- Bakker Memory Laboratory
- Harvard event examines impact of DASH diet
- From our collaborators at Johns Hopkins Medicine | Understanding Inflammation
- Inflammation is a vital part of the human immune system
- When our body’s powers of correction go wrong, however, they can work against us
- Inflammation linked to weight gain and chronic diseases diabetes and cancer
- What can we do to keep it at bay? Let’s look at lupus research
- Why the study of HIV offers insight into medication for inflammation
- Simple lifestyle measures to help prevent chronic inflammation
- Exercise levels predict lifespan better than smoking, medical history
Bakker Memory Laboratory
Our ability to learn and remember new information forms an integral part of human cognition and behavior. Our previous experiences often guide our choices and our ability to maintain a record of our experiences allows us to acquire increasingly specialized skills and knowledge.
The importance of memory function in our daily functioning is particularly evident, when memory fails us, as is the case with the increasingly more prevalent instances of Alzheimer’s disease. Research in our lab focuses on the neural basis of human memory function in health, aging and disease.
We are currently working on a number of projects in the following areas.
Aging is often associated with changes in memory and in some cases with significant impairments in memory function. Increasing numbers of older adults develop Alzheimer’s disease dementia resulting in a complete inability to remember people, places and events with devastating consequences for these patients and their families.
However, the majority of older adults do not develop Alzheimer’s disease and some older adults experience no changes in their memory function with advancing age.
Using behavioral and high-resolution fMRI studies in patients and healthy older adults, our studies aim to understand age-related changes in memory function and the compounding effects of Alzheimer’s disease.
These studies have led us to the development of potential interventions designed to slow the onset of Alzheimer’s disease that are currently being tested through the HOPE4MCI clinical trial.
Our ability to learn and remember different types of information depends a broad network of brain regions that each support a different aspect of memory function but heavily interact and work together to support this fundamental aspect of human cognition. However, exactly what aspects of memory depend on which brain regions and how these networks interact, remains poorly understood.
Using behavioral experiments and functional neuroimaging methods during cognitive tasks and rest, we study how various networks in the brain interact and support memory for facts, events and places.
Many patients with Parkinson’s disease experience significant cognitive symptoms and those who do most often report problems with their memory. In addition, patients with Parkinson’s disease report significantly greater rates of anxiety affecting their learning, memory and decision making.
Our studies in this area employ behavioral experiments and multimodal neuroimaging approaches to focus on the role of memory impairment and anxiety on cognitive impairment and comorbidity in Parkinson’s disease.
Cognitive impairment and particularly impairments in learning and memory are part of a number of neuropsychiatric conditions including, schizophrenia, eating disorders, obsessive-compulsive disorder, depression and anxiety disorders.
Through a number of collaborations our projects focus on the role of brain networks associated with memory function and modulation of memory function in these neuropsychiatric conditions with a focus on opportunities for intervention. In these projects we employ neuropsychological assessment, experimental behavioral assessment and advanced neuroimaging methods to study the various patient groups.
Harvard event examines impact of DASH diet
The diet that may be America’s healthiest may also be its stealthiest. It’s not called paleo or Atkins or Scarsdale, but instead bears the dry acronym of the 1990s studies that confirmed its effectiveness: DASH.
Dietary Approaches to Stop Hypertension was an initiative designed to better understand how diet might mitigate a global killer: high-blood pressure, estimated to affect 1.4 billion around the world. The DASH diet proved effective, lowering blood pressure at a rate equivalent to that of some medications.
“It’s always recommended — the best diet in America — so why haven’t you heard about it?” said Lawrence Appel, the leader of the study and a Johns Hopkins professor. “Maybe we should have a different name. … If only we had called it the South Beach Diet.”
Appel delivered the Stare-Hegsted Lecture on Wednesday at a symposium marking the 75th anniversary of the Harvard T.H. Chan School of Public Health’s Nutrition Department.
Named for two of the department’s founders, Frederick Stare and D.
Mark Hegsted, the talk wrapped up a day that included remarks by department chair Frank Hu, former chair Walter Willett, Nobel Peace Prize winner Bernard Lown, and Dean Michelle Williams.
Launched in 1993, the DASH study involved researchers at four centers around the country, including Harvard, where Professor Frank Sacks played a key role. DASH, Appel said, was a “feeding study,” in which food was provided for 459 participants with an average age of 46. It tested a whole-diet approach.
The study compared a control representing the average U.S. diet with both a produce-heavy regimen and DASH, which emphasized fruits and vegetables, low-fat dairy, whole grains, nuts, poultry and fish, and restricted red meat, saturated fats, and sweets.
The DASH diet proved most effective of the three, lowering blood pressure an average of 5.
5 millimeters of mercury (mm Hg) — the standard unit for blood pressure — for systolic pressure, and 3 mm Hg for diastolic pressure.
The decline was even greater for those suffering from high-blood pressure and for African-Americans, a group that experiences a disproportional prevalence of the disorder.
Three follow-up studies probed what factors made DASH effective and whether it could be further improved.
Those studies lasted through 2011 and added different wrinkles — lowering salt and substituting greater amounts of healthy fats and protein for carbohydrates, and testing different types of carbohydrates.
The DASH-sodium diet found that pairing the DASH diet with lower salt — 1,500 milligrams a day — could cut blood pressure an average of 8.9/4.5 mm Hg, and by 11.5/5.7 mm Hg for those with high-blood pressure.
The studies have been influential among experts, but are less familiar to the public, Appel said.
DASH has been widely cited in the years since it was conducted, and provides a foundation for various nutritional guidelines.
It has been recommended by groups such as the American Heart Association, the National Institutes of Health, and the Department of Agriculture, both for blood pressure and for general health.
The prevalence of high blood pressure means DASH needs to be adapted to different cultures, Appel said.
Additional follow-ups are also needed, and Appel urged the next generation of public health researchers to take up the cause — though he warned that the funding environment is difficult and that politics surrounding foods salt and sugar are tricky.
Areas in need of more research, Appel said, include the effects of the DASH low-sodium diet in different populations, such as children, and conditions, such as chronic kidney disease and heart failure.
“We still need a fleet of people to continue the battle,” Appel said.
From our collaborators at Johns Hopkins Medicine | Understanding Inflammation
Inflammation has been found to be an underlying cause in many diseases, making it a hot topic in the health media. But what do we really know about chronic inflammation and its effects on the body?
As scientists have searched for the mysteries behind the diseases most ly to afflict us, they have alighted on one factor common to virtually all of them: inflammation. Chronic inflammation, headlines now regularly state, has a role in a host of common and often deadly diseases, including Alzheimer’s, arthritis, cancer, diabetes, heart disease, and possibly even depression.
Unsurprisingly, this news brings with it a raft of self-proclaimed remedies purporting to fight inflammation. Diets, herbs, supplements, and exercise regimens have flooded the market with promises to keep inflammation in check and improve overall health.
But is there evidence that over-the-counter products or sweeping lifestyle changes will reduce inflammation’s damaging effects? Scientists caution that despite its current high profile, inflammation remains a mystery.
“Basic science hasn’t yet answered the major questions about inflammation,” says Michelle Petri, a rheumatologist and a director of the Johns Hopkins Lupus Center. Researchers Petri have been studying low-level inflammation as a culprit in a number of diseases for decades.
What they have discovered has led to an emerging understanding of how lifestyle choices— diet, dental health, and exercise—may influence inflammation and its potentially damaging downsides.Despite its current high profile, Petri says, inflammation remains a mystery.
Inflammation is a vital part of the human immune system
When harmful bacteria or viruses enter your body, when you scrape or twist your knee, the body’s defense system kicks into high gear. Chemicals ramp up the body to fight, bathing the damaged area with blood, fluid, and proteins; creating swelling and heat to protect and repair damaged tissue; and setting the stage for healing.
Sentinel cells first alert the immune system to the presence of invaders. Another set of cells releases chemicals that signal the capillaries to leak blood plasma, which surrounds and slows down trespassers.
Another group of sentinels, called macrophages, releases cytokines, which are specialized germ fighters. Immunizing B- and T-cells join in, destroying both the pathogens and the tissues they have damaged.
Finally, a last wave of cytokines is released to end the job and signal the immune system that its work is done. Its mission completed, the immune system calls off its dogs.
When our body’s powers of correction go wrong, however, they can work against us
Think of the acute heat and swelling that protect us during a normal immune response—a fever, or the redness and pain that surround a new injury, for example—and you can get a hint of what chronic inflammation is.
Un the inflammation that follows a sudden infection or injury, the chronic kind produces a steady, low level of inflammation within the body that can contribute to the development of disease. It’s the result, in part, of an over-firing immune system.
Low levels of inflammation can get triggered in the body even when there’s no disease to fight or injury to heal, and sometimes the system can’t shut itself off. Arteries and organs break down under the pressure, leading to other diseases, including cancer and diabetes.
Scientists don’t fully understand how the immune system becomes short-circuited, but they have long known that some diseases, such as lupus and rheumatoid arthritis, emerge after the immune system has gone awry and attacked healthy tissue.
Increasingly, as Americans and other Westerners live longer and get larger (35 percent of Americans are obese), researchers have also found that low-level immune responses triggered by extra weight and a lack of exercise can contribute to the development of other illnesses.
“For a long time, we had the idea that inflammation was involved in certain autoimmune diseases, but now we’re seeing this lower level of inflammation in people who are obese and people who are sedentary,” says Kimberly Gudzune, a physician at Johns Hopkins and a clinical researcher who focuses on obesity. “We see a link between obesity and some diagnostic markers for inflammation, but we don’t know what causes them. We worry that there’s something brewing for these people, that they are at higher risk for heart disease, cancer, and diabetes.”
‘We see a link between obesity and some diagnostic markers for inflammation, but we don’t know what causes them. We worry that there’s something brewing for these people, that they are at higher risk for heart disease, cancer, and diabetes.’
Inflammation linked to weight gain and chronic diseases diabetes and cancer
Researchers have discovered that fat cells can trigger the release of a steady, low hum of cytokines that, in lieu of an invader to attack, go after healthy nerves, organs, or tissues. As we gain weight, the release becomes prolific, affecting our body’s ability to use insulin, sometimes leading to type 2 diabetes.
They have also learned that inflammatory cells can have an effect elsewhere in the body—for example, chronically infected and inflamed gums in the mouth can cause damage that leads to heart attack and stroke. And they know that inflammation contributes to congestive heart failure and uncontrolled hypertension, and that it somehow has a role in the tangled cells that are the hallmarks of Alzheimer’s disease.
Researchers continue to find answers about how inflammation contributes to cancer. Inflammatory cells produce free radicals that destroy genetic material, including DNA, leading to mutations that cause cells to endlessly grow and divide. More immune cells are then called in, creating inflammation that feeds the growth of tumors.
The link between inflammation and cancer can sometimes be direct. When too much stomach acid—a feature of the immune system that evolved to fight foodborne bacteria—creeps up the esophagus, it causes inflammation and chronic heartburn. Extended exposure to this acid changes the nature of the cells lining the esophagus, increasing the risk of cancer.
In colon cancer patients, certain communities of bacteria associated with diarrhea can create cancer with help from inflammatory cytokines.
Cells protected by mucus can become inflamed when that mucus wall is breached by bacteria, says Cynthia Sears, a doctor who specializes in infectious disease research at Johns Hopkins. “The lining in the colon makes peptides”—short chains of amino acids that act to protect the lining of the organ—“to thwart bacteria.
If there aren’t enough peptides, bacteria can get a foothold, which means even more bacteria,” Sears says. As inflammation ramps up to fight it, so does the risk of cancer.
What can we do to keep it at bay? Let’s look at lupus research
If inflammation is the behind-the-curtain factor in so many diseases, what can we do to keep it at bay? Researchers admit that they’re still figuring this out.
Petri has studied lupus for more than three decades and has been investigating the effects of chronic inflammation. “Lupus is basically friendly fire,” Petri explains. “We can’t get the immune system to calm itself down.”
Treating chronic inflammation, whether for lupus or other chronic ailments, is a challenge. Researchers have an idea that inflammation exists as part of a self-reinforcing loop system.
If they could figure out how to interrupt or reverse one stage in that loop, then they might be able to develop drugs to stop it.
But how do you tone down the immune response enough to control the inflammation but not so much that a body can’t fight disease? “We’ve done 20 to 25 years of clinical trials on lupus drugs,” Petri says, by way of example. “We’ve had maybe one success and 30 failures.”
Finding a drug that both interrupts the immune cycle and maintains a healthy immune response is important not just for people battling illness but for all of us as we age.
Currently, there are no prescription drugs that specifically target chronic inflammation. (There are, of course, over-the-counter medications that treat the minor and temporary inflammation and accompanying pain caused by injuries or procedures, such as surgery.
These are not meant to treat chronic inflammation.) Some drugs, such as hydroxychloroquine, once used to battle malaria, are useful in treating some lupus patients, but they don’t cure the disease.
Aspirin and statins have shown promise in reducing inflammation in some people, but researchers aren’t sure how broadly useful such drugs are in that role.
With the exception of far-from-perfect anti-inflammatory drugs, such as prednisone, a corticosteroid that brings with it a slew of side effects, scientists are still researching how best to contain inflammation. “We need something that can work broadly and quickly, and without a lot of side effects,” says Petri.
Finding a drug that both interrupts the immune cycle and maintains a healthy immune response is important not just for people battling illness but for all of us, because as we age, inflammation increases in the body. Scientists aren’t sure how and why, but interestingly, the study of HIV is offering some insight.
Why the study of HIV offers insight into medication for inflammation
HIV triggers chronic inflammation in the body, even after medications have rendered levels of the virus undetectable in blood tests. Certain cytokines involved in that inflammation process can profoundly decrease testosterone levels, leading to muscle loss.
“It’s possible that the chronic inflammation in people with HIV is similar to the chronic inflammation we see in aging,” says Todd Brown, an endocrinologist who researches the link between bodily markers for inflammation and chronic diseases found in people with HIV.
If researchers can understand that process and create treatments to disrupt it in people with HIV, they could potentially translate their findings into treatments for similar muscle loss in aging.
Jeremy Walston is a Johns Hopkins geriatrician who investigates immune system response and muscle function in the elderly. He has been searching for markers that highlight the early signs of inflammation.
Some blood tests for inflammation markers exist, but the researchers have uncovered two new markers that they believe may predict mortality and mark signs of late-in-life decline.
“These are powerful inflammatory molecules that, when chronically expressed, lead to declines in stem cells and a remodulation of the immune system,” says Walston. “They also contribute to cell death,” particularly in the elderly, he says.
Simple lifestyle measures to help prevent chronic inflammation
As the quest for diagnostic measures and therapies continues, researchers point to simple lifestyle measures we can all take to help prevent chronic inflammation
Lose weight. Scientists are skeptical of cure-all claims found in the new crop of anti-inflammation diet books, but they do recommend dropping pounds (and the harmful fat cells that come with obesity) and avoiding the now common American diet high in fats and sugars.
“Losing weight can have profound effects on lowering inflammation,” says Brown, who adds that eating a diet rich in fruits and vegetables and low in fats, processed foods, and sugars is generally a good idea, though more study needs to be done to determine how it might affect inflammation. Exercising, which causes an acute inflammatory response in the short term, but an anti-inflammatory one when we regularly get moving, is another strong step to take, he adds.
For most of us, keeping inflammation in check comes down to common sense basics: eat well, don’t smoke, get moving, get more rest, and see your doctor for regular physicals, which could help stop chronic inflammation before it becomes rampant.
Get enough sleep and manage stresss. Other researchers advise getting plenty of sleep, lowering stress levels, and seeking out treatment for inflammation-inducing culprits, such as gum disease and high cholesterol levels.
Avoid contact with heavy metals such as mercury, which is found in dangerous amounts in some large fish, and limit exposure to substances, such as diesel exhaust and cigarette smoke, that can set off the immune system.
Increase omega-3 and vitamin D. Additional studies by Brown and his colleagues have also shown some advantage in increasing our intake of omega-3 fatty acids and vitamin D, though more research is needed.
Walston and others caution against popping dietary supplements touted as anti-inflammatory cures. Some so-called remedies, such as turmeric, taken in large amounts, may actually be toxic to the liver and other organs.
For most of us, keeping inflammation in check comes down to common sense basics: eat well, don’t smoke, get moving, get more rest, and see your doctor for regular physicals, which could help stop chronic inflammation before it becomes rampant. “All of the things our grandmothers told us were good for us are actually good for us,” says Brown. “Until we have a more nuanced understanding of what inflammation does, that’s what we have to fall back on.”
This article originally appeared in the Johns Hopkins Health Review, and is reprinted here with permission. The information from Johns Hopkins is provided for educational purposes only.
Johns Hopkins, The Johns Hopkins University, their affiliates and their employees disclaim any responsibility for errors or any consequences arising from the use of this information.
All medical information should be reviewed with a health care provider.
Exercise levels predict lifespan better than smoking, medical history
Wearable activity trackers may pave the way for a better method to predict short term death risk, suggests a new study, which found that exercise data was more accurate than other risk factors, such as smoking and medical history.
Share on PinterestNew research suggests that physical activity levels might be a better predictor of lifespan than medical history or other lifestyle choices among older adults.
Being able to make an accurate prediction about a person’s risk of death can help them prolong their lives. Usually, doctors base these estimates on lifestyle choices, such as smoking and alcohol consumption, and health factors, such as cancer or heart disease history.
But new findings published in The Journal of Gerontology: Medical Sciences suggest that wearable activity trackers may provide more reliable predictions.
Researchers at John Hopkins Medicine in Baltimore, MD, studied the association between physical activity and risk of death.
“We’ve been interested in studying physical activity and how accumulating it in spurts throughout the day could predict mortality because activity is a factor that can be changed, un age or genetics,” says professor Ciprian Crainiceanu, Ph.D., from the Johns Hopkins Bloomberg School of Public Health.
Their work is not the first to find such a link, but, according to the team, the results might be some of the first to offer concrete proof that wearable technology works better for predicting a person’s risk of mortality than other means.
The study’s data set came from the National Health and Nutrition Examination Survey (NHANES) carried out in 2003–2004 and 2005–2006.
Involving almost 3,000 U.S. adults between the ages of 50 and 84, it examined more than 30 predictors of 5-year all-cause mortality, using survey responses, medical records, and laboratory test results.
Physical activity made up 20 of these predictors, including total activity, time spent doing moderate to vigorous activity, and time spent not moving at all.
To measure such activity, participants — 51% of whom were men — were asked to wear a wearable activity tracker on their hip for 7 days in a row. They were told only to remove the device when showering, swimming, or sleeping.
The research team was able to use the data to categorize which factors best predicted death risk within the next 5 years. However, they were unable to tell when people were sleeping or whether they had removed the tracker for other reasons.
Wearable trackers predicted the risk of death more accurately than surveys and other methods that doctors commonly use.
“The most surprising finding,” says lead author Ekaterina Smirnova, M.S., Ph.D., “was that a simple summary of measures of activity derived from a hip-worn accelerometer over a week outperformed well-established mortality risk factors, such as age, cancer, diabetes, and smoking.”
Smirnova is an assistant professor of biostatistics at Virginia Commonwealth University, VA.
The wearable trackers designated death risk 30% better than smoking-related information did, and was 40% more accurate than using data involving stroke or cancer history.
The researchers found that total daily physical activity was the strongest mortality predictor. Age came second, followed by time spent performing moderate to vigorous physical exercise.
Specifically, examining the amount of physical activity that a person performed between noon and 2 p.m. proved to be a better indicator of death risk than more established risk factors, such as alcohol consumption and diabetes.
Andrew Leroux, co-author and Ph.D. candidate at John Hopkins, says the study confirms “a link between physical activity and short term mortality risk in an older population.”
But, he adds, “the data [do not] guarantee that one’s risk of mortality is going to be lower with more physical activity.”
This does not take away from the fact that wearable tracker measurements, rather than self-reported data, may help doctors “intervene” more appropriately and therefore improve patient health.
Assistant professor of medicine at the John Hopkins University School of Medicine, Jacek Urbanek, Ph.D., notes that “the technology is readily available and relatively inexpensive, so it seems feasible to be able to incorporate recommendations for its use into a physician’s practice.”
But it does mean that further study is necessary. Researchers are hoping to use their findings in clinical trials designed to strengthen the link between physical activity and lifespan.