Edith Cowan University

About: Edith Cowan University is a education organization based out in Perth, Western Australia, Australia. It is known for research contribution in the topics: Population & Context (language use). The organization has 4040 authors who have published 13529 publications receiving 339582 citations. The organization is also known as: Edith Cowan & ECU.

Clinical and Biomarker Changes in Dominantly Inherited Alzheimer’s Disease

Abstract: A B S T R AC T BACKGROUND The order and magnitude of pathologic processes in Alzheimer’s disease are not well understood, partly because the disease develops over many years. Autosomal dominant Alzheimer’s disease has a predictable age at onset and provides an opportunity to determine the sequence and magnitude of pathologic changes that culminate in symptomatic disease. METHODS In this prospective, longitudinal study, we analyzed data from 128 participants who underwent baseline clinical and cognitive assessments, brain imaging, and cerebrospinal fluid (CSF) and blood tests. We used the participant’s age at baseline assessment and the parent’s age at the onset of symptoms of Alzheimer’s disease to calculate the estimated years from expected symptom onset (age of the participant minus parent’s age at symptom onset). We conducted cross-sectional analyses of baseline data in relation to estimated years from expected symptom onset in order to determine the relative order and magnitude of pathophysiological changes. RESULTS Concentrations of amyloid-beta (Aβ)42 in the CSF appeared to decline 25 years before expected symptom onset. Aβ deposition, as measured by positron-emission tomography with the use of Pittsburgh compound B, was detected 15 years before expected symptom onset. Increased concentrations of tau protein in the CSF and an increase in brain atrophy were detected 15 years before expected symptom onset. Cerebral hypometabolism and impaired episodic memory were observed 10 years before expected symptom onset. Global cognitive impairment, as measured by the Mini–Mental State Examination and the Clinical Dementia Rating scale, was detected 5 years before expected symptom onset, and patients met diagnostic criteria for dementia at an average of 3 years after expected symptom onset. CONCLUSIONS We found that autosomal dominant Alzheimer’s disease was associated with a series of pathophysiological changes over decades in CSF biochemical markers of Alzheimer’s disease, brain amyloid deposition, and brain metabolism as well as progressive cognitive impairment. Our results require confirmation with the use of longitudinal data and may not apply to patients with sporadic Alzheimer’s disease. (Funded by the National Institute on Aging and others; DIAN ClinicalTrials.gov number, NCT00869817.)

Amyloid β deposition, neurodegeneration, and cognitive decline in sporadic Alzheimer's disease: a prospective cohort study.

Abstract: Summary Background Similar to most chronic diseases, Alzheimer's disease (AD) develops slowly from a preclinical phase into a fully expressed clinical syndrome. We aimed to use longitudinal data to calculate the rates of amyloid β (Aβ) deposition, cerebral atrophy, and cognitive decline. Methods In this prospective cohort study, healthy controls, patients with mild cognitive impairment (MCI), and patients with AD were assessed at enrolment and every 18 months. At every visit, participants underwent neuropsychological examination, MRI, and a carbon-11-labelled Pittsburgh compound B ( 11 C-PiB) PET scan. We included participants with three or more 11 C-PiB PET follow-up assessments. Aβ burden was expressed as 11 C-PiB standardised uptake value ratio (SUVR) with the cerebellar cortex as reference region. An SUVR of 1·5 was used to discriminate high from low Aβ burdens. The slope of the regression plots over 3–5 years was used to estimate rates of change for Aβ deposition, MRI volumetrics, and cognition. We included those participants with a positive rate of Aβ deposition to calculate the trajectory of each variable over time. Findings 200 participants (145 healthy controls, 36 participants with MCI, and 19 participants with AD) were assessed at enrolment and every 18 months for a mean follow-up of 3·8 (95% CI CI 3·6–3·9) years. At baseline, significantly higher Aβ burdens were noted in patients with AD (2·27, SD 0·43) and those with MCI (1·94, 0·64) than in healthy controls (1·38, 0·39). At follow-up, 163 (82%) of the 200 participants showed positive rates of Aβ accumulation. Aβ deposition was estimated to take 19·2 (95% CI 16·8–22·5) years in an almost linear fashion—with a mean increase of 0·043 (95% CI 0·037–0·049) SUVR per year—to go from the threshold of 11 C-PiB positivity (1·5 SUVR) to the levels observed in AD. It was estimated to take 12·0 (95% CI 10·1–14·9) years from the levels observed in healthy controls with low Aβ deposition (1·2 [SD 0·1] SUVR) to the threshold of 11 C-PiB positivity. As AD progressed, the rate of Aβ deposition slowed towards a plateau. Our projections suggest a prolonged preclinical phase of AD in which Aβ deposition reaches our threshold of positivity at 17·0 (95% CI 14·9–19·9) years, hippocampal atrophy at 4·2 (3·6–5·1) years, and memory impairment at 3·3 (2·5–4·5) years before the onset of dementia (clinical dementia rating score 1). Interpretation Aβ deposition is slow and protracted, likely to extend for more than two decades. Such predictions of the rate of preclinical changes and the onset of the clinical phase of AD will facilitate the design and timing of therapeutic interventions aimed at modifying the course of this illness. Funding Science and Industry Endowment Fund (Australia), The Commonwealth Scientific and Industrial Research Organisation (Australia), The National Health and Medical Research Council of Australia Program and Project Grants, the Austin Hospital Medical Research Foundation, Victorian State Government, The Alzheimer's Drug Discovery Foundation, and the Alzheimer's Association.

A review of multiobjective test problems and a scalable test problem toolkit

Abstract: When attempting to better understand the strengths and weaknesses of an algorithm, it is important to have a strong understanding of the problem at hand. This is true for the field of multiobjective evolutionary algorithms (EAs) as it is for any other field. Many of the multiobjective test problems employed in the EA literature have not been rigorously analyzed, which makes it difficult to draw accurate conclusions about the strengths and weaknesses of the algorithms tested on them. In this paper, we systematically review and analyze many problems from the EA literature, each belonging to the important class of real-valued, unconstrained, multiobjective test problems. To support this, we first introduce a set of test problem criteria, which are in turn supported by a set of definitions. Our analysis of test problems highlights a number of areas requiring attention. Not only are many test problems poorly constructed but also the important class of nonseparable problems, particularly nonseparable multimodal problems, is poorly represented. Motivated by these findings, we present a flexible toolkit for constructing well-designed test problems. We also present empirical results demonstrating how the toolkit can be used to test an optimizer in ways that existing test suites do not

Global imprint of climate change on marine life

Abstract: Research that combines all available studies of biological responses to regional and global climate change shows that 81–83% of all observations were consistent with the expected impacts of climate change These findings were replicated across taxa and oceanic basins Past meta-analyses of the response of marine organisms to climate change have examined a limited range of locations1,2, taxonomic groups2,3,4 and/or biological responses5,6 This has precluded a robust overview of the effect of climate change in the global ocean Here, we synthesized all available studies of the consistency of marine ecological observations with expectations under climate change This yielded a meta-database of 1,735 marine biological responses for which either regional or global climate change was considered as a driver Included were instances of marine taxa responding as expected, in a manner inconsistent with expectations, and taxa demonstrating no response From this database, 81–83% of all observations for distribution, phenology, community composition, abundance, demography and calcification across taxa and ocean basins were consistent with the expected impacts of climate change Of the species responding to climate change, rates of distribution shifts were, on average, consistent with those required to track ocean surface temperature changes Conversely, we did not find a relationship between regional shifts in spring phenology and the seasonality of temperature Rates of observed shifts in species’ distributions and phenology are comparable to, or greater, than those for terrestrial systems