Aging

So-called Lewy bodies - gumball-like clumps rich in a mystery molecule called alpha-synuclein - abound in Parkinson patients’ brains and are considered the hallmark of the disease. Up to now, researchers have had few solid clues as to what this “black hat” protein is doing in the brain in the first place.

But a team led by Stanford neuroscientists Tom Sudhof, MD, and Axel Brunger, PhD, has revealed a likely critical role played by alpha-synuclein in healthy brains. Their discovery is described in an article just published in the open-access online journal eLife.

Each of the human brain’s roughly 200 billion nerve cells communicates directly with, on average, 10,000 others by squirting signaling chemicals called neurotransmitters at them. It is all this squirting that underpins our thoughts, feelings and movements.

Of course, the brain’s activity is no mob squirt-gun shootout. Consider: The 2 quadrillion separate nerve-cell connections in your brain or mine roughly equal the number of stars in 7,000 Milky Way galaxies. For our most exalted organ to do its job, the signals that nerve cells send must be marked by profound precision, both in their intensity and in their timing.

As I wrote in my release accompanying the eLife article:

Nerve cells don’t simply squirt out neurotransmitters willy-nilly. Within the complex networks that constitute our brains, every individual nerve cell has a lengthy, snaking, tubular extension cord, or axon, that hooks up with thousands of other nerve cells. Neurotransmitters are housed within tiny bubble-like packets in the cell. These packets congregate in myriad small, bulbous nozzles dotting the axon, with each bulb abutting a downstream nerve cell. When an electrical impulse travels down the axon on which those bulbs reside, it triggers the fusion of the neurotransmitter-packed packets with the nerve cell’s outer membrane. The packets’ contents then spill into the narrow space separating the bulbs from the nerve cells they abut.

The Sudhof-and-Brunger team was able to show that alpha-synuclein helps regulate the orderly clustering of the neurotransmitter-loaded packets near their release sites. Alpha-synuclein has to be present in the right amounts, though; too much or too little has untoward consequences - which could explain why previous research has yielded conflicting results.

It’s nice to know, before messing around with it in living people, that in the healthy brain alpha-synuclein is a lot more than just a raw material in a gumball factory. Drug companies may have perhaps been led down some blind alleys as a result of locking in, too early, on the notion that yet another clump-generating protein, A-beta, was the Bad Guy in Alzheimer’s disease and that, it followed, getting rid of it would be a good idea. Maybe not so fast…

Previously: Nervous breakdown: Preventing demolition of faulty proteins counters neurodegeneration in lab mice, Stanford scientist sets sail on new publishing model with launch of open-access, embargo-free journal and Stanford study identifies molecular mechanism that triggers Parkinson’s
Photo by akeg

My sister, Cathleen, recently passed away. She had been in a coma for nearly a year from an accidental fall while visiting her daughter in New York. She lay on a sidewalk after apparently tumbling down the stairs and bled out for nearly 20 minutes until an ambulance arrived. She never regained consciousness.

Many, many times over the past year I wondered what she would have wanted if she had known of her cruel predicament. It was hard to imagine that a woman whose credo was ‘live, live, live’ would have wanted to waste away in a nursing home unconscious with little chance of recovery. Yet she was a fighter. Would she have wanted to grasp for every final bit of air before she breathed her last? Or at some point would she have wanted to just die peacefully?

I never had a conversation with my sister about end-of-life matters. Thankfully I also never had to make any fateful decisions since I wasn’t her legal guardian. Her husband and two daughters were ultimate authorities. But the question still gnaws at me even today, several weeks after her death. What would she have wanted? And in that time, I’ve thought a lot about what I would want if I were in that situation.

Ellen Goodman, the Pulitzer Prize winning columnist from the Boston Globe, never had a conversation with her mother about the end of life either. In the last years of her mother’s life, Goodman found herself swirling in a fog of decisions. They were basic decisions about care, treatment and survival - decisions that her mother was incapable of making:

In the last year of my mom’s life, she was no longer able to decide what she wanted for dinner, let alone what she wanted for medical treatment. So the decisions fell to me. Another bone marrow biopsy? A spinal tap? Pain treatment? Antibiotics? I was faced with cascading decisions for which I was wholly unprepared. After all the years I had written about these issues, I was still blindsided by the inevitable.

After her mother’s death, having keenly observed numerous great social movements throughout her years of reporting, Goodman wanted to create another movement. And so The Conversation Project - an initiative “dedicated to helping people talk about their wishes for end-of-life care” - was born.

I spoke with Goodman for a 1:2:1 podcast when she was out west to evangelize her project and to meet with VJ Periyakoil, MD, director of Stanford’s Palliative Care Education and Training. As a great journalist Goodman knows how to communicate, and she articulately laid out why The Conversation Project is landing at the right moment to launch another historical social movement.

Previously: Talking about a loved one’s end-of-life wishes, The importance of patient-doctor end-of-life discussions, KQED health program focuses on end-of-life care and Facing mortality
Photo in featured entry box by Alyssa L. Miller

Did you see yesterday’s Well blog entry on the growing number of older adults seeking therapy? Abby Ellin reported:

“We’ve been seeing more people in their 80s and older over the past five years, many who have never done therapy before,” said Dolores Gallagher-Thompson, a professor of research in the department of psychiatry at Stanford. “Usually, they’ve tried other resources like their church, or talked to family. They’re realizing that they’re living longer, and if you’ve got another 10 or 15 years, why be miserable if there’s something that can help you?”

Some of these older patients are clinically depressed. The National Alliance on Mental Illness reports that more than 6.5 million Americans over age 65 suffer from depression. But many are grappling with mental health issues unaddressed for decades, as well as contemporary concerns about new living arrangements, finances, chronic health problems, the loss of loved ones and their own mortality.

…

That members of the Greatest Generation would feel comfortable talking to a therapist, or acknowledging psychological distress, is a significant change. Many grew up in an era when only “crazy” people sought psychiatric help. They would never admit to themselves — and certainly not others — that anything might be wrong.

“For people in their 80s and 90s now, depression was considered almost a moral weakness,” said Dr. Gallagher-Thompson. “Fifty years ago, when they were in their 20s and 30s, people were locked up and someone threw away the key. They had a terrible fear that if they said they were depressed, they were going to end up in an institution. So they learned to look good and cover their problems as best they could.”

Previously: The importance of combating loneliness among older adults and Elderly adults turn to social media to stay connected, stave off loneliness

A past report from the Pew Internet & American Life Project shows that older adults have enthusiastically embraced social media tools. Now comes new research indicating that social media and online communities can provide valuable support for elderly patients in managing their health. Consumer Affairs reports:

“For me, it was interesting to learn that there is evidence for a large potential of social media in clinical practices,” said [Dr. Anja Leist of the University of Luxembourg]. “Older adults can use social media to access health-related information and engage in patient-to-patient-doctor conversations. There are many online forums where people in difficult life situations, such as informal caregivers of a spouse with dementia or individuals with depression, can exchange thoughts as well as receive and provide social support.

“Other positive consequences are that lonely adults can overcome loneliness through contact to family and friends and other users with similar interest,” Leist said.

However, researchers cautioned that several challenges need to be addressed before social media can be used in a clinical setting to help manage patients treatment, such as protecting personal health information and assisting seniors in identifying accurate online sources for medical information.

Previously: Study shows Internet can help raise awareness about cancer prevention, A look at social-media use among psoriasis patients and Patient online peer group offers community, drives research

Previous research has shown that elderly patients with an increased risk of stroke have an accelerated rate of cognitive decline. Now researchers at University of California, Los Angeles have combined a brain-imaging tool and stroke risk assessment to detect signs of cognitive decline in people without current symptoms of dementia.

In the study, a group of healthy and mildly cognitively impaired individuals with an average age of 63 completed neuropsychological testing and physical assessments to determine their stroke risk using the Framingham Stroke Risk Score. Additionally, researchers injected participants with a chemical marker called FDDNP and used positron emission tomography (PET) to image their brains. According to a university release:

The study found that greater stroke risk was significantly related to lower performance in several cognitive areas, including language, attention, information-processing speed, memory, visual-spatial functioning (e.g., ability to read a map), problem-solving and verbal reasoning.

The researchers also observed that FDDNP binding levels in the brain correlated with participants’ cognitive performance. For example, volunteers who had greater difficulties with problem-solving and language displayed higher levels of the FDDNP marker in areas of their brain that control those cognitive activities.

“Our findings demonstrate that the effects of elevated vascular risk, along with evidence of plaques and tangles, is apparent early on, even before vascular damage has occurred or a diagnosis of dementia has been confirmed,” said the study’s senior author, Dr. Gary Small… Researchers found that several individual factors in the stroke assessment stood out as predictors of decline in cognitive function, including age, systolic blood pressure and use of blood pressure–related medications.

The work appears in the April issue of the Journal of Alzheimer’s Disease.

Previously: How new imaging technologies may help advance early diagnosis of Alzheimer’s, Alanna Shaikh talks about preparing for Alzheimer’s, Common genetic Alzheimer’s risk factor disrupts healthy older women’s brain function, but not men’s and Alzheimer’s disease: Why research is so critical

Stanford physician VJ Periyakoil, MD, is a strong advocate for palliative care being “woven seamlessly into treatment” to reduce families’ stress levels and improve patients’ quality of life in their final days. As described in a profile piece published yesterday in New America Media, Perivakoil’s commitment and passion for changing the standard of care for patients with serious, chronic illness developed while studying geriatric medicine here. Paul Kleyman writes:

[At Stanford], she discovered another gap in her knowledge from patients who were deemed to have only six months or less left to live. Admitted to hospice care, their cure-oriented medical treatment would often be stopped in favor of “comfort” care.

“I had a hard time giving up on these patients,” she admits.

Her determination to improve the quality of their lives, no matter how much time they had left, led her to realize that palliative treatment should begin as soon as a patient is diagnosed with a life-threatening disease. Care provided only when someone becomes eligible for terminal hospice coverage comes too late to fully help them.

So, for example, the average hospice stay in the United States is now only 19 days. But palliative medicine begun much earlier reduces the agony and stress of disease so well that many patients actually survive longer. And family caregivers, relieved of constant stress, have been shown to live longer following a loved one’s death.

Periyakoil has since become a leading expert and medical educator in end-of-life care. In her role as director of palliative care education and training at Stanford, she continues to promote successful aging and end-of -life care for multi-cultural older adults through the recently launched Internet based Successful Aging (iSAGE) program.

Previously: Stanford introduces web-based mini-fellowship program on successful aging, The importance of patient/doctor end-of-life discussions and A Stanford nurse shares her experience in talking to her aging mother about end-of-life decisions, Talking about a loved one’s end-of-life wishes
Photo by Ani-Bee

Convincing my grandparents to join me in a game of Wii bowling or try their hand at playing Mario Kart would be a long shot, to say the least. But perhaps I could change their minds by telling them about new research from North Carolina State University showing that seniors who play video games have higher levels of well-being.

In the study, researchers surveyed a group of participants aged 63 and older about their video-game playing habits. Individuals then completed a number of tests designed to evaluate emotional and social well-being. Overall, nearly half of the participants said they played a digital game in the past year and a third reported playing once a week. Researchers wrote in the discussion section:

… Much of the psychological research conducted on the impact of digital games has focused on the possible adverse effects of playing digital games. Contrary to these and other studies, the findings of the current investigation suggest that older adults who reported playing digital games score, on average, significantly better than non-digital game playing on measures assessing a number of domains of successful aging. Specifically, older adults who were classified as Regular and Occasional Gamers reported less depression and lower negative affect as well as higher well-being than their non-gaming counterparts. One possibility for these findings is that digital games serve as a source of entertainment, which may lower negative affect and depression and increase well-being. In support of this interpretation, previous studies have found that adults who engage in more leisure activities report better emotional outcomes

The findings are particularly interesting in light of the nation’s aging population and past research showing baby boomers are more depressed than other age groups.

Previously: Improving patients’ lives through video games and Elderly adults turn to social media to stay connected, stave off loneliness
Photo by North Carolina State University

As previously reported here, Stanford researcher Abby King, PhD, and colleagues have been testing different smartphone apps to determine what type of framework best promotes exercise and eating healthy among older adults.

All three apps in her study used the accelerometer in participants’ smartphone and a custom program to monitor how active individuals were during the day. The analytic version used goal-setting and feedback to motivate users. The social comparison design utilized support and competition among a group to encourage participants to meet goals. And the third one, the game-style app, promoted attachment to an avatar, a digital bird, that thrived or languished depending on the healthy habits of its “owner.”

In a talk at last fall’s Stanford Medicine X conference, King shared results from her research and discussed which types of apps were most effective in improving healthy behaviors. The video, which was just posted online, offers some interesting evidence on how mobile device apps can change users’ behavior quicker than traditional methods.

Previously: Computer-generated phone calls shown to help inactive adults get – and keep – moving, Eat a carrot and exercise – or your iBird dies, Research shows remote weight loss interventions equally effective as face-to-face coaching programs and Monitoring patient wellness from a distance

If you’re like me, you sometimes worry about your hearing. Certain tones of voices and noisy places can make it difficult to pick up every word in a crowded room. Although I don’t have a severe problem (yet), many people do. Now Stanford researcher and otolaryngologist Alan Cheng, MD, and his colleagues have published work (subscription required) that one day may help those with what’s been called “the invisible disability.” From my release:

Twenty percent of all Americans, and up to 33 percent of those ages 65-74, suffer from hearing loss. Hearing aids and, in severe cases, cochlear implants can be helpful for many people, but neither address the underlying cause: the loss of hair cells in the inner ear. Cheng and his colleagues identified a class of cells called tympanic border cells that can give rise to hair cells and the cells that support them during a phase of cochlear maturation right after birth.

Hair cells work by swaying in response to the vibrations in the air caused by sound - like seaweed in an ocean current. But when these cells are damaged, that’s that:

“It’s well known that, in mammals, these specialized sensory cells don’t regenerate after damage,” said Alan Cheng, MD, assistant professor of otolaryngology. (In contrast, birds and fish are much better equipped: They can regain their sensory cells after trauma caused by noise or certain drugs.) “Identifying the progenitor cells, and the cues that trigger them to become sensory cells, will allow us to better understand not just how the inner ear develops, but also how to devise new ways to treat hearing loss and deafness.”

Cheng, who is a member of the Stanford Initiative to Cure Hearing Loss, collaborated with Stanford developmental biologist Roel Nusse, PhD, to investigate which cells in the inner ear might be responsive to a developmental pathway called Wnt that drives the renewal and proliferation of many types of stem, or progenitor cells. Together they identified a Wnt-responsive population of cells in the inner ear called the tympanic border cells and showed that, when grown under proper conditions in the laboratory, they could become sensory and supporting cells.

Now the next step is learning whether and how these cells could be coaxed to jump into action in people with hearing loss, says Cheng.

Previously: Regenerating sensory hair cells to restore hearing to noise-damaged ears, Stanford researcher comments on the use of human embryonic stem cells to restore hearing, and Growing new inner-ear cells: a step toward a cure for deafness

Biological aging, as opposed to the chronological kind we celebrate or curse annually, is what makes us describe some people as “ageless” and others as “old beyond their years.” We are collections of cells, and what happens in the cell doesn’t stay in the cell. It generates large-scale effects on our overall appearance, health and longevity.

A new study in JAMA indicates that otherwise healthy adults carrying a cellular signature of biological aging may be more vulnerable to infection and, once infected, more likely to exhibit symptoms. The experimenters first drew blood from 152 Pittsburgh residents, none of them over 55 years old, and dosed them with nose drops containing a common cold virus. Monitoring these volunteers for five days, the researchers took note of who sniffled and sneezed and who didn’t, and saw a correlation between study subjects’ susceptibility to the virus and a measure of biological aging called telomere shortening.

Telomeres, which cap the ends of each chromosome in every cell of all living creatures from fungi right on up to humans, are kind of like those plastic caps ringing each end of a shoelace. They stabilize chromosomes, keeping them from unraveling. (They prevent other damage, too.)

But telomeres aren’t so stable themselves. Rounds of cell division, bouts of stress, and episodes of inflammation cause them to shrink. If a telomere reaches a point where a chromosome’s integrity is challenged, the result could be cancer or some other malfunction in the cell housing the challenged chromosome.

Evolution has engineered protective mechanisms into cells so that if their telomeres get too short they die or, at least, lose their ability to divide any more. But this evolutionary emergency brake has its downside: It contributes to the slow but steady deterioration that manifests visibly in our aging skin and, less visibly, in all the other bodily organs.

In this case, the researchers were specifically interested in those bloodborne cells that comprise the immune system. But it’s widely believed that the state of telomeres in blood cells (the cells examined in the study) reflects their state in other tissues as well.

Just a week ago, a study in PLOS ONE led by Stanford psychopharmacologist Natalie Rasgon, MD, PhD, compared the telomeres in blood cells taken from high-functioning, well-educated, apparently fully healthy middle-aged women with a well-known genetic risk factor for late-onset Alzheimer’s disease (a good 15 percent of us are carriers) to those of otherwise matched non-carriers. The first group’s telomeres shortened by as much in two years as the second group’s did in ten, perhaps shedding some light on how this risk factor, called ApoE4, promotes cognitive decline. The good news was that the accelerated telomere shortening seen in ApoE4 carriers wasn’t observed if they’d been on estrogen-based hormone therapy at the onset of menopause and stayed on it for the study’s two-year duration.

While it might be nice to think longer telomeres are all it takes to ensure longevity, even the lengthiest telomeres are no match for a speeding truck. So be sure to look both ways before you cross the street.

Previously: Hormone therapy halts accelerated aging seen in women with Alzheimer’s genetic risk factor, Hormone therapy soon after menopause onset may reduce Alzheimer’s risk and Common genetic Alzheimer’s risk factor disrupts healthy older women’s brain function, but not men’s
Photo by ultrakickgirl