A roadmap for the prevention of dementia II: Leon Thal Symposium 2008.
ABSTRACT This document proposes an array of recommendations for a National Plan of Action to accelerate the discovery and development of therapies to delay or prevent the onset of disabling symptoms of Alzheimer's disease. A number of key scientific and public-policy needs identified in this document will be incorporated by the Alzheimer Study Group into a broader National Alzheimer's Strategic Plan, which will be presented to the 111th Congress and the Obama administration in March 2009. The Alzheimer's Strategic Plan is expected to include additional recommendations for governance, family support, healthcare, and delivery of social services.
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ABSTRACT: The development of disease-modifying treatments for Alzheimer's disease (AD) faces a number of barriers. Among these are the lack of surrogate biomarkers, the exceptional size and duration of clinical trials, difficulties in identifying appropriate populations for clinical trials, and the limitations of monotherapies in addressing such a complex multifactorial disease. This study sets out to first estimate the consequent impact on the expected cost of developing disease-modifying treatments for AD and then to estimate the potential benefits of bringing together industry, academic, and government stakeholders to co-invest in, for example, developing better biomarkers and cognitive assessment tools, building out advanced registries and clinical trial-readiness cohorts, and establishing clinical trial platforms to investigate combinations of candidate drugs and biomarkers from the portfolios of multiple companies. Estimates based on interviews with experts on AD research and development suggest that the cost of one new drug is now $5.7 billion (95% confidence interval (CI) $3.7–9.5 billion) and could be reduced to $2.0 billion (95% CI $1.5–2.9 billion). The associated acceleration in the arrival of disease-modifying treatments could reduce the number of case years of dementia by 7.0 million (95% CI 4.4–9.4 million) in the United States from 2025 through 2040.Annals of the New York Academy of Sciences 03/2014; DOI:10.1111/nyas.12417 · 4.31 Impact Factor
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ABSTRACT: The amyloid β (Aβ) and tau proteins, which misfold, aggregate, and accumulate in the Alzheimer's disease (AD) brain, are implicated as central factors in a complex neurodegenerative cascade. Studies of mutations that cause early onset AD and promote Aβ accumulation in the brain strongly support the notion that inhibiting Aβ aggregation will prevent AD. Similarly, genetic studies of frontotemporal dementia with parkinsonism linked to chromosome 17 (FTDP-17 MAPT) showing that mutations in the MAPT gene encoding tau lead to abnormal tau accumulation and neurodegeneration. Such genetic studies clearly show that tau dysfunction and aggregation can be central to neurodegeneration, however, most likely in a secondary fashion in relation to AD. Additional pathologic, biochemical, and modeling studies further support the concept that Aβ and tau are prime targets for disease modifying therapies in AD. Treatment strategies aimed at preventing the aggregation and accumulation of Aβ, tau, or both proteins should therefore be theoretically possible, assuming that treatment can be initiated before either irreversible damage is present or downstream, self-sustaining, pathological cascades have been initiated. Herein, we will review recent advances and also potential setbacks with respect to the myriad of therapeutic strategies that are designed to slow down, prevent, or clear the accumulation of either “pathological” Aβ or tau. We will also discuss the need for thoughtful prioritization with respect to clinical development of the preclinically validated modifiers of Aβ and tau pathology. The current number of candidate therapies targeting Aβ is becoming so large that a triage process is clearly needed to insure that resources are invested in a way such that the best candidates for disease modifying therapy are rapidly moved toward clinical trials. Finally, we will discuss the challenges for an appropriate “triage” after potential disease modifying therapies targeting tau and Aβ have entered clinical trials.Experimental Neurology 06/2010; 223(2):252-266. DOI:10.1016/j.expneurol.2009.07.035 · 4.62 Impact Factor
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ABSTRACT: The Cleveland Clinic Lou Ruvo Center for Brain Health (LRCBH) is a unique clinical and translational research enterprise that stems from the passion of Larry Ruvo to honor his father, Lou, a victim of Alzheimer's disease (AD). To attract national attention to AD, Mr. Ruvo convinced architect Frank Gehry to construct the remarkable building complex of the LRCBH in Las Vegas, Nevada. Cleveland Clinic assumed responsibility for running the clinical and research aspects of the LRCBH. The care provided in this novel architectural setting is innovative and emphasizes patients first, care with integration of caregiver programs, and clinical research opportunities. Standardization of care, outcomes measures, and process metrics provide a platform for assessing, studying, and exporting best practices in cognitive care. Clinical trials empower patients to help solve the diseases that afflict them. The combination of a passionate founder, dramatic architecture, clinical excellence, integrated care partner programs, and commitment to development of next generation treatments makes the LRCBH a unique model of integrated care and research.Journal of Alzheimer's disease: JAD 08/2013; 38(1). DOI:10.3233/JAD-130791 · 3.61 Impact Factor