After 30 years of intensive study, momentum in AD research is palpable. Today, scientists are increasingly optimistic about the promise of AD research. Initially, they focused on defining the major characteristics of the disease, its course, and aspects of its etiology. Since then, they have built an enormous base of knowledge about AD and the many factors that contribute to the damage it causes to the brain and body. Researchers are now beginning to apply that knowledge to treatment and prevention strategies. To sustain this momentum, NIH is moving ahead on a number of fronts, described in the sections below.
Improving Basic Understanding
Research must continue to refine the mechanistic understanding of AD. Though we understand much about the disease, important gaps in knowledge remain. Basic research is central to the search for effective new therapies because it allows scientists to understand better the normal biology of the aging brain and what goes wrong in a disease like AD. One promising area of basic research involves studies to learn more about the molecular basis of cognition and how it changes with age. Another area of interest is how the brain adapts to injury. Researchers know that the brain is a remarkably adaptive organ, and they want to learn more about the components that are important to adaptability, the molecular basis of cognitive reserve, and whether strategies to build cognitive reserve can prevent or delay the negative consequences of AD pathology. The Cognitive Aging Summit sponsored by NIA and the McKnight Brain Research Foundation in Washington, D.C., in October 2007 helped identify topics in these areas of basic research that are most likely to bear fruit.
Identifying Genetic Causes and Risk Factors
With the establishment of the Alzheimer’s Disease Genetics Initiative and the Alzheimer’s Disease Genetics Consortium, scientists hope to learn considerably more about the major risk-factor genes for late-onset AD and for cognitive decline. Understanding more about the genetics of cognitive decline and AD will shed light on how much genetic risk they share. Knowing the risk-factor genes will help to pinpoint new pathways that contribute to the early development of AD and to identify people at the greatest genetic risk of cognitive decline or AD.
Understanding Disease Progression
Findings from the Alzheimer’s Disease Neuroimaging Initiative reported over the next few years will likely indicate which combinations of clinical, neuropsychological, imaging, and biomarker tests best predict who will progress from aMCI to AD and how this progression occurs. Improved knowledge in this area also will help accelerate and refine the conduct of clinical trials. A greater understanding of disease progression will eventually allow clinicians to start therapies much earlier in the disease process, when changes in the brain associated with AD are still minimal.
Making the Most of Translational Research and Clinical Trials
Translational initiatives and federally supported clinical trials should provide important new approaches for AD prevention and treatment because they will ensure that researchers with promising therapies have opportunities to develop them. Many compounds that test well in animal models and that have a sound theoretical basis fail in clinical trials because of safety or efficacy problems. It is important to understand why this happens. Many different therapeutic targets must be pursued besides the obvious ones of beta-amyloid and tau.
By funding clinical trials, NIA also hopes to provide the necessary foundation for private industry or NIH to support “follow-up” clinical studies of the most promising leads.
Cultivating Research Infrastructure and Resources
NIH will continue to provide the framework through which investigators can conduct interdisciplinary and collaborative AD research. For example, in 1999, NIA established the National Alzheimer’s Coordinating Center (NACC) (www.alz.washington.edu) so that data on healthy people and patients from the Alzheimer’s Disease Centers could be pooled and shared. By 2005, information on more than 75,000 Alzheimer’s Disease Center study participants and neuropathologic data on more than 9,000 brains from autopsied participants had been collected. Much of this material is available for research by qualified scientists.
In 2006, NACC launched the Alzheimer’s Disease Center Uniform Data Set (UDS), a system that improved upon a previous data collection system by standardizing data collection across research sites. Initially developed to gather information on healthy participants and those with aMCI and early AD, the UDS has since expanded to collect data on participants with frontotemporal dementia, Lewy body dementia, and vascular dementia. More than 15,000 individuals are now being evaluated using the UDS. Data are available to qualified researchers through NACC.
Workshops and meetings, such as the AD Planning Meeting held in October 2006 and the Cognitive Aging Summit held in October 2007, provide an opportunity for experts to gather and assess basic, translational, and clinical research efforts and to assess future strategies for maximizing public investment.
NIA and other NIH Institutes and Centers that conduct research on AD collaborate with many others to push the boundaries of our knowledge about this disease. For example, the Institutes work with the Foundation for the National Institutes of Health to identify appropriate funding opportunities with private industry. NIA collaborates with private foundations, such as the Alzheimer’s Association and the Alzheimer’s Drug Discovery Foundation, on specific initiatives. NIA has worked with both organizations on the Alzheimer’s Disease Neuroimaging Initiative through the Foundation for the National Institutes of Health and with the AD Discovery Foundation on translational research projects. NIH scientists also work with colleagues at the Centers for Disease Control and Prevention, the FDA, and other Federal agencies to ensure expeditious efforts to find the best combinations of behavioral and drug interventions for AD and age-related cognitive decline.
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