Saturday, June 28, 2008

Lewy Body Dementia

I just finished reading Dr Tom Graboys memoir describing his descent into dementia and Parkinson's disease. I give the writing 3 stars, the tremendous effort it must have take to organize and write the book a 4th star, and a big fifth star for the moving poem at the very end that was written by his dying first wife a few years ago. It's a quick read but well worth it.
I was amazed at how many symptoms Dr Graboys experienced that were also part of my dad's disease. My dad suffered from Lewy Body Disease and died in 2004 of an overdose of an anti-psychotic drug-Olanzapine (Zypreza)-after he contracted Neuroleptic Malignant Syndrome, an uncommon but not improbable outcome of overdose with this class of drugs. Dr Grayboys talks about his struggles with driving and with writing. My father clung to his right to drive for as long as he could, even driving my mother to the coast 60 miles from their home just months before he was hospitalized for the last time. When they got to the boarding house that night, he could not figure out how to get the car into the driveway so the hotel owner had to park the car for him as he stood by my mother's side and watched. Looking back, we realize what a tremendous feat of concentration it must have been to drive for 2 hours after dark to take my mum on that last trip. She spoke to me during the holiday, full of dread for the journey home. He made it admirably, going no faster than 30 miles an hour at any time. My dad always loved to drive and once his disease had really taken hold it was one of the few expressions of his utility to the family that he should continue to taxi folks here and there. Later, when he was in the nursing home my mum sold the car (she didn't drive) but we could never tell him it was gone. It would have broken his heart, at least what was left of it.
Dr Grayboys talks about his disease as being primarily Parkinson's Disease with some Lewy Body Dementia. In my father's case, the doctor had suggested he had full blown Lewy Body Disease and that the difficulties with gross motor skills were Parkinson-like rather than actual Parkinson's. After a review of the literature on Lewy Body it seems as though the symptoms define the disease and having Parkinson-like symptoms along with dementia means one has Lewy Body Dementia. Dr Graboys described his stooped appearance and I remember looking at my dad at one point and thinking he was physically reverting almost to the stage of fetal development where the fetus looks looks like a stumpy seahorse. His neck was thickened and stiff so he could not properly look up which emphasized the curvature and his stoop even more. It also gave him an appearance of extreme humility, which was fitting, because my father had always been one of the most humble human beings I have ever known. Dr Graboys seems more aware of his disease than may father was although the extent of denial was similar in each. Every symptom was entertained with an elaborate theory until finally in Dr Graboy's case, he had to give up practicing medicine, and in my father's case, the men in white coats came to take him away.
Lewy Body Dementia is not well-understood and according to the Lewy Body Society, under-diagnosed. 1 in 199 people are afflicted in their later year which adds up to about 150 million people across the States. There is no cure, yet, but Dr Graboys does mention a drug regimen that seems to be helping him- a combination of Aricept and Namenda, both indicated for dementia but usually with little long-term benefit. My father was considered past all help in that department and spent his last two years being calmed with the Zyprexa that eventually killed him. The Lewy Body Dementia Organization has an excellent website at The latest issue of their newsletter has an article on Dr Graboys and a touching picture of him in his local coffee shop which he still drives to everyday. There is also an article on one of the most fascinating symptoms of the disease (although it is not a definitive sign)--REM Sleep Behavior Disorder (RBD), where sleepers act out their dreams. For my dad this started many years before any other symptom and was a source of continual pain in my parents relationship. My mum couldn't help but take it personally when he would lash out is his sleep almost every night, and took to sleeping in a different bed once the flailing began. My dad remembered nothing of these episode of course.
To me, the disease is fascinating, terrifying and deeply sad. I look forward to researching more about the underlying pathophysiology and reporting back on what I find to this blog.

Friday, June 20, 2008

Scanning the mind--a quacker or not?

Another one from that fits the sorcery or science mold (Brain Scans as Mid Readers? Don't Believe the Hype, Wired, May 19, 2008). The article deals with brain scanning using functional and structural tools to determine how 'healthy' the brain is. The writer believes it is sorcery, the doctor he reported on believes it is science. I think it is classic Edge science where both sorcery and science are involved. The scans show particular features of an individual's brains, but the reported argues that this is meaningless without the solid hypothesis generation and testing that is a hallmark of 'real' science. The comments to the article are also interesting in that you get hearty agreement from some that the guys is a quack, while others defend the good doctor with a much vigor. Science at the edge involves observation and tolerance of soft measures. Many are uncomfortable with this, and with good reason. But, it has to be done this way if new advances are to be had.
My take: the images give a doctor data that he can use along with regular clinical data to better form his opinion about what may be troubling the patient. It think the approach is probably more useful to understand brain irregularities when a patient has symptoms rather than just assessing overall brain health. The doctor's recommendation to take Gingko to improve activity in the brain is dubious and doesn't add to his credibility in my opinion. Edge science is by definition unproven. Benefits are often seen before they can be explained or clearly predicted. In fact, that is true of even pharmaceuticals if one takes the data on a person-to-person level. I'm reluctant to endorse these tools for marketing purposes but already we see them employed to this end. I don't know why i don't like it; it just feels a bit too predatory I guess.
I think we must remain open to the possibilities highlighted in Dr Amen's work for brain assessment as it accompanies more traditional psychological and psychiatric methods. The reporter is judging the work and his own 'diagnosis' by Amen based on reductionist values and he can't be blamed for that. Science has relied on these values since the Renaissance. We are now moving towards less reductionist approaches to science and medicine (we know too much to settle for pure reductionism in this day and age) and, provided we stay grounded in our objective of genuine enquiry, I think brain scanning in all its guises must be observed, debated, and eventually included (or not) as an important tool in the diagnosis and treatment of psychiatric brain dysfunction. It's role in marketing, however, requires some ethical debate. The article asks the right kinds of questions; the comments back show the polarized thinking that usually occurs at the Edges.
See: Wired Magazine 16.06 on 19th May 2008

Thursday, June 19, 2008

Gene testing under threat in California

Oh boy. Some interesting news today on about the recent cease-and-desist letters sent to 13 genetic testing companies in the state of California. The letters can be found at and basically state the the companies, which include 23andme, and Navigenics, are breaching 7 statutes regarding patient testing and lab certification by procuring clients directly rather than through prescription. What is at issue here is the role of physicians in genetic testing, and much rests on whether genetic tests results are considered merely information for the consumer, or more significantly, diagnostic for the patient.

I recently had a conversation with someone who had taken a genetic test and is now in possession of her genetic profile and its associated risks. She assumed the risks were definitive and that we would progress to certain diseases states if she id not take action. So, she began taking the potions sold by the gene testing company in order to protect herself from what would otherwise be genetic certainties. There are a few things wrong with this picture. Firstly, the tests are not usually definitive. As I said in a previous blog, diseases are the result of complex interactions between genes, physiology and environment. There is simply not enough research to pin a particular disease on most genetic variants...yet. It may come one day but for now we have indications of potential risk and that is all. There are certain genes that do confer serious and significant risk; the Huntington's Disease gene tests are predictive for example and testing should, and is, approached with caution (see previous blog). Secondly, most individuals are not sufficiently knowledgeable about genes and their effects to know how to interpret the genetic 'information' they get back from gene testing. The lady I spoke to believed they were definitive, but also believed the vitamin concoctions she had purchased would prevent bad things. Again, there are signs that supplements may be helpful in preventing some diseases, but most claims are not backed up by rigorous study. Gene tests can seem self-serving when they are packaged with convenient supplements to assuage the fear wrought by the tests in the first place.

The action of the health department in California is intended to protect the public as far as I can see. The situation seems complex but I think it is simple at one level. Personalized medicine is touted as the next big thing by the media and the companies who provide the tools. The benefits are obvious; targeting the right medicines to the right people to reduce side effects and improve effectiveness. The public wants personalized medicine and sees genetic testing as a first step to take control over their 'personal health'. It is natural and to be expected that someone will want to make a business out of it. It is also natural that the doctors feel they have lost control over an important health parameter especially since the data requires objective interpretation to be useful. My vote would be to keep gene testing as an option for folks who want it, ensure it is ordered through physicians, require ordering physicians to maintain a state-of-the-art understanding of the implications of gene testing and the risks it can potentially identify to the patient so that they can counsel the patient on findings, and, ideally, ensure all gene-tested subjects are entered into an anonymized database that also tracks their disease development should it occur. This way, the knowledge base on genetic risk grows and informs future interpretations.
In the article the CEO of Navigenics says she hopes the health department officials understand the difference between a genetic risk and a diagnostic. As I see it, the real question is, do the patients?

Wednesday, June 11, 2008

Huntington's disease--a case of genetic determinism

After yesterday's blog I said that most genes are not deterministic and the some genes confer some risk of some disease either alone or in combination with other genes. The Huntington's Disease gene is different. Inherit this one and the disease is yours. For a truly gripping account of one man's decision to test or not test, check out the June 16th New York Magazine, Mind Bomb by Kevin Baker. Kevin's mother has the disease and he has watched her decline over the past 13 years. Is he witnessing his future? You have to read the article to find out but regardless of his fate, the very act of taking the test is fraught with caution, process and bravery. This test is not one that is undertaken lightly. As one nurse put it, once you know, you cannot not know.
Read the article. It's an enlightening tale of what all of our futures could be like as we learn more about what our own genes mean for our future health.

Tuesday, June 10, 2008

Health advances-not so fast

A section of New York Magazine, June 16th 2008, begins with the words, ‘medicine advances at astonishing speeds’. It’s a profound statement but is it accurate? Of course it depends on what you mean by astonishing speed, but I think medicine progresses quite slowly considering the rate at which we accumulate new insights into disease and it’s potential treatments. We hypothesis and test at an alarming rate, but it can take an interminably long time for a new medicine to reach the pharmacy, or for a medical paradigm to shift. Take the Human Genome Project for example. This was a 13-year old project coordinated by the National Institutes of Health and the US dept of energy. Multiple countries participated as did the Wellcome Trust, a premier UK research foundation. Much was made of the effort which identified most of the 12-25,000 genes estimated to make up the human genome, and determined the sequence of the 3 billion chemical base bases that make up human DNA. (ref: As it neared completion, widespread anticipation grew among the general public about the slew of medicines that would surely follow the last gene identified. We are now 5 years on and there is little to show for it in terms of medical breakthroughs. The NIH itself admits that the analyses of the data will continue for many years. The most obvious outcome to date is the availability of a relatively cheap way to get a genetic profile for those that are brave enough. Even this though, is not a definitive depiction of the future for those that take the test. Genes are rarely deterministic, depending on environmental conditions to trigger and support their directives to vulnerable cells and systems. Some companies that administer the tests also supply the putative nutritional safeguards that go along with each potential risk, playing on the fears of the patient and pocketing the rewards as a result. Not that genetic testing is bad; rather that it needs to be kept in perspective. Knowing your genetic risk can be a good thing if the risk is well characterized and there are things you can do to off-set the disease. For most genetic risks, that is not the case. Human physiology in health and disease is fascinating and complicated and inherently unique. Understanding the interactions of genes with each other and the environment in which they operate requires lengthy research and analysis. We should learn to set our expectations. Accumulation of observations is indeed fabulously fast. But translation to, and acceptance of, real benefit will always be, by comparison, painstakingly slow.