scholarly journals APPLICATIONS OF GENETIC STOCHASTIC PROCESS MODEL IN STUDIES OF DEVELOPMENT OF ALZHEIMER’S DISEASE

2017 ◽  
Vol 1 (suppl_1) ◽  
pp. 1150-1151
Author(s):  
I.Y. Zhbannikov ◽  
K. Arbeev ◽  
O. Bagley ◽  
M. Duan ◽  
A.I. Yashin ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Stochastic Process ◽  
Process Model

scholarly journals Applications of Stochastic Process Models to Constructing Predictive Models of Alzheimer’s Disease

2020 ◽  
Vol 4 (Supplement_1) ◽  
pp. 263-263
Author(s):  
Konstantin Arbeev ◽  
Olivia Bagley ◽  
Arseniy Yashkin ◽  
Hongzhe Duan ◽  
Igor Akushevich ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Stochastic Process ◽  
Repeated Measures ◽  
Process Model ◽  
Large Scale ◽  
Disease Onset ◽  
Building Blocks ◽  
Process Models ◽  
Polygenic Scores

Abstract Large-scale population-based data collecting repeated measures of biomarkers, follow-up data on events (incidence of diseases and mortality), and extensive genetic data provide excellent opportunities for applying statistical models for joint analyses of longitudinal dynamics of biomarkers and time-to-event outcomes that allow investigating dynamics of biomarkers and other relevant factors (including genetic) in relation to risks of diseases and death and how this may propagate to the future. Here we applied one such model, the stochastic process model (SPM), to data on longitudinal trajectories of different variables (comorbidity index, body mass index, cognitive scores), other relevant covariates (including genetic factors such as APOE polymorphisms and polygenic scores, PGS), and data on onset of Alzheimer’s disease (AD) in the Health and Retirement Study. We observed that different aging-related characteristics estimated from trajectories of respective variables in SPM are strongly associated with risks of onset of AD and found that these associations differ by sex, APOE status (carriers vs. non-carriers of APOE e4) and by PGS groups. The approach allows modeling and estimating time trends (e.g., by birth cohorts) in relevant dynamic characteristics in relation to the disease onset. These results provide building blocks for constructing the models for forecasting future trends and burden of AD that take into account dynamic relationships between individual trajectories of relevant repeatedly measured characteristics and the risk of the disease. Such models also provide the analytic framework for understanding AD in the context of aging and for finding genetic underpinnings of such links between AD and aging.

scholarly journals The Business Process Model and Notation Used for the Representation of Alzheimer’s Disease Patients Care Process

Data ◽  
2020 ◽  
Vol 5 (1) ◽  
pp. 16 ◽  
Author(s):  
Martin Kopecky ◽  
Hana Tomaskova
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Business Process ◽  
Process Model ◽  
Care Process ◽  
Cost Calculation ◽  
Business Process Model ◽  
Whole Process ◽  
Care Processes ◽  
Number Of Patients

Currently, the number of patients with neurological diseases is increasing, especially those older than 65 suffering from Alzheimer’s disease. This development increases the emphasis on understanding and mapping treatment and care processes, not only for the elderly. Service providers (of both treatment and care) are under general pressure to decrease charges and maintain or improve existing levels of care. This situation is significantly influenced by a comprehensive knowledge of the whole process and its values. This publication therefore aims to describe the fundamental procedural aspects of caring for patients with Alzheimer’s disease, using Business Process Model and Notation (BPMN). It also aims to show the possibilities of using BPMN in the description of treatment and care. Modeling of the business process is more frequently being applied not only by businesses but also by scientists involved in process models. It is used to model medical topics, with approximately 10% of its publications only, and most of these publications deal only with clinical pathways, not with overall treatment and care processes. However, the BPMN model allows the whole process of medical and nonmedical care for patients with Alzheimer’s disease to be described, including the decomposition of partial activities into individual threads and sub-processes or atomic tasks. This paper presents the BPMN modeling and mapping of the specific care path for neurodegenerative patients. The text provides a new perspective on the BPMN modeling of Alzheimer’s disease. The presented model offers the option of expanding treatment cost calculation to simulate the process using graphical tools and languages. The overall view of this system creates a much more complex concept of the system and its surroundings.

scholarly journals A Nelson-Aalen Estimate of the Incidence Rates of Early-Onset Alzheimer's Disease Associated with the Presenilin-1 Gene

2002 ◽  
Vol 32 (1) ◽  
pp. 1-42 ◽  
Author(s):  
Eng Hock Gui ◽  
Angus Macdonald
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Early Onset ◽  
Life Histories ◽  
Process Model ◽  
Single Gene ◽  
Later Life ◽  
Incidence Rates ◽  
Presenilin 1 ◽  
Early Onset Alzheimer’S Disease

AbstractWe analyse, in a probabilistic setting, Newcombe's (1981) life table method of estimating rates of onset of high-penetrance single-gene disorders, and extend this to a counting process model for individual life histories, including movement between risk groups arising from genetic testing and onset in relatives. A key result is that estimates of rates of onset at any age x must be conditioned only on information available when subjects were age x, even though their later life histories might be available to the investigator. This determines the data that must be included in pedigrees. We derive a Nelson-Aalen-type estimate of a function of the rate of onset, and show that when all that is known is that the persons in the study inherited a mutation with probability 1/2, the function estimated is bounded. In practice, the treatment of censored observations or the methods of ascertainment might cause the estimate to exceed this bound, which results in infinite estimates of the rate of onset but might be a useful diagnostic check on the presence of these features. We summarise the literature on mutations in the Presenilin-1 (PSEN-1) gene, associated with early-onset Alzheimer's disease (EOAD), and from published pedigrees we estimate rates of onset of EOAD.

scholarly journals A 2-process model for neuropathology of Alzheimer's disease

2014 ◽  
Vol 35 (2) ◽  
pp. 301-308 ◽  
Author(s):  
Dan Mungas ◽  
Rochelle Tractenberg ◽  
Julie A. Schneider ◽  
Paul K. Crane ◽  
David A. Bennett
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Process Model

Longitudinal analysis of a two-component model of the memory deficit in Alzheimer's disease

1992 ◽  
Vol 22 (2) ◽  
pp. 437-445 ◽  
Author(s):  
James T. Becker ◽  
Olurotimi Bajulaiye ◽  
Christine Smith
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Process Model ◽  
Memory Loss ◽  
Memory Deficit ◽  
Dysexecutive Syndrome ◽  
Initial Observation ◽  
Amnesic Syndrome ◽  
Rapid Information Processing ◽  
One Year

SYNOPSISThe memory deficit in Alzheimer's disease (AD) has been characterized as consisting of multiple components. The purpose of this study was to confirm the utility of a two-process model, and to examine changes in the nature and extent of the neuropsychological deficits after a one-year interval. The results replicate the initial observation that the memory loss in AD can be described as consisting of a focal amnesic syndrome and a dysexecutive syndrome characterized by failure of rapid information processing and search of both episodic and semantic memory. One year after the initial observation, all dysexecutive patients and the majority of the amnesic patients had become non-focal. No patient developed a dysexecutive syndrome, but 18 patients developed amnesic syndromes. These results suggest that, like other aspects of the cognitive deficits of AD, the memory loss is multifactorial. These results have implications for understanding the pathophysiology of AD, and for designing pharmacotherapeutic intervention.

Cognitive control constrains memory attributions

2019 ◽  
Vol 42 ◽  
Author(s):  
Colleen M. Kelley ◽  
Larry L. Jacoby
Keyword(s):  
Alzheimer’S Disease ◽  
Older Adults ◽  
Alzheimer's Disease ◽  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Cognitive Control

Abstract Cognitive control constrains retrieval processing and so restricts what comes to mind as input to the attribution system. We review evidence that older adults, patients with Alzheimer's disease, and people with traumatic brain injury exert less cognitive control during retrieval, and so are susceptible to memory misattributions in the form of dramatic levels of false remembering.

Formation of paired helical filaments in Alzheimer's disease

1984 ◽  
Vol 42 ◽  
pp. 302-303
Author(s):  
J. Metuzals ◽  
D. F. Clapin ◽  
V. Montpetit
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Frontal Lobe ◽  
Giant Axon ◽  
Paired Helical Filaments ◽  
Normal Brain ◽  
Protein Assemblies ◽  
Electron Microscopic ◽  
Helical Symmetry ◽  
Structural Levels

Information on the conformation of paired helical filaments (PHF) and the neurofilamentous (NF) network is essential for an understanding of the mechanisms involved in the formation of the primary lesions of Alzheimer's disease (AD): tangles and plaques. The structural and chemical relationships between the NF and the PHF have to be clarified in order to discover the etiological factors of this disease. We are investigating by stereo electron microscopic and biochemical techniques frontal lobe biopsies from patients with AD and squid giant axon preparations. The helical nature of the lesion in AD is related to pathological alterations of basic properties of the nervous system due to the helical symmetry that exists at all hierarchic structural levels in the normal brain. Because of this helical symmetry of NF protein assemblies and PHF, the employment of structure reconstruction techniques to determine the conformation, particularly the handedness of these structures, is most promising. Figs. 1-3 are frontal lobe biopsies.

Computer-aided methods for 3-D visualization of serial sections and thick biological specimens

1992 ◽  
Vol 50 (2) ◽  
pp. 1060-1061
Author(s):  
Mark Ellisman ◽  
Maryann Martone ◽  
Gabriel Soto ◽  
Eleizer Masliah ◽  
David Hessler ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Three Dimensional ◽  
Neuritic Plaque ◽  
Dimensional Structure ◽  
Data Sets ◽  
Molecular Physiology ◽  
Research Activities ◽  
Computer Aided ◽  
Dimensional Reconstruction

Structurally-oriented biologists examine cells, tissues, organelles and macromolecules in order to gain insight into cellular and molecular physiology by relating structure to function. The understanding of these structures can be greatly enhanced by the use of techniques for the visualization and quantitative analysis of three-dimensional structure. Three projects from current research activities will be presented in order to illustrate both the present capabilities of computer aided techniques as well as their limitations and future possibilities.The first project concerns the three-dimensional reconstruction of the neuritic plaques found in the brains of patients with Alzheimer's disease. We have developed a software package “Synu” for investigation of 3D data sets which has been used in conjunction with laser confocal light microscopy to study the structure of the neuritic plaque. Tissue sections of autopsy samples from patients with Alzheimer's disease were double-labeled for tau, a cytoskeletal marker for abnormal neurites, and synaptophysin, a marker of presynaptic terminals.

Liquid crystalline ordering of paired helical filaments in neurofibrillary tangles of Alzheimer's disease

1986 ◽  
Vol 44 ◽  
pp. 348-349
Author(s):  
D.F. Clapin ◽  
V.J.A. Montpetit
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Neurofibrillary Tangles ◽  
Liquid Crystalline ◽  
Amyloid Fibrils ◽  
Geometric Analysis ◽  
Paired Helical Filaments ◽  
Microscopic Level ◽  
Light Microscopic Level ◽  
Regular Spacing

Alzheimer's disease is characterized by the accumulation of abnormal filamentous proteins. The most important of these are amyloid fibrils and paired helical filaments (PHF). PHF are located intraneuronally forming bundles called neurofibrillary tangles. The designation of these structures as "tangles" is appropriate at the light microscopic level. However, localized domains within individual tangles appear to demonstrate a regular spacing which may indicate a liquid crystalline phase. The purpose of this paper is to present a statistical geometric analysis of PHF packing.

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