Advancing Alzheimer's disease diagnosis, treatment, and care: Recommendations from the Ware Invitational Summit

Institute on Aging, University of Pennsylvania, Philadelphia, PA, USA
Alzheimer's & dementia: the journal of the Alzheimer's Association (Impact Factor: 12.41). 09/2012; 8(5):445-52. DOI: 10.1016/j.jalz.2012.08.001
Source: PubMed


To address the pending public health crisis due to Alzheimer's disease (AD) and related neurodegenerative disorders, the Marian S. Ware Alzheimer Program at the University of Pennsylvania held a meeting entitled "State of the Science Conference on the Advancement of Alzheimer's Diagnosis, Treatment and Care," on June 21-22, 2012. The meeting comprised four workgroups focusing on Biomarkers; Clinical Care and Health Services Research; Drug Development; and Health Economics, Policy, and Ethics. The workgroups shared, discussed, and compiled an integrated set of priorities, recommendations, and action plans, which are presented in this article.

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    • "13.8 million Americans will be afflicted with AD dementia by the year 2050, with healthcare costs for them costing $1.2 trillion [3]. There is consequently an urgent need for development of novel treatments of AD within the next decade [12]. Among the most promising of those now in development target brain insulin resistance (i.e., reduced neuronal responsiveness to extracellular insulin), which is an early, common, and major feature in AD cases with and without diabetes [13] [14]. "
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    ABSTRACT: Alzheimer's disease (AD) is an age-related neurodegenerative disease leading over the course of decades to the most common form of dementia. Many of its pathologic features and cognitive deficits may be due in part to brain insulin resistance recently demonstrated in the insulin receptor→insulin receptor substrate-1 (IRS-1) signaling pathway. The proximal cause of such resistance in AD dementia and amnestic mild cognitive impairment (aMCI) appears to be serine inhibition of IRS-1, a phenomenon likely due to microglial release of inflammatory cytokines triggered by oligomeric Aβ. Studies on animal models of AD and on human brain tissue from MCI cases at high risk of AD dementia have shown that brain insulin resistance and many other pathologic features and symptoms of AD may be greatly reduced or even reversed by treatment with FDA-approved glucagon-like peptide-1 (GLP-1) analogs such as liraglutide (Victoza). These findings call attention to the need for further basic, translational, and clinical studies on GLP-1 analogs as promising AD therapeutics.
    Full-text · Article · Feb 2014 · Alzheimer's & dementia: the journal of the Alzheimer's Association
    • "Aging society coupled with increasing incidence and prevalence of dementia (Fendrich and Hoffmann, 2007; Hampel et al., 2011) is a major challenge for the German healthcare system. Since causal treatment of dementia is still out of sight, there is a considerable need for new and more effective ways of dementia care to address the impending healthcare crisis (Naylor et al., 2012). "
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    ABSTRACT: Background: Increasing prevalence of dementia is a major challenge for the German healthcare system. The study DelpHi-MV (“Dementia: life- and person-centered help in Mecklenburg-Western Pomerania”) aims to implement and evaluate an innovative subsidiary support system for persons with dementia (PwDs) living at home and their caregivers. Methods: DelpHi-MV is a GP-based cluster randomized controlled intervention trial. DelpHi-Intervention aims to provide “optimum care” by integrating multi-professional and multimodal strategies to individualize and optimize treatment of dementia within the framework of the established healthcare and social service system. The intervention is conducted by Dementia Care Managers (DCMs) – nurses with dementia-specific training – at the people's homes. Based on German guidelines for evidence-based diagnoses and treatment of dementia, a comprehensive set of 95 intervention modules – the “DelpHi-Standard” – was defined. Each module consists of predefined trigger condition(s), a subsequent intervention task, as well as at least one criterion for its completion. The intervention begins with a comprehensive assessment of the care situation, needs, and resources. The DCM develops and implements an intervention plan tailored to the individual conditions in close cooperation with the GP. Expected Results and Conclusions: We expect statistically significant differences between control and intervention group in primary outcomes (quality of life, behavioral and psychological symptoms of dementia, pharmacotherapy, caregiver burden). Results can provide evidence for the effectiveness and efficacy of dementia care management according to the “Delphi-Standard” – prerequisites for implementing this concept into routine healthcare.
    Preview · Article · Oct 2013 · International Psychogeriatrics
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    • "It is therefore difficult to make sub-groups according to symptomatology, progression, and biomarkers. This is a serious drawback for the design of clinical trials and the development of new criteria, except perhaps those that rely solely on the presence of Aβ (Naylor et al., 2012). "
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    ABSTRACT: Alzheimer's disease (AD) is the most common form of dementia. Its most important pathological hallmarks are profound neuronal loss, presence of intracellular neurofibrillary tangles, and extracellular deposition of beta-amyloid protein (Aβ) as beta-amyloid plaques. One of the most important risk factors for AD is age and with the increase of life-expectancy AD has become the most common form of dementia. The current "Holy Grail" is to be able to diagnose variants of AD before they manifest clinically and before irreparable brain damage is done. To be able to do so, we need robust and reliable biomarkers which reflect the pathogenesis of AD. This is essential because such biomarkers might indicate pathways that could be targeted for interventions aiming at disease prevention or amelioration. Although much attention has been focused on Aβ in this respect, it may not be as attractive a target as thought if current doubts concerning its causative role are substantiated. This review will be in two parts, the first part dealt with the current clinical knowledge and the questions raised by the Aβ cascade hypothesis in the pathogenesis of AD and this second part aims to synthesize our current knowledge and new data suggesting how immunity may contribute to the development of AD and may itself be targeted in future treatments.
    Full-text · Article · Feb 2013 · Discovery medicine
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