Dong Song is a research associate professor of biomedical engineering at USC, and he recently presented his findings on a “memory prosthesis” during a meeting of the Society for Neuroscience in Washington D.C. According to a New Scientist report, the device is the first to effectively improve the human memory.
To test his device, Song’s team enlisted the help of 20 volunteers who were having brain electrodes implanted for the treatment of epilepsy.
Once implanted in the volunteers, Song’s device could collect data on their brain activity during tests designed to stimulate either short-term memory or working memory. The researchers then determined the pattern associated with optimal memory performance and used the device’s electrodes to stimulate the brain following that pattern during later tests.
Based on their research, such stimulation improved short-term memory by roughly 15 percent and working memory by about 25 percent. When the researchers stimulated the brain randomly, performance worsened.
As Song told New Scientist, “We are writing the neural code to enhance memory function. This has never been done before.”
A Growing Problem
While a better memory could be useful for students cramming for tests or those of us with trouble remembering names, it could be absolutely life-changing for people affected by dementia and Alzheimer’s.
As Bill Gates noted when announcing plans to invest $100 million of his own money into dementia and Alzheimer’s research, the disease is a multi-level problem that’s positioned to get even worse.
Age is the greatest risk factor for Alzheimer’s, according to the Alzheimer’s Association, with the vast majority of sufferers over the age of 65. With advances in medicine and healthcare continuously increasing how long we live, that segment of the population is growing dramatically, and by 2030, 20 percent of U.S. citizens are expected to be older than 65.
This increase in the number of potential dementia sufferers can be costly in both a financial and emotional sense. In 2016, the total cost of healthcare and long-term care for those suffering from dementia and Alzheimer’s disease was an estimated $236 billion, and according to the Alzheimer’s Association, the more severe a person’s cognitive impairment, the higher the rates of depression in their familial caregivers.
Of course, further testing is required before Song’s device could be approved as a treatment for dementia or Alzheimer’s, but if it is able to help those patients regain even part of their lost memory function, the impact would be felt not only by the patients themselves, but their families and even the economy at large.
In the United States, one in nine people above the age of 65 has Alzheimer’s disease, a brain disease that slowly destroys memory and mental function. Amongst the nation’s top ten causes of death, it’s the only one with no significant medical treatment. Now, Microsoft co-founder Bill Gates is investing in Alzheimer’s research in the hopes of changing that fact.
The billionaire has pledged $50 million of his own money toward the Dementia Discovery Fund, a venture capital fund for both industry and government efforts investigating dementia, as well as an additional $50 million toward as-yet-unnamed start-ups specifically researching Alzheimer’s disease.
“It’s a huge problem, a growing problem, and the scale of the tragedy — even for the people who stay alive — is very high,” Gates told Reuters.
According to a blog post, Gates is investing in Alzheimer’s research in the hopes that researchers will be able to achieve any or all of the the five goals that he believes will make the biggest difference:
“By improving in each of these areas, I think we can develop an intervention that drastically reduces the impact of Alzheimer’s,” wrote Gates.
Older Population, Higher Risks
As medical advancements allow people to live longer than ever before, the number of people older than 65 — when risk factors for Alzheimer’s are highest — is increasing. As Gates noted in his blog post, that means the cost and impact of Alzheimer’s is only expected to increase in the coming years.
With the first wave of baby boomers currently aging past 65, the Alzheimer’s Association estimates that the number of elderly Americans with Alzheimer’s will reach 7.1 million by 2025, a 40 percent increase from 2016 numbers. If no significant treatments are found by 2050, that number could reach 13.8 million.
According to his blog post, Gates is investing in Alzheimer’s research in part because of its costs.
Unlike many chronic diseases, a patient with Alzheimer’s can live for decades, requiring extensive long-term care. As a result, Alzheimer’s patients spend four times more on healthcare out-of-pocket than seniors without a neurodegenerative disease. Additionally, Medicaid payments for Alzheimer’s patients are nearly three times higher than those for elderly citizens without a form of dementia.
“Absent a major breakthrough, expenditures will continue to squeeze healthcare budgets in the years and decades to come,” Gates wrote. “This is something that governments all over the world need to be thinking about, including in low- and middle-income countries where life expectancies are catching up to the global average and the number of people with dementia is on the rise.”
The financial costs are easier to quantify, but Gates also has personal reasons for his investment. He’s watched members of his own family struggle with Alzheimer’s and noted the significant emotional toll that the disease takes.
“I know how awful it is to watch people you love struggle as the disease robs them of their mental capacity, and there is nothing you can do about it,” wrote Gates. “It feels a lot like you’re experiencing a gradual death of the person that you knew.”
As Jeremy Hughes, chief executive of the Alzheimer’s Society charity, told Reuters, Gates is a welcome ally in the fight against Alzheimer’s: “With Bill Gates now joining all those already united against dementia, there is new hope for advances in the care and cure of dementia.”
Scientists from Canada and China have found evidence that the neurological disorder Alzheimer’s starts outside the brain. Their research has been published in the journal Molecular Psychiatry.
Alzheimer’s develops following the breakdown of key neurons in the brain. This neuron death has been linked to the build-up of one protein (beta-amyloid) and the deformation of another (tau).
Beta-amyloids can be produced anywhere in the body, and they are capable of permeating the cells between blood vessels and the brain’s gray matter. These characteristics led the researchers to wonder if the proteins could be originating from somewhere besides the brain.
To test the theory, the researchers conducted a procedure called parabiosis on mice. Half of the mice in their study were genetically modified to contain a mutant gene that triggers high levels of beta-amyloid production, while the other half weren’t. Mice from each group were surgically joined together, and a year later, the non-modified mice all developed Alzheimer’s-like symptoms.
A New Treatment Paradigm
Most Alzheimer’s treatments focus on the brain, which is a complex and extremely delicate target. By revealing that Alzheimer’s starts outside the brain, this research could lead to treatments for the disease that are more effective. For example, these future drug therapies could target the kidneys or liver to eliminate the toxic proteins even before they reach the brain.
The possibility of such treatments provide hope for the more than 44 million people all over the world affected by Alzheimer’s disease or related dementia. The costs associated with caring for Alzheimer’s patients, currently estimated to be around $236 billion in the U.S. alone back in 2016, could also drop if such treatments were made widely available.
Advances in medical research and diagnosis are continually improving our understanding of how the human body works, and ultimately, that knowledge will help us develop better treatments for serious neurological disorders such as Alzheimer’s.
As University of British Columbia researcher Weihong Song said in a press release, “Alzheimer’s disease is clearly a disease of the brain, but we need to pay attention to the whole body to understand where it comes from and how to stop it,” so while this study alone may not bring an end to Alzheimer’s, it marks another step forward on the path to a cure.
A new study from the European Society of Cardiology suggests that blood-thinning drugs used to lower the risk of stroke and heart attack in patients with atrial fibrillation (AF) could also significantly decrease the chances of developing dementia. The breakthrough discovery, published in the European Heart Journal on Tuesday, provides a huge opportunity for at-risk patients to avoid developing dementia — which currently affects over 50 million people worldwide, according to Alzheimer’s Disease International.
The researchers arrived at this conclusion by studying health data from 444,000 Swedish patients with AF, diagnosed between 2006 and 2014. They followed and checked which drugs were prescribed and dispensed to these patients, resulting in a swath of data that is (by adding each patient’s distinct trial time) worth 1.5 million years of follow-up, where some 26,210 patients were diagnosed with dementia at that time.
“As a clinician I know there are AF patients who have a fatalistic view on stroke. Either it happens or it does not. Few patients are fatalistic about dementia, which gradually makes you lose your mind,” co-author Dr. Leif Friberg at the Karolinska Institute in Stockholm, Sweden, said in a statement. “No brain can withstand a constant bombardment of microscopic clots in the long run. Patients probably want to hang on to as many of their little grey cells for as long as they can.”
For Immediate Use
However the findings could not establish a clear cause and effect between blood thinning drugs (also known as anticoagulants), AF, and dementia. To explicate, they “strongly suggested” that presribed anticoagulants — like warfarin, apixaban, dabigatran, edoxaban and rivaroxaban — protected AF patients against dementia. Experts believe that AF increases the risk of stroke and developing blood clots, which could later end up in the brain and cause dementia.
Dr. Friberg and his colleague, Dr. Mårten Rosenqvist, also acknowledged that their study has other limitations, such as not having an access to the complete medical histories of the patients and details of other diseases, as well as the fact that dementia is an insidious disease because it’s not necessarily immediately diagnosed. In short, the reported cases of dementia could constitute a lower population than reality.
Despite the uncertainty, Dr. Friberg was quick to recommend that AF patients continue taking anticoagulants, or (at least) to start taking them as soon as possible. “Doctors should not tell their patients to stop using oral anticoagulants without a really good reason. To patients, I would say don’t stop unless your doctor says so,” he said. The fact is, taking anticoagulants worked, although more work is needed to better explain the underlying mechanisms behind the effect.
Commenting on the study, which made no distinction between the effectiveness of using the older anticoagulant warfarin and newer pills, Alzheimer’s Research UK head of science Dr. Carol Routledge said “The findings highlight a need to investigate this link further, but the nature of the study prevents us from firmly concluding that anticoagulants reduce the risk of dementia,” she told The Guardian. “It will be important to see the results of other ongoing studies in this area, as well as teasing apart the exact relationship between anticoagulants and the risk of different types of dementia.”
One of aging’s most obvious signs is a decrease in cognitive function and learning ability. Usually, these issues express themselves in the form of memory deficiency. While this decrease in memory retention and recall is considered normal, it is often associated with more serious disorders, such as Alzheimer’s or dementia. Now, a team of scientists from the University of Bonn and their colleagues from The Hebrew University of Jerusalem discovered a potential treatment to reverse aging in the brain.
In their research, which was published in the journal Nature Medicine, the team showed how that a cannabis-based treatment successfully reversed the biological state of the brains of mice 12 months and 18 months old. This is notable, as mice age remarkably fast and serve as a viable animal model when research potential treatments in humans.
“The treatment completely reversed the loss of performance in the old animals.”
The team used two-month-old mice as a control group. The older mice were given an active ingredient in hemp called tetrahydrocannabinol (THC) for a period of four weeks in non-intoxicating doses. Their tests revealed that mice who received THC displayed cognitive abilities as good as the control group mice.
Meanwhile, those older mice who received a placebo displayed the usual learning capacity and memory performance appropriate to older mice. The findings that stem from this are simply remarkable. “The treatment completely reversed the loss of performance in the old animals,” said researcher Andreas Zimmer, from the University of Bonn’s Institute of Molecular Psychiatry [emphasis added].
Resetting the Clock
This age-reversing effects of cannabis occur as THC imitates the effect of naturally produced cannabinoids in the body, which are crucial for some of the brain’s important functions. “With increasing age, the quantity of the cannabinoids naturally formed in the brain reduces,” Zimmer explained. “When the activity of the cannabinoid system declines, we find rapid aging in the brain.”
Furthermore, the researchers realized that cannabis reverses aging by making the brain cells in the mice younger. To this end, they saw that links between nerve cells increased and their molecular signature resembled those of young animals. “It looked as though the THC treatment turned back the molecular clock,” Zimmer added.
The treatment, once tested and proven to be effective in humans, could help improve the conditions of people suffering from dementia. This disease, which affects more than 47 million people worldwide, often leads to cognitive disabilities — memory loss and behavioral disorders — that hinder a patient from performing day-to-day tasks.
Svenja Schulze, science minister of North Rhine-Westphalia,outlines exactly how helpful this study could be for future treatment in the elderly. “The promotion of knowledge-led research is indispensable, as it is the breeding ground for all matters relating to application,” he stated in the press release. “Although there is a long path from mice to humans, I feel extremely positive about the prospect that THC could be used to treat dementia, for instance.” To that end, Zimmer and his team are now preparing for human clinical trials.
Neurodegenerative diseases produce the symptoms of dementia by causing cells in the spinal cord and brain to die. Loss of these cells and their functions mean a reduced ability to control movement, make decisions effectively, and recall memories. Neurodegeneration is devastating because there is no simple way to regenerate these kinds of cells.
Neurodegenerative diseases include Alzheimer’s disease, Huntington’s disease, multiple sclerosis, and Parkinson’s disease. In 2015, 46.8 million people around the world suffered from dementia. If current trends continue, by 2030 that number will be 74.7 million, and by 2050 it will reach 131.5 million. In other words, the problem is massive, and it is set to get even bigger.
Now, scientists may have found two drugs that can make all neurodegenerative brain diseases, including dementia, part of humanity’s past.
An End To Dementia?
Dementia can be caused by a natural defense mechanism that brain cells have against against viruses and their proteins: a shutdown response that stops protein protection and keeps the virus from spreading. Many neurodegenerative diseases cause neurons to produce faulty proteins, so that shutdown response is observed in brain cells. However, the diseased brain cells stay in shutdown mode too long, and they starve themselves until they die.
In 2013, researchers found a compound that stopped brain cells in animals from dying by halting the protein shutdown mode, but later discovered that it caused organ damage in people. Now, in their search for other drugs that produce the same effects, they have found two drugs already used by people that have the same protective effect on brain cells. The researchers’ published their results in the journal Brain.
The more widely known drug is trazodone, which is commonly taken for depression. The lesser known drug is dibenzoylmethane, which is being tested in cancer patients. Since trazodone is already know to be safe for human use, if the team is successful in showing it works for this new application, the time it takes to reach the market should be relatively short.
They are hoping to begin clinical trials soon and have confirmation of their theory within two or three years. The study’s lead, Giovanna Mallucci of the UK Medical Research Council, told the BBC that the two drugs have so far been shown to be “very highly protective and prevented memory deficits, paralysis, and dysfunction of brain cells.”
Mallucci commented in the interview that these drugs had the potential to help many people with neurodegenerative diseases. “We’re very unlikely to cure them completely, but if you arrest the progression you change Alzheimer’s disease into something completely different so it becomes livable,” Mallucci said.
Alzheimer’s disease is a progressive brain disease that eventually strips sufferers of their ability to remember, communicate and live independently. By 2050, it is projected to affect nearly 14 million Americans and their families, with an economic cost of one trillion dollars – more than the estimated combined total for treating heart disease and cancer.
Of the leading causes of death in America, Alzheimer’s disease is the only one that we currently cannot prevent, cure or even stall. Our latest research seeks to change this situation by providing a better understanding of the environmental causes and mechanisms behind the disease.
Our findings lead us to conclude that outdoor air pollution, in the form of tiny particles released from power plants and automobiles that seep into our lungs and blood, could nearly double the dementia risk in older women. If our results are applicable to the general population, fine particulate pollution in the ambient air may be responsible for about one out of every five cases of dementia.
This study, the first to combine human epidemiologic investigation with animal experiments, adds to a growing body of research from around the world that links air pollution to dementia. It also provides the first scientific evidence that a critical Alzheimer’s risk gene, APOE4, interacts with air particles to accelerate brain aging.
Where There’s Smoke
Previous research at the University of Southern California has already established that air pollution accelerates the risk of having a heart attack. Based on this work, we established the AirPollBrain Group to examine whether and how exposure to fine particulate matter – known as PM2.5 because the particles measure 2.5 micrometers or less in diameter – impacts the aging brain.
We designed this study to answer three broad questions. First, we wanted to know whether older people living in locations with higher levels of outdoor PM2.5 have an increased risk for cognitive impairment, especially dementia. We also wanted to know whether people who carry the high-risk gene for Alzheimer’s disease, APOE4, are more sensitive to the damage potentially caused by long-term exposure to PM2.5 in the air.
Our third question was whether similar findings could be observed with controlled exposures to particles in mice modified to carry human Alzheimer’s disease genes. If we found similar effects in mice, it could shed light on possible mechanisms underlying what is happening in human brains.
We focused on older women and female mice because APOE4 confers a greater Alzheimer’s disease risk in women than in men.
For the human epidemiologic study component, we collaborated with investigators from the Women’s Health Initiative Memory Study, or WHIMS, which followed a large group of older women nationwide, starting in the late 1990s when these women were 65 to 79 years old but did not have dementia or any significant cognitive impairment.
We combined EPA monitoring data and air quality simulations to build a mathematical model that allowed us to estimate the everyday outdoor PM2.5 level in various locations where these women lived from 1999 through 2010. Because the WHIMS followed its study participants very closely, we were able to gather detailed information on other factors that may affect an individual’s risk for dementia, such as smoking, exercise, body mass index, hormone therapy and other clinical risk factors like diabetes and heart disease. This allowed us to account for these other factors and better isolate the effects of air pollution exposure.
We found that women exposed to higher levels of PM2.5 had faster rates of cognitive decline and a higher risk of developing dementia. Older women living in places where PM2.5 levels exceeded the U.S. Environmental Protection Agency’s standard had an 81 percent greater risk of global cognitive decline and were 92 percent more likely to develop dementia, including Alzheimer’s. This environmental risk raised by long-term PM2.5 exposure was two to three times higher among older women with two copies of the APOE4 gene, compared with women who had only the background genetic risk with no APOE4 gene.
For the laboratory studies, we exposed female mice with Alzheimer genes to nano-sized air pollution for 15 weeks. The air particle collection technology, invented by our colleague Constantinos Sioutas from USC’s Viterbi School of Engineering, collects air particles from the edge of USC’s campus as a representative air sample from urban areas.
The experimental data showed that mice systematically exposed to this particulate matter accumulated larger deposits of proteins called beta-amyloid in their brains. In humans, beta-amyloid is considered as a pathological driver of neurodegeneration and is a major target of therapeutic interventions to prevent the onset of Alzheimer’s or slow its progress. Similar to our epidemiologic observation in older women, these effects were stronger for APOE4 female mice, which are predisposed to Alzheimer’s disease.
Our future studies will look at whether these findings also apply to men, and whether any drugs under development may provide protection against air pollution exposure. More work is also needed to confirm a causal relationship and to understand how air pollution enters and harms the brain.
Brain aging from exposure to air pollution may start at development, so we also want to look at early life exposure to air pollution in relation to Alzheimer’s disease. We already know that obesity and diabetes are Alzheimer’s risk factors. We also know that children who live closer to freeways tend to be more obese, an effect that is compounded if adults in the household are smokers.
Based on existing mouse models, one would predict that developmental exposure to air pollution could increase risk for Alzheimer’s disease. This is an important piece of the scientific puzzle that we’d like to better understand.
Air Pollution, Public Health and Policies
Air pollution knows no borders. This gives our study global implications that should be taken seriously by policymakers and public health officials.
The Clean Air Act requires the Environmental Protection Agency to develop National Ambient Air Quality Standards that provide an adequate margin of safety to protect sensitive populations, such as children and the elderly. In 2012 the EPA tightened the U.S. standard for PM2.5. Nonetheless, in 2015 nearly 24 million people lived in counties that still had unhealthful year-round levels of particle pollution, and over 41 million lived in counties that experienced short-term pollution spikes.
Recent studies have shown that the prevalence of dementia in the United States declined between 2000 and 2012. However, we don’t know whether this trend is connected to air pollution regulations, or if exposures to lower levels of PM2.5 in recent years still pose some degree of long-term threat to older Americans, especially those at risk for dementia.
If long-term PM2.5 exposure indeed increases the risk for dementia, this would imply that public health organizations are underestimating the already large disease burden and health care costs associated with air pollution. For instance, the World Health Organization’s latest assessment of the global burden of disease caused by PM2.5 does not include dementia. Air pollution levels are much higher in India, China and many other developing nations than U.S. levels.
Similarly, EPA has estimated that the Clean Air Act will provide almost US$2 trillion in benefits between 1990 and 2020, much of it from reduced deaths and illnesses. If there is a connection between particulate pollution and dementia, the Clean Air Act may be providing even larger benefits than EPA’s estimate.
The U.S. National Plan to Address Alzheimer’s Disease, which was mandated by legislation enacted in 2011, aims to prevent or effectively treat Alzheimer’s disease by 2025. We believe any measures that undermine EPA’s operation or loosen clear air regulations will have unintended consequences that will make it challenging to meet this goal.
In the U.S. alone, approximately 5.1 million people may have Alzheimer’s disease. Although not associated directly with the aging process, older age groups are at higher risk of developing it. The illness doesn’t seem to be slowing down either. Between 2010 and 2050, the number of Americans age 65 and older will more than double to 88.5 million, the equivalent of 20 percent of the entire population.
Unfortunately, these are the harsh facts behind Alzheimer’s. But with advances in neuroscience and technology, scientists are on the verge of finding more effective treatments, or rather a solution to combatting the iconic symptoms of the disease.
Researchers at the Washington University School of Medicine in Missouri are looking at a particular protein and the gene responsible for its production in the body. It’s called the tau protein, and in a healthy brain, it helps to maintain the functioning of neurons. But in someone living with Alzheimer’s, the tau protein morphs into ‘tangles’ that are toxic to the brain.
To test if these tau protein tangles could be reversed, the researchers took genetically engineered ‘tangled’ mice and injected them with antisense oligonucleotides, or RNA, four times a month. The result – tau levels plummeted, and existing tangles seemed to disappear. The protein even stopped spreading in older mice. Their life expectancy was longer than mice treated without antisense, and they were able to recover some traits lost from the mutation.
Will It Work On Humans?
With monkeys, the test results weren’t as hopeful. They found that tau protein levels only dropped by 20 percent, leading them to believe that future tests on humans could potentially produce adverse effects. Scientists aren’t completely sure where a reduction of tau in the human brain could lead. Normal operation could cease to function, or function abnormally as a result.
Other possible Alzheimer’s treatments were tested in recent years, and many failed to reverse the effects of the disease. It will still be a long way until people are able to experiment with human subjects, and the clock is ticking as the number of Alzheimer’s patients continues to increase each year.
Professor Bart De Strooper, the Belgian neuroscientist recently appointed as director of the U.K.’s Dementia Research Institute (DRI), is optimistic that dementia will be a treatable condition by 2025. “We won’t be celebrating in 2025 that dementia is cured, but I hope that by then there will be groups of patients who can be treated in much the same way HIV-Aids is treated today,” he said after the announcement that he would be the institute’s director.
As head of the DRI, De Strooper will assemble a multi-disciplinary team of doctors, biologists, engineers, and data specialists to expand study outside of the long-standing “amyloid hypothesis” on which most Alzheimer’s research is based. He believes that the hypothesis is dated and an over-simplification of dementia. If he’s right, this new research approach based on the premise that dementia is actually a complicated, multi-factorial condition could pave the way for treatments that can better manage it and other neurodegenerative diseases.
A Treatable Condition
De Strooper likens the promise of advancements in the study of dementia to those of HIV/Aids or cancer. In the 1970s and ’80s, those diseases were synonymous to a death sentence — incurable and debilitating. Today, both diseases, if caught early, can be manageable and treatable.
“I’m a scientist, so I don’t look into crystal balls, but I would put a lot of money on saying that the next generation will have a completely different view of dementia disorders,” says De Strooper.
Because the brain is the most plastic organ of the body, the right treatment could potentially allow patients to regain lost brain function. If we improve our understanding of how dementia attacks the brain significantly enough, scientists could potentially find ways to stabilize dementia disorders early or even intervene before symptoms surface.
“If we could step in 10 years before massive damage to the brain occurs, it would be a very nice thing,” De Strooper concludes.