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De La Torre J.C.,Banner Sun Health Research Institute
Neurodegenerative Diseases | Year: 2010

The vascular hypothesis of Alzheimer's disease (AD) which we first proposed in 1993, has become a useful concept in identifying vascular risk factors for AD or vascular dementia that can be modified through appropriate treatment to prevent, reduce or delay the onset of cognitive impairment and dementia onset. Among the more than two dozen vascular risk factors already identified for AD, are cardiovascular disease and carotid artery atherosclerosis, which may exert their pathology by chronically lowering cerebral hypoperfusion during aging. We propose and plan to initiate a clinical study to screen middle-aged, cognitively intact individuals, with carotid artery ultrasound and echocardiography to identify potentially progressive pathology in the heart and carotid artery that is considered modifiable with optimal medical treatment. This clinical strategy, if found effective in preventing pathologic conditions suspected of contributing to severe cognitive impairment, could significantly reduce AD prevalence if applied on a wide scale and help promote healthier mental and physical aging while providing a compelling economic benefit to society. Copyright © 2010 S. Karger AG, Basel. Source

Lue L.-F.,Santa Fe Institute | Kuo Y.-M.,National Cheng Kung University | Beach T.,Civin Laboratory of Neuropathology | Walker D.G.,Banner Sun Health Research Institute
Molecular Neurobiology | Year: 2010

Inflammatory regulators, including endogenous anti-inflammatory systems, can down-regulate inflammation thus providing negative feedback. Chronic inflammation can result from imbalance between levels of inflammatory mediators and regulators during immune responses. As a consequence, there are heightened inflammatory responses and irreversible tissue damage associated with many age-related chronic diseases. Alzheimer's disease (AD) brain is marked by prominent inflammatory features, in which microglial activation is the driving force for the elaboration of an inflammatory cascade. How the regulation of inflammation loses its effectiveness during AD pathogenesis remains largely unclear. In this article, we will first review current knowledge of microglial activation and its association with AD pathology. We then discuss four examples of anti-inflammatory systems that could play a role in regulating microglial activation: CD200/CD200 receptor, vitamin D receptor, peroxisome proliferatoractivated receptors, and soluble receptor for advanced glycation end products. Through this, we hope to illustrate the diverse aspects of inflammatory regulatory systems in brain and neurodegenerative diseases such as AD. We also propose the importance of neuronal defense systems, because they are part of the integral inflammatory and antiinflammatory systems. Augmenting the anti-inflammatory defenses of neurons can be included in the strategy for restoration of balanced immune responses during aging and neurodegenerative diseases. © 2010 Springer Science+Business Media, LLC. Source

Sabbagh M.,Banner Sun Health Research Institute | Edgin J.,University of Arizona
Current Alzheimer Research | Year: 2016

Down syndrome is an intellectual disability requiring periodic monitoring of cognition given the near universal presence of Alzheimer’s Disease related neuropathology and high rates of dementia in middle adulthood. We review current approaches to detecting decline in this population, including informant-based measures, dementia screening tools, and neuroimaging techniques. The challenges for detecting decline in this group are discussed, including the need to take into account premorbid cognitive function as well as medical comorbidity. © 2016 Bentham Science Publishers. Source

De La Torre J.C.,Banner Sun Health Research Institute
Journal of Alzheimer's Disease | Year: 2011

Two centuries ago, the German bacteriologist Robert Koch proposed three postulates to support a causal relationship between a specific microbe and an infectious disease. Similarly, three postulates are formulated here to help evaluate hypothetical proposals attempting to explain the pathogenesis of Alzheimer's disease (AD). The first postulate requires that the cause of AD precedes the cognitive decline and neurodegenerative pathology that characterize AD. This rule identifies a primary event from a neuropathological effect generated by the disease process. The second postulate stipulates that interventions aimed at the proposed causal event should prevent or reverse the cognitive and neurodegenerative pathology associated with AD prior to disease onset. This postulate emphasizes prevention or reversal of emerging neurocognitive pathology considerably before AD onset. If the first and second postulate requirements are met, the third postulate follows that interventions targeting the causal event should significantly lower the incidence of AD. For a causal hypothesis to be considered "likely" pathogenic to AD, support from all three postulates is a requisite. The pragmatic potential of the three postulates was applied to seven proposals using evidence-based meta-analysis mainly from randomized controlled trials. Proposals included the amyloid-β, cell cycle, cholinergic, inflammatory, oxidative stress, tau, and vascular hypotheses. Clinical evidence derived from each proposal formed the basis for an inferential conclusion based on the level of confidence provided by the trial data. The three postulates may challenge or help validate a proposed cause-effect relationship to AD and serve as a useful model for designing more intelligent therapeutic interventions aimed at preventing AD. © 2011 IOS Press and the authors. All rights reserved. Source

De La Torre J.C.,Banner Sun Health Research Institute
Journal of Alzheimer's Disease | Year: 2010

The dramatic rising incidence and costs of Alzheimer's disease (AD) require that research efforts and funding be primarily directed on either finding a cure or applying preventive measures to curb this disorder. A cure for AD appears unlikely when significant cognitive loss has occurred because the neuronal networks that controlled the perturbed cognitive abilities are either dead or irreversibly damaged and replacing them, even if it were technically possible, would not reconstruct the intellectual identity of the host. Prevention of risk factors to sporadic AD is a more realistic stratagem and treatment, when indicated, ideally should begin in cognitively intact individuals as part of a mass screening effort. Prevention of modifiable risk factors to AD is cost-effective because it reduces hospice or hospital stay, repeated doctor visits, and long-term care. Presently, neurocognitive and neuroimaging tests are used with partial success in identifying persons at higher risk of AD but these tests can not pinpoint either a cause or a specific intervention that could attenuate disease progress. We previously proposed that carotid artery ultrasound +echocardiography together with ankle-brachail index (CAUSE+ABI) as mass screening tests in asymptomatic persons could detect not only cardio-cerebrovascular risk factors to AD, but also identify an indicated intervention. CAUSE+ABI are simple to perform, cost-effective, non-invasive, and reasonably accurate for the intended purpose. Additionally, detection of cardio-cerebrovasacular abnormalities long before expression of cognitive deterioration allows higher success rate with earlier treatment. Evidence-based medicine is recommended for optimizing clinical decision-making in evaluating AD risk factors and their treatment. © 2010 - IOS Press and the authors. Source

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