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Alzheimer Disease Investigators Develop ‘Roadmap’ for Preventing Dementia


doi: 10.1097/01.NT.0000333574.11857.05

Dozens of Alzheimer disease (AD) experts have devised a roadmap for the prevention of dementia that calls for major changes in the way new drugs are developed and tested.

Their recommendations were developed at a meeting late last year that drew leaders in the field from universities, government, the pharmaceutical industry, federal administrators, and representatives from AD organizations.

It was a novel think-tank group with a mission to figure out new targets for drug development, barriers to developing preventions, and problems with current methods of financing clinical trials. The goal is to develop recommendations that they can eventually take to Congress for funding support.

Zaven S. Khachaturian, PhD, formerly of the National Institute on Aging and director of the Lou Ruvo Brain Institute in Las Vegas, held the meeting in honor of Leon Thal, MD, one of the pioneers in Alzheimer therapy research who died in a plane crash last year.

“We have the tools to identify Alzheimer disease earlier,” Dr. Khachaturian said. “We need to understand the barriers to therapy development and shift towards prevention.”

“These recommendations will help move the field forward,” said Dr. Khachaturian. “We need to stimulate dialogue on a national level,” Dr. Khachaturian added. (See “A Road Map on Dementia Prevention: Recommendations.”)

In the May issue of Alzheimer's & Dementia, several scientists posited views on where this roadmap should take the field in the next decade. The AD investigators agreed that there needs to be a new crop of ideas if the strategies now on the table don't pan out.

Ronald C. Petersen, MD, PhD, professor of neurology at the Mayo Clinic and director of its Alzheimer's Disease Research Center in Rochester, MN, said: “We don't have the ‘cholesterol’ for Alzheimer disease. The field needs good biomarkers to identify patients as early as possible and provide them with ways to halt the disease, or if not, have markers to follow disease progression and response to treatment. We can't wait for the cardiovascular approach to pan out.”

The hope is that this roadmap will point scientists and policy makers in the right direction to develop the tools necessary to identify the disease before symptoms ever begin.

Some of the roadblocks are obvious and seem insurmountable. Pharmaceutical companies have the money to develop drugs but patent issues make it risky to develop and test preventive medicines.

Dr. Petersen and the team that drafted the recommendations say that the FDA will have to rethink the way medicines are tested and approved. The FDA does not have provisions in place to study experimental medicines for people who have biological signs of disease but no symptoms. They also said that there needs to be a large trial following thousands of normal older people over a long period of time, much like the cardiovascular epidemiological studies have done to find risk factors and ways to prevent illness.

Peter J. Snyder, PhD, professor of clinical neuropsychology and cognitive neuroscience at the University of Connecticut said that investigators may also have to reconsider how clinical trials are carried out. Right now, two-thirds of the patients treated in memory clinics around the country are not signing on for any clinical trials. “When patients are first diagnosed, symptoms are bothersome but not burdensome yet. They don't understand that they need to be part of the research process if scientists are to figure out ways to stop this disease.”



“This is not an easy disease to tackle,” said Paul S. Aisen, MD, professor of neurology at the University of California-San Diego and director of the Alzheimer's Disease Cooperative Study. “We need ways to measure cognitive progression and define markers of the pathology.”

The group agreed that the field is transitioning from symptomatic relief to prevention and disease-modifying strategies, but there is just not enough information known about the targets for prevention. “We need to diversify on many levels,” added Dr. Khachaturian. “We don't have enough targets to develop good preventions, and we need to encourage investment into prevention strategies. We need to get beyond the current theories and foster new ideas.”

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A national think tank drawing representatives from industry, academia, and patient advocacy groups has developed recommendations to foster prevention strategies for Alzheimer disease and dementia.

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The ‘roadmap’ identifies these among other recommendations:

  • Substantially increase the pipeline of therapies targeting the pathogenic mechanism
  • Demonstrate the efficacy of compounds designed to modify, slow, or stop the pathogenesis of the disease
  • Discover and validate early biomarkers in the prodromal stages of the disease
  • Modify the NIH current grant review process to support long-term or high-risk projects
  • Increase the efficiency and capacity of integrated clinical trial networks
  • Evaluate the consequences of poor [or lack of] Medicare and other third-party reimbursements on prevention trials and clinical care for dementia patients
  • Assess potential economic incentives [such as a commitment from The Center of Medicare and Medicaid Services to make subjects in longitudinal prevention studies eligible for reimbursement] to stimulate therapy development for prevention
  • Amend current patent protection laws, as an incentive for investment and promotion of therapies for prevention
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• Khachaturian ZS, Petersen RC, Khachaturian S, et al. A roadmap for the prevention of dementia: The inaugural Leon Thal symposium. Alzheimer's Dementia 2008;4(3):156–163.
    ©2008 American Academy of Neurology