New mechanism proposed for NSAID reduction of Alzheimer's disease incidence

The Lancet ◽  
2001 ◽  
Vol 358 (9293) ◽  
pp. 1616
Author(s):  
Jane Bradbury
2012 ◽  
Vol 8 (4S_Part_12) ◽  
pp. P452-P452
Author(s):  
Perry Ridge ◽  
Taylor Maxwell ◽  
Chris Corcoran ◽  
JoAnn Tschanz ◽  
Richard Cawthon ◽  
...  

2017 ◽  
Vol 13 (7S_Part_17) ◽  
pp. P848-P848
Author(s):  
Stacey Charles ◽  
Albert W.C. Lin ◽  
Matthew Protas ◽  
Marisa Deliso ◽  
Manita Chaum ◽  
...  

Author(s):  
Nasim S. Sabounchi

ABSTRACT ObjectivesAs estimated there are about 5.3 million who suffer from Alzheimer’s disease in United States. The incidence is increasing as the population is aging. Due to the increasing trend of Alzheimer’s disease, there is a lot of discussion on prevention efforts or slowing the incidence. Also, models that could predict individual risk of cognitive impairment are needed to assist in prevention efforts.  In general dementia development has been associated with growth in various vascular, lifestyle and other risk factors. Epidemiological research provides evidence of some vascular, lifestyle and psychological risk factors that are modifiable and protective of disease incidence either independently or while interacting with other factors. However, as reported by National Institute of Aging, it is not yet clear whether health or lifestyle factors can prevent Alzheimer’s disease. The objective of this research project is to adopt a system dynamics modeling approach to study the interaction of several key factors including vascular, lifestyle and psychological aspects over the life course of individuals, to gain further understanding of Alzheimer’s disease incidence and evaluate prevention strategies. Both datasets of ‘Alzheimer's Disease Neuroimaging Initiative (ADNI)’ and ‘Health and Retirement Study (HRS)’ will be used for model development and validation. ApproachA system dynamics approach is an optimal choice for addressing the goal of this proposal because different key factors interact over time and make Alzheimer’s disease incidence a complex problem. Furthermore, system dynamics approaches focus on understanding the relationship between the structure of a system and the resulting dynamic behaviors generated through multiple interacting feedback loops. Such an approach could be invaluable in studying dynamic problems arising in complex health, social, economic, or ecological systems. ResultsFor the purpose of the proposal, the following stages are planned:1. Develop a system dynamics simulation model at individual level that predicts the Alzheimer’s disease incidence over the life course, and aggregates individual level models to predict population level trends 2. Calibrate the resulting simulation model based upon longitudinal data trends employed from Alzheimer's Disease Neuroimaging Initiative (ADNI) database. Both cohorts with Alzheimer’s disease and control subjects from this database will be used to fine-tune the simulation model. ConclusionThe final validated model would be used to test different hypotheses and evaluate various strategies and/or their combinations to help evaluate the efficacy of prevention strategies on Alzheimer’s disease incidence and its growth.


2021 ◽  
Vol 17 (7) ◽  
pp. e1009114
Author(s):  
Michael R. Lindstrom ◽  
Manuel B. Chavez ◽  
Elijah A. Gross-Sable ◽  
Eric Y. Hayden ◽  
David B. Teplow

Oligomers of the amyloid β-protein (Aβ) have been implicated in the pathogenesis of Alzheimer’s disease (AD) through their toxicity towards neurons. Understanding the process of oligomerization may contribute to the development of therapeutic agents, but this has been difficult due to the complexity of oligomerization and the metastability of the oligomers thus formed. To understand the kinetics of oligomer formation, and how that relates to the progression of AD, we developed models of the oligomerization process. Here, we use experimental data from cell viability assays and proxies for rate constants involved in monomer-dimer-trimer kinetics to develop a simple mathematical model linking Aβ assembly to oligomer-induced neuronal degeneration. This model recapitulates the rapid growth of disease incidence with age. It does so through incorporation of age-dependent changes in rates of Aβ monomer production and elimination. The model also describes clinical progression in genetic forms of AD (e.g., Down’s syndrome), changes in hippocampal volume, AD risk after traumatic brain injury, and spatial spreading of the disease due to foci in which Aβ production is elevated. Continued incorporation of clinical and basic science data into the current model will make it an increasingly relevant model system for doing theoretical calculations that are not feasible in biological systems. In addition, terms in the model that have particularly large effects are likely to be especially useful therapeutic targets.


2014 ◽  
Vol 10 ◽  
pp. P296-P297 ◽  
Author(s):  
Sujuan Gao ◽  
Adesola Ogunniyi ◽  
Kathleen Steele Hall ◽  
Olesegun Baiyewu ◽  
Frederick Unverzagt ◽  
...  

2007 ◽  
Vol 3 (3S_Part_3) ◽  
pp. S168-S169 ◽  
Author(s):  
Kathryn Ziegler-Graham ◽  
Ron Brookmeyer ◽  
Elizabeth Johnson ◽  
H. Michael Arrighi

2021 ◽  
Vol 30 (1) ◽  
pp. 35-61
Author(s):  
Daniel R Baer ◽  
Andrew B Lawson ◽  
Jane E Joseph

Alzheimer’s disease is an increasingly prevalent neurological disorder with no effective therapies. Thus, there is a need to characterize the progression of Alzheimer’s disease risk in order to preclude its inception in patients. Characterizing Alzheimer’s disease risk can be accomplished at the population-level by the space–time modeling of Alzheimer’s disease incidence data. In this paper, we develop flexible Bayesian hierarchical models which can borrow risk information from conditions antecedent to Alzheimer’s disease, such as mild cognitive impairment, in an effort to better characterize Alzheimer’s disease risk over space and time. From an application of these models to real-world Alzheimer’s disease and mild cognitive impairment spatiotemporal incidence data, we found that our novel models provided improved model goodness of fit, and via a simulation study, we demonstrated the importance of diagnosing the label-switching problem for our models as well as the importance of model specification in order to best capture the contribution of time in modeling Alzheimer’s disease risk.


Sign in / Sign up

Export Citation Format

Share Document