Research Your Resolution: Boost Your Brain Health With Social Connections

ResearchResolution-Salinas

Joel Salinas, MD
Joel Salinas, MD

Joel Salinas, MD, is a behavioral neurologist, neuropsychiatrist, and social epidemiologist at the Massachusetts General Hospital Institute for Brain Health. To learn more about his research, please visit his lab website.


When we make social connections with other people, we live better and have healthier brains for longer.

This might mean re-connecting with old friends, making new friends, joining a group or a class, teaching someone something new, volunteering or offering to help others, or using technology to keep in touch, getting a pet, or simply sharing a smile.

Studying over 3,000 members of the Framingham, MA, community since 1948, and across multiple generations, we found that people who are the most socially isolated have lower blood levels of a molecule known as brain-derived neurotrophic factor (or BDNF) which is critical for keeping brain cells healthy and forming new connections between cells.

However, people who have someone available to listen to them or receive emotional support from someone else most or all of the time not only seem to have increased levels of BDNF, but they also have a lower risk of developing stroke and dementia.

There is no cure yet for many age-related brain diseases, but there is a cure for social isolation.

By addressing what we can change in our life to reduce our risk for brain disease, there may be a way to delay and eventually prevent these diseases and prolong the span of our brain health.


Research Your Resolution

Do you have goals for improving your health in the New Year? This month, investigators from the Mass General Research Institute are discussing the science behind some common New Year’s resolutions, and offering tips and advice based on their research into exercise, diet, healthy aging, heart health, and much more. See more posts in the series.

Massachusetts General Hospital is home to the largest hospital-based research program in the United States, a community of more than 10,000 people working across 30 departments, centers and institutes. The Mass General Research Institute works to support, guide and promote these research initiatives.

12 Days of Research at Mass General: Untangling the Connections Between Alzheimer’s Disease and Mental Illness

Banner 12 days of researchIn the 12 days leading up to our holiday hiatus, we are looking back on the past year and sharing some highlights in Massachusetts General Hospital research news from each month of 2017.

But before we get to the research, we want to thank you for following along with the Research Institute in 2017! We’ll be taking a short break over the holidays, but we can’t wait to continue sharing all the exciting research news and breakthroughs from Mass General in 2018!

December 2017:

Gatchel Untangles the Causes of Mood and Anxiety Symptoms and Loss of Brain Function in Aging Populations

Jennifer Gatchel studying Alzheimer's disease

Often referred to as the golden years, life after retirement can sometimes turn out to be less than sunny.

Dramatic lifestyle changes such as admittance to an assisted care facility and loss of mobility or independence can take a toll on mental health.

In fact, twenty percent of people over 55 suffer from a mental disorder, and two-thirds of nursing home residents exhibit mental and behavioral problems.

As a geriatric psychiatrist at Massachusetts General Hospital and McLean Hospital, Jennifer Gatchel MD, PhD, works with adults ages 60 and over to help them cope with life’s transitions.

For many of her patients, symptoms of mental illness are often compounded by symptoms that indicate the onset of degenerative conditions like Alzheimer’s disease.

“These are conditions I see every day in my practice that I find highly compelling,” says Gatchel. “Could psychiatric symptoms in older adults be driven in part by Alzheimer’s disease pathology and proteins impacting brain circuitry? If so, it would represent an important shift in the way we think about treating older adults presenting with these symptoms.”

Gatchel is using a combination of neuroimaging, cognitive testing, clinical assessments, and her ongoing interactions with patients to inform her research on the relationships between mood and anxiety symptoms and dementia.

She ultimately hopes to improve care and brain health for older patients and help them make the most of their golden years.

Measuring changes in brain structure and function

Gatchel uses positron-emission tomography (PET) neuroimaging to visualize amyloid and tau, the two proteins thought to be the core pathological drivers of Alzheimer’s disease, in living older adults.

By looking at amyloid and tau concurrently, both at a single time point and over time, she can follow individuals to see how the changes in their brain map onto the changes they are experiencing clinically.

To measure brain function and mental health, Gatchel asks participants and their families about observable changes in their mood, memory and performance of day-to-day activities. Participants also complete cognitive tests sensitive enough to pick up on small changes that may indicate degeneration in the brain.

Chicken or the egg scenario

In analyzing the data, Gatchel has found that the relationships between psychiatric and cognitive symptoms are very complex and akin to a chicken or the egg scenario.

“On the one hand, symptoms of depression or anxiety may be a precursor of Alzheimer’s disease, and may be among the earliest signs of the disease,” she explains.

“On the other end of the spectrum, recurrent episodes of depression may serve as risk factor for dementia. Also, older adults who have a diagnosis of Alzheimer’s disease may experience a reactive depression. It’s a complex question depending on which stage of the disease we’re looking at.”

She has unearthed some intriguing findings by looking at a cohort of older adults over the age of 60 with no reported cognitive impairments or psychiatric conditions enrolled in the Harvard Aging Brain Study, led by Drs. Reisa A. Sperling and Keith A.  Johnson.

Results thus far show that subclinical depressive symptoms in cognitively normal older adults are associated with accumulations of tau in a brain region affected in aging and early stages of Alzheimer’s disease.

She has also carried out work with a cohort of younger adults from Colombia. This research, led by Dr. Yakeel T. Quiroz, looks at individuals who may carry a mutation in a single gene that gives rise to early onset Alzheimer’s disease. Similar to the Harvard Aging Brain Study, participants in the study had no reported cognitive impairments or psychiatric conditions at study entry.

Interestingly, Gatchel has found that subclinical symptoms of anxiety are associated with amyloid buildup, rather than tau pathology in this younger cohort.

Intrigued by these results, Gatchel plans to conduct future research to further disentangle the underlying pathology of depressive and anxiety symptoms, and to determine whether this differs across a range of symptom severity and in late onset vs. early onset Alzheimer’s disease.

One next step is to recruit an additional cohort of older adults with more severe psychiatric symptoms to complement the existing participants in the Harvard Aging Brain Study.

“We may be observing only a modest relationship between depressive symptoms and tau because individuals with more severe depressive symptoms were excluded from the study at entry,” says Gatchel.

“Would we see a stronger relationship if we examined individuals who had more severe depressive symptoms? Would we still observe a relationship with tau as compared to amyloid? Also, if we follow individuals over time, do those with more significant depressive or anxiety symptoms accumulate pathology more rapidly? These are just some of the questions we hope to address in the next phase of work.”

Gatchel will also continue to look to patients and clinical research participants to help her refine her research questions.

“It’s been incredibly helpful to maintain clinical practice as a psychiatrist,” she says. “My clinical encounters and relationships with patients are critical to informing the research process, and are continually changing the way I think about designing studies.

“It’s also extremely motivating to know that something you’re doing—a research question you are trying to tackle—could impact or improve clinical practice.”

You can find the original article here

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12 Days of Research at Mass General: Modeling Alzheimer’s Disease in 3D

Banner 12 days of researchIn the 12 days leading up to our holiday hiatus, we are looking back on the past year and sharing some highlights in Massachusetts General Hospital research news from each month of 2017.

October 2017:

How a 3D Model of Alzheimer’s Disease is Providing New Hope in the Search for Treatments

Reigning in Alzheimer’s disease continues to be a challenge — more than 10 million families are affected by this degenerative neurological disease, and the number of patients dying from the disease has increased 68 percent since 2010.

In the past decade, attempts at developing drugs to slow or halt the progression of Alzheimer’s disease have been unsuccessful. The traditional path for early testing of promising therapies – mouse models – has been ineffective, and more than a dozen major clinical trials have failed.

But scientists and clinicians at Massachusetts General Hospital’s Institute for Neurodegenerative Disease (MIND) have developed an innovative new approach that could significantly improve the drug development process.  The laboratory teams of Doo Yeon Kim, PhD, an investigator in the Genetics and Aging Research Unit at MIND, and Rudy Tanzi, PhD, have found a way to grow human neural stem cells in a three-dimensional gel matrix.

This gel system allows the neural cells to grow more naturally and form into 3-D networks just like they do in the brain. It also provides a more accurate model of the signature plaques and tangles that develop around these neurons in Alzheimer’s disease.

The stem cells used in this lab model are genetically engineered to produce two proteins that are the hallmarks of Alzheimer’s disease – β-amyloid and tau. In the brains of people with Alzheimer’s, excessive accumulation of β-amyloid results in the formation of plaques in the spaces between neural cells, while tau is the main component of destructive neurofibrillary tangles within the cells.

Until Dr. Kim’s success, no single model of Alzheimer’s disease contained both amyloid plaques and neurofibrillary tangles. It usually takes a year to develop plaques in mouse models, it took only six weeks to develop both plaques and tangles in the “dish.”

Dr. Kim is now working with a consortium of labs to test thousands of FDA-approved drugs in this “Alzheimer’s in a dish” model to see if any of the drugs are effective in reducing levels of p-tau, a protein that is increased in Alzheimer’s patients.

Of the 2,400 drugs that have been tested, the team had approximately 40 promising hits that they can now investigate further.

Learn more: https://giving.massgeneral.org/fresh-alzheimers-approach-sparks-hope/

You can find the original post here.

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12 Days of Research at Mass General: Do Alzheimer’s Patients Suffer Silent Seizures?

Banner 12 days of researchIn the 12 days leading up to our holiday hiatus, we are looking back on the past year and sharing some highlights in Massachusetts General Hospital research news from each month of 2017.

May 2017:

Researchers Detect “Silent” Seizures in Alzheimer’s Patients

First let’s define a key word:
Hippocampus: The brain structure responsible for memory development. The hippocampus is a key part of the brain affected by Alzheimer’s disease, and also a common source of seizures in people with epilepsy.

New research from Massachusetts General Hospital suggests a potential new connection between the devastating memory loss associated with Alzheimer’s disease (AD) and “silent” seizures in the memory center of the brain.

The small study enrolled two female patients in their 60s with early AD and no known history of seizures. Because electrodes placed on the scalp are often unable to detect seizure activity deep in the brain, researchers surgically implanted electrodes on both sides of the brain through the foramen ovale (FO), a narrow opening at the base of the skull, in addition to scalp EEG. Each patient’s brain activity was monitored for 24 to 72 hours.

The FO electrodes recorded evidence of seizures in the hippocampuses of both patients, while the scalp EEG readings did not detect any abnormal electrical activity. Most notably, these seizures primarily occurred when patients were asleep, a critical time for memory consolidation.

“While it is not surprising to find dysfunction in brain networks in Alzheimer’s disease, our novel finding that networks involved in memory function can become silently epileptic could lead to opportunities to target that dysfunction with new or existing drugs to reduce symptoms or potentially alter the course of the disease,” says Andrew Cole, MD, Director of the Mass General Epilepsy Service and senior author of the Nature Medicine paper.

One patient received anti-seizure medicine as a treatment following the scan, which seemed to cut down on AD-linked symptoms such as confusion and repeating the same question. The other patient started on the medication but it had to be discontinued due to adverse effects on her mood.

A recent study led by Alice Lam, MD, PhD, also of the MGH Epilepsy Service and lead author of the current study, demonstrated a novel tool for detecting hippocampal seizures not detectible by scalp EEGs in patients with epilepsy. Cole and his team are working to refine this tool and apply it to AD.

Due to the small size of the study, further research is also needed to validate the results with a broader population.

You can find the original post here.

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Gatchel Untangles the Causes of Mood and Anxiety Symptoms and Loss of Brain Function in Aging Populations

Jennifer Gatchel studying Alzheimer's disease

Massachusetts General Hospital researcher Jennifer Gatchel, MD, PhD, is using brain imaging technology to learn more about the connections between mental illness and cognitive decline in aging populations.


Often referred to as the golden years, life after retirement can sometimes turn out to be less than sunny.

Dramatic lifestyle changes such as admittance to an assisted care facility and loss of mobility or independence can take a toll on mental health.

In fact, twenty percent of people over 55 suffer from a mental disorder, and two-thirds of nursing home residents exhibit mental and behavioral problems.

As a geriatric psychiatrist at Massachusetts General Hospital and McLean Hospital, Jennifer Gatchel MD, PhD, works with adults ages 60 and over to help them cope with life’s transitions.

For many of her patients, symptoms of mental illness are often compounded by symptoms that indicate the onset of degenerative conditions like Alzheimer’s disease.

“These are conditions I see every day in my practice that I find highly compelling,” says Gatchel. “Could psychiatric symptoms in older adults be driven in part by Alzheimer’s disease pathology and proteins impacting brain circuitry? If so, it would represent an important shift in the way we think about treating older adults presenting with these symptoms.”

Gatchel is using a combination of neuroimaging, cognitive testing, clinical assessments, and her ongoing interactions with patients to inform her research on the relationships between mood and anxiety symptoms and dementia.

She ultimately hopes to improve care and brain health for older patients and help them make the most of their golden years. Continue reading “Gatchel Untangles the Causes of Mood and Anxiety Symptoms and Loss of Brain Function in Aging Populations”

Study Predicts Alzheimer’s Cases to Double in US by 2060. How Mass General Researchers are Fighting Back.

Alzheimer's disease crumbling brainScientists at the National Institutes of Health (NIH) released some unsettling new estimates about the number of individuals affected with Alzheimer’s disease this week—and how that number is expected to skyrocket in the near future.

The NIH team estimates that there are 6 million Americans who currently have either Alzheimer’s disease or some form of cognitive impairment, and that number is expected to more than double to 15 million by 2060.

These staggering statistics highlight the pressing need to better understand how and why Alzheimer’s disease develops, as well as how to treat it.

Here are just some of the ways researchers at Massachusetts General Hospital are working on new strategies to improve diagnosis and treatment.

How “Alzheimer’s in a Dish” Could Improve Research and Treatment Efforts

Scientists and clinicians at Mass General’s Institute for Neurodegenerative Disease (MIND) have developed a creative solution to overcome the challenges of modeling Alzheimer’s disease in the lab.

The laboratory teams of Doo Yeon Kim, PhD, an investigator in the Genetics and Aging Research Unit at MIND, and Rudy Tanzi, PhD, have found a way to grow human neural stem cells in a three-dimensional gel matrix.

One of the challenges in studying the progression of Alzheimer’s disease in the laboratory is that the brain exists in three-dimensions. A Petri dish is flat. Thus it has been difficult to replicate the disease solely by culturing neuronal stem cells and growing them in a dish.

The new 3D model is capable of housing and supporting neuronal stem cells that have been genetically engineered to develop the same plaques and tangles found in the genetic form of Alzheimer’s disease.

The gel not only provides a more brain-like environment for the neurons, allowing them to create more connections, it also helps to retain the Alzheimer’s-linked proteins that are produced by the genetically engineered neuronal cells.

This new model could represent a big step forward in Alzheimer’s research, as it will allow investigators to test thousands of chemical compounds against a more realistic model of the disease, which could speed development of new therapies.

Learn more

Scent Recognition and Recall Test Could Better Predict Onset of Alzheimer’s Disease

A Mass General research team, led Mark Albers, MD, PhD, of the Center for Alzheimer’s Research, has developed a series of four tests designed to measure early indications of Alzheimer’s disease based on an individual’s ability to recognize, remember and distinguish among odors.

The 30-minute scent test was given to 183 people between 60 and 80 years old – some with mild cognitive impairment or possible Alzheimer’s disease—and of those, about 20 percent showed signs of olfactory deficiencies.

Genetic and imaging testing revealed that that these same individuals had other deficiencies that have been linked to the illness, including thickening of certain brain structures and a mutation in a gene associated with increased risk of Alzheimer’s disease.

Learn more

New Brain Scans Used to Detect Risk

Researchers at the Martinos Center for Biomedical Imaging are using a computer aided system called BrainPrint to analyze MRI brain scans to help distinguish individuals who are having minor memory issues from those who are in the silent, early stages of Alzheimer’s disease.

The research, led by Martin Reuter, PhD, has shown there are more pronounced asymmetrical differences in the shapes of critical structures between the left and right sides of the brain in individuals who are later diagnosed with Alzheimer’s.

A better understanding of the early signs of Alzheimer’s could improve detection and treatment strategies, and delay or prevent the significant cognitive decline that occurs in later stages of the disease.

Learn more

Non-Invasive Imaging Techniques Help Researchers See Tau and Amyloid Development

Jorge Sepulcre, MD, PhD, and team at Mass General’s Gordon Center for Medical Imaging have been working to improve noninvasive tests to detect amyloid plaques and tau tangles. Specifically, they are investigating the pathways through which tau spreads and amyloid builds up over time.

Their research has found that the tau and amyloid proteins use different brain pathways to reach the areas where they accumulate.

These findings could help researchers describe the stage of the disease in a given patient and may improve their ability to track responses to potential therapeutic interventions, says Sepulcre.

Studying A Small Group in South America Could Help Alzheimer’s Patients Worldwide

The Familial Dementia Neuroimaging Lab, led by Yakeel T. Quiroz, PhD, is investigating how brain changes may lead to memory loss or dementia later in life. Their research is focused on a large group of related individuals Colombia who carry a genetic mutation that predisposes them to develop an inherited form of Alzheimer’s disease.

“If our findings only apply to our population from Colombia, we will still help thousands of people”, says Edmarie Guzman-Velez, PhD, a postdoc in Quiroz’s lab. “But if what we find can also be applied to those who develop sporadic (non-hereditary) Alzheimer’s disease, we could help millions of people around the world.”

New Screening Technique Makes Waves in The Quest for Earlier Diagnosis of Alzheimer’s Disease

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How could the study of patients under anesthesia lead to a new way to diagnose Alzheimer’s disease? It could all come down to brainwaves.

Patrick Purdon, PhD, a researcher with the Massachusetts General Hospital Department of Anesthesia, Critical Care and Pain Medicine, is investigating how changes in brainwave patterns could potentially detect early signs of Alzheimer’s disease.

For the past decade, Purdon and his colleagues have been using electroencephalogram, called EEG, to measure the brainwaves of patients under sedation. That research has demonstrated that different anesthetic drugs produce distinct brainwave patterns in patients.  After finding these brainwave patterns in elderly patients under anesthesia were slower and smaller than those of younger adult patients, Purdon and colleagues examined the areas that were affected by age and discovered they align with brain areas that typically undergo degeneration in Alzheimer’s.

This led to an intriguing possibility—could EEG measurements be used as a diagnostic tool for Alzheimer’s disease?

With a grant from the NIH, Purdon is now studying the brainwave patterns of early Alzheimer’s patients, and monitoring how those brainwaves change over the progression of the disease.  Purdon and his team hope to determine whether EEG can provide a clearer picture of the process of neurodegeneration and changes in brain function.

If they’re successful, EEG could be used as an inexpensive alternative for screening of neurodegenerative problems, potentially leading to earlier diagnosis of Alzheimer’s disease, where treatments could be more effective at slowing or halting its progression. Brainwave measurements could also provide a more accurate measure of the disease’s progression over time.

Read the full story in Proto Magazine here.

How a 3D Model of Alzheimer’s Disease is Providing New Hope in the Search for Treatments

Reigning in Alzheimer’s disease continues to be a challenge — more than 10 million families are affected by this degenerative neurological disease, and the number of patients dying from the disease has increased 68 percent since 2010.

In the past decade, attempts at developing drugs to slow or halt the progression of Alzheimer’s disease have been unsuccessful. The traditional path for early testing of promising therapies – mouse models – has been ineffective, and more than a dozen major clinical trials have failed.

But scientists and clinicians at Massachusetts General Hospital’s Institute for Neurodegenerative Disease (MIND) have developed an innovative new approach that could significantly improve the drug development process.  The laboratory teams of Doo Yeon Kim, PhD, an investigator in the Genetics and Aging Research Unit at MIND, and Rudy Tanzi, PhD, have found a way to grow human neural stem cells in a three-dimensional gel matrix.

This gel system allows the neural cells to grow more naturally and form into 3-D networks just like they do in the brain. It also provides a more accurate model of the signature plaques and tangles that develop around these neurons in Alzheimer’s disease.

The stem cells used in this lab model are genetically engineered to produce two proteins that are the hallmarks of Alzheimer’s disease – β-amyloid and tau. In the brains of people with Alzheimer’s, excessive accumulation of β-amyloid results in the formation of plaques in the spaces between neural cells, while tau is the main component of destructive neurofibrillary tangles within the cells.

Until Dr. Kim’s success, no single model of Alzheimer’s disease contained both amyloid plaques and neurofibrillary tangles. It usually takes a year to develop plaques in mouse models, it took only six weeks to develop both plaques and tangles in the “dish.”

Dr. Kim is now working with a consortium of labs to test thousands of FDA-approved drugs in this “Alzheimer’s in a dish” model to see if any of the drugs are effective in reducing levels of p-tau, a protein that is increased in Alzheimer’s patients.

Of the 2,400 drugs that have been tested, the team had approximately 40 promising hits that they can now investigate further.

Learn more: https://giving.massgeneral.org/fresh-alzheimers-approach-sparks-hope/

Researchers and Clinicians Revolutionize Prevention Efforts for Brain Disease

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What if you had a strong family history of Alzheimer’s disease, but weren’t currently showing any symptoms? What could you do to stave off the cognitive decline and loss of memory associated with this devastating disease? A team of researchers and clinicians at Massachusetts General Hospital wants to be your resource in situations like these.

The Institute for Brain Health at Mass General is revolutionizing the way we treat brain disease by developing new strategies for prevention, risk reduction and early treatment. They work with individuals who are at high genetic risk for brain diseases as well as healthy individuals who want to maintain good brain function as they age.

The Institute encourages life-long relationships with its patients to support the establishment of healthy brain habits and to provide guidance when new illnesses develop that can impact the brain. In doing so, the research team is able to collect longitudinal data about the development and progression of brain diseases throughout the life cycle. This data is helping to advance understanding about the progression of diseases like Alzheimer’s, in which so much is still unknown.

Learn more about the Institute for Brain Health in this article.

The Research Institute:
Saving Lives Through Science
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The Massachusetts General Hospital Research Institute is the largest hospital-based research program in the United States, with a community of over 10,000 people working across more than 30 institutes, centers and departments.

Our researchers work side-by-side with physicians to pioneer the latest scientific advancements for curing disease and healing patients in Boston, across the United States and around the world.

To learn more about the Research Institute, please visit our website.

Both Patients and Researchers Have a Role to Play in Preserving Brain Function

Reposted from the Mass General Giving Website

green-braintreeBrain health is key to living a long and happy life.

Too many Americans suffer from Alzheimer’s and other brain conditions that rob them of their memories, their independence and their lives. In fact, 1 of every 3 seniors dies due to Alzheimer’s and other forms of dementia.

Here are some tips for improving brain health:

First, exercise is essential.

Promoting blood flow to the brain is vitally important, so exercise is a key part of maintaining brain health. Keeping your heart pumping provides the vital oxygen your brain requires to stay active.

Second, be social.

Those who have social networks maintain healthier brains than those who are isolated. So, visit with your friends, family and neighbors. Seek out social occasions and fight back against isolation.

Third, maintain a healthy balance.

Focus upon a diet that is high in fiber and fruit, be sure to get at least 7 to 8 hours of sleep each night, and avoid stress as much as possible.

An active brain is more likely to stay a healthy brain. You must constantly challenge your brain.

Fourth, use it or lose it.

An active brain is more likely to stay a healthy brain. You must constantly challenge your brain. Puzzles alone are not enough. Learn new things. Constantly educate your mind, because learning results in positive, physical changes in our brain.

 

Mass General created the Institute for Brain Health to integrate our research into Alzheimer’s, strokes, Parkinson’s, ALS and other brain-related diseases and conditions that affect too many Americans. The doctors and staff are working to develop new treatments to preserve brain function and prevent these diseases.

The Institute’s co-founder Jonathan Rosand, MD, MSc, chief of the Division of Neurocritical Care and Emergency Neurology, has led groundbreaking research into preventing brain disease, and Bradford Dickerson, MD, director of Clinical Applications, is studying older adults who have maintained the resilient minds of younger people.

While our researchers do their job to fight brain diseases, please do your part to protect your brain by keeping it active. Check out our Brain Health Quiz, learn something new and keep your brain healthy today.