Will New Funding Improve Alzheimer’s Dementia Outcomes?

Alzheimer dementia mortality is increasing in the United States, while heart disease and cancer death rates have decreased at least 25% recently.1  New cardiac and cancer treatments frequently make headlines.  However, the assessment of Alzheimer’s therapy is stark: “…there are currently no treatments that change the course of this progressive brain disorder,” [original italics] so stated in the 2014-2015 Alzheimer Disease Progress Report by the National Institute of Aging (NIA).2

President Obama signed the National Alzheimer’s Project Act in 2011, with a goal of having effective therapy by 2025.  Now five years later, lists fewer than 120 Alzheimer drug trials in the US recruiting subjects, with nearly 500,000 new patients each year. Heart disease has almost 800 drug trials, while adult cancer has almost 4000 drug trials listed.

Clinical research efforts in a disease are reflected by the number of pertinent clinical trial publications. We examined Pub Med data along with US mortality statistics to show the juxtaposition of those measures for Alzheimer’s disease, heart disease, cancer and six other leading causes of death, (Figure 1).3,4  

Reductions in US disease mortality have been proportional to the number of trials conducted in each disease except Alzheimer’s, during the years 2000-2013. Alzheimer’s disease is a significant outlier, since mortality is increasing while the number of peer-reviewed publications lags behind other conditions.

One could argue that research efforts and subsequent publications are dependent on funding.  Dementia research funding has usually been a fraction of cancer funding, as an example, by four to ten fold less at the National Institutes of Health. The 2015 US Congress will be improving this situation, specifically increasing funds for dementia research by $350M.

Nevertheless, in NIA projected budgets, dementia clinical trials are allocated less than a third of the funds. Last summer’s Congressional Bypass Budget for Alzheimer’s and related dementias lists the “Translational Research and Clinical Interventions” portion at only 29%. The budget otherwise lists 71% for research in genetics, imaging, biomarkers, epidemiology and other areas not directly therapeutic.5

The assumption is that laboratory science will discover the right target, and a designer drug will modify the progression of dementia.  But in cancer, even with proven molecular targets, we still need multiple chemotherapy agents to effect a cure.

Over $300M has been spent yearly in dementia research through the NIA since 2011. In contrast, the national Children’s Oncology Group (COG), granted about $25M yearly, provides comprehensive leadership, strategic coordination and multi-institutional collaboration in over 200 pediatric cancer centers for nearly 100 clinical trials. COG trials have a substantial record of improving survival and quality of life in childhood cancer.

Investigators examined a decade of dementia drug discovery efforts, and found a 99% failure rate.6Undaunted, researchers have proposed creative ideas for comprehensive trials of existing drugs, supplements and combinations of therapy, but to our knowledge few have come to fruition.

So how will the new money be spent? To find effective therapy, the NIA has presented rational recommendations, emphasizing basic science. Recently, commercially developed monoclonal immunotherapy and certain chemotherapy agents have shown some promise, but an overall strategy for discovering new agents and sustaining clinical development seems lacking in NIA documents.

Unconventional approaches may be necessary. Budgets may need to be re-proportioned to emphasize clinical trials. With a deadline of 2025, perhaps the lengthy grant process should be bypassed to commission trials at clinical research organizations. Pragmatic, strategic, directive, creative, ambitious and accountable clinical leadership will be necessary.

Neither author reports any conflicts of interest with this submission, financial interests, activities, relationships or affiliations. The work has not been published, is not a duplication of other publications and is not under consideration elsewhere. Both authors had extensive contributions to this submission and full access to the data presented.  There were no financial sponsors or grants involved
  1. Mortality From Alzheimer’s Disease in the United States: Data for 2000 and 2010. Accessed February 17, 2016.
  2. 2014-2015 Alzheimer’s disease progress report: Advancing research toward a cure. Accessed January 23, 2016.
  3. Surveillance, Epidemiology, and End Results (SEER) Program ( SEER*Stat Database: Mortality – All COD, Aggregated With State, Total U.S. (1969-2012) <Katrina/Rita Population Adjustment>, National Cancer Institute, DCCPS, Surveillance Research Program, Surveillance Systems Branch, released April 2015.  Underlying mortality data provided by NCHS ( Accessed January 23, 2016.
  4. PubMed. National Center for Biotechnology Information, U.S. National Library of Medicine, National Institutes of Health, 8600 Rockville Pike, Bethesda MD, 20894 Accessed January 23, 2016.
  5. Reaching for a cure: Alzheimer’s disease and related dementias research at NIH. Accessed January 23, 2016.
  6. Cummings JL, Morstorf T, Zhong K. Alzheimer’s disease drug-development pipeline: few candidates, frequent failures. Alzheimer’s Research & Therapy. 2014;6(4):37.


Figure Title
Figure 1:  Average percent change (APC) in the death rate and number of peer-reviewed publications compared for the top ten causes of death in the US, excluding suicide, 2000 to 2013.
Figure Legend
Death rates from the National Cancer Institute Surveillance, Epidemiology and End Results database.Publication numbers from PubMed.4 ^Square root of average number of publications during 2000-2013

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JohnSnowNortin HadlerWilliam Palmer MD Recent comment authors
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This article is very useful. The doctors’ efforts are certainly commendable. It is sad that Alzheimer’s disease has still not garnered concrete research and adequate clinical trials, like cancer. If hardly 120 Alzheimer’s drug trials have been conducted over the past six years, then the future of Alzheimer’s cure looks bleak.

Nortin Hadler
Nortin Hadler

Drs. Louie and Bleyer are pediatric oncologists. As such, they have witnessed the most dramatic advances in the treatment of neoplastic disease. They wield effective regimens, regimens that can make it possible for children and young adults to come back from the jaws of death to enjoy decades of a life as full as they can make it. At this point, advances in the treatment of this population are incremental at best and trials are limited by the ethical issues of constituting a “control” or referent limb. If only any other area of oncology, or for that matter any other… Read more »

William Palmer MD
William Palmer MD

This article is a model of excellence for contributors to THCB. Thank you. Superb.