The Phenomenology, Pathophysiology and Progression of the Core Features of Lewy Body Dementia

Lewy body dementias – Dementia with Lewy bodies (DLB) and Parkinson’s disease dementia (PDD) - are disabling neurodegenerative conditions defined pathologically by the presence of intraneuronal α-synuclein rich aggregates (‘Lewy bodies’ and ‘Lewy neurites’). These disorders are characterized by a set of ‘core’ clinical features, namely cognitive fluctuations, visual hallucinations, motor parkinsonism, and most recently added, REM sleep behaviour disorder. These features are central to the diagnosis of Lewy bodies dementias (especially DLB) and discriminate them from other neurodegenerative disorders. Despite decades of research, the etiopathogenesis underlying Lewy body disorders is poorly understood. This accounts for the relative lack of objective biomarkers and both symptomatic and disease modifying therapies. The present thesis comprises a series of investigations that seeks to understand the phenomenology, pathophysiology, and clinical progression of Lewy body dementias through focus on each of the core clinical features. Systematic review and empiric studies are organized under the respective headings of cognitive fluctuations, visual hallucinations, REM sleep behaviour disorder, motor features, interrelationships, and clinical progression of the core features. Novel clinical and pathophysiological insights are obtained which have implications for the prediction and diagnosis of core features, the development of new objective biomarkers, and clinical endpoints of disease progression. From these studies, a shared pathophysiological basis for the core features is postulated and potential avenues for future directions are highlighted, focusing on replication and validation of new biomarkers and clinical measures, discovery of new biomarkers and mechanisms, and translation to prodromal and patient cohorts

An adaptive measure of visuospatial impairment in dementia with Lewy bodies

Background: Background Dementia with Lewy bodies (DLB) is a common cause of dementia with poor prognosis and high hospitalization rates. DLB is frequently misdiagnosed, with clinical features that overlap significantly with other diseases including Parkinson’s disease (PD). Clinical instruments that discriminate and track the progression of cognitive impairment in DLB are needed. Objectives: Objectives The current study was designed to assess the utility of a mental rotation (MR) task for assessing visuospatial impairments in early DLB. Methods: Methods Accuracy of 22 DLB patients, 22 PD patients and 22 age-matched healthy controls in the MR task were compared at comparing shapes with 0°, 45° and 90° rotations. Results: Results Healthy controls and PD patients performed at similar levels while the DLB group were significantly impaired. Further, impairment in the visuospatial and executive function measures correlated with MR poor outcomes. Conclusion: Conclusion These findings support the MR task as an objective measure of visuospatial impairment with the ability to adjust difficulty to suit impairments in a DLB population. This would be a useful tool within clinical trials

Dynamic network impairments underlie cognitive fluctuations in Lewy body dementia

Cognitive fluctuations are a characteristic and distressing disturbance of attention and consciousness seen in patients with Dementia with Lewy bodies and Parkinson’s disease dementia. It has been proposed that fluctuations result from disruption of key neuromodulatory systems supporting states of attention and wakefulness which are normally characterised by temporally variable and highly integrated functional network architectures. In this study, patients with DLB (n = 25) and age-matched controls (n = 49) were assessed using dynamic resting state fMRI. A dynamic network signature of reduced temporal variability and integration was identified in DLB patients compared to controls. Reduced temporal variability correlated significantly with fluctuation-related measures using a sustained attention task. A less integrated (more segregated) functional network architecture was seen in DLB patients compared to the control group, with regions of reduced integration observed across dorsal and ventral attention, sensorimotor, visual, cingulo-opercular and cingulo-parietal networks. Reduced network integration correlated positively with subjective and objective measures of fluctuations. Regions of reduced integration and unstable regional assignments significantly matched areas of expression of specific classes of noradrenergic and cholinergic receptors across the cerebral cortex. Correlating topological measures with maps of neurotransmitter/neuromodulator receptor gene expression, we found that regions of reduced integration and unstable modular assignments correlated significantly with the pattern of expression of subclasses of noradrenergic and cholinergic receptors across the cerebral cortex. Altogether, these findings demonstrate that cognitive fluctuations are associated with an imaging signature of dynamic network impairment linked to specific neurotransmitters/neuromodulators within the ascending arousal system, highlighting novel potential diagnostic and therapeutic approaches for this troubling symptom

Necessary Skills and Knowledge for Staff Providing Telehealth Services

Background Although motor abnormalities have been flagged as potentially the most sensitive and specific clinical features for predicting the future progression to Parkinson's disease, little work has been done to characterize gait and balance impairments in idiopathic rapid eye movement sleep behavior disorder (iRBD). Objective The objective of this study was to quantitatively determine any static balance as well as gait impairments across the 5 independent domains of gait in polysomnography-confirmed iRBD patients using normal, fast-paced, and dual-task walking conditions. Methods A total of 38 participants (24 iRBD, 14 healthy controls) completed the following 5 different walking trials across a pressure sensor carpet: (1) normal pace, (2) fast pace, (3) while counting backward from 100 by 1s, (4) while naming as many animals as possible, (5) while subtracting 7s from 100. Results Although no gait differences were found between the groups during normal walking, there were significant differences between groups under the fast-paced and dual-task gait conditions. Specifically, in response to the dual tasking, healthy controls widened their step width without changing step width variability, whereas iRBD patients did not widen their step width but, rather, significantly increased their step width variability. Similarly, changes between the groups were observed during fast-paced walking wherein the iRBD patients demonstrated greater step length asymmetry when compared with controls. Conclusions This study demonstrates that iRBD patients have subtle gait impairments, which likely reflect early progressive degeneration in brainstem regions that regulate both REM sleep and gait coordination. Such gait assessments may be useful as a diagnostic preclinical screening tool for future fulminant gait abnormalities for trials of disease-preventive agents. (c) 2019 International Parkinson and Movement Disorder Societ

Motor cortical excitability and pre-supplementary motor area neurochemistry in healthy adults with substantia nigra hyperechogenicity

Substantia nigra (SN) hyperechogenicity, viewed with transcranial ultrasound, is a risk marker for Parkinson\u27s disease. We hypothesized that SN hyperechogenicity in healthy adults aged 50 – 70 years is associated with reduced short-interval intracortical inhibition in primary motor cortex, and that the reduced intracortical inhibition is associated with neurochemical markers of activity in the pre-supplementary motor area (pre-SMA). Short-interval intracortical inhibition and intracortical facilitation in primary motor cortex was assessed with paired-pulse transcranial magnetic stimulation in 23 healthy adults with normal (n = 14; 61 ± 7 yrs) or abnormally enlarged (hyperechogenic; n = 9; 60 ± 6 yrs) area of SN echogenicity. Thirteen of these participants (7 SN − and 6 SN+) also underwent brain magnetic resonance spectroscopy to investigate pre-SMA neurochemistry. There was no relationship between area of SN echogenicity and short-interval intracortical inhibition in the ipsilateral primary motor cortex. There was a significant positive relationship, however, between area of echogenicity in the right SN and the magnitude of intracortical facilitation in the right (ipsilateral) primary motor cortex (p = .005; multivariate regression), evidenced by the amplitude of the conditioned motor evoked potential (MEP) at the 10 – 12 ms interstimulus interval. This relationship was not present on the left side. Pre-SMA glutamate did not predict primary motor cortex inhibition or facilitation. The results suggest that SN hyperechogenicity in healthy older adults may be associated with changes in excitability of motor cortical circuitry. The results advance understanding of brain changes in healthy older adults at risk of Parkinson\u27s disease

Interaction de l'hydrogène atomique et moléculaire sur des surface de glace d'eau amorphe simulant les grains de poussière interstellaire

The interstellar medium (ISM) is the place surrounding the stars. It is constituted of gas and dust coming from the ejecta of some stars and the explosion of some others. Interstellar dust grains can be carbonaceous or composed of silicates, iron and magnesium. Over 120 molecular and atomic species are detected so far in the ISM. Molecular hydrogen is the most abundant and by far the most important since it is found in three of four molecules essential for life: water (H2O), methane (CH4), ammonia (NH3) and carbon monoxide (CO). The physical-chemistry that leads to the formation of molecules and of stars afterwards can be divided in two: the gas phase chemistry and the gas-surface chemistry. In the extreme conditions (very low both temperature and gas density) that exist in some places of the ISM, gas phase reactions are highly inecient, especially for the formation of molecular hydrogen whose abundance can only be explained by its formation occurring on the surface of dust grains. These grains play the role of catalysts and help evacuating the excess energy released by the molecules formed. This thesis is mainly an experimental contribution to the study of the interaction and formation of molecular hydrogen on water ice surfaces mimicking the ice mantles that cover dust grains in the dark clouds of the ISM. For this purpose, combining ultra-high vacuum techniques, cryogenic systems, atomic and molecular beams, mass spectrometry as well as theoretical modelling, several experiments is conducted using the FORMOLISM (FORmation of MOLecules in the InterStellar Medium) experimental set-up. In this thesis work, the sticking of molecular hydrogen and deuterium is studied in detail and the sticking coecient is found to be highly dependent on the gas temperature and mass. In dark clouds, where grains are covered with ice and Tgrain=Tgas=10 K, the sticking of H2 is found to be 74% and that of D2 82%. Other experiments highlight the mobility of hydrogen atoms on porous water ice at 10 K. This mobility has been questioned for a long time and has never been really proved experimentally. The diusion barrier of the atoms is found to be equal to 22+-2 meV, in agreement with several theoretical calculations. This value is equivalent to a diffusion time of 12 ms from one adsorption site to a neighbour site. A final set of experiments have been conducted in order to study the formation and de-excitation of nascent hydrogen molecules on porous and non-porous amorphous water ice in the conditions of quiescent dark clouds. These experiments have shown that more than 90% of the formation energy is deposited into the ice in the porous case. This energy transfer can be explained by two phenomena: (1) the saturation coverage of the ice surface by H2, and (2) the porosity of the ice that recaptures the nascent molecule helping it to relax. These experiments show that less than 10% of the newly formed molecules are released in the gas phase in an excited ro-vibrational states both in the porous and the non-porous ice cases. These results may explain why the observations of several teams trying to detect excited molecular hydrogen in dark quiescent clouds were unsuccessful.Parmi les différentes structures de l'univers existe ce qu'on appelle le milieu interstellaire (MIS). C'est un endroit où gaz et poussière co-existent et interagissent en parfaite harmonie. L'hydrogène moléculaire est l'espèce la plus abondante et de loin la plus importante du gaz interstellaire. Elle est à la base de trois sur quatre des molécules les plus essentielles à l'apparition de la vie : l'eau, le méthane, l'amine et le monoxyde de carbone. La physico-chimie du MIS qui mène à la formation de nouvelles molécules est divisée en deux : les réactions en phase gazeuse et les réactions sur les grains de poussière qui s'est révélée la voie de formation la plus efficace pour l'hydrogène moléculaire. Ce travail de thèse est une contribution expérimentale à l'étude de l'interaction et de la formation de l'hydrogène moléculaire sur les surface de glace d'eau amorphe qui couvrent les grains de poussière dans les nuages sombres du MIS. Dans ce but, en réunissant techniques ultravides, systèmes cryogéniques, jets atomiques et moléculaires, spectrométrie de masse et modélisation, plusieurs expériences ont été faites en utilisant le dispositif FORMOLISM (FORmation of MOLecules in the InterStellar Medium)

The next Generation residential space

Technological developments and new user expectations have placed considerable strain on businesses to adopt innovative, flexible, and customized new models. As thecovid-19 pandemic contributed also to the disruption of the residential sector and skeptic the benefits of home service, the question remains on how to anticipate new demand to lure back consumers and gain back their trust. The purpose of this paper, to study the factors influencing user demand characteristics and get a comprehensive ideaof the prevalence and expansion of demand for space and services to better understand the meaning of "New demand" and its implications on real estate and facilitymanagement. In addition, this paper serves as a guidance for designers and businesses operating in the residential sector, providing them with user-centered concepts and models to integrate in their design and services. The study starts with a focused literature review and continues with a multiple case study methodology, as the impactof Covid-19 is in the early stages of theory development. The result shows that demand for space is shifting towards sustainability and energy efficiency as users become more sensible about the environment and climate change. In addition to a shift toward different structural model like co-living and serviced apartment, especially for millennials where they prefer even to invest more in exchange for high quality and convenient services. The result also shows that the impact of Covid-19 on residential sector has not been as severe as it is in other industries. The consequences of covid-19 reflected reduced demand for co-living models, student residences and apartment versus a boost in demand for smart, individual, and mobile houses. Demand for homeoffice space is expected to increase by 90% as 50% of employees have started working from home and 44% of home office employees are planning to adopt a hybrid employment agreement even after the end of lockdown. Covid-19 has reoriented consumers spending on entertainment, vacations and commuting towards on-demandhome services which has created an opportunity for home service providers (specially cleaning, contracting, and landscaping) to take advantage of it by pivoting theirservices to align with the new demand for home improvement. Drawing on these findings, the next decades will witness substantial changes to home-life through technological advancement in response to societal, demographic and climate changes.The family home of the future will evolve to be more resilient and more adaptable to society’s ever-evolving needs.11

Interaction de l'hydrogène atomique et moléculaire avec des surfaces de glace d'eau amorphe simulabt des grains de poussière interstellaire

Parmi les différentes structures de l univers existe ce qu on appelle le milieu interstellaire (MIS). C est un endroit où gaz et poussière co-existent et interagissent en parfaite harmonie. L hydrogène moléculaire est l espèce la plus abondante et de loin la plus importante du gaz interstellaire. Elle est à la base de trois sur quatre des molécules les plus essentielles à l apparition de la vie : l eau, le méthane, l amine et le monoxyde de carbone. La physico-chimie du MIS qui mène à la formation de nouvelles molécules est divisée en deux : les réactions en phase gazeuse et les réactions sur les grains de poussière qui s est révélée la voie de formation la plus efficace pour l hydrogène moléculaire. Ce travail de thèse est une contribution expérimentale à l étude de l interaction et de la formation de l hydrogène moléculaire sur les surface de glace d eau amorphe qui couvrent les grains de poussière dans les nuages sombres du MIS. Dans ce but, en réunissant techniques ultravides, systèmes cryogéniques, jets atomiques et moléculaires, spectrométrie de masse et modélisation, plusieurs expériences ont été faites en utilisant le dispositif FORMOLISM (FORmation of MOLecules in the InterStellar Medium).Among the different structures of the universe exists what we call the interstellar medium (ISM). It is a place where gas and dust coexist and interact in perfect harmony. In this medium, molecular hydrogen is the most abundant gaseous species and by far the most important one. It is the principal constituent of three of four molecules essential to the existence of life: water, methane, amine and carbon monoxide. The physico-chemistry of the ISM that leads to the formation of new molecules is divided in two: the gas-phase reactions and the gas-dust reactions. The second one being the most efficient route of molecular hydrogen in space. This thesis work is an experimental contribution to study the interaction and the formation of molecular hydrogen on the surface of amorphous water ice surfaces covering dust grains in dark clouds. For this, by uniting ultra-high vacuum techniques, cryogenic systems, atomic and molecular beams, mass spectroscopy and modelling, several experiments have been conducted by using the FOMOLISM experimental set-up (FORmation of MOLecules in the InterStellar Medium).CERGY PONTOISE-BU Neuville (951272102) / SudocSudocFranceF

Mobility of D atoms on porous amorphous water ice surfaces under interstellar conditions

International audienceAims: The mobility of H atoms on the surface of interstellar dust grains at low temperature is still a matter of debate. In dense clouds, the hydrogenation of adsorbed species (i.e., CO), as well as the subsequent deuteration of the accreted molecules depend on the mobility of H atoms on water ice. Astrochemical models widely assume that H atoms are mobile on the surface of dust grains even if controversy still exists. We present here direct experimental evidence of the mobility of H atoms on porous water ice surfaces at 10 K. Methods: In a UHV chamber, O2 is deposited on a porous amorphous water ice substrate. Then D atoms are deposited onto the surface held at 10 K. Temperature-Programmed Desorption (TPD) is used and desorptions of O2 and D2 are simultaneously monitored. Results: We find that the amount of O2 that desorbs during the TPD diminishes if we increase the deposition time of D atoms. O2 is thus destroyed by D atoms even though these molecules have previously diffused inside the pores of thick water ice. Our results can be easily interpreted if D is mobile at 10 K on the water ice surface. A simple rate equation model fits our experimental data and best fit curves were obtained for a D atom diffusion barrier of 22 ± 2 meV. Therefore hydrogenation can take place efficiently on interstellar dust grains. These experimental results are consistent with most calculations and validate the hypothesis used in several models

Gas temperature dependent sticking of hydrogen on cold amorphous water ice surfaces of interstellar interest

International audienceUsing the King and Wells method, we present experimental data on the dependence of the sticking of molecular hydrogen and deuterium on the beam temperature onto nonporous amorphous solid water ice surfaces of interstellar interest. A statistical model that explains the isotopic effect and the beam temperature behavior of our data is proposed. This model gives an understanding of the discrepancy between all known experimental results on the sticking of molecular hydrogen. Moreover, it is able to fit the theoretical results of Buch et al. [Astrophys. J. 379, 647 (1991)] on atomic hydrogen and deuterium. For astrophysical applications, an analytical formula for the sticking coefficients of H, D, H2, D2, and HD in the case of a gas phase at thermal equilibrium is also provided at the end of the article