A Flicker of Hope

It’s interesting what catches our attention when we surf the apps on our smartphones nowadays. Some of the more provocative articles have dubious sources, of course, but with a little digging the original study can often be found and the claims checked. The problem, however, is that even these results need to be reproducible in case either the methodology or the results were unreliable –and also the conclusions drawn from them. That’s why it’s often unwise to believe everything you see reported –or, on the other side, to report everything you want to believe… Fear and Hope are wonderful incentives, and so the issues in the study need to be thoroughly researched and vetted for bias and innuendo and references to the original study need to be included.

Perhaps because I am now retired, any article about time-related changes catches my eye more easily. So I find myself particularly interested in studies that suggest progress is being made -not with respect to age itself, but more the evolving process of aging: the gerund. It was with considerable interest that I read the BBC news on the use of flashing light therapy for Alzheimer’s http://www.bbc.com/news/health-38220670

I also attempted to read the original paper from MIT (entitled Gamma frequency entrainment attenuates amyloid load and modifies microglia) published in the December 2016  issue, of the journal Nature should you wish to struggle though it, but I have to confess that for me, even the title was difficult…

At any rate, the article suggested that flashing light in the eyes of mice that were genetically engineered to have Alzheimer’s-type damage in their brain, ‘encouraged protective cells to gobble up the harmful proteins that accumulate in the brain in this type of dementia. The perfect rate of flashes was 40 per second – a barely perceptible flicker, four times as fast as a disco strobe.’ And ‘Build-up of beta amyloid protein is one of the earliest changes seen in the brain in Alzheimer’s disease. It clumps together to form sticky plaques and is thought to cause nerve cell death and memory loss.’ Research has focused on ways to prevent this plaque formation using drugs, but with limited success so far. If a non-invasive method like a flickering light can activate the immune system to do it by itself, so much the better. ‘The researchers say the light works by recruiting the help of resident immune cells called microglia. Microglia are scavengers. They eat and clear harmful or threatening pathogens -in this instance, beta amyloid. It is hoped that clearing beta amyloid and stopping more plaques from forming could halt Alzheimer’s and its symptoms.’ Fine with me.

I did, however, initially wonder about how bothersome the flickering would be –news reports on television usually caution their audience whenever even flash photography is found in the report, presumably because of the risk of triggering epileptic seizures. But, as the article discussed: ‘For the patient, it should be entirely painless and non-invasive “We can use a very low intensity, very ambient soft light. You can hardly see the flicker itself. The set-up is not offensive at all,” they said, stressing it should be safe and would not trigger epilepsy in people who were susceptible.’ Better and better! It’s just preliminary stuff, of course, but at least it opens up new pathways and ideas for further research.

As if even reading about the concept was in itself therapeutic, the article immediately triggered what, at first blush, would seem to be a non-sequitur memory of a patient I saw many years ago. The issue as I recall was not so much about mental aberration -although the patient herself was apparently suffering from paranoid schizophrenia- but more about her speculation on the possible effects of flickering light on mental function.

I was, I think, in my first year of residency training in the gynaecology program and was doing a rotation in one of the older teaching hospitals in the city. In those days, things were very busy on the wards and so our tasks were apportioned according to our seniority, the senior residents doing the lion’s share of new consultations, while we juniors were given those jobs that, while important, required less experience -pap smears, usually.

My senior’s name was Sara, I remember, and she decided I should be the one to go to the psychiatric ward to do a pap smear on one of their more ‘unusual patients’ as she said to tease me.

“What do you mean ‘unusual’?” I asked. Sara didn’t like to go onto that ward, for some reason, so she usually made some excuse.

She stared at me for a moment before answering, I remember. “Oh, you know, she has paranoid delusions and hallucinates, or something…” But it was clear that Sara really had no idea why our department had been asked to do the pap, nor had she any intention of doing it herself.

I was beginning to suspect this was merely another sluff. Sara fancied herself a consultant now and able to delegate things she didn’t want to do. “But if she’s paranoid and hallucinates, wouldn’t it be better if the doctor doing the pap smear was female?”

Her expression turned angry at that point, and I recall her almost attacking me with her eyes. “Oh for god’s sake, there’ll be a nurse there with you the whole time… Or maybe they said two…” she added, uncertainty softening her glare, but not her resolve to send me to that ward.

I showed up at the psychiatric area and was allowed in only after identifying myself via the phone just outside the door. Then I was led to the brightly lit nursing station, and a rather large matronly nurse handed me the chart of the woman needing the pap.

“She hasn’t had a pap smear in years,” the nurse said in a soft voice, so it couldn’t be heard in the corridor outside of the station. “And her voices told her she has cervix cancer…”

“Her voices?” I should have been more professional, but I was already feeling a bit apprehensive about being inside a locked ward. “I mean, shouldn’t we wait until she’s feeling a bit better before we…”

“We can’t seem to find any good medication for her yet,” the nurse interrupted. “The doctor thought that we could at least calm her by checking her cervix.”

Greta –I still remember her name- was already in the examination room, sitting in her gown on a little table that had a set of rickety old metal stirrups at one end. They’d apparently had to borrow everything from another ward for the job. As soon as I entered with the nurse, Greta examined me from top to bottom with suspicious eyes.

“You’re a man,” she said before we were even introduced.

The nurse, whose name I forget, walked over to Greta and held her hand. “You remember we talked about this, Greta,” she said in the same soft voice she’d used before. “And you said it was okay…”

Greta nodded, smiled and lay back to put her feet in the stirrups. “They said I should show you my cervix,” she said, the italics staring at me between her knees. “Not the one with cancer, though…  I’m supposed to keep that one hidden.”

“Her voices,” the nurse quickly whispered in my ear as I sat on a little stool they’d also borrowed for the occasion along with a light on a long, flexible metal pole. It looked as old as the stirrups.

I got the speculum and the pap smear paraphernalia ready as the nurse readied the light. The bulb kept flickering, though. I fiddled with the bulb to see if it was loose, but it seemed tight enough. And it was obviously plugged into the wall. On, off, on, off… the light was beginning to annoy me. I snapped the switch a few times, but still, it insisted on flickering. On, off, on, off…

“I’ve got a flashlight,” the nurse said, but when she turned it on, it was so weak, I knew I wouldn’t be able to see cervix high up in the vagina with it.

“Well, maybe I can do the pap smear with the flickering light,” I said and shrugged.

Suddenly Greta raised her head and stared at me again. “Sometimes the prongs don’t make good contact in the wall. Everything’s so old in this place,” she added, shaking her head. “Take the plug out and squeeze the prongs.”

By this time I had the speculum in my hand, so I nodded to the nurse to try Greta’s suggestion. Sure enough, squeezing the prongs stopped the flickering.

Greta was still staring at me through her legs. “I may be crazy, doctor, but I’m not stupid…”

I put the speculum down on the medical tray I had on my lap. I sensed Greta wanted to explain something. “It’s a signal, you know.” I didn’t think I should reply. “The light’s always trying to tell you something –sometimes it’s angry, but more often it’s just trying to help…” Her feet still in the stirrups, she raised herself onto one elbow and continued. “It gets right into the brain to help, you know. It doesn’t stay there long enough, though, and that’s why it has to keep going in and out, in and out… And each time it tries, it flickers…” Then she stopped talking for a moment and stared at the nurse with an amazed expression on her face. “That’s what the doctors should be trying –not all those horrible pills…”

Maybe that incident stands out because it was the first pap smear I’d ever done. I don’t remember the result in Greta’s case –I was near the end of my rotation in that hospital- but I do remember Sara asking me what I’d done with that patient.

“Why?” I asked, afraid Greta had accused me of doing something improper.

“The ward told me that your patient seemed much calmer after you left and she apparently kept telling everybody you’d come up with a new treatment, or something…” And then I remember Sara smiling condescendingly at me, as if to say that junior residents could never do anything of the sort.

 

 

 

 

 

 

 

 

 

 

 

 

 

 

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A test for Alzheimer’s Disease…

Now here’s a scientific and epidemiologic conundrum: Suppose you develop a test that will give you advance warning of a fatal disease you can neither treat nor prevent. But that foreknowledge might allow an understanding of the really early aspects of the disease -while it was still asymptomatic- that could eventually lead to a treatment. Especially if the disease, as most are, was potentially more treatable in its early stages. What should you do with the test? You need a lot of people to take the test so you can more appropriately generalize the information obtained and yet you can do nothing for them.  And what are the subjects in the test to do with the information? Suppose it is falsely positive and, despite what the results suggest, despite the worry and possible suicides contemplated, they will not actually get the disease. No test is perfect.

In other words, should you screen a particular population with the test, when the value is not so much for the individual tested as for the knowledge that might eventually be useful to someone else? How ethical is it? How cruel is it..?

People have thought about this, fortunately, and some guidelines were offered in 1968 by the World Health Organization for screening criteria. Among them are the suggestions that, not only should the condition be an important problem, but there should also be a treatment for the condition and an ability to diagnose it accurately. They also suggested the condition should have a latent stage when treatment would be expected to be more efficacious.

The problem I have set forth, of course, is exemplified by the recently announced test for Alzheimer’s Disease. (I have included two articles, the Huffington Post summary being the more easily assimilable of the two.)

http://www.medscape.com/viewarticle/821982?src=iphone&ref=email

http://www.huffingtonpost.co.uk/2014/03/10/dementia-early-detection-blood-test_n_4933188.html

It is obvious that Alzheimer’s disease and dementia are both important health concerns in a time when populations are aging in many countries. It would be helpful to know what facilities might be needed so the appropriate infrastructure could be planned for that particular demographic. But equally, it would be useful to know more about who in that population are particularly at risk so they could be studied. A recent report from the Alzheimer’s Association, for example, suggested that women over 60 are two times as likely to develop Alzheimer’s disease over the rest of their lives as breast cancer:

http://www.alz.org/news_and_events_women_in_their_60s.asp

Perhaps of paramount importance is studying the disease at an early stage to search for the cause. To devise a cure. And yet I can’t help thinking about the helpless laboratory animals in our research facilities, poked, prodded and experimentally assigned… But not for their own good. What constitutes a laboratory animal..?

Under what conditions, then, would it be permissible to undertake such a study? Informed consent is mandatory, of course, but what exactly would the participants be consenting to? To knowing about an inexorable decline in cognitive functioning that would rob them of that which they hold the dearest: themselves? We are our pasts -they are what knit the fabric of our identities into a pattern we and others can recognize from one day to the next. The present is a transient gift that constantly slips behind us so we have to pull it along like a shadow as we walk through time. We collect each present and store it on an accessible shelf like books we’ve read. Without them, we become functionally illiterate. Lost. Wandering endlessly through unmarked time as in a dense mist with no signposts we can see, let alone understand.

That this vision may encompass the tundra that is Alzheimer’s is obviously more pessimistic than may obtain: no doubt it is a condition that varies on a spectrum. But the prospects are not appealing, nor the amplitude of changes likely predictable -and I, personally, would not want to know about it until it has captured me and shrouded my awareness of what I had lost.

I suspect this is the reason for the cautionary statements of the investigators and the thrust of the caveats of the WHO parameters. I’m not sure what to do with the test they describe. It is obviously an important step on the road to understanding dementia and yet… I am reminded of that famous “To be, or not to be” speech by Hamlet in which he talks about death, but describes it in terms the more pessimistic among us might suggest could equally apply to Alzheimer’s disease:

The undiscovered country from whose bourn
No traveler returns, puzzles the will
And makes us rather bear those ills we have
Than fly to others that we know not of
I’m sorry, but I don’t think most of us are ready for the test just yet… Or is it only me?