domains were assessed. We also compared two representative subtypes, with minimal symptom overlap, referred to here as predominant PIGD (p-PIGD) and predominant TD (p-TD). One hundred and six patients with PD performed the iTUG. Significant correlations were found between iTUG measures and the PIGD score, but not with TD score. Thirty p-PIGD and 31 p-TD patients were identified. Both groups were similar with respect to age and disease duration (p > 0.75). The p-PIGD patients took significantly longer to complete the iTUG (p = 0.026), used more steps (p = 0.031), albeit with similar step duration (p = 0.936). In the sit-to-stand transition, the p-PIGD patients exhibited lower anterior-posterior jerk (p = 0.04) and lower pitch range (p = 0.012). During the turn, the p-PIGD patients had a lower yaw amplitude (p < 0.038). Cognitive domains were correlated with iTUG measures in the p-PIGD patients, but not in the p-TD. These findings demonstrate that a single sensor can identify axial and cognitive correlates using subcomponents of the iTUG and reveals subtle alterations between the PD motor subtypes.
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High rates and the risk factors for emergency room visits and hospitalization in Parkinsons disease.
Parkinsonism Relat. Disord.
PUBLISHED: 06-02-2013
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Parkinsons disease (PD) patients are hospitalized more frequently than their peers as a result of falls, psychosis, infections and other medical complications. However, patient-specific risk factors for hospitalization are unclear.
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Characterizing freezing of gait in Parkinsons disease: models of an episodic phenomenon.
Mov. Disord.
PUBLISHED: 05-27-2013
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Freezing of gait (FOG) is a very disabling and common gait disorder in Parkinsons disease (PD). The first aim of this article was to provide a methodological and critical review of the most common research approach to understand FOG, ie, comparing the behavior of freezers with that of non-freezers. The review demonstrates that studies often fall short in clearly defining the freezer on-freezer groups and in controlling for disease severity and other confounders. These problems complicate data interpretation on FOG. The second aim of this article was to summarize the literature on the potential mechanisms behind the episodic nature of FOG in the following four models: (1) The threshold model assumes that FOG occurs when the accumulation of various motor deficits reinforce each other to a point of motor breakdown; (2) the interference model proposes that FOG represents an inability to deal with concurrent cognitive, limbic, and motor input, causing an interruption of locomotion; (3) the cognitive model views FOG as induced by a failure to process response conflict, leading to behavioral indecision; and (4) the decoupling model sees FOG as a disconnection between preparatory programming and the intended motor response as a result of which automatic movement generation gets stuck. These four theoretical premises are still incomplete and do not fully explain FOG. The depletion of motor and cognitive reserves and an increasingly complex response to levodopa with disease progression will also have an impact on the emergence of FOG episodes.
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Fall risk and gait in Parkinsons disease: the role of the LRRK2 G2019S mutation.
Mov. Disord.
PUBLISHED: 05-18-2013
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Patients with Parkinsons disease (PD) who carry the G2019S mutation (a glycine to serine substitution at amino acid 2019) in the leucine-rich repeat kinase 2 (LRRK2) gene are generally believed to be clinically indistinguishable from patients with sporadic PD. There are, however, conflicting reports on the relationship between the mutation and the motor phenotype. We quantitatively compared gait and mobility in patients with PD carriers of the G2019S mutation to non-carrier patients with PD to better understand the genotype-phenotype relationship. Fifty patients with PD carriers of the G2019S LRRK2 mutation and 50 age, disease duration, and disease severity matched PD non-carriers were studied. An accelerometer quantified gait under three walking conditions: usual-walking, dual-tasking, and fast-walking. The Unified Parkinsons Disease Rating Scale classified patients into PD sub-types and the Timed Up and Go quantified mobility and fall risk. In all three walking conditions, gait variability was larger and the walking pattern was less consistent among the PD mutation carriers (P?
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Parkinson disease phenotype in Ashkenazi jews with and without LRRK2 G2019S mutations.
Mov. Disord.
PUBLISHED: 05-10-2013
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The phenotype of Parkinsons disease (PD) in patients with and without leucine-rich repeat kinase 2 (LRRK2) G2019S mutations reportedly is similar; however, large, uniformly evaluated series are lacking. The objective of this study was to characterize the clinical phenotype of Ashkenazi Jewish (AJ) PD carriers of the LRRK2 G2019S mutation. We studied 553 AJ PD patients, including 65 patients who were previously reported, from three sites (two in New York and one in Tel-Aviv). Glucocerebrosidase (GBA) mutation carriers were excluded. Evaluations included the Montreal Cognitive Assessment (MoCA), the Unified Parkinsons Disease Rating Scale (UPDRS), the Geriatric Depression Scale (GDS) and the Non-Motor Symptoms (NMS) questionnaire. Regression models were constructed to test the association between clinical and demographic features and LRRK2 status (outcome) in 488 newly recruited participants. LRRK2 G2019S carriers (n?=?97) and non-carriers (n?=?391) were similar in age and age at onset of PD. Carriers had longer disease duration (8.6 years vs. 6.1 years; P?5 years (P?=?0.042). Performance on the UPDRS, MoCA, GDS, and NMS did not differ by mutation status. PD in AJ LRRK2 G2019S mutation carriers is similar to idiopathic PD but is characterized by more frequent lower extremity involvement at onset and PIGD without the associated cognitive impairment. © 2013 International Parkinson and Movement Disorder Society.
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Classification of gait disturbances: distinguishing between continuous and episodic changes.
Mov. Disord.
PUBLISHED: 05-08-2013
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The increased awareness of the importance of gait and postural control to quality of life and functional independence has led many research groups to study the pathophysiology, epidemiology, clinical, and therapeutic aspects of these motor functions. In recognition of the increased awareness of the significance of this topic, the Movement Disorders journal is devoting this entire issue to gait and postural control. Leading research groups provide critical reviews of the current knowledge and propose future directions for this evolving field. The intensive work in this area throughout the world has created an urgent need for a unified language. Because gait and postural disturbances are so common, the clinical classification should be clear, straightforward, and simple to use. As an introduction to this special issue, we propose a new clinically based classification scheme that is organized according to the dominant observed disturbance, while taking into account the results of a basic neurological exam. The proposed classification differentiates between continuous and episodic gait disturbances because this subdivision has important ramifications from the functional, prognostic, and mechanistic perspectives. We anticipate that research into gait and postural control will continue to flourish over the next decade as the search for new ways of promoting mobility and independence aims to keep up with the exponentially growing population of aging older adults. Hopefully, this new classification scheme and the articles focusing on gait and postural control in this special issue of the Movement Disorders journal will help to facilitate future investigations in this exciting, rapidly growing area.
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Effects of walking speed on asymmetry and bilateral coordination of gait.
Gait Posture
PUBLISHED: 04-12-2013
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The mechanisms regulating the bilateral coordination of gait in humans are largely unknown. Our objective was to study how bilateral coordination changes as a result of gait speed modifications during over ground walking. 15 young adults wore force sensitive insoles that measured vertical forces used to determine the timing of the gait cycle events under three walking conditions (i.e., usual-walking, fast and slow). Ground reaction force impact (GRFI) associated with heel-strikes was also quantified, representing the potential contribution of sensory feedback to the regulation of gait. Gait asymmetry (GA) was quantified based on the differences between right and left swing times and the bilateral coordination of gait was assessed using the phase coordination index (PCI), a metric that quantifies the consistency and accuracy of the anti-phase stepping pattern. GA was preserved in the three different gait speeds. PCI was higher (reduced coordination) in the slow gait condition, compared to usual-walking (3.51% vs. 2.47%, respectively, p=0.002), but was not significantly affected in the fast condition. GRFI values were lower in the slow walking as compared to usual-walking and higher in the fast walking condition (p<0.001). Stepwise regression revealed that slow gait related changes in PCI were not associated with the slow gait related changes in GRFI. The present findings suggest that left-right anti-phase stepping is similar in normal and fast walking, but altered during slow walking. This behavior might reflect a relative increase in attention resources required to regulate a slow gait speed, consistent with the possibility that cortical function and supraspinal input influences the bilateral coordination of gait.
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The p.L302P mutation in the lysosomal enzyme gene SMPD1 is a risk factor for Parkinson disease.
Neurology
PUBLISHED: 03-27-2013
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To study the possible association of founder mutations in the lysosomal storage disorder genes HEXA, SMPD1, and MCOLN1 (causing Tay-Sachs, Niemann-Pick A, and mucolipidosis type IV diseases, respectively) with Parkinson disease (PD).
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Gray matter atrophy distinguishes between Parkinson disease motor subtypes.
Neurology
PUBLISHED: 03-20-2013
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To assess differences in gray matter (GM) atrophy between 2 Parkinson disease (PD) subtypes: the tremor dominant (TD) subtype and the postural instability gait difficulty (PIGD) subtype.
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Cognitive decline after stroke: relation to inflammatory biomarkers and hippocampal volume.
Stroke
PUBLISHED: 02-26-2013
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Inflammation may contribute to cognitive impairment after stroke. Inflammatory markers are associated with hippocampal atrophy. We tested whether markers of inflammation, erythrocyte sedimentation rate (ESR), and serum levels of C-reactive protein are associated with reduced hippocampal volume and poor cognitive performance among stroke survivors.
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The safety and tolerability of rotigotine transdermal system over a 6-year period in patients with early-stage Parkinsons disease.
J Neural Transm
PUBLISHED: 02-15-2013
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This open-label extension (SP716; NCT00599196) of a 6-month, double-blind, randomized study (SP513) investigated the safety and tolerability of rotigotine transdermal system over up to ~6 years in patients with Parkinsons disease (PD; early-stage PD at double-blind enrollment). Eligible patients completing the 6-month study received optimal dose open-label rotigotine (? 16 mg/24 h) for up to ~6 years. Adjunctive levodopa was permitted. Primary outcomes included adverse events (AEs) and extent of rotigotine exposure. Analysis of adjunctive levodopa use, dyskinesias [unified Parkinsons disease rating scale (UPDRS) IV], and efficacy (UPDRS II + III total score) were also assessed. Of 381 patients enrolled in the open-label extension, 52 % were still in the study at time of closure; 24 % withdrew because of AEs and 6 % because of lack of efficacy. Patients received rotigotine for a median duration of 1,564.5 days (~4 years, 3 months; range 5-2, 145 days). 69 % of patients started supplemental levodopa; median time to levodopa was 485 days (~1 year, 4 months). Most common AEs (% per patient-year) were somnolence (18 %), application site reactions (12 %), nausea (9 %), peripheral edema (7 %), and fall (7 %). AEs indicative of impulsive-compulsive behavior were recorded in 25 (7 %) patients. Dyskinesias were experienced by 65 (17 %) patients; the majority [47 of 65 (72 %)] reported first dyskinesia after starting levodopa. Mean UPDRS II + III total scores remained below double-blind baseline for 4 years (assessment of all patients). In conclusion, rotigotine was generally well tolerated for up to ~6 years in patients with early-stage PD. The AEs reported were in line with previous studies of rotigotine transdermal system, with typical dopaminergic side effects and application site reactions seen.
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White matter hyperintensities in Parkinsons disease: do they explain the disparity between the postural instability gait difficulty and tremor dominant subtypes?
PLoS ONE
PUBLISHED: 01-31-2013
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Brain white matter hyperintensities (WMHs) commonly observed on brain imaging of older adults are associated with balance and gait impairment and have also been linked to cognitive deficits. Parkinsons disease (PD) is traditionally sub-classified into the postural instability gait difficulty (PIGD) sub-type, and the tremor dominant (TD) sub-type. Considering the known association between WMHs and axial symptoms like gait disturbances and postural instability, one can hypothesize that WMHs might contribute to the disparate clinical sub-types of patients with PD.
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The contribution of postural control and bilateral coordination to the impact of dual tasking on gait.
Exp Brain Res
PUBLISHED: 01-08-2013
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The simultaneous performance of a cognitive task while walking typically alters the gait pattern. In some populations, these alterations have been associated with an increased risk of falls, motivating study of this response from the clinical perspective. The mechanisms responsible for these effects are not fully understood. The concurrent requirement to control upright posture and stepping, a bilaterally coordinated rhythmic task, may be the cause of this so-called dual-tasking effect. To evaluate this possibility, the present study was designed to isolate the individual contribution of these two demands by assessing the effects of cognitive loading on standing (i.e., postural control without bilateral coordination of stepping), cycling (i.e., bilateral coordination similar to stepping, but with minimal postural demands), and walking. We also investigated the effects of aging and parkinsonism on the performance of these three tasks in response to cognitive loading, also referred to as a dual task. Twenty-one healthy young adults, 15 healthy older adults, and 18 patients with Parkinsons disease were assessed while walking, standing, and cycling, with and without an additional cognitive load. In the young adults, the performance on the two motor tasks that involved bilateral coordination deteriorated significantly in response to the dual task, while standing was not impacted. Similar results, although less robust, were observed among the healthy older adults. In contrast, among the patients with Parkinsons disease, the dual-task costs, i.e., the impact of the simultaneously performed cognitive task on the gait pattern, were high in all motor tasks. These findings suggest that walking is especially vulnerable to cognitive loading, in part, because of the unique sensitivity of bilateral coordination of limb movements to the effects of dual tasking.
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Neural correlates of executive functions in healthy G2019S LRRK2 mutation carriers.
Cortex
PUBLISHED: 01-07-2013
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The G2019S mutation in the leucine rich repeat kinase 2 (LRRK2) gene is prevalent among Ashkenazi Jewish patients with Parkinsons disease (PD). Cognitive deficits are common in early stage PD. We aimed to characterize the effect of the G2019S mutation on neural mechanisms of executive function processing by testing whether healthy mutation carriers who are an "at risk" population for the future development of PD differed from non-carriers on an functional magnetic resonance imaging (fMRI) Stroop interference task.
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Emotional processing of personally familiar faces in the vegetative state.
PLoS ONE
PUBLISHED: 01-01-2013
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The Vegetative State (VS) is a severe disorder of consciousness in which patients are awake but display no signs of awareness. Yet, recent functional magnetic resonance imaging (fMRI) studies have demonstrated evidence for covert awareness in VS patients by recording specific brain activations during a cognitive task. However, the possible existence of incommunicable subjective emotional experiences in VS patients remains largely unexplored. This study aimed to probe the question of whether VS patients retain a brain ability to selectively process external stimuli according to their emotional value and look for evidence of covert emotional awareness in patients.
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Predictors for poststroke outcomes: the Tel Aviv Brain Acute Stroke Cohort (TABASCO) study protocol.
Int J Stroke
PUBLISHED: 11-02-2011
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Recent studies have demonstrated that even survivors of mild stroke experience residual damage, which persists and in fact increases in subsequent years. About 45% of stroke victims remain with different levels of disability. Identifying factors associated with poststroke cognitive and neurological decline could potentially yield more effective therapeutic opportunities.
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Toward automated, at-home assessment of mobility among patients with Parkinson disease, using a body-worn accelerometer.
Neurorehabil Neural Repair
PUBLISHED: 10-13-2011
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To develop an automated and objective method to assess mobility in Parkinson disease (PD) patients in daily-life settings and to investigate whether accelerometer-derived measures discriminate between PD and healthy controls as they walk and simulate activities of daily living (ADL).
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The age at motor symptoms onset in LRRK2-associated Parkinsons disease is affected by a variation in the MAPT locus: a possible interaction.
J. Mol. Neurosci.
PUBLISHED: 08-04-2011
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The current paradigm on Parkinsons disease (PD) pathogenesis and course suggests the involvement of multiple genes and the interaction between them. Recently, it was reported that a variation (rs2435207) in the MAPT gene region influenced the age of motor symptoms onset (AO) in 44 PD patients from 19 families, carriers of leucine-rich repeat kinase 2 (LRRK2) mutations, all of European and North American origin. To examine whether genetic factors within the MAPT locus exert a similar effect on AO in a different population of LRRK2-associated PD patients, 99 unrelated Ashkenazi patients with the LRRK2 p.G2019S mutation were analyzed. Three SNPs in the MAPT region were studied, rs393152, rs2435207, and rs11079727; the latter is located in the first intron of MAPT. Among carriers of the single LRRK2 p.G2019S mutation that did not carry a founder Ashkenazi GBA mutation too (n?=?84), the AO in minor rs11079727 A allele carriers (C/A genotype) was significantly older (62.5?±?10.6 years) compared to the AO (55.7?±?11.6) among carriers of the C/C genotype (p?=?0.025). Our results further support a possible interaction between genetic factors in the MAPT region and the LRRK2 gene, which influence the clinical course of PD patients.
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Freezing of gait: moving forward on a mysterious clinical phenomenon.
Lancet Neurol
PUBLISHED: 07-23-2011
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Freezing of gait (FoG) is a unique and disabling clinical phenomenon characterised by brief episodes of inability to step or by extremely short steps that typically occur on initiating gait or on turning while walking. Patients with FoG, which is a feature of parkinsonian syndromes, show variability in gait metrics between FoG episodes and a substantial reduction in step length with frequent trembling of the legs during FoG episodes. Physiological, functional imaging, and clinical-pathological studies point to disturbances in frontal cortical regions, the basal ganglia, and the midbrain locomotor region as the probable origins of FoG. Medications, deep brain stimulation, and rehabilitation techniques can alleviate symptoms of FoG in some patients, but these treatments lack efficacy in patients with advanced FoG. A better understanding of the phenomenon is needed to aid the development of effective therapeutic strategies.
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The interplay between gait, falls and cognition: can cognitive therapy reduce fall risk?
Expert Rev Neurother
PUBLISHED: 07-05-2011
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In this article, we briefly summarize the incidence and significant consequences of falls among older adults, the insufficient effectiveness of commonly used multifactorial interventions and the evidence linking falls and cognitive function. Recent pharmacologic and nonpharmacologic studies that evaluated the effects of cognitive therapy on fall risk are reviewed. The results of this article illustrate the potential utility of multiple, diverse forms of cognitive therapy for reducing fall risk. The article also indicates that large-scale, randomized controlled trials are warranted and that additional research is needed to better understand the pathophysiologic mechanisms underlying the interplay between human mobility, fall risk and cognitive function. Nonetheless, we suggest that multimodality interventions that combine motor and cognitive therapy should, eventually, be incorporated into clinical practice to enable older adults and patients to move safer and with a reduced fall risk.
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Appreciation of humor is decreased among patients with Parkinsons disease.
Parkinsonism Relat. Disord.
PUBLISHED: 06-07-2011
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To test whether appreciation of humor might be a non-motor function affected by Parkinsons disease (PD).
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Homozygosity for the MTX1 c.184T>A (p.S63T) alteration modifies the age of onset in GBA-associated Parkinsons disease.
Neurogenetics
PUBLISHED: 05-05-2011
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A strong association was established between the GBA gene and Parkinsons disease (PD) worldwide. The most frequent GBA mutation among the Ashkenazi population (p.N370S) was previously associated with the c.1051T>C (p.F351L) alteration in the closely located MTX1 gene. We further studied the association between these two genes and its possible effect on PD. The entire coding region and exon-intron boundaries of MTX1 were analyzed in 81 PD patient carriers of GBA mutations, 15 healthy controls that carry GBA mutations, and in 25 non-carrier patients. Among them, the MTX1 c.184T>A (p.S63T) variation was detected in 93% of GBA mutation carriers (both patients and healthy controls) and in 64% of non-carrier patients (p?=?0.0008). This alteration was analyzed in 600 consecutively recruited Ashkenazi PD patients and in 353 controls, all genotyped for the LRRK2 p.G2019S and GBA founder mutations. A significantly higher frequency of the MTX1 c.184A allele was found in carriers of GBA mutations compared to non-carriers (0.67 and 0.45, respectively, p?
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A training program to improve gait while dual tasking in patients with Parkinsons disease: a pilot study.
Arch Phys Med Rehabil
PUBLISHED: 04-20-2011
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Impairments in the ability to perform another task while walking (ie, dual tasking [DT]) are associated with an increased risk of falling. Here we describe a program we developed specifically to improve DT performance while walking based on motor learning principles and task-specific training. We examined feasibility, potential efficacy, retention, and transfer to the performance of untrained tasks in a pilot study among 7 patients with Parkinsons disease (PD). Seven patients (Hoehn and Yahr stage, 2.1±0.2) were evaluated before, after, and 1 month after 4 weeks of DT training. Gait speed and gait variability were measured during usual walking and during 4 DT conditions. The 4-week program of one-on-one training included walking while performing several distinct cognitive tasks. Gait speed and gait variability during DT significantly improved. Improvements were also seen in the DT conditions that were not specifically trained and were retained 1 month after training. These initial findings support the feasibility of applying a task-specific DT gait training program for patients with PD and suggest that it positively affects DT gait, even in untrained tasks. The present results are also consistent with the possibility that DT gait training enhances divided attention abilities during walking.
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Fighting the risk of developing Parkinsons disease; clinical counseling for first degree relatives of patients with Parkinsons disease.
J. Neurol. Sci.
PUBLISHED: 03-15-2011
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Parkinsons disease (PD) has a long pre-diagnosis phase that may span as long as 10-20 years. The ability to identify at risk populations raises the possibility of early intervention to delay or prevent the onset of motor symptoms. In Israel, there is a large group of Ashkenazi Jews at risk of developing PD due to high frequency of PD associated mutations in 2 genes (GBA and LRRK2).
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Computer-based, personalized cognitive training versus classical computer games: a randomized double-blind prospective trial of cognitive stimulation.
Neuroepidemiology
PUBLISHED: 02-10-2011
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Many studies have suggested that cognitive training can result in cognitive gains in healthy older adults. We investigated whether personalized computerized cognitive training provides greater benefits than those obtained by playing conventional computer games.
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Gait alterations in healthy carriers of the LRRK2 G2019S mutation.
Ann. Neurol.
PUBLISHED: 02-01-2011
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To test for an association between the LRRK2-G2019S mutation and gait, we studied 52 first-degree relatives of patients with Parkinsons disease (PD) who carry this mutation. An accelerometer quantified gait during usual-walking, fast-walking, and dual-tasking. Noncarriers (n = 27) and carriers (n = 25) were similar with respect to age, gender, height, and gait speed during all conditions. During dual-tasking and fast-walking, gait variability and the amplitude of the dominant peak of the accelerometer signal were significantly altered among the carriers. These findings support the possibility of previously unidentified, presymptomatic motor changes among relatives who have an increased risk of developing PD.
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Decreased expression of B cell related genes in leukocytes of women with Parkinsons disease.
Mol Neurodegener
PUBLISHED: 01-24-2011
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Parkinsons disease (PD) is a complex disorder caused by genetic, environmental and age-related factors, and it is more prevalent in men. We aimed to identify differentially expressed genes in peripheral blood leukocytes (PBLs) that might be involved in PD pathogenesis. Transcriptomes of 30 female PD-patients and 29 age- and sex-matched controls were profiled using GeneChip Human Exon 1.0 ST Arrays. Samples were from unrelated Ashkenazi individuals, non-carriers of LRRK2 G2019S or GBA founder mutations.
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Postural instability and fall risk in Parkinsons disease: impaired dual tasking, pacing, and bilateral coordination of gait during the "ON" medication state.
Exp Brain Res
PUBLISHED: 01-06-2011
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The interplay between gait and specific cognitive faculties, in particular executive function (EF) and dual tasking abilities, has been described in healthy adults and in patients with Parkinsons disease (PD). There is, however, little direct evidence on the relationship between cognitive function, gait, and fall risk in PD, especially in the "ON" state (i.e., under the influence of the anti-parkinsonian medications). To address this issue, we evaluated cognitive function and gait under usual walking and dual-task conditions in 30 patients with PD in the ON state of the medication cycle. Subjects were classified as fallers or non-fallers based on their history. A computerized battery quantified cognitive function. Gait was assessed under three conditions: (1) Usual walking, (2) While subtracting serial 3 s, and (3) While subtracting serial 7 s. The EF and attention scores were lower in the fallers, compared to non-fallers (P ? 0.037), but general measures of cognition, e.g., memory, (P = 0.341) were not. Gait speed, variability, and the bilateral coordination of gait were worse in the fallers in all conditions. The DT effects on gait variability and bilateral coordination were larger in the fallers (P = 0.044, P = 0.061, respectively). These results suggest that patients with PD who have a high risk of falling are more sensitive to DT effects, perhaps as a result of relatively poor EF. These cognitive and motor deficits may increase the likelihood of loss of balance during everyday attention-demanding tasks among patients with PD.
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Virtual reality for gait training: can it induce motor learning to enhance complex walking and reduce fall risk in patients with Parkinsons disease?
J. Gerontol. A Biol. Sci. Med. Sci.
PUBLISHED: 11-24-2010
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Gait and cognitive disturbances are common in Parkinsons disease (PD). These deficits exacerbate fall risk and difficulties with mobility, especially during complex or dual-task walking. Traditional gait training generally fails to fully address these complex gait activities. Virtual reality (VR) incorporates principles of motor learning while delivering engaging and challenging training in complex environments. We hypothesized that VR may be applied to address the multifaceted deficits associated with fall risk in PD.
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Heart rate changes during freezing of gait in patients with Parkinsons disease.
Mov. Disord.
PUBLISHED: 08-20-2010
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Freezing of gait (FOG) is one of the most disabling symptoms that affect patients with Parkinsons disease (PD). Although the pathophysiology underlying FOG largely remains an enigma, several lines of evidence suggest that the autonomic nervous system might be involved. To this end, we tested the hypothesis that heart rate (HR) increases during FOG and, further, that HR increases just before FOG. To evaluate these hypotheses, 15 healthy older adults, 10 patients with PD who experienced FOG, and 10 patients who did not were studied. Patients with PD were tested during their "off" medication state. HR and HR variability were measured as subjects carried out tasks that frequently provoke FOG; 120 FOG episodes were evaluated. During FOG, HR increased (P = 0.001) by an average of 1.8 bpm, compared with HR measured before the beginning of FOG. HR also increased just before FOG, by 1 bpm (P < 0.0001). In contrast, during sudden stops and 180° turns, HR decreased by almost 2 bpm (P < 0.0001). HR variability was not associated with FOG. To our knowledge, these findings are the first to document the association of FOG to autonomic system activation, as manifested by HR dynamics. One explanation is that the changes in HR before and during FOG may be a sympathetic response that, secondary to limbic activation, contributes to the development of freezing. Although further studies are needed to evaluate these associations, the current results provide experimental evidence linking impaired motor blockades to autonomic nervous system function among patients with PD.
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Effects of cognitive function on gait and dual tasking abilities in patients with Parkinsons disease suffering from motor response fluctuations.
Exp Brain Res
PUBLISHED: 08-15-2010
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Recent studies have demonstrated that cognitive loading aggravates the gait impairments that are typically seen in Parkinsons disease (PD). To better understand the relationship between cognition and gait in PD, we evaluated 30 subjects with PD who suffer from motor response fluctuations. The subjects were clinically and cognitively assessed using standard clinical (e.g., Unified Parkinsons Disease Rating Scale) and cognitive tests while in the "ON" period of the medication cycle. In addition, the subjects wore force-sensitive insoles to quantify the timing of the gait cycles during 80-m walks at a self-selected, comfortable pace during three randomly presented gait conditions: (1) usual-walking, (2) dual tasking (DT), performing serial 3 subtractions (DT_S3), and (3) DT_S7. Stride length, gait speed, gait variability and bilateral coordination of gait were affected by DT, compared to the usual-walking (P < 0.001) as was gait asymmetry (P = 0.024). Stepwise regression analyses showed that a subset of the cognitive performance scores accounted for the changes seen in the gait parameters during DT, e.g., set shifting capabilities as expressed by the Trial Making Test Scores (P < 0.001). Affect (e.g., anxiety) was not associated with DT-related gait changes. For most gait features, DT had a large impact on the DT_S3 condition with only minimal additional effect in the DT_S7 condition. These results demonstrate that the complex cognitive-motor interplay in the control of gait in patients with PD who suffer from motor response fluctuations has a profound and marked effect during DT conditions on gait variability, asymmetry and bilateral coordination, even in the "ON" state when patients are likely to be most active, mobile and vulnerable to the negative effects of dual tasking.
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What can we learn from freezing of gait in Parkinsons disease?
Curr Neurol Neurosci Rep
PUBLISHED: 06-19-2010
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Freezing of gait (FOG) is defined as an episodic inability to generate effective stepping in the absence of any known cause, other than parkinsonism or high-level gait disorders. Substantial effort has been made to describe the clinical and kinematic characteristics of patients with FOG. In our review, we highlight the distinctive features of FOG in Parkinsons disease (PD) and apply the knowledge of its pathophysiology in PD to other clinical situations and conditions. It is possible that FOG in PD represents the ultimate break in the frontal lobe-basal ganglia-cerebellar-brainstem network that controls gait. Dysrhythmic and discoordinated gait with abnormal scaling of stride length, as well as gait festination, likely is the primary and continuous abnormality of "the gait network" in PD, and FOG represents its extreme and complete but transient disruption.
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Objective detection of subtle freezing of gait episodes in Parkinsons disease.
Mov. Disord.
PUBLISHED: 06-15-2010
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Freezing of gait (FOG) is a clinically defined phenomenon of Parkinsons disease (PD). Recent evidence suggests that subtle FOG episodes can be elicited in a gait laboratory using suddenly appearing obstacles during treadmill walking. We evaluated which quantitative gait parameters identify such subtle FOG episodes. We included 10 PD patients with FOG, 10 PD patients without FOG, and 10 controls. Subjects walked on a motorized treadmill while avoiding unexpectedly appearing obstacles. Treadmill walking was videotaped, and FOG episodes were identified by two independent experts. Gait was also analyzed using detailed kinematics. Knee joint signals were processed using time-frequency analysis with combinations of sliding fast Fourier transform and wavelets transform. Twenty FOG episodes occurred during treadmill walking in 5 patients (all with clinically certified FOG), predominantly in relation to obstacle avoidance. FOG was brief when it occurred just before or after obstacle crossing and was characterized by short, rapid steps. Frequency analysis showed a typical qualitative pattern: before the FOG episode an increase in dominant frequency in the 0 to 3 Hz band (festination), followed by decreased power in 0 to 3 Hz band and an increased power in the 3 to 8 Hz band during the FOG episode. This pattern led to an increased FOG index as a qualitative measure. These approaches detected even very brief FOG with acceptable sensitivity (75-83%) and specificity (>95%). We conclude that time-frequency analysis is an appropriate approach to detect brief and subtle FOG episodes. Future work will need to decide whether this approach can support or even replace expert clinical opinion.
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Executive control deficits as a prodrome to falls in healthy older adults: a prospective study linking thinking, walking, and falling.
J. Gerontol. A Biol. Sci. Med. Sci.
PUBLISHED: 05-19-2010
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Executive function (EF) deficits may increase fall risk, even among older adults with no overt cognitive impairment. Indeed, the effects of dual tasking (DT) on gait, a challenge to executive control, are more exaggerated in persons with a history of falls. Prospective evidence is, however, lacking.
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Piloting the NPF data-driven quality improvement initiative.
Parkinsonism Relat. Disord.
PUBLISHED: 05-11-2010
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To pilot a data-driven quality care program in National Parkinson Foundation (NPF) Centers of Excellence.
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Rotigotine transdermal system for control of early morning motor impairment and sleep disturbances in patients with Parkinsons disease.
J Neural Transm
PUBLISHED: 03-24-2010
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This open-label study (NCT00243945) investigated the efficacy of rotigotine transdermal system in 54 Parkinsons disease (PD) patients with unsatisfactory control of early morning motor impairment and sleep disturbances. Rotigotine dose was up titrated for 8 weeks and maintained for 4 weeks. Mean rotigotine dose at end of maintenance was 11.83 mg/24 h (SD 3.86). Patients had two overnight hospital stays at baseline and end of treatment during which early morning motor performance was assessed, prior to first morning dose of regular oral antiparkinsonian medication. Rotigotine improved mean Unified Parkinsons Disease Rating Scale (UPDRS) part III score by -9.3 points, mean Timed Up and Go test duration by -1.4 s and mean morning finger tapping by 26.5 taps/min; 46% of patients were considered responders (?30% improvement of UPDRS III). Mean Nocturnal Akinesia, Dystonia and Cramps Sum Score was reduced by 61%; mean number of nocturias decreased by 32%. Rotigotine also improved sleep quality. These results suggest a role for rotigotine in treatment of nocturnal and early morning motor disabilities in PD patients.
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Presentation, diagnosis, and management of multiple system atrophy in Europe: final analysis of the European multiple system atrophy registry.
Mov. Disord.
PUBLISHED: 03-22-2010
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Multiple system atrophy (MSA) is a Parkinsons Disease (PD)-like ?-synucleinopathy clinically characterized by dysautonomia, parkinsonism, cerebellar ataxia, and pyramidal signs in any combination. We aimed to determine whether the clinical presentation of MSA as well as diagnostic and therapeutic strategies differ across Europe and Israel. In 19 European MSA Study Group centres all consecutive patients with a clinical diagnosis of MSA were recruited from 2001 to 2005. A standardized minimal data set was obtained from all patients. Four-hundred thirty-seven MSA patients from 19 centres in 10 countries were included. Mean age at onset was 57.8 years; mean disease duration at inclusion was 5.8 years. According to the consensus criteria 68% were classified as parkinsonian type (MSA-P) and 32% as cerebellar type (MSA-C) (probable MSA: 72%, possible MSA: 28%). Symptomatic dysautonomia was present in almost all patients, and urinary dysfunction (83%) more common than symptomatic orthostatic hypotension (75%). Cerebellar ataxia was present in 64%, and parkinsonism in 87%, of all cases. No significant differences in the clinical presentation were observed between the participating countries. In contrast, diagnostic work up and therapeutic strategies were heterogeneous. Less than a third of patients with documented orthostatic hypotension or neurogenic bladder disturbance were receiving treatment. This largest clinical series of MSA patients reported so far shows that the disease presents uniformly across Europe. The observed differences in diagnostic and therapeutic management including lack of therapy for dysautonomia emphasize the need for future guidelines in these areas.
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Automated detection of near falls: algorithm development and preliminary results.
BMC Res Notes
PUBLISHED: 03-05-2010
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Falls are a major source of morbidity and mortality among older adults. Unfortunately, self-report is, to a large degree, the gold-standard method for characterizing and quantifying fall frequency. A number of studies have demonstrated that near falls predict falls and that near falls may occur more frequently than falls. These studies suggest that near falls might be an appropriate fall risk measure. However, to date, such investigations have also relied on self-report. The purpose of the present study was to develop a method for automatic detection of near falls, potentially a sensitive, objectivemarker of fall risk and to demonstrate the ability to detect near falls using this approach.
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Parkinsons disease-related LRRK2 G2019S mutation results from independent mutational events in humans.
Hum. Mol. Genet.
PUBLISHED: 03-02-2010
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Mutations in the leucine-rich-repeat kinase 2 (LRRK2) gene have been identified in families with autosomal dominant Parkinsons disease (PD) and in sporadic cases; the G2019S mutation is the single most frequent. Intriguingly, the frequency of this mutation in PD patients varies greatly among ethnic groups and geographic origins: it is present at <0.1% in East Asia, approximately 2% in European-descent patients and can reach frequencies of up to 15-40% in PD Ashkenazi Jews and North African Arabs. To ascertain the evolutionary dynamics of the G2019S mutation in different populations, we genotyped 74 markers spanning a 16 Mb genomic region around G2019S, in 191 individuals carrying the mutation from 126 families of different origins. Sixty-seven families were of North-African Arab origin, 18 were of North/Western European descent, 37 were of Jewish origin, mostly from Eastern Europe, one was from Japan, one from Turkey and two were of mixed origins. We found the G2019S mutation on three different haplotypes. Network analyses of the three carrier haplotypes showed that G2019S arose independently at least twice in humans. In addition, the population distribution of the intra-allelic diversity of the most widespread carrier haplotype, together with estimations of the age of G2019S determined by two different methods, suggests that one of the founding G2019S mutational events occurred in the Near East at least 4000 years ago.
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Properties of the timed up and go test: more than meets the eye.
Gerontology
PUBLISHED: 01-26-2010
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The timed up and go test (TUG) is a simple, quick and widely used clinical performance-based measure of lower extremity function, mobility and fall risk. We speculated that its properties may be different from other performance-based tests and assessed whether cognitive function may contribute to the differences among these tests in a cohort of healthy older adults.
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Cognition in multiple system atrophy: neuropsychological profile and interaction with mood.
J Neural Transm
PUBLISHED: 01-21-2010
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We evaluated cognitive functions and mood in two groups of patients with multiple system atrophy (MSA) in order to determine the influence of mood on cognitive performance. Our aim was to differentiate between parkinsonism-predominant (MSA-P) and cerebellar-predominant (MSA-C) MSA based on those parameters. Fifteen MSA-P and 10 MSA-C patients underwent neuropsychological tests that examined executive functions (working memory, response inhibition, and verbal reproduction), verbal learning and memory, verbal and visual reasoning, and processing speed. Anxiety and depression were also assessed. The findings on their cognitive performance and mood were compared to those of healthy controls and also discussed in relation to a group of Parkinsons disease (PD) patients. The results showed that cognitive and mood characteristics could distinguish MSA-P from MSA-C and that anxiety and depression are related to cognitive decline. Compared with healthy controls, MSA-P patients showed reduced verbal retrieval (immediate, P < 0.019; long-term, P < 0.018) while MSA-C patients had difficulties in learning new verbal information (P < 0.022) and in controlling attention (P < 0.023). These data indicate that MSA-P and MSA-C appear to have, at least in part, different cognitive and mood profiles. The neuropsychological assessments of MSA patients should test for and then take into account their level of anxiety and depression, insofar as it might have an adverse effect on their cognitive performance.
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How does explicit prioritization alter walking during dual-task performance? Effects of age and sex on gait speed and variability.
Phys Ther
PUBLISHED: 12-18-2009
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Previous studies have demonstrated that the performance of a secondary task during walking alters gait.
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Wearable assistant for Parkinsons disease patients with the freezing of gait symptom.
IEEE Trans Inf Technol Biomed
PUBLISHED: 11-10-2009
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In this paper, we present a wearable assistant for Parkinsons disease (PD) patients with the freezing of gait (FOG) symptom. This wearable system uses on-body acceleration sensors to measure the patients movements. It automatically detects FOG by analyzing frequency components inherent in these movements. When FOG is detected, the assistant provides a rhythmic auditory signal that stimulates the patient to resume walking. Ten PD patients tested the system while performing several walking tasks in the laboratory. More than 8 h of data were recorded. Eight patients experienced FOG during the study, and 237 FOG events were identified by professional physiotherapists in a post hoc video analysis. Our wearable assistant was able to provide online assistive feedback for PD patients when they experienced FOG. The system detected FOG events online with a sensitivity of 73.1% and a specificity of 81.6%. The majority of patients indicated that the context-aware automatic cueing was beneficial to them. Finally, we characterize the system performance with respect to the walking style, the sensor placement, and the dominant algorithm parameters.
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JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

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In developing our video relationships, we compare around 5 million PubMed articles to our library of over 4,500 methods videos. In some cases the language used in the PubMed abstracts makes matching that content to a JoVE video difficult. In other cases, there happens not to be any content in our video library that is relevant to the topic of a given abstract. In these cases, our algorithms are trying their best to display videos with relevant content, which can sometimes result in matched videos with only a slight relation.