Operationalizing compensation over time in neurodegenerative disease.
Ontology highlight
ABSTRACT:
SUBMITTER: Gregory S
PROVIDER: S-EPMC5382953 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:Understanding the ecological processes that maintain community function in systems experiencing species loss, and how these processes change over time, is key to understanding the relationship between community structure and function and predicting how communities may respond to perturbations in the Anthropocene. Using a 30-year experiment on desert rodents, we show that the impact of species loss on community-level energy use has changed repeatedly and dramatically over time, due to (1) the addition of new species to the community, and (2) a reduction in functional redundancy among the same set of species. Although strong compensation, initially driven by the dispersal of functionally redundant species to the local community, occurred in this system from 1997 to 2010, since 2010, compensation has broken down due to decreasing functional overlap within the same set of species. Simultaneously, long-term changes in sitewide community composition due to niche complementarity have decoupled the dynamics of compensation from the overall impact of species loss on community-level energy use. Shifting, context-dependent compensatory dynamics, such as those demonstrated here, highlight the importance of explicitly long-term, metacommunity, and eco-evolutionary perspectives on the link between species-level fluctuations and community function in a changing world.
| S-EPMC9287087 | biostudies-literature
Project description:BackgroundAlthough subtypes of chronic obstructive pulmonary disease are recognized, it is unknown what happens to these subtypes over time. Our objectives were to assess the stability of cluster-based subtypes in patients with stable disease and explore changes in clusters over 1 year.MethodsMultiple correspondence and cluster analysis were used to evaluate data collected from 543 stable patients included consecutively from 5 respiratory outpatient clinics.ResultsFour subtypes were identified. Three of them, A, B, and C, had marked respiratory profiles with a continuum in severity of several variables, while the fourth, subtype D, had a more systemic profile with intermediate respiratory disease severity. Subtype A was associated with less dyspnea, better health-related quality of life and lower Charlson comorbidity scores, and subtype C with the most severe dyspnea, and poorer pulmonary function and quality of life, while subtype B was between subtypes A and C. Subtype D had higher rates of hospitalization the previous year, and comorbidities. After 1 year, all clusters remained stable. Generally, patients continued in the same subtype but 28% migrated to another cluster. Together with movement across clusters, patients showed changes in certain characteristics (especially exercise capacity, some variables of pulmonary function and physical activity) and changes in outcomes (quality of life, hospitalization and mortality) depending on the new cluster they belonged to.ConclusionsChronic obstructive pulmonary disease clusters remained stable over 1 year. Most patients stayed in their initial subtype cluster, but some moved to another subtype and accordingly had different outcomes.
| S-EPMC5017635 | biostudies-literature
Project description:RNA was purified from fusiform gyrus tissue sections of autopsy-confirmed Alzheimer's cases and neurologically normal age-matched controls. The "SAM.ID" sample characteristic is a sample identifier internal to Genentech. The ID of this project in Genentech's ExpressionPlot database is PRJ0007261
2017-12-20 | GSE95587 | GEO
Project description:Aphasia classifications and specialized language batteries differ across the fields of neurodegenerative disorders and lesional brain injuries, resulting in difficult comparisons of language deficits across etiologies. In this study, we present a simplified framework, in which a widely-used aphasia battery captures clinical clusters across disease etiologies and provides a quantitative and visual method to characterize and track patients over time. The framework is used to evaluate populations representing three disease etiologies: stroke, primary progressive aphasia (PPA), and post-operative aphasia. A total of 330 patients across three populations with cerebral injury leading to aphasia were investigated, including 76 patients with stroke, 107 patients meeting criteria for PPA, and 147 patients following left hemispheric resective surgery. Western Aphasia Battery (WAB) measures (Information Content, Fluency, answering Yes/No questions, Auditory Word Recognition, Sequential Commands, and Repetition) were collected across the three populations and analyzed to develop a multi-dimensional aphasia model using dimensionality reduction techniques. Two orthogonal dimensions were found to explain 87% of the variance across aphasia phenotypes and three disease etiologies. The first dimension reflects shared weighting across aphasia subscores and correlated with aphasia severity. The second dimension incorporates fluency and comprehension, thereby separating Wernicke's from Broca's aphasia, and the non-fluent/agrammatic from semantic PPA variants. Clusters representing clinical classifications, including late PPA presentations, were preserved within the two-dimensional space. Early PPA presentations were not classifiable, as specialized batteries are needed for phenotyping. Longitudinal data was further used to visualize the trajectory of aphasias during recovery or disease progression, including the rapid recovery of post-operative aphasic patients. This method has implications for the conceptualization of aphasia as a spectrum disorder across different disease etiology and may serve as a framework to track the trajectories of aphasia progression and recovery.
| S-EPMC7801263 | biostudies-literature
Project description:In recent years, genomic, animal and cell biology studies have implicated deficiencies in retromer-mediated trafficking of proteins in an increasing number of neurodegenerative diseases including Alzheimer's Disease (AD), Parkinson's Disease (PD) and Frontotemporal Lobar Degener-ation (FTLD). The retromer complex, which is highly conserved across all eukaryotes, regulates the sorting of transmembrane proteins out of endo-somes to the cell surface or to the trans-Golgi network. Within retromer, cargo selection and binding are performed by a trimer of the Vps26, Vps29 and Vps35 proteins, named the "Cargo-Selective Complex (CSC)". Sorting of cargo into tubules for distribution to the trans-Golgi network or the cell sur-face is achieved through the dimeric sorting nexin (SNX) component of retromer and accessory proteins such as the WASH complex which medi-ates the formation of discrete endosomal tubules enabling the sorting of cargo into distinct pathways through production of filamentous actin patch-es. In the present article, we review the molecular structure and function of the retromer and summarize the evidence linking retromer dysfunction to neurodegenerative disease.
| S-EPMC5930449 | biostudies-other
Project description: Not available
| S-EPMC7612114 | biostudies-literature
Project description:BACKGROUND/OBJECTIVES:Population-based incidence estimates of dementia and Alzheimer disease (AD) provide important information for public health policy and resource allocation. We conducted a meta-analysis of published studies that reported age-specific incidence rates of dementia and AD to determine whether dementia and AD incidence rates are changing over time. DESIGN:PubMed and MEDLINE were searched for publications through June 30, 2017, using key words "dementia", "Alzheimer", and "incidence." Inclusion criteria for the meta-analysis are: (1) population-based studies using personal interviews and direct examinations of the study subjects, (2) standardized clinical diagnosis criteria, (3) reporting age-specific incidence rates, (4) published in English, and (5) sample size of 500 or greater and length of follow-up of 2 years or greater. Mixed-effects models were used to determine the association between birth year and incidence rates. MEASUREMENTS:Age-specific dementia/AD incidence rates and their standard errors reported in each study. RESULTS:Thirty-eight articles with 53 cohorts on dementia incidence and 31 articles with 35 cohorts on AD incidence met the inclusion criteria. There were significant associations between later birth years and decreased dementia incidence rates in all three age groups (65-74, 75-84, and 85 years and older). There were no significant associations between birth year and AD incident rates in any of the three age groups. In particular, AD incidence rates reported from Western countries stayed steady in all age groups, while studies in non-Western countries showed significantly increased AD incidence rates for the 65 to 74 years age group (odds ratio = 2.78; P =?.04), but a nonsignificant association for the 75 to 84 or 85 years and older groups. CONCLUSION:Dementia incidence declined over the past four decades, but AD incidence did not decline. Further research, especially from non-Western countries, is needed to elucidate the mechanism underlying the trends in dementia and AD incidence over time.
| S-EPMC6612587 | biostudies-literature
Project description:ObjectiveTo study the longitudinal changes in autofluorescence in Stargardt disease to reveal aspects of disease progression not previously evident. Changes in autofluorescence reflect changing fluorophore compositions of lipofuscin and melanin in retinal pigment epithelial cells, which has been hypothesized to contribute to Stargardt disease pathogenesis.MethodsWe examined the temporospatial patterns of fundus autofluorescence with excitation at both 488 nm (standard fundus autofluorescence) and 795 nm (near-infrared autofluorescence) in a longitudinal case series involving 8 eyes of 4 patients (range of follow-up, 11-57 months; mean, 39 months). Image processing was performed to analyze spatial and temporal cross-modality associations.ResultsLongitudinal fundus autofluorescence imaging of fleck lesions revealed hyperautofluorescent lesions that extended in a centrifugal direction from the fovea with time. Patterns of spread were nonrandom and followed a radial path that left behind a trail of diminishing autofluorescence. Longitudinal near-infrared autofluorescence imaging also demonstrated centrifugal lesion spread but with fewer hyperautofluorescent lesions, suggestive of more transient hyperautofluorescence and more rapid decay at longer wavelengths. Fundus autofluorescence and near-infrared autofluorescence abnormalities were spatially correlated with each other, and together they reflect systematic progressions in fleck distribution and fluorophore composition occurring during the natural history of the disease.ConclusionsStargardt disease fleck lesions do not evolve randomly in location but instead follow consistent patterns of radial expansion and a systematic decay of autofluorescence that reflect changing lipofuscin and melanin compositions in retinal pigment epithelial cells. These progressive foveal-to-peripheral changes are helpful in elucidating molecular and cellular mechanisms underlying Stargardt disease and may constitute potential outcome measures in clinical trials.
| S-EPMC3768260 | biostudies-literature
Project description:Cognitive deficits are a recognised component of Parkinson's disease (PD). However, particularly within the domain of short-term memory, it is unclear whether these impairments are masked, or caused, by patients' dopaminergic medication. The effect of medication on pure maintenance in PD patients has rarely been explored, with most assessments examining maintenance intercalated between other executive tasks. Moreover, few studies have utilised methods that can measure the quality of mental representations, which can enable the decomposition of recall errors into their underlying neurocognitive components. Here, we fill this gap by examining pure maintenance in PD patients in high and low dopaminergic states. Participants had to encode the orientation of two stimuli and reproduce these orientations after a short (2 s) or long (8 s) delay. In addition, we also examined the performance of healthy, age-matched older adults to contextualise these effects and determine whether PD represents an exacerbation of the normal ageing process. Patients showed improved recall OFF compared to ON their dopaminergic medication, but only for long-duration trials. Moreover, PD patients OFF their medication actually performed at a level superior to age-matched controls, indicative of a paradoxical enhancement of memory in the low dopaminergic state. The application of a probabilistic model of response selection suggested that PD patients made fewer misbinding errors in the low, compared with high, dopaminergic state for longer-delay trials. Thus, unexpectedly, the mechanisms that prevent memoranda from being corrupted by misbinding over time appear to be enhanced in PD patients OFF dopaminergic medication. Possible explanations for this paradoxical effect are discussed.
| S-EPMC6683156 | biostudies-literature
Project description:Evolutionary transitions in individuality (hereafter, ETIs), such as the transition to multi-cellularity and the transition to social colonies, have been at the centre of evolutionary research, but only few attempts were made to systematically operationalize this concept. Here, we devise a set of four indicators intended to assess the change in complexity during ETIs: system size, inseparability, reproductive specialization and non-reproductive specialization. We then conduct a quantitative comparison across multiple taxa and ETIs. Our analysis reveals that inseparability has a crucial role in the process; it seems irreversible and may mark the point where a group of individuals becomes a new individual at a higher hierarchical level. Interestingly, we find that disparate groups demonstrate a similar pattern of progression along ETIs.
| S-EPMC7031674 | biostudies-literature