Where Does Memory Begin? Johns Hopkins Neuroscientists Think They Know

(Johns Hopkins University) By tracking brain activity when an animal stops to look around its environment, neuroscientists at Johns Hopkins University believe they can mark the birth of a memory.

Using lab rats on a circular track, James Knierim, professor of neuroscience in the Zanvyl Krieger Mind/Brain Institute at Johns Hopkins, and a team of brain scientists noticed that the rats frequently paused to inspect their environment with head movements as they ran. The scientists found that this activated a place cell in the rodents brains, which helps the animal construct a cognitive map, a pattern of activity in the brain that reflects the animal’s internal representation of its environment.

In a paper recently published in the journal, Nature Neuroscience, the researchers state that when the rodents passed that same area of the track seconds later, place cells fired again, a neural acknowledgement that the moment had imprinted itself in the brain’s cognitive map in the hippocampus.

The hippocampus is the brain’s warehouse for long- and short-term processing of episodic memories, such as memories of a specific experience like a trip to Maine or a recent dinner. What no one knew was what happens in the hippocampus the moment an experience imprints itself as a memory.

“This is like seeing the brain form memory traces in real time,” said Knierim, senior author of the research. “Seeing for the first time the brain creating a spatial firing field tied to a specific behavioral experience suggests that the map can be updated rapidly and robustly to lay down a memory of that experience.”

A place cell is a type of neuron within the hippocampus that becomes active when an animal or human enters a particular place in its environment. The activation of the cells help create a spatial framework, much like a map, that allows humans and animals to know where they are in any given location. Place cells can also act like neural flags that “mark” an experience on the map, like a pin that you drop on Google maps to mark the location of a restaurant.

“We believe that the spatial coordinates of the map are delivered to the hippocampus by one brain pathway, and the information about the things that populate the map, like the restaurant, are delivered by a separate pathway,” Knierim said. “When you experience a new item in the environment, the hippocampus combines these inputs to create a new spatial marker of that experience.”

In the experiments, researchers placed tiny wires in the brains of the rats to monitor when and where brain activity increased as they moved along the track in search of chocolate rewards. About every seven seconds, the rats stopped moving forward and turned their heads to the perimeter of the room as they investigated the different landmarks, a behavior called “head-scanning.”

“We found that many cells that were previously silent would suddenly start firing during a specific head-scanning event,” Knierim said. “On the very next lap around the track, many of these cells had a brand new place field at that exact same location and this place field remained usually for the rest of the laps. We believe that this new place field marks the site of the head scan and allows the brain to form a memory of what it was that the rat experienced during the head scan.”

Knierim said the formation and stability of place fields and the newly-activated place cells requires further study. The research is primarily intended to understand how memories are formed and retrieved under normal circumstances, but it could be applicable to learning more about people with brain trauma or hippocampal damage due to aging or Alzheimer’s.

“There are strong indications that humans and rats share the same spatial mapping functions of the hippocampus, and that these maps are intimately related to how we organize and store our memories of prior life events,” Knierim said. “Since the hippocampus and surrounding brain areas are the first parts of the brain affected in Alzheimer’s, we think that these studies may lend some insight into the severe memory loss that characterizes the early stages of this disease.”

Other authors on this research are: Joseph Monaco, a post-doctoral fellow with the Johns Hopkins Mind/Brain Institute and the Biomedical Engineering Department at the Johns Hopkins School of Medicine; Geeta Rao, a researcher at the Johns Hopkins Mind/Brain Institute; and Eric D. Roth, an assistant professor at the University of Delaware.



Cancer Drugs Block Dementia-linked Brain Inflammation

(University of California Irvine) Research represents novel approach to lessening impact of Alzheimer’s, Parkinson’s.

A class of drugs developed to treat immune-related conditions and cancer – including one currently in clinical trials for glioblastoma and other tumors – eliminates neural inflammation associated with dementia-linked diseases and brain injuries, according to UC Irvine researchers.

In their study, assistant professor of neurobiology & behavior Kim Green and colleagues discovered that the drugs, which can be delivered orally, eradicated microglia, the primary immune cells of the brain. These cells exacerbate many neural diseases, including Alzheimer’s and Parkinson’s, as well as brain injury.

“Because microglia are implicated in most brain disorders, we feel we’ve found a novel and broadly applicable therapeutic approach,” Green said. “This study presents a new way to not just modulate inflammation in the brain but eliminate it completely, making this a breakthrough option for a range of neuroinflammatory diseases.”

The researchers focused on the impact of a class of drugs called CSF1R inhibitors on microglial function. In mouse models, they learned that inhibition led to the removal of virtually all microglia from the adult central nervous system with no ill effects or deficits in behavior or cognition. Because these cells contribute to most brain diseases – and can harm or kill neurons – the ability to eradicate them is a powerful advance in the treatment of neuroinflammation-linked disorders.

Green said his group tested several selective CSF1R inhibitors that are under investigation as cancer treatments and immune system modulators. Of these compounds, they found the most effective to be a drug called PLX3397, created by Plexxikon Inc., a Berkeley, Calif.-based biotechnology company and member of the Daiichi Sankyo Group. PLX3397 is currently being evaluated in phase one and two clinical trials for multiple cancers, including glioblastoma, melanoma, breast cancer and leukemia.

Crucially, microglial elimination lasted only as long as treatment continued. Withdrawal of inhibitors produced a rapid repopulation of cells that then grew into new microglia, said Green, who’s a member of UC Irvine’s Institute for Memory Impairments and Neurological Disorders.

This means that eradication of these immune cells is fully reversible, allowing researchers to bring microglia back when desired. Green added that this work is the first to describe a new progenitor/potential stem cell in the central nervous system outside of neurogenesis, a discovery that points to novel opportunities for manipulating microglial populations during disease.

Study results appear in today’s issue of Neuron. Monica Elmore, Allison Najafi, Maya Koike, Nabil Dagher, Elizabeth Spangenberg and Rachel Rice of UC Irvine; Bernice Matusow, Hoa Nguyen and Brian West of Plexxikon Inc.; and Masashi Kitazawa of UC Merced contributed to the research, which received support from the National Institute of Neurological Disorders & Stroke (grants 1R01NS083801 and F31NS086409).

About the University of California, Irvine: Located in coastal Orange County, near a thriving high-tech hub in one of the nation’s safest cities, UC Irvine was founded in 1965. One of only 62 members of the Association of American Universities, it’s ranked first among U.S. universities under 50 years old by the London-based Times Higher Education. The campus has produced three Nobel laureates and is known for its academic achievement, premier research, innovation and anteater mascot. Led by Chancellor Michael Drake since 2005, UC Irvine has more than 28,000 students and offers 192 degree programs. It’s Orange County’s second-largest employer, contributing $4.3 billion annually to the local economy.



How a Silly Putty Ingredient Could Advance Stem Cell Therapies

(University of Michigan) The sponginess of the environment where human embryonic stem cells are growing affects the type of specialized cells they eventually become, a University of Michigan study shows.

The researchers coaxed human embryonic stem cells to turn into working spinal cord cells more efficiently by growing the cells on a soft, utrafine carpet made of a key ingredient in Silly Putty. Their study is published online at Nature Materials on April 13.

This research is the first to directly link physical, as opposed to chemical, signals to human embryonic stem cell differentiation. Differentiation is the process of the source cells morphing into the body’s more than 200 cell types that become muscle, bone, nerves and organs, for example.

University of Michigan researchers have found that mechanical forces in the environment of human embryonic stem cells influences how they differentiate, or morph into the body's different cell types. To arrive at the findings, they cultured the stem cells on ultrafine carpets made of microscopic posts of a key ingredient in Silly Putty. Image credit: Ye Tao, Rose Anderson, Yubing Sun, and Jianping Fu

University of Michigan researchers have found that mechanical forces in the environment of human embryonic stem cells influences how they differentiate, or morph into the body’s different cell types. To arrive at the findings, they cultured the stem cells on ultrafine carpets made of microscopic posts of a key ingredient in Silly Putty. Image credit: Ye Tao, Rose Anderson, Yubing Sun, and Jianping Fu

Jianping Fu, U-M assistant professor of mechanical engineering, says the findings raise the possibility of a more efficient way to guide stem cells to differentiate and potentially provide therapies for diseases such as amyotrophic lateral sclerosis (Lou Gehrig’s disease), Huntington’s or Alzheimer’s.

In the specially engineered growth system—the ‘carpets’ Fu and his colleagues designed—microscopic posts of the Silly Putty component polydimethylsiloxane serve as the threads. By varying the post height, the researchers can adjust the stiffness of the surface they grow cells on. Shorter posts are more rigid—like an industrial carpet. Taller ones are softer—more plush.

The team found that stem cells they grew on the tall, softer micropost carpets turned into nerve cells much faster and more often than those they grew on the stiffer surfaces. After 23 days, the colonies of spinal cord cells—motor neurons that control how muscles move—that grew on the softer micropost carpets were four times more pure and 10 times larger than those growing on either traditional plates or rigid carpets.

“This is extremely exciting,” Fu said. “To realize promising clinical applications of human embryonic stem cells, we need a better culture system that can reliably produce more target cells that function well. Our approach is a big step in that direction, by using synthetic microengineered surfaces to control mechanical environmental signals.”

Fu is collaborating with doctors at the U-M Medical School. Eva Feldman, the Russell N. DeJong Professor of Neurology, studies amyotrophic lateral sclerosis, or ALS. It paralyzes patients as it kills motor neurons in the brain and spinal cord.

Researchers like Feldman believe stem cell therapies—both from embryonic and adult varieties—might help patients grow new nerve cells. She’s using Fu’s technique to try to make fresh neurons from patients’ own cells. At this point, they’re examining how and whether the process could work, and they hope to try it in humans in the future.

“Professor Fu and colleagues have developed an innovative method of generating high-yield and high-purity motor neurons from stem cells,” Feldman said. “For ALS, discoveries like this provide tools for modeling disease in the laboratory and for developing cell-replacement therapies.”

Fu’s findings go deeper than cell counts. The researchers verified that the new motor neurons they obtained on soft micropost carpets showed electrical behaviors comparable to those of neurons in the human body. They also identified a signaling pathway involved in regulating the mechanically sensitive behaviors. A signaling pathway is a route through which proteins ferry chemical messages from the cell’s borders to deep inside it. The pathway they zeroed in on, called Hippo/YAP, is also involved in controlling organ size and both causing and preventing tumor growth.

Fu says his findings could also provide insights into how embryonic stem cells differentiate in the body.

“Our work suggests that physical signals in the cell environment are important in neural patterning, a process where nerve cells become specialized for their specific functions based on their physical location in the body,” he said.

The paper is titled “Hippo/YAP-mediated rigidity-dependent motor neuron differentiation of human pluripotent stem cells.” Fu collaborated with researchers at the School of Dentistry and the Department of Molecular, Cellular and Developmental Biology in the U-M College of Literature, Science, and the Arts.



Researchers Discover New Molecules Against Alzheimer’s

(University of Valencia) Researchers of the Unit of Medicine Design and Molecular Topology (Department of Physics Chemistry) of the University of Valencia (UV) have discovered eight new active molecules against Alzheimer by a novel mechanism of action, different to the currently used medicines. The work has just been published in the “Plos One” magazine.

One of the most relevant aspects of the work is that the new molecules have been designed following a mechanism which not only implies the inhibition of the deposit of the beta-amyloid protein, which causes the disease to originate and the creation of small fragments of protein, called oligomers, which originate in the initial stages of the disease and seem to play a determinant role in the development of the process.

The director of the team, the full university professor Jorge Galvez, specifies that molecules have been designed “following a methodology called molecular topology, the team has been working on that methodology since the Eighties”.

The laboratory testing which have confirmed the activity of the new molecules have been carried out by the prestigious Mount Sinai School of Medicine of New York, under the direction of Giulio M. Pasinetti, professor of neurology in the at that centre and director of the Centre of Excellence for complementary treatment of Alzheimer of that institution. In the tests on molecules, which have shown activity both in vitro (neuronal cellular cultures) and in live (in transgenic mice), it has also taken part Japanese and North American researchers.

The group of Medicine Design and Molecular Topology of the UV has worked under the leadership of the professors Gálvez y García-Domenech in the design of many other kinds of medicines (including anticancer medicines, antihistamines, analgesics, food additives and pesticide residues, quoting some examples) being authors of more than a hundred of scientific publications on the issue in international magazines, as well as several national and international patents.

According to Jorge Galvez, “this information demonstrates that nce more molecular typology is a potent tool to the design of new medicines and, in general, of new active molecules in different applications, including agriculture, food, etc…”



New Mouse Model Could Revolutionize Research in Alzheimer’s Disease

(RIKEN Brain Institute) In a study published today in Nature Neuroscience, a group of researchers led by Takaomi Saido of the RIKEN Brain Science Institute in Japan have reported the creation of two new mouse models of Alzheimer’s disease that may potentially revolutionize research into this disease.

Alzheimer’s disease, the primary cause of dementia in the elderly, imposes a tremendous social and economic burden on modern society. In Japan, the burden of the disease in 2050 is estimated to be a half a trillion US dollars, a figure equivalent to the government’s annual revenues.

Unfortunately, it has proven very difficult to develop drugs capable of ameliorating the disease. After a tremendous burst of progress in the 1990s, the pace of discoveries has slowed. Dr. Saido believes that part of the difficulty is the inadequacy of current mouse models to replicate the real conditions of Alzheimer’s disease and allow an understanding of the underlying mechanisms that lead to neurodegeneration. In fact, much of the research in Alzheimer’s disease over the past decade may be flawed, as it was based on unrealistic models.

The problem with older mouse models is that they overexpress a protein called amyloid precursor protein, or APP, which gives rise to the amyloid-beta (Abeta) peptides that accumulate in the brain, eventually leading to the neurodegeneration that characterizes Alzheimer’s disease. However, in mice the overexpression of APP gives rise to effects which are not seen in human Alzheimer’s disease.

Abeta pathology in first model (APPNL-F/NL-F) brains. Brain sections from 9 to 24-month-old mice were immunostained with the anti- Abeta antibody, 4G8. Plaque areas were quantified as indicated in the right graph (n = 4, 5, 6, 6, 6, 4 and 6 mice/indicated time point, respectively).

Abeta deposition in the second model (APPNL-G-F/NL-G-F) brains. Brain sections from 2 to 9-month-old APPNL-G-F/NL-G-F mice were immunostained using anti-Abeta-42 antibody. Cortical, hippocampal and subcortical immunoreactive plaque areas were quantified as shown in the right graph (n = 3, 3, 4 and 4 mice/indicated time point, respectively).

For example, the APP mutant mice often die of unknown causes at a young age, and the group believes this may be related to the generation of toxic fragments of APP, such as CTF-beta. In addition, some of the fragments of APP could be neuroprotective, making it difficult to judge whether drugs are being effective due to their effect on Abeta peptides, which are known to be involved in human AD, or whether it is due to other effects that would not be seen in human disease. In addition, the gene for expressing APP is inserted in different places in the genome, and may knock out other genes, creating artifacts that are not seen in humans.

With this awareness, more than a decade ago Dr. Saido launched a project to develop a new mouse model that would allow more accurate evaluation of therapies for the disease. One of the major hurdles involved a part of the gene, intron 16, which they discovered was necessary for creating more specific models.

The first mice model they developed (NL-F/NL-F) was knocked in with two mutations found in human familial Alzheimer’s disease. The mice showed early accumulation of Abeta peptides, and importantly, were found to undergo cognitive dysfunction similar to the progression of AD seen in human patients. A second model, with the addition of a further mutation that had been discovered in a family in Sweden, showed even faster initiation of memory loss.

These new models could help in two major areas. The first model, which expresses high levels of the Abeta peptides, seems to realistically model the human form of AD, and could be used for elucidating the mechanism of Abeta deposition. The second model, which demonstrates AD pathology very early on, could be used to examine factors downstream of Abeta-40 and Abeta-42 deposition, such as tauopathy, which are believed to be involved in the neurodegeneration. These results may eventually contribute to drug development and to the discovery of new biomarkers for Alzheimer’s disease. The group is currently looking at several proteins, using the new models, which have potential to be biomarkers.

According to Dr. Saido,

“We have a social responsibility to make Alzheimer’s disease preventable and curable. The generation of appropriate mouse models will be a major breakthrough for understanding the mechanism of the disease, which will lead to the establishment of presymptomatic diagnosis, prevention and treatment of the disease.”



Redesigning Systems of Care for Older Adults with Alzheimer’s Disease

(Indiana University) The number of older adults with dementia in the United States is forecast to more than double over the next 40 years. Caring for these individuals will have a significant impact on caregivers as well as the health care system and its workforce.

In a paper published in the April issue of the peer-reviewed journal Health Affairs, Regenstrief Institute investigator Christopher M. Callahan, M.D., founding director of the Indiana University Center for Aging Research, reviews two new dementia care models that seek to decrease stress for caregivers, reduce health care costs and improve quality of care for older adults.

Among the most significant features of both of these care models, Dr. Callahan said, are caregivers’ close involvement with the medical team and an underlying understanding that decisions should be based on attaining agreed upon goals — goals that may rule out burdensome treatments for the older adult with dementia.

“To date, the development of a cure for Alzheimer’s disease remains elusive. We need to devote more resources to providing humane, high-touch, less costly care today and for many years to come for the large number of individuals who are and will be affected,” said Dr. Callahan, the Cornelius and Yvonne Pettinga Professor in Aging Research at the IU School of Medicine. “It’s time to think about going back to the basics to improve the quality of life for both the patient and the caregivers.”

Dr. Callahan is a geriatrician whose own research has focused on depression in older adults and on the care of older adults by primary care physicians. He and co-authors reviewed two care models that offer promise for implementation on a national scale: Optimizing Patient Transfers, Impacting Medical Quality and Improving Symptoms: Transforming Institutional Care, known as OPTIMISTIC; and the Healthy Aging Brain Center. Both care models were developed by Regenstrief and IU clinician-researchers with support from the Center for Medicare and Medicaid Innovation and in collaboration with Eskenazi Health.

Features of both care models profiled in the review article — such as a team-based approach to care; a focus on the caregiver, who may be a family member or a paid health care worker; and the long-term management of symptoms — are not easily applied within the current structure of primary care. Thus, these new models require a redesign of the health care system and changes in the workforce. And, significantly, the models run counter to financial incentives in the current health care delivery system.

Each model is being implemented on a broad scale, with the goal of demonstrating improved dementia care quality and outcomes, accompanied by cost savings, in both community-based and institutional care settings.

“The larger question, however, is what the United States is willing to pay for this care — and researchers, health care systems, payers, and the American public all need to address that question,” the paper concluded. “Achieving the goals of better outcomes and lower costs will require leadership from academe, industry, government, and advocacy groups to advance the debate about what is the optimal approach to care for older adults with dementia who are nearing the end of life.”



Older People with Faster Decline in Memory and Thinking Skills May Have Lower Risk of Cancer Death

(American Academy of Neurology) Older people who are starting to have memory and thinking problems, but do not yet have dementia may have a lower risk of dying from cancer than people who have no memory and thinking problems, according to a study published in the April 9, 2014, online issue of Neurology®, the medical journal of the American Academy of Neurology.

“Studies have shown that people with Alzheimer’s disease are less likely to develop cancer, but we don’t know the reason for that link,” said study author Julián Benito-León, MD, PhD, of University Hospital 12 of October in Madrid, Spain. “One possibility is that cancer is underdiagnosed in people with dementia, possibly because they are less likely to mention their symptoms or caregivers and doctors are focused on the problems caused by dementia. The current study helps us discount that theory.”

The study involved 2,627 people age 65 and older in Spain who did not have dementia at the start of the study. They took tests of memory and thinking skills at the start of the study and again three years later, and were followed for an average of almost 13 years. The participants were divided into three groups: those whose scores on the thinking tests were declining the fastest, those whose scores improved on the tests, and those in the middle.

During the study, 1,003 of the participants died, including 339 deaths, or 34 percent, among those with the fastest decline in thinking skills and 664 deaths, or 66 percent, among those in the other two groups. A total of 21 percent of those in the group with the fastest decline died of cancer, according to their death certificates, compared to 29 percent of those in the other two groups.

People in the fastest declining group were still 30 percent less likely to die of cancer when the results were adjusted to control for factors such as smoking, diabetes and heart disease, among others.

“We need to understand better the relationship between a disease that causes abnormal cell death and one that causes abnormal cell growth,” Benito-León said. “With the increasing number of people with both dementia and cancer, understanding this association could help us better understand and treat both diseases.”

The study was supported by the Spanish Health Research Agency, the Spanish Office of Science and Technology, the National Institutes of Health and the European Commission.

To learn more about brain health, please visit www.aan.com/patients.



Alzheimer’s Tests on the Horizon?

(National Geographic) Can Alzheimer’s disease be predicted? And if it could, would you want to take the test?

Those questions are being sparked by three new studies, each of which presents a potential method for foretelling, years in advance, the memory loss and cognitive impairment that are the hallmarks of the debilitating brain disease.

Researchers have already identified genetic risk factors that give some people higher odds of one day contracting Alzheimer’s. The new studies are different: They propose that certain “biomarkers” of the disease may be detectable after it has begun to affect the brain, but before symptoms have become apparent.

The three studies target different biomarkers in different places: one in the blood, one in the cerebrospinal fluid, and one in the brain itself, as seen in PET scans. None of the tests are close to being available in doctors’ offices and clinics. All will require more years of research.

What they share is the potential to “help us understand the early stages of the disease,” says Dean Hartley, director of science initiatives for the Alzheimer’s Association—and to improve treatment.

A Slow, Invisible Progression

Researchers believe that for perhaps as long as two decades before symptoms appear, the disease follows a steady, damaging course. It’s characterized by a buildup in the brain of clumps, or plaques, of beta-amyloid protein and somewhat later by twisted tangles of another protein called tau protein. By the time the Alzheimer’s diagnosis is made, the brain damage is already extensive.

The hope is that findings gleaned from earlier detection and diagnosis will also help encourage and speed the development of new therapies that can intervene that much earlier.

“The earlier you are able to treat, the more you will be able to do to help, and the prognosis will probably be much better,” Hartley says.

For now, however, the options for treating Alzheimer’s are limited. The Food and Drug Administration has approved five drugs. All offer temporary relief for some people from the symptoms of Alzheimer’s, but none treat the underlying disease.

That’s the rub with the idea of earlier diagnosis. On the one hand, the possibility of a test for a disease that currently affects about 35 million people worldwide, including some five million Americans—numbers that are expected to grow larger as the population ages—heralds hope for even more research breakthroughs. On the other hand, with treatment options so limited, potential patients may be leery of foreseeing their future.

“If someone told me that there is a great test for someone like me, I wouldn’t want it,” says Jason Karlawish, professor of medicine, medical ethics, and health policy at the University of Pennsylvania Perelman School of Medicine. “It would be knowledge that would add to my level of existential anxiety.”

Harbinger in the Blood

Perhaps the simplest and least invasive test would be the blood test currently under development by researchers led by Howard Federoff, professor of neurology and executive dean of the Georgetown University School of Medicine. Federoff and his colleagues from six other medical institutions collected blood samples and administered cognitive and memory tests to 525 people aged 70 and over. They then repeated the tests annually.

At the start of the study, 46 participants had some cognitive impairment; by the third year, another 28 had developed symptoms. The researchers discovered that the people with impairment had lower levels of ten blood lipids, even at the beginning of the study, than those who had remained cognitively healthy. The blood lipid levels could distinguish, with an accuracy of over 90 percent, who would remain cognitively normal and who would develop symptoms of Alzheimer’s or of mild cognitive impairment over the next few years.

Blood lipids might predict Alzheimer’s even farther in advance than that, Federoff says; to find out, he and his team are hoping to get access to archival blood samples from an older longitudinal study.

The researchers don’t fully understand why blood lipids would be such good predictors of Alzheimer’s. They’ll need to understand more, and their study will need to be replicated, before there’s any chance of a blood test for Alzheimer’s becoming publicly available.

Spinal Taps and PET Scans

The other two potential tests are more involved. Claudio Soto, director of the Mitchell Center for Alzheimer’s Disease and Related Brain Disorders at the University of Texas Medical School at Houston, has developed a test that detects misfolded beta-amyloid protein in tiny quantities in the cerebrospinal fluid of Alzheimer’s patients—but not in patients with other neurological diseases.

“What we have shown so far is that we can find these particles and you can differentiate” Alzheimer’s from non-Alzheimer’s patients, Soto says. His study suggests these tiny beta-amyloid particles may be precursors of the plaques in the brain that are characteristic of Alzheimer’s. He also wants to see if his technology can be applied to blood and urine samples—much easier to collect than cerebrospinal fluid, which requires a painful spinal tap.

PET scans can already detect beta-amyloid plaque in the brains of Alzheimer’s patients. In the third new study, Murali Doraiswamy, professor of psychiatry and director of the neurocognitive disorders program at Duke University, showed that PET scans using the radioactive dye Amyvid can predict a high risk for developing Alzheimer’s symptoms in patients that don’t yet have them.

“If there are no plaques, the dye has nothing to stick to, so the PET scan is negative,” Doraiswamy explains. “But if there are a lot of plaques,” they will show up on the scan.

At the start of the study, 152 adults aged 50 and over were given PET scans as well as cognitive tests. Three years later they repeated the cognitive tests. Those with positive PET scans had a much greater rate of cognitive decline and were more likely to have been diagnosed with dementia than those whose scans had been negative.

But even a positive scan is not a perfect predictor, Doraiswamy cautions: “It does not mean you’re going to get Alzheimer’s.”

To Know or Not To Know?

Once such tests become available, how do you decide whether to get one? “Counseling would be in order,” says Federoff. It would focus, he says, on establishing whether the patient is ready for the potential results of a test—and also prepared to act on them. Getting treatment is only one possible action; planning financially and for the care that will be needed are others.

Soto sees the development of reliable diagnostic tools as essential for the development of effective treatments.

“The main reason there is not good treatment is that there is not good early diagnosis,” he says. “When you start [treatment] when the brain is destroyed, the treatment is less likely to work.”