Shraddha Chakradhar

Category: Medicine

Alzheimer’s Disease and Sleep

NPR’s Morning Edition is doing a “Fade to Darkness” series about Alzheimer’s Disease all week. To go along with it, I figured I’d write about this study I read a few weeks about Alzheimer’s and sleep.

Researchers at Washington University in St. Louis’ School of Medicine and Sleep Medicine Center have found an interesting trend in what they call a “marker” for Alzheimer’s Disease.

According to the study, the level of amyloid beta, the protein chain primarily responsible for the development of Alzheimer’s, fluctuates throughout the day. What’s particularly interesting about this new finding is that the fluctuation echoes the sleep-wake cycle.

Alzheimer’s Disease (AD) occurs when tangles of amyloid beta protein form plaques in the brain. These plaques form in existing tissue, and, depending on how advanced the disease is, disrupt functions of the brain and nervous tissue. This causes memory loss and other phenomena that we recognize as being symptomatic of AD.

Amyloid beta plaque in nervous tissue

While the trend had been previously observed in mouse models, this was the first study to observe it in human beings. Three different groups of people–people who had been diagnosed with amyloid plaques, people in the risk age group (over 60 years) with no plaques, and a younger, healthy group (mean age 35) that was not at immediate risk of developing plaques–were given lumbar punctures to extract cerebrospinal fluid and check for amyloid beta levels. The fluid was extracted every hour for 36 hours, and during this time period, the researchers also video recorded the subjects to look for possible connections between behavior and what the fluid levels reflected.

In regards to the link between sleep and amyloid beta levels, the researchers found that there was a 6 hour lag when compared to the sleep pattern. For instance, if the peak hour of sleep was at 4AM, then the lowest levels of amyloid beta were found to be at 10AM. Similarly, if peak hour of wakefulness was at 4PM, then highest levels of amyloid beta were at 10PM. They also found that this distinct peak-and-crest model was primarily in the healthy and non-plaque risk group. The model in the group with diagnosed plaques was relatively flat.

“As you age, your sleep is disrupted,” said Rachel Potter, research technician and one of the authors of the study, “and so what our study shows is that with people who are older, the more their sleep is disrupted, or the less sleep they get, the less their amyloid beta levels fluctuate.” And this likely means that there is more of a chance that the protein aggregates and forms plaques.

When asked if this meant that being deprived of sleep was an indication that you might be at risk for getting Alzheimer’s, Potter said that it was too soon to jump to conclusions. “For now, it’s just important to know that amyloid beta follows this pattern of fluctuation. Future studies will determine how important this pattern actually is.”


Boston Book Festival

Book lovers from all over the North East descended upon Copley Square yesterday to partake in the Boston Book Festival. Not even the chilly wind and threatening rain clouds could keep the fans from lining up outside the various panel locations to listen to their favorite authors speak. I was one of these people, giddy with the prospect of listening to famous authors speak, and better yet, getting my books signed by them (I have my priorities sorted, I know).

The most interesting panel I attended yesterday was “Frontiers of Science,” with Siddhartha Mukherjee, Lisa Randall, and Stephen Greenblatt, with WBUR’s Christopher Lydon as the moderator. Each of the panelists began the session with a brief introduction of their latest book. Greenblatt began with his book, The Swerve, and spoke about the connections between the humanities and the sciences. Randall spoke about her book, Knocking on Heaven’s Door, and Mukherjee, clearly the most popular of the three, spoke about his book, The Emperor of All Maladies.

What was most interesting to me, as a patron of both the humanities and the sciences, was the ease with which these three writers, (with some help from Lydon, of course) were able to see their own work in each others’ novels. Greenblatt’s The Swerve tells the story, among other things, of the ancient poet Lucretius’ idea of the world being made up of tiny particles that collide with each other in a “swerve-like” motion.  As a professor of English at Harvard, he likely does not work with scientific subjects on a regular basis, and yet Lisa Randall, a professor of theoretical physics at Harvard, was able to pick up from Greenblatt’s description of these “tiny particles” and apply it to work being done with the Large Hadron Collider in Switzerland. Similarly, Mukherjee, a cancer physician and professor at Columbia, identified the importance of fundamental particles in any system and described the role of genes in cancer development.

In the end, each of the writers emphasized the idea of continuity. Lucretius was working in the century before the Common Era, and yet his idea didn’t have any merit until 20th century experiments with nuclear and quantum physics proved his conjectures to be true. And just like atoms were found not to be the smallest part of matter, so too were cells proven not to be the smallest part of an organism. The discovery of genes and DNA revolutionized the field of medicine, especially of cancer.

And it is with the faith that science will eventually prove or disprove conjectures that Randall and Mukherjee take comfort in their (often bleak) work. Greenblatt, on the other hand, seemed like he was just happy to tell the audience a story that was still relevant today.


A Plague On Both Your Houses!

The famous words by Shakespeare (via Mercutio in Romeo and Juliet) are immortal, and so is, apparently, the plague’s influence. The plague, the Black Death, the one that Mercutio is referring to when he curses the Capulets and Montagues, is still around today. The same one that killed nearly half of the world’s population in the mid-14th century, plus or minus a few changes in the DNA structure. I know this now because I had to write a 600-word story about it this morning. I had between the hours of 9AM and noon to research and write a story about the Black Death. Needless to say, it was nerve-wracking. But I actually had a lot of fun doing it. For one, the topic was fascinating. As I was telling a colleague of mine, “I love medieval Europe and anything related to medieval Europe.” And second, I couldn’t afford to meditate for longer than a few seconds on the construction of a particular sentence. The urgency to get the story done and let little things go was refreshing from my usual routine of obsessing over using one word over another.

Anyway, I am posting my final product here. How do you think I did for 3 hours of work? (Bear in mind, we have thus far been giving a week to do something like this)


A collaboration of scientists from Germany and Canada has sequenced what they call a “draft” of the genome of Yersinia pestis, the bacterium responsible for the Black Death in Europe. Their paper was published online in Nature on October 12, 2011.

In an interview for NatureVideo, University of Cambridge Historian John Hatcher said, “The Black Death was an epidemic on an unimaginable scale. It swept across Europe in the mid-14th century, killing…up to half of the population, 1 in 2 of the population in a space of 7 years.”

The collaborative team was led by Kirsten I. Bos of McMaster University in Ontario and Johannes Krause of the University of Tübingen in Germany. Using the remains of teeth and bones they found in an ancient burial ground for Black Death victims in East Smithfield outside London, England, the team was able to sequence and reconstruct the ancient DNA of Y. pestis.

Discovered in 1894 by scientist Alexandre Yesin of the Pasteur Institute, Y. pestis has been infecting both human and animal populations for centuries. It originally evolved as a harmless soil-dwelling organism. The pathogenic strain, however, is found in fleas, which spread it to rats, which in turn spread it to human beings. And this pathway was how the Black Death spread so rapidly.

While most people are familiar with the devastating effects of the Black Death, fewer still know that the bacterium continues to infect people today, albeit in a less severe manner. “Although we think of the [Black Death] plague as something that happened a long time ago and [it] decimated European populations then, it’s still very much an ongoing concern, and a very important pathogen today,” said senior editor of Nature Magdalena Skipper in the NatureVideo interview.

In a Nature podcast interview, Johannes Krause said that there were approximately 2,000 cases a year worldwide in countries like the United States and Mexico, parts of Africa, as well as Asian countries such as China and India.

What the researchers were interested to know, Krause revealed in the same podcast interview, was how different current strains of the bacteria are from the ancient strains. What they found was surprising:

“We found almost no difference between the ancient plague and the modern plague strains” said Krause.  The difference was a matter of a few positions in the DNA sequence. These few positions, he elaborated, are ancestral to the modern strain. In other words, all the strains of Y. pestis that affect humans today descended from the ancient plague’s strain.

Why this is surprising is because of the effect that these similar strains have on human populations. The Black Death killed half the existing population, whereas the plague today affects less than 1% of the world’s seven billion population.

The reason for the difference is that medieval Europe was exposed to the plague for the first time when it was “unleashed” according to Krause. They had no prior immunity to protect themselves against it. Other reasons for the severity of the Black Death lie in factors that distinguish the mid-14th century world from the modern world: factors such as difference in climate and environment, as well as social and lifestyle changes.

What we can learn from the study is how quickly a pathogen can wreak havoc on a population that has no previous exposure.

“Paradoxically, society was able to cope much better in the 14th century with deaths on this horrendous scale than we would be able to cope today” said John Hatcher. “Today we have such complex interconnections that anything on that scale today would cause complete chaos.”

The Doctor Recommends…better communication?

The idea that the healthcare you receive depends on where you live is not new. Access to health care, income level, education level and cultural beliefs are all factors that play into the healthcare that is available to you. But does this affect what doctors recommend to you?

A study conducted by a team of communication and public health researchers at Ohio State University found that when it comes to the human papillomavirus (HPV) vaccine, what doctors tell parents about the vaccine depends on where they live. The area that the team was interested in was Appalachian regions in West Virginia and Kentucky. The HPV vaccine, which was developed to prevent infection that led to cervical cancer, was of particular interest because of the high rates of cervical cancer in Appalachia.

To see what doctors in the area were doing to curb the rates of cervical cancer, the team decided to survey pediatricians in West Virginia and Kentucky’s Appalachian regions. They also surveyed pediatricians in the non-Appalachian counties of the two states as a comparison. Of the 334 pediatricians who
responded to the survey (129 in Appalachia and the rest out of Appalachia), the study found that the pediatricians in Appalachia were less likely to recommend the HPV vaccine to applicable patients.

“We think that either the pediatricians in Appalachia don’t know that their patients are at a higher risk for cervical cancer, or that they are hesitant to recommend the HPV vaccine because they may be met with difficulty in convincing the parents,” said Janice Krieger, PhD, assistant professor of communication at Ohio State about why there was such a disparity between Appalachian and non-Appalachian pediatricians.

Neither of the hypotheses that Krieger proposed is comforting. The real problem underlying the issue, according to her, is communication. Pediatricians in Appalachia need to be better informed about the HPV vaccine and its effects on their patient population. The pediatricians also need to do a better job of informing their patients regardless of the qualms that they may have.

This leads to larger questions: should doctors change their recommendations based on the overall patient population? If pediatricians in Appalachia know that their patients are likely not going to be able to afford the HPV vaccine, should they refrain from informing them about the vaccine’s effects? Should the doctors inform their patients anyway?

Atul Gawande on Coaching in the Professional World

I recently had the opportunity to attend Atul Gawande‘s session titled “Do Surgeons Need Coaches?” at this year’s New Yorker Festival in New York City. Being an avid reader of The New Yorker magazine and an admirer of Dr. Gawande’s work (both medical and literary), I was excited and tried to keep my ridiculous excitement in check as he sauntered onto the stage from a side door and waited for the applause to die before he spoke.

Dressed simply in a white shirt, jeans and a brown suede jacket, he began with an introduction, a request to not photograph him (my heart sunk a little) and then jumped into his speech about personal coaches. He got interested in the topic of coaching, he said, based on his interest in two other themes.

“Number one is complexity,” he said, “the feeling that we are in a world that is requiring us to know more, master more in order to make some of the basic functions in society…feasible. The volume of information and ability you have to have just to get through the day has exploded, and it seems to only be accelerating.”

The second theme that interested him is how he improves as a surgeon. Up until recently, his surgical career and his ability to be better at his job were rising steadily. However, of late, it had taken to look more like a “plateau.” He was still a good surgeon, he said, but there was no progress.

And that’s when he looked into not only his own profession, but other professions as well, to see how people improve. Based on his research, he arrived at two basic ways of how people get better at what they do/want to do: the teaching model and the coaching model. In the teaching model, people, including surgeons like Gawande, train for several years in a classroom-type setting/atmosphere and then are, essentially, on their own to implement what they learned in school and hopefully, along the way, improve their methods and technique. In the coaching model, which is used by professionals such as athletes, no matter how good the team or how good the individual player, a coach is always present and is always finding ways to improve the game.

Wondering why more professions didn’t take advantage of the coaching model, Gawande decided to take on a personal coach for himself. Dr. Robert Osteen, a retired surgical oncologist at Brigham and Women’s Hospital, Boston, agreed to come in and observe one of Gawande’s surgeries. “I actually thought it went extremely well,” said Gawande about the first operation he had Dr. Osteen observe, “but he had a dense notepad of comments to make.” Dr. Osteen pointed out that Gawande had neglected to notice small things, and that these small things were what made the difference when cutting complication rates.

“When I operate, I operate with magnifying loops so that I can see the nerves and other things that I’m operating around, but that means that I’m not aware of everything that is happening around the room.” Some of the things Dr. Osteen observed were that one of the nurses had trouble with some of the equipment, the anesthesiologist had a blood pressure problem during part of the operation, and the lights had swung out of the wound area for nearly 30 minutes. “I was oblivious to it because I was in my tunnel,” said Gawande, motioning with his hands to mimic the effect.

So what if Gawande got a personal coach who helped him improve?

Gawande’s argument is that the medical world, as it is currently set up, employs a teaching model when it should perhaps consider a coaching model. Instead of only worrying about the number of procedures conducted by a doctor, Gawande believes that quality of care is going to begin playing a larger role.

When Gawande spoke to Dr. Osteen about coming into his operating theatre more, he said, “I’ll pay you.” To which Dr. Osteen astutetly replied, “Are you kidding? I’ll pay you.” Osteen saw the value in the approach that Gawande took.Coaches help us to step back from our complicated world, to step back from the “tunnel,” look at the bigger picture, and reassess our strengths and weaknesses. Coaches give us a better understanding of how to function in our own world.

Now if only I could find a way to convince Atul Gawande to be my writing coach, I could save my writing career from possibly plateauing.

I got the screen before Gawande came on stage, but I wasn’t allowed to photograph him, so here’s a CC-licensed picture from another event.