New thinking about thinking

This issue of Alzheimer's & Dementia presents the meeting report [1] of the inaugural Leon Thal Symposium on the Prevention of Dementia (LTS), convened by the Lou Ruvo Brain Institute on December 3–4, 2007 in Las Vegas, Nevada. The meeting served not only as a tribute to Dr Leon Thal's extraordinary career as a clinician, researcher, teacher, and mentor but also to showcase his dream of developing therapies to prevent dementia.

The symposium sought to facilitate discussions of ways to change the current paradigm for dementia therapy development. The recommendations in this report, a work in progress, are the result of the think-tank style deliberations on what needs to be done to accelerate the process of discovery, development, and validation of treatments for dementia prevention. The meeting examined such questions as what are some of the major barriers to progress, do we have the right target, are current study designs and analytical methods adequate or appropriate for prevention trials, are there any changes in public laws governing drug development and/or patents that would accelerate the process.

The symposium brought together many of the world's leading dementia researchers to discuss the various scientific, economic, and regulatory barriers that stymie development of preventive therapies. The report identifies the need to demonstrate efficacy for therapies targeting disease pathogenesis and the absence of validated biomarkers as important scientific hurdles. Other recommendations include modifying the present National Institutes of Health grants review process to support long-term or high-risk projects, the need to increase the efficiency and capacity of integrated clinical trial networks, and the consequences to Alzheimer's disease (AD) patient clinical care efforts as a result of poor Medicare and other third-party reimbursement. The report discusses potential economic incentives to stimulate therapy development such as a commitment from the Center for Medicare and Medicaid Services to make subjects recruited for longitudinal and other AD research studies eligible for reimbursement. Suggestions are also presented for modification of current patent protection laws. Finally, the report notes that “overcoming any of these scientific, structural, economic, and social barriers will require commitment not only from the AD research community but from the public as well.”

The recommendations proposed by this report are not new or complete. Thirty years ago, Ernest Gruenberg asked, “can't we find new ways to encourage research which will emphasize chronic disease prevention?” [2]. In 1992, the editor-in-chief of this Journal proposed the “The Five-Five, Ten-Ten Plan for Alzheimer's Disease” [3] to mobilize national resources toward the goals of disease-modifying treatments and prevention.

Although central governments across the planet have sponsored initiatives and programs on various forms of interventions, the pace of progress has not been satisfactory. If current optimistic projections of efficacy for investigational drugs prove incorrect, then there is a real possibility for at-risk baby boomers to lack new treatments that are more effective than those available to their parents' generation. Even with the publication of this report, there is a clear need for a reiterative examination of our current assumptions and paradigms for therapy development.

Readers of Alzheimer's & Dementia should be aware that this report represents a starting point for crafting a road map forward. During the coming months, organizers for the 2008 LTS will incorporate alternative perspectives and important criticisms that will be published in future issues of the Journal. To further refine and expand the recommendations presented in this inaugural report, the Lou Ruvo Brain Institute will reconvene the LTS on December 7–9, 2008 in Las Vegas, Nevada.