6 September 2011. Alzheimer’s researchers in the U.S. have felt the pinch of shrinking budgets and reduced National Institute on Aging (NIA) paylines this past year, but some glimmers of hope suggest this grim outlook could improve. In one such sign, the U.S. 2011 federal budget includes a $15 million allocation to create an Alzheimer’s research program within the Department of Defense (DoD) (see ARF related news story). The program will focus on issues central to military personnel, in particular, the links between head injury, post-traumatic stress disorder, and dementia, but it is expected to benefit civilian AD research as well. The DoD program provides an alternative funding avenue for AD researchers worldwide. Though the amount of money is small in comparison to the research need, the program “is really a huge win in our view,” said Alzheimer’s Association representative Maria Carrillo. “We look at it as the beginning of an added contribution from the federal government to Alzheimer’s disease [research].”

The U.S. Government recently signaled the importance it places on AD research by passing the National Alzheimer’s Project Act, which requires the government to develop a national plan to take on AD. However, NAPA does not authorize any appropriations (see ARF related news story and ARF news story). Money remains scarce in a tight budget climate where overall NIH funding is down, and the NIA has been squeezed particularly hard (see ARF related news story and follow-up ARF story). The current 2011 NIA budget pays through the 11 percentile for most applications, which is better than initially expected, but nonetheless represents a drop in the number of approved applications from 2010 levels (see NIA funding line policy for fiscal year 2011). In addition, successful applications see an 18 percent across-the-board slash in funds. In a still-brutal budget climate, next year’s NIA payline remains uncertain.

In this environment, the recent allocation for DoD Alzheimer’s research is all the more remarkable. It reflects the growing concern that military personnel who suffer brain injuries or develop post-traumatic stress disorder face elevated risks for dementia and other neurodegenerative diseases (see ARF related news story). Despite a focus on military needs, the DoD program will yield benefits for both service members and civilians, said Karl Friedl, director of the DoD’s Telemedicine & Advanced Technology Research Center (TATRC), which runs the new program. TATRC handles numerous military medical research programs. “We count ourselves as the research and technology scouts,” Friedl told ARF. Friedl noted that such dual-use research models have proved highly successful for other DoD programs, for example, in osteoporosis, where investigations into stress fractures in young female service members led to new insights into bone remodeling and osteoporosis mechanisms. USAgainstAlzheimer’s co-founder George Vradenburg, who helped advocate for the DoD AD program, told ARF the program will provide a much-needed avenue for financing more translational AD research.

One target area for the AD program will be the pathophysiology of head injuries and post-traumatic stress disorder, and how the underlying pathways might contribute to neurodegenerative disease. This is also a concern in the civilian field, where growing evidence shows that repeated sports concussions can lead to a neurodegenerative condition (see ARF Live Discussion). Other interests include neuroimaging technologies for diagnosis and management of both traumatic brain injury and AD, biomarkers of head injury that might help in differential diagnosis, and the effect of protective lifestyle factors such as exercise, weight loss, and dietary modifications.

The program also encourages proposals in the areas of neuropsychological testing, cognitive training, and rehabilitation, Friedl said. Currently, every soldier and marine takes a baseline neuropsychological test before deployment. In the future, Friedl suggested, a neuropsych test could be part of an annual physical, with any deficits flagging a service member for cognitive rehabilitation training. The new health care bill, called the Affordable Health Care Act, stipulates an annual cognitive screen for Medicare patients.

Another interest area is genetics, which could provide insight into what makes some people more susceptible to certain types of injury. “As we move increasingly into the era of personalized medicine, we need to know who needs what sort of treatment or additional protection,” Friedl noted. In addition, the program emphasizes interventions to improve the quality of life for people with neurodegenerative disease, or allow them to remain longer in their homes. "There is a huge spectrum of opportunity here," Friedl told ARF.

Because of the extended congressional wrangling over the 2011 budget, the program did not receive funds for fiscal year 2011 (which ends September 30) until quite recently. Anthony Pacifico, who manages the DoD AD program, said his team is therefore awarding the 2011 funds in targeted research areas through an expedited process in order to get the money to researchers as quickly as possible. TATRC expects to make award announcements in mid-December, Pacifico said, but the DoD AD program is not currently taking proposals. For 2012, the House of Representatives has earmarked an additional $12 million for the program, although its allocation remains tentative until the budget passes. If the money holds, Pacifico said, he expects to issue a call for 2012 proposals on the TATRC website early next year. Program grants typically run one to three years.

Although the call for 2012 proposals is pending, Friedl noted that he welcomes pre-proposals at any time. Pre-proposals are brief, informal statements, about two pages long, describing the research concept, what it might cost, and why it is important. They can be submitted through TATRC’s Broad Agency Announcement. TATRC evaluates pre-proposals weekly and provides quick feedback, Friedl said. Responses might include encouraging researchers to submit a formal proposal at the next funding opportunity, or could entail digging up funds from other appropriate federal agencies. “This is one of the things we have done with great success. We can help leverage AD research with other related programs, bringing in traumatic brain injury money, for example,” Friedl noted. “We would love to turn $15 million into $100 million of leveraged funding.” Friedl also pointed out that the DoD program welcomes international submissions. “We will go anywhere in the world, to anyone who has a good idea, to help us solve the problem,” Friedl explained.

One feature that distinguishes the DoD program from other federal programs is its philosophy of “activist management,” Friedl told ARF. “We try to work alongside the principal investigators all the way through, and stay with our racehorses until they cross the finish line,” Friedl said. This can mean finding additional money or lengthening the timeframe for a project that takes an unexpected turn, or it can mean arranging collaborations with other scientists. “We are intent on solving the problem,” Friedl said, as opposed to sticking to a rigid schedule. Pacifico noted that part of his job is to “make sure we are getting the best value out of this funding, and accelerate progress as quickly as possible to get medicines or technology out there to the community that needs them.”

The $15 million initial allocation may seem like a drop in the bucket for AD research. For comparison, it is about the same amount as the Alzheimer’s Association’s research budget, but less than 1 percent of the $2 billion in funding previously requested by the 2009 Alzheimer’s Breakthrough Act. The 2011 version of the act, recently introduced in the House, does not request a specific allocation, but instead requires the NIH to assess the research need and make annual budget requests for the necessary funds to meet it. Carrillo said the DoD program represents a significant contribution. “Some of the projects that are being considered for funding are really seminal projects that have the potential to open up new avenues of research,” she said. She pointed out that several opinion leaders in the AD field have joined the advisory panel for the DoD AD program to help shape a scientific agenda that will most effectively use research dollars, Carrillo said, adding, “We need to show Congress that some really important work that has military and Alzheimer’s relevance can be done with even this amount [of money] if invested wisely.” Given the new mandate for AD research provided by the National Alzheimer’s Project Act, the Association is hopeful that this amount will continue to grow over the next several years, Carrillo said.—Madolyn Bowman Rogers.