Author
Anat Mirelman
Other affiliations: Harvard University, Ben-Gurion University of the Negev, Tel Aviv University ...read more
Bio: Anat Mirelman is an academic researcher from Tel Aviv Sourasky Medical Center. The author has contributed to research in topics: Gait (human) & Medicine. The author has an hindex of 47, co-authored 208 publications receiving 9246 citations. Previous affiliations of Anat Mirelman include Harvard University & Ben-Gurion University of the Negev.
Topics: Gait (human), Medicine, Parkinson's disease, Gait, Cognition
Papers
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National Institutes of Health1, Norwegian University of Science and Technology2, National Research Council3, University of São Paulo4, University of Tübingen5, University of Coimbra6, University of Paris7, French Institute of Health and Medical Research8, Chang Gung University9, Columbia University10, Mayo Clinic11, Tel Aviv University12, Technion – Israel Institute of Technology13, Rambam Health Care Campus14, Tel Aviv Sourasky Medical Center15, University of Rostock16, University Health Network17, National Taiwan Normal University18, University of Washington19, University of Tokyo20, Kobe University21, Magna Græcia University22, University of Toronto23, Singapore General Hospital24, Duke University25
TL;DR: Data collected demonstrate that there is a strong association between GBA mutations and Parkinson's disease, and those with a GBA mutation presented earlier with the disease, were more likely to have affected relatives, and were morelikely to have atypical clinical manifestations.
Abstract: Background Recent studies indicate an increased frequency of mutations in the gene encoding glucocerebrosidase (GBA), a deficiency of which causes Gaucher's disease, among patients with Parkinson's disease. We aimed to ascertain the frequency of GBA mutations in an ethnically diverse group of patients with Parkinson's disease. Methods Sixteen centers participated in our international, collaborative study: five from the Americas, six from Europe, two from Israel, and three from Asia. Each center genotyped a standard DNA panel to permit comparison of the genotyping results across centers. Genotypes and phenotypic data from a total of 5691 patients with Parkinson's disease (780 Ashkenazi Jews) and 4898 controls (387 Ashkenazi Jews) were analyzed, with multivariate logistic-regression models and the Mantel–Haenszel procedure used to estimate odds ratios across centers. Results All 16 centers could detect two GBA mutations, L444P and N370S. Among Ashkenazi Jewish subjects, either mutation was found in 15% of p...
1,629 citations
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TL;DR: Among healthy older adults, individuals with poorer EF are more prone to falls, and optimal screening, early detection, and treatment of falls should, apparently, also target this cognitive domain.
Abstract: BACKGROUND: 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. METHODS: We prospectively evaluated whether EF predicts falls over a 2-year period among 262 community-living, healthy, and well-functioning older adults, focusing on the 201 who reported no falls during the previous year. At baseline, participants completed a computerized cognitive battery that generated an index of EF and other cognitive domains. Gait was assessed using performance-based tests and by quantifying walking during single- and dual-task conditions. RESULTS: The 262 participants (mean age: 76.3 +/- 4.3 years, 60.3% women) had intact cognitive function on testing, a low comorbidity index, and good mobility. The EF index predicted future falls. Among those who reported no previous falls, participants in the worst EF quartile were three times more likely to fall during the 2 years of follow-up, and they were more likely to transition from nonfaller to faller sooner. DT gait variability also predicted future falls and multiple falls, whereas other measures of cognitive function, gait, and mobility did not. CONCLUSIONS: Among healthy older adults, individuals with poorer EF are more prone to falls. Higher-level cognitive functions such as those regulated by the frontal lobes are apparently needed for safe everyday navigation that demands multitasking. Optimal screening, early detection, and treatment of falls should, apparently, also target this cognitive domain. Language: en
428 citations
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TL;DR: Among community-living older adults, the risk of future falls was predicted by performance on EF and attention tests conducted 5 years earlier, indicating that screening EF will likely enhance fall risk assessment, and that treatment of EF may reduce fall risk.
Abstract: Background: Recent findings suggest that executive function (EF) plays a critical role in the regulation of gait in older adults, especially under complex and challenging conditions, and that EF deficits may, therefore, contribute to fall risk. The objective of this study was to evaluate if reduced EF is a risk factor for future falls over the course of 5 years of follow-up. Secondary objectives were to assess whether single and dual task walking abilities, an alternative window into EF, were associated with fall risk. Methodology/Main Results: We longitudinally followed 256 community-living older adults (age: 76.464.5 yrs; 61% women) who were dementia free and had good mobility upon entrance into the study. At baseline, a computerized cognitive battery generated an index of EF, attention, a closely related construct, and other cognitive domains. Gait was assessed during single and dual task conditions. Falls data were collected prospectively using monthly calendars. Negative binomial regression quantified risk ratios (RR). After adjusting for age, gender and the number of falls in the year prior to the study, only the EF index (RR: .85; CI: .74–.98, p=.021), the attention index (RR: .84; CI: .75–.94, p=.002) and dual tasking gait variability (RR: 1.11; CI: 1.01–1.23; p=.027) were associated with future fall risk. Other cognitive function measures were not related to falls. Survival analyses indicated that subjects with the lowest EF scores were more likely to fall sooner and more likely to experience multiple falls during the 66 months of follow-up (p,0.02). Conclusions/Significance: These findings demonstrate that among community-living older adults, the risk of future falls was predicted by performance on EF and attention tests conducted 5 years earlier. The present results link falls among older adults to cognition, indicating that screening EF will likely enhance fall risk assessment, and that treatment of EF may reduce fall risk.
372 citations
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TL;DR: The results indicate that TT + VR is viable in PD and may significantly improve physical performance, gait during complex challenging conditions, and even certain aspects of cognitive function.
Abstract: Background Gait and cognitive disturbances are common in Parkinson's 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. Methods Twenty patients received 18 sessions (3 per week) of progressive intensive treadmill training with virtual obstacles (TT + VR). Outcome measures included gait under usual-walking and dual-task conditions and while negotiating physical obstacles. Cognitive function and functional performance were also assessed. Results Patients were 67.1 ± 6.5 years and had a mean disease duration of 9.8 ± 5.6 years. Posttraining, gait speed significantly improved during usual walking, during dual task, and while negotiating overground obstacles. Dual-task gait variability decreased (ie, improved) and Trail Making Test times (parts A and B) improved. Gains in functional performance measures and retention effects, 1 month later, were also observed. Conclusions To our knowledge, this is the first time that TT + VR has been used for gait training in PD. The results indicate that TT + VR is viable in PD and may significantly improve physical performance, gait during complex challenging conditions, and even certain aspects of cognitive function. These findings have important implications for understanding motor learning in the presence of PD and for treating fall risk in PD, aging, and others who share a heightened risk of falls.
345 citations
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TL;DR: It is important to establish clear links between specific gait impairments, their underlying mechanisms, and disease progression to foster the acceptance and usability of quantitative gait measures as outcomes in future disease-modifying clinical trials.
Abstract: Summary Gait impairments are among the most common and disabling symptoms of Parkinson's disease. Nonetheless, gait is not routinely assessed quantitatively but is described in general terms that are not sensitive to changes ensuing with disease progression. Quantifying multiple gait features (eg, speed, variability, and asymmetry) under natural and more challenging conditions (eg, dual-tasking, turning, and daily living) enhanced sensitivity of gait quantification. Studies of neural connectivity and structural network topology have provided information on the mechanisms of gait impairment. Advances in the understanding of the multifactorial origins of gait changes in patients with Parkinson's disease promoted the development of new intervention strategies, such as neurostimulation and virtual reality, aimed at alleviating gait impairments and enhancing functional mobility. For clinical applicability, it is important to establish clear links between specific gait impairments, their underlying mechanisms, and disease progression to foster the acceptance and usability of quantitative gait measures as outcomes in future disease-modifying clinical trials.
308 citations
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9,362 citations
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TL;DR: In this paper, the authors present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macro-autophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes.
Abstract: In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes.
For example, a key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process versus those that measure flux through the autophagy pathway (i.e., the complete process including the amount and rate of cargo sequestered and degraded). In particular, a block in macroautophagy that results in autophagosome accumulation must be differentiated from stimuli that increase autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. It is worth emphasizing here that lysosomal digestion is a stage of autophagy and evaluating its competence is a crucial part of the evaluation of autophagic flux, or complete autophagy.
Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. Along these lines, because of the potential for pleiotropic effects due to blocking autophagy through genetic manipulation, it is imperative to target by gene knockout or RNA interference more than one autophagy-related protein. In addition, some individual Atg proteins, or groups of proteins, are involved in other cellular pathways implying that not all Atg proteins can be used as a specific marker for an autophagic process. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular assays, we hope to encourage technical innovation in the field.
5,187 citations
01 Jan 2000
3,536 citations
01 Jan 2016
TL;DR: This is an introduction to the event related potential technique, which can help people facing with some malicious bugs inside their laptop to read a good book with a cup of tea in the afternoon.
Abstract: Thank you for downloading an introduction to the event related potential technique. Maybe you have knowledge that, people have look hundreds times for their favorite readings like this an introduction to the event related potential technique, but end up in malicious downloads. Rather than reading a good book with a cup of tea in the afternoon, instead they are facing with some malicious bugs inside their laptop.
2,445 citations