The National Institutes of Health hosted a meeting earlier this month as leaders in Alzheimer’s and other diseases met in Bethesda, Maryland, for the AD Research Summit 2015. The first such meeting since the National Plan to Address Alzheimer’s Disease was put into action in 2012, the summit served to spur the field on toward the goal of preventing and effectively treating Alzheimer’s by 2025. Over the two-day meeting, researchers proposed ways of finding therapeutic targets outside of the familiar Aβ and tau fields. Data sharing was a big theme for this goal. Speakers also weighed in on how to enlarge patient cohorts, capture better phenotypic data, engage minority communities, and harness citizen science to analyze vast quantities of data.
Alzheimer’s Disease Research Summit 2015: Three Years In
On February 9 and 10, leaders from academia, industry, and non-profit organizations gathered at the Natcher Auditorium of the National Institutes of Health (NIH) in Bethesda, Maryland, for the Alzheimer’s Disease Research Summit 2015. They discussed the progress made since the last such meeting in 2012 (see May 2012 conference series) and outlined new recommendations going forward. The first day’s sessions were on current and future clinical trials, finding new drug targets, and seeking methods of prevention. The second day covered ongoing projects to share data more widely, ways to engage participants in research, and how to involve citizen scientists in helping analyze large datasets (see Part 2 of this series). Overall, the meeting served to refresh the field’s plan to prevent and better treat Alzheimer’s disease by 2025.
“This was an attempt on the part of the NIA to step back, take a survey of the field, and try to figure out what has been working, what hasn’t been working, and what new things should we be trying,” said David Bennett, Rush University Medical Center, Chicago.
“The field has begun to come together in ways that it never has before, in identifying an overall strategy for the field,” George Vradenburg of UsAgainstAlzheimer’s in Chevy Chase, Maryland, commented after the meeting. “There’s a sense of urgency associated with the 2025—it’s finally taking hold in a real way.”
NIH director Francis Collins set the tone when he said in his opening remarks, “Our charge for this meeting is to rededicate ourselves to this critically important work and to identify the highest priorities for biomedical research on Alzheimer’s disease and related conditions.” Richard Hodes, who directs the National Institute on Aging (NIA) in Bethesda, added that the recommendations from the meeting would serve to update the National Plan to Address Alzheimer’s disease.
Altering the Scope of Clinical Trials
A key area of progress in the field is that four secondary prevention trials of Aβ monotherapies are underway and several more are in the planning stages (see Dec 2014 news). However, at the summit Reisa Sperling of Harvard Medical School, who is directing one of those trials, urged researchers to start planning the next set of therapeutic trials. She advocated treating even earlier in disease, and evaluating combinations of investigational drugs. FDA official Rusty Katz forcefully recommends combination trials as well (see Nov 2014 conference news). Reminding the audience of Katz’s recent speech, Sperling pointed out that the current prevention trials will take years to read out, and argued that the field cannot wait to see if they work before taking the next step. She advised combining an Aβ therapy with a tau therapy, given that tau pathology leads to faster memory decline in the presence of Aβ buildup (see Feb 2015 conference news). Since such trials may require cooperation between companies, she suggested building resources that encourage pharmaceutical cooperation, such as trial-ready cohorts of participants and easier communication with regulatory authorities.
Julie Stone, from Merck in West Point Pennsylvania, cautioned that combination trials are highly complex, given that researchers still struggle to interpret trials with one drug candidate. Stone uses quantitative systems pharmacology. This discipline integrates experimental data from different sources to model complex biological systems and help design late-stage trials. This approach lets her map out an underlying disease process, figure out what doses of drugs might perturb it, and predict outcomes of trials. Stone explained how Merck has partnered with academic researchers to build a model of the amyloid pathway, with secretases and biomarkers, and empirical results from multiple Phase 1 studies of Merck’s BACE inhibitor. This model used data on the degree of Aβ reduction achieved in smaller studies and helped the company choose the doses of MK-8931 now used in the Phase 3 program. Given that the researchers now know more about the drug’s effects on amyloid, the resulting trial should be a solid test of the amyloid hypothesis, Stone said. She encouraged experimental scientists to partner with systems pharmacologists to help build similar models. They help scientists revisit data from previous failed trials and figure out whether they actually tested their underlying hypothesis, she said.
Careful analysis of failed trials would accelerate the field’s efforts toward its 2025 goal, agreed Samantha Budd Haeberlein from Biogen Idec in Cambridge, Massachusetts. Since papers on negative trials are rarely published, at least not with full data, some of the reasons for failure are doomed to be repeated. Rather, these analyses could be encouraged and openly shared, Budd proposed.
Hunting for Effective Targets
Even as trials are underway for Aβ therapies, and drugs aimed at tau are entering early stage trials, researchers are actively searching for new targets for Alzheimer’s disease. At the summit, David Bennett of Rush University, Chicago, reviewed the complexity of the protein pathologies underlying age-related dementing disorders. In his view, even if Aβ and tau treatments prove successful, they might treat only half of all people with AD dementia, Bennett said.
Speakers at the summit recommended going after a wide range of candidates. One prime suspect is the immune system, which research indicates is highly involved in AD but has been elusive in terms of yielding druggable new targets. Philip de Jager, Brigham and Women’s Hospital, Boston, described some of his recent work, including his finding that monocytes are more important in AD than T cells (see May 2014 news). De Jager proposed studying communication between the peripheral and central immune systems and how this could render someone susceptible to AD. He also suggested gaining a better understanding of how the immune system ages, and how that could contribute to the disease.
Vascular changes themselves could make an interesting target, said Berislav Zlokovic, University of Southern California, Los Angeles. His recent studies suggest that in aging, the blood-brain barrier starts to break down in the hippocampus, more so in people with mild cognitive impairment (see related Webinar). He proposed testing whether such vascular changes precede Alzheimer’s, if AD genes affect vascular function, and if treating dysfunction influences neurological disorders.
What about the synapse? As the functional unit of the nervous system vulnerable to both Aβ and tau, the synapse could hold new insights into the biology of AD. Several speakers at the summit, particularly Li-Huei Tsai of MIT and Bradley Hyman of Harvard University, advocated using modern techniques such as optogenetics to gain a deeper understanding of synaptic biology in aging and neurodegenerative diseases, and urged neurochemists to get involved in developing PET ligands that image synaptic function in patients to track the disease.
Gerard Schellenberg, University of Pennsylvania, Philadelphia, argued that new therapeutic targets could be found by ramping up genetics research to unravel the full genetic burden of Alzheimer’s disease. Sometimes rare functional variants prove to be good starting points for therapy development. Schellenberg cited a recent success in heart disease, where a cholesterol-clearing, loss-of-function mutation in the PCSK9 gene was first reported to be protective in 2006 (see Cohen et al., 2006). This inspired the development of therapeutic antibodies to the affected protein, which have proven safe and effective in Phase 2 and 3 trials (see Rodriguez and Knowles, 2015). For AD, Schellenberg proposed boosting sample sizes in genetics studies by sharing data, while using more high-throughput biology methods to translate findings into therapeutic targets.
Alison Goate, Mt. Sinai Hospital, New York, suggested the time was right to focus on finding protective variants against AD. In particular, she recommended looking at people who carry two copies of the ApoE4 allele but have maintained normal cognition into old age, or who have an autosomal-dominant mutation but stay cognitively healthy past their family’s mean age of onset. Both these types of person are rare, but some are known to science and willing to participate in research.
Moving beyond the genome, Jonathan Mill, King’s College London, noted that epigenetic changes are reversible and could make therapeutic targets. He reviewed work on methylation differences in ANK1, a gene involved in cell mobility and structure, in the cortices of people with AD (see Aug 2014 news). This gene also emerges as a hit from GWAS of Type 2 diabetes. Since it is unclear whether epigenetic changes are a cause or a result of neurodegeneration, Mill recommended conducting longitudinal studies to assess when they occur relative to better-known brain markers of AD. He also suggested developing methods to sample purified cell cultures from the brain to look at epigenetic changes with higher resolution.
Claes Wahlestedt, University of Miami, pointed out that hundreds of enzymes modify chromatin in a redundant way, and drugs can therefore target some of those enzymes without wide-ranging side effects. As examples, he mentioned BET bromodomain inhibitors, which are entering clinical trials for cancer. Compared to HDAC inhibitors, these drugs affect far fewer genes in the brain, Wahlestedt said. Similar therapies could hit epigenetic targets that simultaneously affect a number of factors relevant to AD.
Clues to Prevention
While many scientists are looking into potential treatment targets for AD, others are vetting factors that could prevent it. Kenneth Langa, University of Michigan, Ann Arbor, said that global trends in AD hint that better education and control of cardiovascular risk factors are lowering incidence in some high-income countries. This decline is a public health success that could moderate the steep growth in AD cases otherwise expected in the coming decades as a consequence of rising obesity and diabetes in aging populations (see Jul 2014 news). Langa suggested performing more research on these potential preventative pathways. Martin Prince, Kings College, London, followed with data on global dementia trends that suggest low education in early life, as well as hypertension, diabetes, and smoking in mid- to later life, all contribute to the risk for AD. He advocated that countries launch public health campaigns that actively promote the idea of AD as a preventable condition. Above all, more countries should closely monitor rates of dementia over time and see how they correlate with other risk factors, Prince said.
Some scientists would like to systematically probe environmental factors that could alter risk for AD. Chirag Patel, Harvard Medical School, introduced the concept of the exposome, the sum total of a person’s exposures during their lifetime. Patel proposed conducting environment-wide association studies for AD, cataloging chemicals, pesticides, vitamins, drugs, metal, etc., to see how such factors modify a person’s risk for AD. Several technologies could help give an unbiased look at possible exposures, such as methods that measure analytes in serum and urine, he added. Patel recommended building a database to store publicly available longitudinal data on environmental exposures (see Patel and Ioannidis, 2014). Using similar biochemical tools, RimaKaddurah-Daouk, Duke University, Durham, North Carolina, is working with scientists in the Alzheimer’s Disease Neuroimaging Initiative (ADNI) consortium to characterize changes in the metabolome over the course of AD. By adding a metabolomics layer to the genomic, neuropsychological, and imaging data already collected, researchers may find new biomarkers and therapeutic targets relevant for Alzheimer’s, she said.
A good night’s slumber might also protect against AD, according to David Holtzman of Washington University in St. Louis. During sleep, the brain generates fewer and clears more Aβ monomers (see May 2014 news). Holtzman advised the NIH to encourage more research on how sleep affects underlying Alzheimer’s pathology, and suggested it could lead to better diagnosis and treatment. Holtzman also made the argument that while more money is going toward Alzheimer’s research, it has not funded enough additional R01 grants. He strongly recommended that the NIH boost the percentiles of funded R01s to support more basic and translational science that could address priorities articulated at the summit. His comment garnered a round of applause.
With a number of proposed targets presented on day one, Howard Fillit, Alzheimer’s Drug Discovery Foundation in New York City, wondered how to prioritize them given that the field has limited resources with which to develop a therapy by 2025. Bennett responded that choosing the best candidates will depend in part on data being shared among scientists, who should rigorously try to replicate each other’s work and run extensive computational models before preclinical or clinical testing.
Some scientists remarked privately to Alzforum that they had hoped the meeting would include more cutting-edge science. Others were disappointed that most speakers had pitched their own area, rather than seeking a broader consensus on the most promising ones to take forward.
Click here to view the webcast for day 1.—Gwyneth Dickey Zakaib
Alzheimer's Disease Research Summit 2015: Expanding the Horizon
The first day of the Alzheimer’s Disease Research Summit 2015, hosted by the National Institutes of Health February 9-10 in Washington, D.C., focused on finding therapeutic targets for Alzheimer’s and testing them in clinical trials (see Part 1 of this series). On the second day, speakers switched gears and brainstormed creative ways to share and analyze big data sets, attract more research participants, and use developing technology to glean data from novel sources. These talks seemed to inspire a renewed sense of energy and excitement from audience members. “A number of the topics this year were quite different than we had in 2012,” said Neil Buckholtz, National Institute on Aging (NIA), Bethesda, Maryland. Buckholtz especially highlighted discussions on patient-oriented groups and technological developments. Steve Estus, University of Kentucky, Lexington, wrote to Alzforum that he considered these talks the most interesting at the summit. Laurie Ryan, NIA, also called attention to the potential for citizen science to expedite data analysis, and easier informed consent to draw in new participants.
Maximizing the Available Data
A prominent theme at the summit focused on means of sharing data. Several speakers noted that data sets could gain new life in the hands of more researchers, who could reanalyze the information for new knowledge about AD. A prime example comes from the Accelerating Medicines Partnership (AMP), which aims to find new biomarkers and therapeutic targets for AD. It will help pay for four research groups to generate data on molecular pathways involved in the disease and make it publicly available online prior to publication (see Feb 2014 news; Sep 2013 news). The four projects—one headed jointly by Philip De Jager, Brigham and Women’s Hospital in Boston, and David Bennett, Rush University Medical Center in Chicago, the others by Eric Schadt, Icahn School of Medicine at Mount Sinai, New York, Todd Golde, University of Florida, Gainesville, and Allan Levey, Emory University, Atlanta—are generating clinical, pathological, genomic, epigenomic, transcriptomic, and proteomic data on both human brain tissue and animal models of AD (for details, see the FNIH AMP webpage. So far, these researchers have been collaborating every other week to look across the raw data sets on a shared online platform and draw connections between them.
This month, the first of this network analysis data will be released publicly. It will be available upon request on the AMP-AD Knowledge Portal, accessible through the Synapse online registry hosted by Sage Bionetworks in Seattle. As more data are generated, periodic additions will follow this first release, said Stephen Friend of Sage Bionetworks, who collaborates with the AMP on this project. “The ultimate goal is to encourage as many users as possible to query [the data], develop new methods, and look for AD targets,” Bennett told Alzforum. He has already seen others use his data in ways that would not have occurred to him. For instance, one research group used his data to validate their integrated-systems approach to finding gene networks involved in late-onset AD (see Zhang et al., 2013). Bennett has since hired an author on that paper to develop the technique further and apply it more systematically to his own data.
Golde added, “If the public paid for these data sets to be generated, they should be shared to do the greatest good.” Golde said the investigators had felt some reservation about sharing the data before publication. They were especially concerned about junior investigators on the team receiving proper credit for generating the data. Other speakers at the summit, too, urged that ways be found for junior investigators in large, shared group projects to be recognized in ways that support their careers. Meanwhile, the AMP project has given Golde new opportunities to collaborate with people outside his specialty who offer new perspectives and suggest ways to analyze his data. Both Bennett and Golde said that to undertake these projects, they needed no preconceived notion of particular targets to seek, allowing them to take an unbiased, data-driven approach.
Continuing the theme of aggressively expanding data collection and sharing, Simon Lovestone, University of Oxford, described initiatives in Britain. He announced that Alzheimer’s Research UK is funding a new, £30 million ($46.3 million) Drug Discovery Alliance. It will launch three drug-discovery institutes at Oxford and Cambridge universities, as well as University College London. The aim is to hire up to 90 research scientists. They will build on ideas from academic researchers and identify and develop AD targets, by, for example, solving their structures, generating assays, and screening for early stage compounds. All this data will be made freely available.
Lovestone also highlighted the Dementias Platform UK. t aims to repurpose 22 current research cohorts, as well as their data and samples. This initiative brings together data on more than 2 million people aged 50 and older, he said. One cohort in particular, the UK Biobank, is being enhanced.Half a million volunteers have given genomic data and biological samples to the biobank, 100,000 will have whole-body MRIs, and 10,000 will have repeat scans. In a separate pilot study, a cohort of 24 people with preclinical AD will undergo amyloid and tau imaging once, followed by structural and functional MRI, magnetoencephalography, electroencephalography, optical tomography, assessment of gait and cognition, as well as blood and CSF collection, about every two months for half a year. After researchers determine how often patients are willing and able to undergo this kind of intensive, frequent testing, they will enroll for a larger trial of 300 people. All of that data will be made freely accessible, so that researchers can look for a signature of change in preclinical AD, Lovestone said.
While these initiatives will obtain and share network analysis and drug-discovery data, the Alzheimer’s Association is funding an effort to link results from clinical studies, said Maria Carrillo of the Association. Called the Global Alzheimer's Association Interactive Network, GAAIN is a big-data community. This platform so far includes clinical data about Alzheimer’s and other neurodegenerative diseases on more than 280,000 patients from 11 so-called data partners, Carrillo said. The partners include the Alzheimer’s Disease Neuroimaging Initiative (ADNI), the National Alzheimer’s Coordinating Center (NACC), and the French National Alzheimer Disease Database (see the GAAIN scoreboard). GAAIN is a federated platform where each data partner retains rights and access rules to their data, but registered researchers can query the combined data sets via interactive graphs. With a feature called the GAAIN Interrogator, researchers can define their own patient groups and variables of interest. GAAIN is meant to bridge silos of existing data sets and allow other researchers to mine them for new insights, said Carrillo.
The Alzheimer’s Drug Discovery Foundation (ADDF) has developed its own project to bridge the gap between basic and translational science. Called ADDF Access, the new, Web-based platform operates a bit like Match.com for drug development scientists, quipped Diana Shineman, director of scientific affairs at ADDF. It connects scientists in academia, biotech, or pharma who need particular services for translational or drug-discovery research, with providers of such services, primarily contract research organizations (CROs). In essence, service providers can register and describe their services at no cost, academic or pharma scientists can find those services, and when they contract with a service provider, ADDF charges a broker’s fee. The site also provides project management tools and links for other useful research services. Through ADDF Access, scientists can message providers directly, issue requests for proposals, compare bids, and even provide anonymous feedback about these communications. Ultimately, ADDF hopes this will speed the development of therapies for dementia.
Engaging More Patients
Meanwhile, several speakers showcased innovative ways by which other fields engage more people and patients in research projects. Sharon Terry of Genetic Alliance, Washington, D.C., launched the Platform for Engaging Everyone Responsibly. PEER originated in the orphan disease field and helps build cohorts for participant tracking. Participants upload health data and genomic information, answer research questions, and set up privacy layers. Sally Okun, of Patients Like Me in Cambridge, Massachusetts, talked about her company’s similar platform. Patients sign up for their condition to connect with others who have that disease and learn from them. They can track their symptoms and responses to various treatments, and share and discuss that data with others.
While the main purpose of both sites is to help connect patients, they also allow their members to participate in research. Most participants in Patients Like Me want to do that, said Okun. They generate a rich set of de-identified and aggregated longitudinal health data, which can be used to answer research questions, she said, noting that 50 publications have come out of Patients Like Me data (e.g., Tran et al., 2014). Okun recommended that Alzheimer’s researchers engage their patients through these types of platform to help develop active communities and harness their interest in research.
Another theme that emerged at the summit was the need for more diversity in clinical trials. “Racial, ethnic, and educational factors are not just nuisance variables to get out of way,” said Jennifer Manly, Columbia University Medical Center, New York. “They offer rich, important variability critical for understanding the biology of Alzheimer’s disease.” Minorities will make up the majority of the U.S. population in the coming decades, said Lisa Barnes of Rush University. They carry greater risk for Alzheimer’s, and their health will increasingly determine that of the nation, she said. Based on successful recruitment strategies at Rush, Barnes recommended that researchers cultivate relationships with communities before asking them to participate in research. Building networks with leaders, creating culturally tailored programs, and including minority staff in their studies all work to build trust. Stephanie Monroe of the African American Network Against Alzheimer’s added that institutions should employ a community-outreach representative and actively engage primary physicians, who are often the first people potential participants ask when they are interested in joining a study. Contradicting common notions about distrust of medical research among African-Americans, Monroe cited surveys indicating that 80 to 90 percent of African-Americans say they would indeed be willing to participate in studies if only they were asked.
To make it easier for more people to enroll in studies, John Wilbanks at Sage Bionetworks is tackling the problem of onerous consent forms. Informed consent is legally required, but the language used is often shrouded in legalese and can stop some people from signing up for a study. Wilbanks is working on digitizing the process into a mobile app. Using graphic icons to represent items on the consent form, and simple language to explain each point, he aims to break down a complicated set of information into simple concepts. A toolkit to adapt this consent process for other research studies is freely available.
Mining New and Improved Sources of Data
Besides broadening data sharing and attracting new interest in research participation, innovation is also needed in the type of behavioral data researchers collect in clinical trials, said Jeffrey Kaye, Oregon Health and Science University, Portland. The cognitive performance of research participants varies day to day, he said, so the sparse data points gathered in quarterly tests during clinic visits capture, at best, a coarse trajectory of change. By contrast, passive sensors built into the home or wearable technology can generate data on movement between rooms, computer use, gait speed, and sleep. This enables scientists to track behavioral factors continuously in a natural setting, Kaye said. By outfitting several hundred homes in Portland with such sensors, Kaye and colleagues have found that physical activity is much more variable in people with MCI than in people who are aging normally. They walk more slowly, wake less during the night, forget their medication more often, and gradually use their computers less. The latter variable correlates with atrophy in the temporal lobe, Kaye’s group has found. Using these types of measures to build models of behavior in clinical trials could track disease progress at high resolution, lower required sample sizes, and reduce the time it takes trials to read out, he proposed.
Barry Greenberg, Toronto Dementia Research Alliance, asked how Kaye would cross-validate those outcomes against standard clinical trial measures. Kaye responded that he would prefer to see proof-of-concept trials that test whether a treatment improves sleep, physical activity, or medication use. In response to an audience question about when this technology will be ready for routine home health care, Kaye said that it requires more work but may be useful for clinical trials in the near future.
Given all the data that will pour in from big cohorts and continuous monitoring, how will researchers analyze it? Pietro Michelucci, of the Human Computation Institute in Fairfax, Virginia, touted the power of citizen science to tackle the challenge. The general idea is that instead of a small team analyzing all the data, the task of analysis gets broken down into manageable parts and distributed among thousands of people, each of whom spends a small amount of time on them. Michelucci highlighted one project in which his institute is crowd-sourcing the analysis of brain microvessels in AD. This particular analysis is a time-consuming, manual task, and Michelucci estimates that his distributed strategy will reduce analysis time from 60 years to two. “Citizen-science projects give the general public the feeling of being part of something bigger, and of making a real difference,” Michelucci said.
The NIH also has a citizen-science working group. Its co-coordinator, Jennifer Couch of the National Cancer Institute, said that much of the data that will be coming from sensors described by Kaye will lend itself to this kind of analysis. By turning data analysis into a “game” and giving people the tools they need to answer a question, researchers can benefit from the problem-solving skills of the public. “People are creative and interested in helping,” Couch told the audience. “There are opportunities for data collection and also insights that wouldn’t be obtainable through conventional research approaches.” Couch cited examples in protein-folding and cancer, where research has benefitted from this approach. She noted that the group is still working out the ethical, legal, social implications of citizen science.
Scientific research journals can also play a role in improving the research landscape, said Diane Stephenson of the Critical Path Institute in Tucson, Arizona. She suggested that when a journal publishes a paper about a new biomarker, the NIA could fund independent replication of the results, and the same journal that ran the original report should commit to publishing the replication attempt as well, regardless of whether it is positive or negative. That will give the field and regulatory agencies confidence that the biomarker finding is robust enough for use in clinical trials, Stephenson said. Preclinical treatment studies sometimes are followed up in this way (see May 2013 news). Stephenson further recommended that funders require researchers to share their raw biomarker data, as well as encourage researchers to use data standards created by the Clinical Data Interchange Standards Consortium (CDISC) in ongoing and prospective clinical trials (see Nov 2011 news). Starting in 2016, the FDA will require new drug applications to conform to CDISC standards.
The Way Forward
Immediately following the summit, world health leaders from the G7 countries, Alzheimer’s advocates, and others held follow-up meetings in Washington, D.C. A writing group of AD experts, NIH staff, and representatives from other funding agencies and the National Alzheimer’s Project Act Council distilled recommendations from the summit meeting to refine the NAPA research milestones and assign a dollar value to research needed to fulfill the requirements of the Alzheimer’s Accountability Act (see Apr 2014 news). Separately, the health ministers of the G7 countries gathered for an update on their respective countries’ research efforts in AD, while the World Dementia Council met to review progress in 2014 and strategies to maintain their momentum in 2015.
On February 11, the Alzheimer’s Association, Weston Brain Institute in Canada, and Alzheimer’s Research UK announced their launch of an $1.25 million international research funding initiative called MEND, short for MEchanisms of cellular death in NeuroDegeneration. It will support new projects, especially research collaborations that examine the reasons behind brain cell death underlying multiple types of dementia.
Click here to view the second day of talks at the AD Research Summit 2015.—Gwyneth Dickey Zakaib
On May 1, the National Institutes of Health issued recommendations for a revised framework for Alzheimer’s disease research. These guidelines were formulated by a panel of 60 experts in Alzheimer’s and chronic diseases who participated in the Alzheimer’s Disease Research Summit 2015, convened by the National Institute on Aging (NIA) and the U.S. Department of Health and Human Services, February 9 to 10 in Washington, D.C. (see Part 1 and Part 2 of this conference series).
After being reviewed and approved by the NIA National Advisory Council on Aging at its meeting on May 12 and 13, the recommendations will help update the research milestones of the National Alzheimer’s Project Act, which were developed after the 2012 AD Summit. The NIH will in turn use those milestones to propose an AD funding budget, as required by the recently passed Alzheimer’s Accountability Act (see Apr 2014 news).
The recommendations run the gamut of topics covered at the summit. They call for scientists to maximize their understanding of the genetic, epigenetic, and lifestyle factors underlying AD in both existing human cohorts and in vivo models. They encourage researchers to explore environmental and health factors that influence disease risk across the lifespan and examine how race and gender modify those risks.
Regarding clinical trials, the expert panel suggests that scientists pay particular attention to people who escape AD as they age, especially those who do so despite being at high genetic risk for the disease. They also advise researchers to integrate molecular, cellular, and physiological data along with information from developing technologies, such as wearable sensors and mobile phone apps, into comprehensive predictive models of AD. At the same time, trials should take advantage of updated designs and incorporate failure analysis to better understand whether and why a drug didn’t work. The recommendations urge that systems biology and systems pharmacology be used to construct models of disease that aid the search for drug targets and drug repurposing.
The panel also dealt with patient care, suggesting improving early diagnosis and addressing disparities among ethnic minorities. Researchers should explore new models of care, while also developing ways to enhance caregiver support, education, and partnerships with community health services.
More should be done to engage culturally and ethnically diverse participants in research projects, such as by more effectively reaching out to the community and including representative people among faculty and staff. Scientists should make trial participation less burdensome for participants while harnessing crowd-sourcing to speed up data analysis.
The recommendations also suggest infusing the field with new blood by incorporating people from various specialties into cross-disciplinary groups that can both develop new monitoring technologies and help translate findings. To facilitate collaboration, they recommend that scientists and funding agencies build infrastructure that encourages wider data sharing.
View the full set of recommendations on the NIA website.—Gwyneth Dickey Zakaib