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Reisa A Sperling,
Paul S Aisen,
Laurel A Beckett,
David A Bennett,
Suzanne Craft,
Anne M Fagan,
Takeshi Iwatsubo,
Clifford R Jack,
Jeffrey Kaye,
Thomas J Montine, [......],
Eric M Reiman,
Christopher C Rowe,
Eric Siemers,
Yaakov Stern,
Kristine Yaffe,
Maria C Carrillo,
Bill Thies, Marcelle Morrison-Bogorad,
Molly V Wagster,
Creighton H Phelps
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ABSTRACT: The pathophysiological process of Alzheimer's disease (AD) is thought to begin many years before the diagnosis of AD dementia. This long "preclinical" phase of AD would provide a critical opportunity for therapeutic intervention; however, we need to further elucidate the link between the pathological cascade of AD and the emergence of clinical symptoms. The National Institute on Aging and the Alzheimer's Association convened an international workgroup to review the biomarker, epidemiological, and neuropsychological evidence, and to develop recommendations to determine the factors which best predict the risk of progression from "normal" cognition to mild cognitive impairment and AD dementia. We propose a conceptual framework and operational research criteria, based on the prevailing scientific evidence to date, to test and refine these models with longitudinal clinical research studies. These recommendations are solely intended for research purposes and do not have any clinical implications at this time. It is hoped that these recommendations will provide a common rubric to advance the study of preclinical AD, and ultimately, aid the field in moving toward earlier intervention at a stage of AD when some disease-modifying therapies may be most efficacious.
Alzheimer's & dementia: the journal of the Alzheimer's Association 05/2011; 7(3):280-92. · 5.90 Impact Factor
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Zaven S Khachaturian,
Deborah Barnes,
Richard Einstein,
Sterling Johnson,
Virginia Lee,
Allen Roses,
Mark A Sager,
William R Shankle,
Peter J Snyder,
Ronald C Petersen, [......],
Creighton Phelps,
Eric Reiman,
Marwan Sabbagh,
Mary Sano,
Lon S Schneider,
Eric Siemers,
Pierre Tariot,
Jacques Touchon,
Bruno Vellas,
Lisa J Bain
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ABSTRACT: Among the major impediments to the design of clinical trials for the prevention of Alzheimer's disease (AD), the most critical is the lack of validated biomarkers, assessment tools, and algorithms that would facilitate identification of asymptomatic individuals with elevated risk who might be recruited as study volunteers. Thus, the Leon Thal Symposium 2009 (LTS'09), on October 27-28, 2009 in Las Vegas, Nevada, was convened to explore strategies to surmount the barriers in designing a multisite, comparative study to evaluate and validate various approaches for detecting and selecting asymptomatic people at risk for cognitive disorders/dementia. The deliberations of LTS'09 included presentations and reviews of different approaches (algorithms, biomarkers, or measures) for identifying asymptomatic individuals at elevated risk for AD who would be candidates for longitudinal or prevention studies. The key nested recommendations of LTS'09 included: (1) establishment of a National Database for Longitudinal Studies as a shared research core resource; (2) launch of a large collaborative study that will compare multiple screening approaches and biomarkers to determine the best method for identifying asymptomatic people at risk for AD; (3) initiation of a Global Database that extends the concept of the National Database for Longitudinal Studies for longitudinal studies beyond the United States; and (4) development of an educational campaign that will address public misconceptions about AD and promote healthy brain aging.
Alzheimer's & dementia: the journal of the Alzheimer's Association 03/2010; 6(2):89-97. · 5.90 Impact Factor
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Alzheimer's & dementia: the journal of the Alzheimer's Association 11/2008; 4(6):443-6. · 5.90 Impact Factor
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Zaven S Khachaturian,
Ronald C Petersen,
Serge Gauthier,
Neil Buckholtz,
Jodey P Corey-Bloom,
Bill Evans,
Howard Fillit,
Norman Foster,
Barry Greenberg,
Michael Grundman, [......],
Paul S Aisen,
John C S Breitner,
Jeffrey L Cummings,
Claudia Kawas,
Creighton Phelps,
Judes Poirier,
Marwan Sabbagh,
Jacques Touchon,
Ara S Khachaturian,
Lisa J Bain
Alzheimer's & dementia: the journal of the Alzheimer's Association 05/2008; 4(3):156-63. · 5.90 Impact Factor
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ABSTRACT: The public Alzheimer's disease (AD) research enterprise began in earnest in the mid-1970s with the creation by Congress of the National Institute on Aging at the National Institutes of Health. Today, AD research is a maturing field of study, with federal effort seeking to encourage the creativity and insights of individual investigators, and targeting special areas for emphasis. It is inspired by the legacy of our friend and colleague Leon Thal, whose innovative and collaborative approach to scientific research serves as a guidepost as we move toward the discovery of new and effective ways to prevent AD or slow its progression. This article describes the progress to date and potentially promising areas of study from the vantage point of the National Institute on Aging.
Alzheimer's & dementia: the journal of the Alzheimer's Association 01/2008; 4(1 Suppl 1):S37-47. · 5.90 Impact Factor
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Alzheimer's & dementia: the journal of the Alzheimer's Association 05/2007; 3(2 Suppl):S80-5. · 5.90 Impact Factor
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ABSTRACT: Advances in understanding aging processes and their consequences are leading to the development of therapies to slow or reverse adverse changes formerly considered to be "normal" aging and processes that underlie multiple age-related conditions. Estimating the effectiveness of candidate aging therapies, whose effects on human aging may require many years to determine, is a particular challenge. Strategies for identifying candidate interventions can be developed through multiple approaches, including the screening of molecular targets and pathways in vitro and in animal models, informed as well by evidence from human genetic and epidemiologic data. A number of recently established programs and networks can serve as resources for such research. For all these research approaches, from in vitro molecular studies to clinical trials, contributions of cell and molecular biology are crucial and offer the prospect of therapeutic advances that address fundamental biological processes as well as the clinically important challenges of aging.
Cell 03/2005; 120(4):557-67. · 32.40 Impact Factor
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ABSTRACT: Once considered a rare disorder, Alzheimer disease (AD) is now recognized as a major public health problem. In more than 90% of cases, AD develops after the age of 65 years (late-onset AD), with its prevalence doubling with every successive decade of life. There are cases of early-onset AD in which onset can range from the fourth decade of life until age 65 years, although these are much more rare. Despite these differences in age of onset, the clinical signature of the disease, as well as the neuropathology, is very similar in all cases. It is estimated that AD currently afflicts approximately 4 million Americans and that it occurs in nearly half of people aged 85 years and older. In addition, AD has a profound effect on the millions of spouses, relatives, and friends who make up the extensive informal network of those who provide care for people with this
JAMA The Journal of the American Medical Association 277(10):837-840. · 30.03 Impact Factor
