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Patrizia Lopresti - One of the best experts on this subject based on the ideXlab platform.
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Inducible Expression of a Truncated Form of Tau in Oligodendrocytes Elicits Gait Abnormalities and a Decrease in Myelin: Implications for Selective CNS Degenerative Diseases
Neurochemical Research, 2015Co-Authors: Patrizia LoprestiAbstract:The cytoskeleton protein Tau present in oligodendrocytes (OLGs) promotes cellular process outgrowth and myelination; whereas abnormally hyperphosphorylated Tau has been shown to be present in the most debilitating form of multiple sclerosis and in selective dementias. This research examined the functional consequences of expressing a truncated form of Tau in OLGs during the second postnatal life. In particular, this truncated form of Tau (∆Tau) retains the Fyn-binding domain but lacks the microtubule-binding domain. Similar to hyperphosphorylated Tau, ∆Tau cannot bind the cytoskeleton and is missorted. The Cre/loxP recombination system was used to generate transgenic (TG) founder lines, which contain a Floxed LacZ-STOP cassette to prevent expression of enhanced green fluorescence protein (EGFP)–∆Tau. The founder lines were then crossed with a Tamoxifen (TM)-inducible proteolipid protein (PLP)-dependent Cre driver line. Myelin PLP is the major myelin protein in the central nervous system (CNS). TM was given at postnatal day (p) 12 for 3 days, and CNS tissues were collected at p22. Only TG mice with both EGFP–∆Tau and Cre manifested an overt phenotype of loss of balance and stumbles starting around p18. CNS tissues obtained from TM-treated EGFP–∆Tau/Cre double transgenic mice had recombined PCR products, GFP, and diminished brain myelin. GFP was expressed in OLGs, but not in neurons or astrocytes. On the contrary, TM-treated TG mice with only one of the two transgenes, i.e., Cre or Tau, did not have recombinant PCR products, GFP, diminished myelin, or abnormal phenotype. Thus, this inducible model shows for the first time that a non-microtubule-associated Tau protein in OLGs elicits both myelin decrease and Gait Abnormalities, similar to the occurrence in selective demyelinating and neurodegenerative diseases.
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Inducible Expression of a Truncated Form of Tau in Oligodendrocytes Elicits Gait Abnormalities and a Decrease in Myelin: Implications for Selective CNS Degenerative Diseases.
Neurochemical Research, 2015Co-Authors: Patrizia LoprestiAbstract:The cytoskeleton protein Tau present in oligodendrocytes (OLGs) promotes cellular process outgrowth and myelination; whereas abnormally hyperphosphorylated Tau has been shown to be present in the most debilitating form of multiple sclerosis and in selective dementias. This research examined the functional consequences of expressing a truncated form of Tau in OLGs during the second postnatal life. In particular, this truncated form of Tau (∆Tau) retains the Fyn-binding domain but lacks the microtubule-binding domain. Similar to hyperphosphorylated Tau, ∆Tau cannot bind the cytoskeleton and is missorted. The Cre/loxP recombination system was used to generate transgenic (TG) founder lines, which contain a Floxed LacZ-STOP cassette to prevent expression of enhanced green fluorescence protein (EGFP)–∆Tau. The founder lines were then crossed with a Tamoxifen (TM)-inducible proteolipid protein (PLP)-dependent Cre driver line. Myelin PLP is the major myelin protein in the central nervous system (CNS). TM was given at postnatal day (p) 12 for 3 days, and CNS tissues were collected at p22. Only TG mice with both EGFP–∆Tau and Cre manifested an overt phenotype of loss of balance and stumbles starting around p18. CNS tissues obtained from TM-treated EGFP–∆Tau/Cre double transgenic mice had recombined PCR products, GFP, and diminished brain myelin. GFP was expressed in OLGs, but not in neurons or astrocytes. On the contrary, TM-treated TG mice with only one of the two transgenes, i.e., Cre or Tau, did not have recombinant PCR products, GFP, diminished myelin, or abnormal phenotype. Thus, this inducible model shows for the first time that a non-microtubule-associated Tau protein in OLGs elicits both myelin decrease and Gait Abnormalities, similar to the occurrence in selective demyelinating and neurodegenerative diseases.
Joe Verghese - One of the best experts on this subject based on the ideXlab platform.
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Gait Dysfunction in Motoric Cognitive Risk Syndrome.
Journal of Alzheimer's Disease, 2019Co-Authors: Emmeline Ayers, Joe VergheseAbstract:BACKGROUND Motoric cognitive risk (MCR) syndrome is a cognitive-motor syndrome associated with increased risk of transition to dementia. The clinical phenotype of MCR is not yet established. OBJECTIVE To systematically assess clinical Gait Abnormalities in older adults with MCR. METHODS Of the 522 community-dwelling non-demented adults aged 65 and older enrolled in the Central Control of Mobility in Aging study, 43 were diagnosed with MCR (47% women) based on presence of cognitive complaints and slow Gait velocity (MCRv). Four additional subtypes of MCR were defined by substituting slow Gait with short stride length (MCRsl, n = 41), slow swing time (MCRsw, n = 21), high stride length variability (MCRslv, n = 24), and high swing time variability (MCRswv, n = 25). The prevalence of clinical Gait Abnormalities (neurological or non-neurological) in MCR overall (n = 81) and subtypes was studied. We also examined if Gait Abnormalities predicted further cognitive and functional decline in MCR cases. RESULTS Most clinical Gait Abnormalities were mild (walked without assistance) in the five MCR subtypes (44 to 61%). Neurological (range 24 to 46%) and non-neurological Gait Abnormalities (33 to 61%) were common in all MCR subtypes. Neurological Gaits were most frequent in MCRsl (46%) and non-neurological Gaits in MCRv (61%). Over a median 3.02 years of follow-up, presence of Gait abnormality in MCR cases at baseline predicted worsening disability scores (estimate 0.17, p-value = 0.033) but not decline on cognitive scores (p-value = 0.056). CONCLUSION Clinical Gait Abnormalities are common in MCR syndrome and its subtypes, and are associated with accelerated functional decline.
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qualitative neurological Gait Abnormalities cardiovascular risk factors and functional status in older community dwellers without neurological diseases the healthy brain project
Experimental Gerontology, 2019Co-Authors: Marco Inzitari, Joe Verghese, Andrea L Metti, Caterina Rosano, Cristina Udina, Laura Monica Perez, Gabriela Carrizo, Anne B Newman, Stephanie A Studenski, Andrea L RossoAbstract:Abstract Background Neurologic Gait Abnormalities (NGA) increase risk for falls and dementia, but their pathophysiologic substrates or association with disability have been poorly investigated. We evaluated the association of NGA with clinical characteristics and functional status in older community-dwellers. Methods Gait characteristics were measured in older community-dwellers without neurological or psychological diseases participating to the Health Aging Body Composition study. NGA were rated using standardized readings of video-recorded short walks, combined with standard neurological exam. We tested cross-sectional associations with demographics, vascular risk factors, comorbidities, cognitive function and disability. Results Of 177 participants (median age [IQR] = 82 [4] years, 55% women, 58% Caucasian), 49 (27.7%) had NGA. The most prevalent sub-types were unsteady (10.7%), hemiparetic (4.5%) and parkinsonian (4%). In multivariable logistic regression models, diabetes was associated with higher risk (OR = 3.24, 95% CI = 1.38–7.59), whereas higher physical activity (OR = 0.89, 95% CI = 0.80–0.99) and Gait speed (OR = 0.04, 95% CI = 0.005–0.27) with lower risk of NGA. Prevalence of NGA was associated with difficulty in at least 1 activity of daily living, adjusting for confounders (OR = 2.90, 95% CI = 1.11–7.58). After adjusting for Gait speed, this association was attenuated to non-significance (OR = 2.13, 95% CI = 0.71–6.37). Conclusions In our sample of community-dwelling older adults without neurological diseases, NGA, detected with a standardized neurological exam, part of usual physicians' training, were common. The relationships with diabetes and reduced physical activity might suggest vascular dysfunction as an underlying contributor to NGA. These results, if confirmed by longitudinal studies, which should also disentangle the relationship between NGA, Gait speed and disability, might add information for preventing and managing mobility disability.
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Gait Abnormalities and the Risk of Falls in CKD.
Clinical Journal of the American Society of Nephrology, 2019Co-Authors: Jeannie Tran, Joe Verghese, Emmeline Ayers, Matthew K. AbramowitzAbstract:Background and objectives Older adults with CKD are at high risk of falls and disability. It is not known whether Gait Abnormalities contribute to this risk. Design, setting, participants, & measurements Quantitative and clinical Gait assessments were performed in 330 nondisabled community-dwelling adults aged ≥65 years. CKD was defined as an eGFR 2 . Cox proportional hazards models were created to examine fall risk. Results A total of 41% ( n =134) of participants had CKD. In addition to slower Gait speed, participants with CKD had Gait cycle Abnormalities including shorter stride length and greater time in the stance and double-support phases. Among people with CKD, lower eGFR was independently associated with the severity of Gait cycle Abnormalities (per 10 ml/min per 1.73 m 2 lower eGFR: 3.6 cm [95% confidence interval (95% CI), 1.4 to 5.8] shorter stride length; 0.7% [95% CI, 0.3 to 1.0] less time in swing phase; 1.1% [95% CI, 0.5 to 1.7] greater time in double-support phase); these Abnormalities mediated the association of lower eGFR with slower Gait speed. On clinical Gait exam, consistent with the quantitative Abnormalities, short steps and marked swaying or loss of balance were more common among participants with CKD, yet most had no identifiable Gait phenotype. A Gait phenotype defined by any of these abnormal signs was associated with higher risk of falls among participants with CKD: compared with people without CKD and without the Gait phenotype, the adjusted hazard ratio was 1.72 (95% CI, 1.06 to 2.81) for those with CKD and the phenotype; in comparison, the adjusted hazard ratio was 0.71 (95% CI, 0.40 to 1.25) for people with CKD but without the phenotype ( P value for interaction of CKD status and Gait phenotype =0.01). Conclusions CKD in older adults is associated with quantitative Gait Abnormalities, which clinically manifest in a Gait phenotype that is associated with fall risk.
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Neurological Gait Abnormalities Moderate the Functional Brain Signature of the Posture First Hypothesis.
Brain Topography, 2015Co-Authors: Roee Holtzer, Joe Verghese, Gilles Allali, Meltem Izzetoglu, Cuiling Wang, Jeannette R. MahoneyAbstract:The posture first hypothesis suggests that under dual-task walking conditions older adults prioritize Gait over cognitive task performance. Functional neural confirmation of this hypothesis, however, is lacking. Herein, we determined the functional neural correlates of the posture first hypothesis and hypothesized that the presence of neurological Gait Abnormalities (NGA) would moderate associations between brain activations, Gait and cognitive performance. Using functional near-infrared spectroscopy we assessed changes in oxygenated hemoglobin levels in the pre-frontal cortex (PFC) during normal walk and walk while talk (WWT) conditions in a large cohort of non-demented older adults (n = 236; age = 75.5 ± 6.49 years; female = 51.7 %). NGA were defined as central (due to brain diseases) or peripheral (neuropathic Gait) following a standardized neurological examination protocol. Double dissociations between brain activations and behavior emerged as a function of NGA. Higher oxygenation levels during WWT were related to better cognitive performance (estimate = 0.145; p < 0.001) but slower Gait velocity (estimate = -6.336, p < 0.05) among normals. In contrast, higher oxygenation levels during WWT among individuals with peripheral NGA were associated with worse cognitive performance (estimate = -0.355; p < 0.001) but faster Gait velocity (estimate = 14.855; p < 0.05). Increased activation in the PFC during locomotion may have a compensatory function that is designed to support Gait among individuals with peripheral NGA.
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Epidemiology of Tandem Gait Abnormalities in Aging (P5.209)
Neurology, 2014Co-Authors: Ilya Bragin, Vijayaleskhmi Nair, Joe VergheseAbstract:OBJECTIVE: To describe the epidemiology and motoric correlates of isolated tandem Gait Abnormalities (ITGA) in community-dwelling older-adults. BACKGROUND: There has been limited systematic study of components of the neurological Gait examination. Observing patients during straight or tandem walk is essential to assess integrity of the neuroaxis. Tandem walking places different balance or Gait demands than straight walking, and can serve as a stressor to unearth subtle mobility problems. DESIGN/METHODS: We examined Gait patterns in 391 adults (age蠅65y) participating in the Central Control of Mobility and Aging study. ITGA was diagnosed in the presence of marked sway, loss of balance or falls while walking in tandem without any Abnormalities while walking straight. ITGA cases were frequency matched by age and sex to 128 controls with normal (straight and tandem) Gait. The groups were compared on quantitative Gait (Gait velocity, stride length), balance (unipedal stance time, double-support time) and functional measures (Short Physical Performance Battery and 3-step climbing time), applying Bonferroni corrections. RESULTS: 178 out of the 391 participants had tandem Gait Abnormalities,71 ITGA (mean age 77.9±6.9y, 62% women) and 79 in association with other Gait Abnormalities. The prevalence of ITGA was 18.2%(95% CI: 14.4-22.0). ITGA cases had worse unipedal stance (20.0 vs. 9.7s, p
Roongroj Bhidayasiri - One of the best experts on this subject based on the ideXlab platform.
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The spectrum of preclinical Gait disorders in early Parkinson’s disease: subclinical Gait Abnormalities and compensatory mechanisms revealed with dual tasking
Journal of Neural Transmission, 2013Co-Authors: Pattamon Panyakaew, Roongroj BhidayasiriAbstract:Patients with early Parkinson’s disease (PD) may not complain of Gait difficulties but subtle Gait Abnormalities may be revealed as part of a “preclinical Gait syndrome” when they are challenged by dual tasks. 21 early PD patients (n = 21, mean age 63.5 years, H&Y 1.62, disease duration
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the spectrum of preclinical Gait disorders in early parkinson s disease subclinical Gait Abnormalities and compensatory mechanisms revealed with dual tasking
Journal of Neural Transmission, 2013Co-Authors: Pattamon Panyakaew, Roongroj BhidayasiriAbstract:Patients with early Parkinson’s disease (PD) may not complain of Gait difficulties but subtle Gait Abnormalities may be revealed as part of a “preclinical Gait syndrome” when they are challenged by dual tasks. 21 early PD patients (n = 21, mean age 63.5 years, H&Y 1.62, disease duration <5 years, mean UPDRS-III 7.7) who did not have Gait complaints were as compared to age- and gender-matched healthy controls (n = 21). Memory function was not different between the two groups. Under normal walking conditions, there were no significant differences in Gait parameters between the patients and the control group. In both groups, normalized Gait velocity decreased in response to dual tasking in a parallel fashion (p < 0.001). Similarly, Gait variability increased in both groups with dual tasking although not statistically significant. In PD patients, the performance of an additional task resulted in an increased number of cadences (p = 0.04), a reduction in swing time (p = 0.02) and cycle time (p = 0.04) compared with the control group but there was no significant reduction in normalized velocity. Stride width also increased in the PD patients. The addition of a cognitive task may affect certain aspects of Gait and is able to elicit subclinical deficits in early PD patients. In an attempt to maintain velocity, early PD patients develop compensatory mechanisms by increasing cadence and decreasing swing time and cycle time. Increased step width helps support balance, and prevents going beyond the base-of-support which may predispose to unsteadiness and falls. We propose that these findings occur as part of a spectrum of a “preclinical Gait syndrome” and longitudinal studies are needed to assess the predictive values of these early markers of Gait deficits.
Rainer Bader - One of the best experts on this subject based on the ideXlab platform.
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accuracy of a custom physical activity and knee angle measurement sensor system for patients with neuromuscular disorders and Gait Abnormalities
Sensors, 2015Co-Authors: Frank Feldhege, Anett Maumoeller, Tobias Lindner, Albert Hein, Andreas Markschies, Uwe Klaus Zettl, Rainer BaderAbstract:Long-term assessment of ambulatory behavior and joint motion are valuable tools for the evaluation of therapy effectiveness in patients with neuromuscular disorders and Gait Abnormalities. Even though there are several tools available to quantify ambulatory behavior in a home environment, reliable measurement of joint motion is still limited to laboratory tests. The aim of this study was to develop and evaluate a novel inertial sensor system for ambulatory behavior and joint motion measurement in the everyday environment. An algorithm for behavior classification, step detection, and knee angle calculation was developed. The validation protocol consisted of simulated daily activities in a laboratory environment. The tests were performed with ten healthy subjects and eleven patients with multiple sclerosis. Activity classification showed comparable performance to commercially available activPAL sensors. Step detection with our sensor system was more accurate. The calculated flexion-extension angle of the knee joint showed a root mean square error of less than 5° compared with results obtained using an electro-mechanical goniometer. This new system combines ambulatory behavior assessment and knee angle measurement for long-term measurement periods in a home environment. The wearable sensor system demonstrated high validity for behavior classification and knee joint angle measurement in a laboratory setting.
Kazuhisa Domen - One of the best experts on this subject based on the ideXlab platform.
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Diffusion tensor imaging in elderly patients with idiopathic normal pressure hydrocephalus or Parkinson’s disease: diagnosis of Gait Abnormalities
Fluids and Barriers of the CNS, 2012Co-Authors: Kohei Marumoto, Tetsuo Koyama, Masashi Hosomi, Norihiko Kodama, Hiroji Miyake, Kazuhisa DomenAbstract:Background Gait Abnormalities in the elderly, characterized by short steps and frozen Gait, can be caused by several diseases, including idiopathic normal pressure hydrocephalus (INPH), and Parkinson’s disease (PD). We analyzed the relationship between these two conditions and their association with Gait Abnormalities using laboratory test data and findings from diffusion tensor imaging (DTI). Methods The study involved 10 patients with INPH, 18 with PD, and 10 healthy individuals (control group). Fractional anisotropy (FA) of five brain areas was measured and compared among the three groups. In addition, the association of INPH and PD with Gait capability, frontal lobe function, and FA of each brain area was evaluated. Results The INPH group had significantly lower FA for anterior thalamic radiation (ATR) and forceps minor (Fmin) as compared to the PD group. The Gait capability correlated with ATR FA in the INPH and PD groups. We found that adding DTI to the diagnosis assisted the differential diagnosis of INPH from PD, beyond what could be inferred from ventricular size alone. Conclusions We expect that DTI will provide a useful tool to support the differential diagnosis of INPH and PD and their respective severities.
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diffusion tensor imaging in elderly patients with idiopathic normal pressure hydrocephalus or parkinson s disease diagnosis of Gait Abnormalities
Fluids and Barriers of the CNS, 2012Co-Authors: Kohei Marumoto, Tetsuo Koyama, Masashi Hosomi, Norihiko Kodama, Hiroji Miyake, Kazuhisa DomenAbstract:Gait Abnormalities in the elderly, characterized by short steps and frozen Gait, can be caused by several diseases, including idiopathic normal pressure hydrocephalus (INPH), and Parkinson’s disease (PD). We analyzed the relationship between these two conditions and their association with Gait Abnormalities using laboratory test data and findings from diffusion tensor imaging (DTI). The study involved 10 patients with INPH, 18 with PD, and 10 healthy individuals (control group). Fractional anisotropy (FA) of five brain areas was measured and compared among the three groups. In addition, the association of INPH and PD with Gait capability, frontal lobe function, and FA of each brain area was evaluated. The INPH group had significantly lower FA for anterior thalamic radiation (ATR) and forceps minor (Fmin) as compared to the PD group. The Gait capability correlated with ATR FA in the INPH and PD groups. We found that adding DTI to the diagnosis assisted the differential diagnosis of INPH from PD, beyond what could be inferred from ventricular size alone. We expect that DTI will provide a useful tool to support the differential diagnosis of INPH and PD and their respective severities.
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Diffusion tensor imaging in elderly patients with idiopathic normal pressure hydrocephalus or Parkinson’s disease: diagnosis of Gait Abnormalities
Fluids and Barriers of the CNS, 2012Co-Authors: Kohei Marumoto, Tetsuo Koyama, Masashi Hosomi, Norihiko Kodama, Hiroji Miyake, Kazuhisa DomenAbstract:Gait Abnormalities in the elderly, characterized by short steps and frozen Gait, can be caused by several diseases, including idiopathic normal pressure hydrocephalus (INPH), and Parkinson’s disease (PD). We analyzed the relationship between these two conditions and their association with Gait Abnormalities using laboratory test data and findings from diffusion tensor imaging (DTI). The study involved 10 patients with INPH, 18 with PD, and 10 healthy individuals (control group). Fractional anisotropy (FA) of five brain areas was measured and compared among the three groups. In addition, the association of INPH and PD with Gait capability, frontal lobe function, and FA of each brain area was evaluated. The INPH group had significantly lower FA for anterior thalamic radiation (ATR) and forceps minor (Fmin) as compared to the PD group. The Gait capability correlated with ATR FA in the INPH and PD groups. We found that adding DTI to the diagnosis assisted the differential diagnosis of INPH from PD, beyond what could be inferred from ventricular size alone. We expect that DTI will provide a useful tool to support the differential diagnosis of INPH and PD and their respective severities.
