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Biotech Medicine

New Blood Test Offers Early Warning for Alzheimer's Onset 86

Georgetown researcher (and executive dean of Georgetown's medical school) Howard Federoff has taken a "systems" approach to diagnostics for certain chronic diseases. By comparing blood samples taken from patients who subsequently developed Alzheimer's to blood samples after the disease has manifested, Federoff has identified markers and created a blood test that is described as "90 percent accurate" (the BBC article does not delve into the ratio of false positives to false negatives) in predicting whether a currently healthy patient is likely to develop Alzheimer's in the following three years. Understandably, this raises some ethical and practical questions. What would you do differently if this test came back positive for yourself? Or for a parent? Here's the (paywalled) paper, at Nature Medicine.
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New Blood Test Offers Early Warning for Alzheimer's Onset

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  • As a neurologist. (Score:5, Informative)

    by MPAB ( 1074440 ) on Sunday March 09, 2014 @05:34PM (#46441771)

    The main symptom that brings people to the neurologist is forgetfulness. Most of the time it's subjective (ie. I know someone with Alzheimer's and I begin to notice and worry about the times I meet people and the names won't come to my head). We look for signs of cognitive impairment, with tests that include memory and other mind processes. Of course, YMMV depending on your previous performance, career, educational level, etc.
    Once we get proof of MCI, we can make some tests because Alzheimer's isn't the only thing that can cause it. The usual stuff ranges from depression or unfelt strokes to syphillis. The CAT scan/MRI only tells us if the brain is intact, somewhat like trying to work out if a car works by just opening the hood.
    Alzheimer's itself can only be diagnosed under the microscope right now. Not a thing we'd agree to to do a live brain.
    Other than this blood test, there are radioactive tracer tests and CSF tests. In all of them the result is a chance or ratio telling the possibility of the MCI to be a sign of Alzheimer's against something else.
    So, it's a disease for which there is no prevention nor a cure and the current tests just tell us "yes your worries about that time you left the keys on the toilet are related to a 75% propability of having Alzheimer's". We should get into positive and negative predictive values here.
    As I tell my patients: "No: there is no sign of cognitive impairment right now. If I knew you were to develop a demence, I'd suggest you settle your pending issues right away, but I don't see a reason not to do that, anyway, You don't know what awaits you at the turn of the corner."

    • Re:As a neurologist. (Score:5, Informative)

      by ljw1004 ( 764174 ) on Sunday March 09, 2014 @07:36PM (#46442269)

      So, it's a disease for which there is no prevention nor a cure

      But there are some candidates in Phase 3 clinical trials at the moment, which all will work best if they can have an early diagnosis. I think that's why news of diagnostics tests is good. If any of these candidates pass their phase3 trials, they'd probably be on the market in 2017 - 2018.

      * Solanezumab [datamonitor.com] from Lilly
      * BACE1 inhibitor [alzforum.org] from Merck
      * LMTX [alzheimersstudies.com] from TauRx

      Disclaimer: I have family working on LMTX.

      • by pepty ( 1976012 ) on Sunday March 09, 2014 @09:27PM (#46442741)
        Alzheimer's has been a multi billion dollar graveyard for Pharma over the past ten years - and Solanezumab isn't looking too healthy. Best of luck to Merck and TauRx.
        • Alzheimer's has been a multi billion dollar graveyard for Pharma over the past ten years - and Solanezumab isn't looking too healthy. Best of luck to Merck and TauRx.

          I think the issue is that they are trying to solve a complex aging issue with a pill. It's like being able to solve old age with a pill.
          There are certain things that can help. Taking an aspirin can reduce the chance of a heart attack and a different pill might lower
          blood pressure but you aren't going to find a single pill to cure heart disease either. Until we figure out a way to eliminate the
          signs of aging and the way the body starts to break down, most of these "cures" are nothing more than stopgaps.

          • by pepty ( 1976012 )

            It's worse than that: by the time things like Alzheimer's or cardiovascular disease are symptomatic a lot of damage has already been done. To prevent the damage you may have to start treating a decade or more in advance of any symptoms, since healing the damage will only be partial at best. To develop a therapy and determine its efficacy means running clinical trials over a decade or more, something no Pharma wants to face. You can improve the situation a lot via biomarker tests - or just complicate it furt

      • Not just that, but I'd wager that a blood test is way cheaper than being scheduled for an MRI. Plus if you have 3 tests, and they all come back high probability, your confidence in the diagnosis is increased.
    • by Roger W Moore ( 538166 ) on Monday March 10, 2014 @01:13AM (#46443439) Journal

      If I knew you were to develop a demence, I'd suggest you settle your pending issues right away, but I don't see a reason not to do that, anyway, You don't know what awaits you at the turn of the corner.

      It's not so much "pending issues" I'd want to settle it's more a case of holidays. Having had a father who died of alzheimer's last year my mum was trapped at home with him for several years and got very few trips away. If my dad had known that he was going to develop the disease in a few years then they would likely have taken more holidays, visited family etc. a lot more because there was a limited window to do so. As it was it was about a one year window from diagnosis to my dad being too confused to travel.

      This is not the sort of thing that you would do without knowing knowing that you were developing alzheimer's since, if you took all that travel at once, you'd be stuck at home for several years afterwards. So if there is still no cure when I get to the age to worry about alzheimer's I would certainly find a 3 year advance warning useful - it gives you time to visit the family and travel while you know what you are doing. It's also easier to put your affairs in order before you start to suffer from the symptoms since financial matters are hard enough to get right with your full mental faculties.

      • See "Final Exit" method. As for knowing, though, you may be disappointed. Brain disorders are fascinating and terrifying. When reality doesn't make sense to your brain because of physical errors in processing, your brain simply confabulates whatever details it needs so that things do make sense internally. These confabulations are not amenable to outside reasoning or exposure to evidence that contradicts them. This is equally true with dementia disorders such as Alzheimers as it is with brain damage from
        • You are completely missing the point. That's why I would want the blood test. It tells you that you will develop the disease BEFORE you have symptoms so you have several years to go travelling and visit family before your brain starts to shut down.
    • by Udom ( 978789 )
      The approach locks understanding of alzheimers to body chemistry and that's certainly one component, but there are other elements that go unaddressed. In western nuclear families children grow up and move elsewhere and the elderly often end up living alone. Exclusion and isolation are painful and severe punishments, particularly for women. Elderly women typically fret constantly about their sons, daughters and grandchildren, whom they are lucky to see once a month. In this position little else seems import
  • Work to protect my assets from Medicaid.

    • Format a few drives.
    • Re:What would I do? (Score:5, Interesting)

      by akozakie ( 633875 ) on Sunday March 09, 2014 @08:27PM (#46442503)

      Heh... Easy question, unfortunately.

      Top priority: prepare an easy and painless way out. Guns are illegal here, so it would take a bit of thinking, organizing, saving money, etc. Probably the best solution would be an international trip to a clinic that will help me, but I would need a backup plan if someone decided to stop me. Better do it early and be ready for later, with a plan simple enough to execute when the illness already has a significant effect (but before it makes me forget I have that option). Later I may not be able to do this and noone will help me. Hell, I wouldn't even ask for it, I don't want that helpful person to go to jail.

      Oh, I could have other priorities, if I could achieve this just by making my wish clear. But as long as euthanasia is not legal here, I'd have to rely on myself, so waiting too long would be risky. I will not reach the final, infant-like stages if I can help it. I prefer to keep my dignity, thank you.

      So, this is the most important thing. Number two is obvious too - research into current best practices and applying them (diet, activity, training, whatever). Even if it buys me just a few more months of mostly normal life, it's worth it.

      Not to suggest that anyone should do the same. If your views or priorities are different, feel free to do whatever you want.

      • Heh... Easy question, unfortunately.

        Top priority: prepare an easy and painless way out.

        My familiy is under orders to put me on a jet to Alaska, and from there, a bush plane to as far north as possible, and deliver me to Inuits, with instructions to set me out in the weather as senilicide. For that, I'll make a sizable contribution to the village.

        Only an hour or so at -20, and I'll be polar bear food.

        • You'll probably end up getting rolled in Anchorage and get stuck at the Motel 6.

          That would be a horrible way to go.

          • You'll probably end up getting rolled in Anchorage and get stuck at the Motel 6.

            That would be a horrible way to go.

            As compared to most of my relatives, catheterized and on anti-Psychotics, bedridden and bedsores? Wearing diapers so they can shit themselves with impunity. Not knowing who they were, if they were lucky, their skin peeiling off? One took 10 years to die that way.

            The good news is the nursing homes took pretty much every cent they had, so the will recipients didn't have anything to fight over. Yeah, that's so much better than freezing to death in a couple hours.

            • Agree completely. When it's my time, I'm taking the long walk. I will meet my maker, or oblivion, under a starry winter night sky far from civilization. That's how I want to go.
              • Agree completely. When it's my time, I'm taking the long walk. I will meet my maker, or oblivion, under a starry winter night sky far from civilization. That's how I want to go.

                And really, that is so much better. None of us gets out of here alive, and the concept of fighting in agony to spend that last few seconds is incredibly masochistic.

                Anyone thinking this is so awful, simply needs to compare your rather poetic description of an end to life, to the long, and morally bankrupt forced "life" in the Terri Schiavo case. Forcing bodily functions on a corpse that long ago had her brain converted to cerebrospinal fluid is something that an evil doctor in a horror film might do.

      • Top priority: prepare an easy and painless way out. ... Better do it early and be ready for later, with a plan simple enough to execute when the illness already has a significant effect (but before it makes me forget I have that option).

        It would take a little bit of thinking but the best solution if you really wanted to do this would be some sort
        of dead man's switch that exploited your forgetfulness. i.e. a drawer that explodes if you open it. A
        bottle of soda in the fridge that is poisonous, etc... You could easily have multiple booby traps in your
        house rigged to go off if you forget they are there. As long as you were of sound mind, you would know
        not to trigger them but how to do this safely without accidently endangering a caretake

  • Is if you forget to go to your appointment to take this blood test.
  • by Dr. Spork ( 142693 ) on Sunday March 09, 2014 @05:49PM (#46441817)
    If the test is 90% accurate and then has 10% false positives, then one out of ten people who fail the test is actually free of Alzheimer's. But if only 5% of the general population actually develop Alzheimer's, then even if you fail the test, you are still most probably (67%) in the clear. Granted, it's a reason for concern, because your odds of being in the clear dropped from 95% to 67%, but it's certainly not as big an update of your odds as you might have expected from a 90% accurate test that you just failed. (Right? Or did I screw up the math?)
    • Apparently there is a big difference between 99% and 99.9%
      http://idle.slashdot.org/story... [slashdot.org]
      I'm sure it gets even bigger when you're down to 90%

    • by Jmc23 ( 2353706 )
      You even sporked the words up!
    • Its hard to say if 90% really means 10% false positive rate. It might mean 0% false positive but that 10% of people who will get Alzheimer's will not show up positive on the test. Think about pregnancy tests. If it shows positive, you most likely are. If it's negative, there's chance you might still be pregnant.
      • by raynet ( 51803 )

        Think about pregnancy tests. If it shows positive, you most likely are. If it's negative, there's chance you might still be pregnant.

        And your example is of a test that has false positives and false negatives.

        The OP is right in that the 90% accuracy is not very useful until we know how common Alzheimer's is in the population taking the test

        Good example of this was 99% accurate HIV test if it is applied to random sampling of all people. As HIV is so rare, if 100.000 people take the test, it will flag 1.000 as having HIV even when don't and correctly identify 10 real HIV cases and miss 1. (numbers pulled from memory and probably not accurat

        • by pepty ( 1976012 )
          In the sample 10% (53 out of 525) had or developed Alzheimers or other cognitive impairments within 5 years.
          • by raynet ( 51803 )

            So that means 90% accurate tests will correctly identify 425 non-Alzheimers cases, miss 5 cases, detect 48 Alzheimers cases and give out 47 false-positives. So in this case when the test flags you, there is 50% chance that you are false-positive.

    • by pepty ( 1976012 )

      They used mass spectrometry to analyse the blood plasma of 53 participants with mild cognitive impairment or Alzheimer’s disease, including 18 who developed symptoms during the study, and 53 who remained cognitively healthy. They found ten phospholipids that were present at consistently lower levels in the blood of most people who had, or went on to develop, cognitive impairment. The team validated the results in a set of 41 further participants.

      I think they will need to look at a much bigger sample before calculated odds will be meaningful. Also, the test may well lose its predictive power if applied to the general population as opposed to people over 70.

  • As this is just more way to get the pre existing condition black list and job based health insurance is slowly fading away as well.

    The ACA did kill off the junk plans that some jobs used to offer that did not cover anything any ways.

  • If it were me (Score:5, Interesting)

    by transporter_ii ( 986545 ) on Sunday March 09, 2014 @06:38PM (#46442023) Homepage

    I would change my diet very quickly and take up jogging:

    Is Alzheimer’s Type 3 Diabetes?
    http://opinionator.blogs.nytim... [nytimes.com]

    Also, I would look specifically at anti-inflammatory diets, because Alzheimers, like many chronic modern diseases, is linked to chronic inflammation (in this case, in the brain):

    > Since the late 1980s, various studies have found hints that the chronic inflammation found in Alzheimer’s hastens the disease process

    See the connection?

    http://www.webmd.com/diabetes/... [webmd.com]

    Inactivity and obesity increase the risk for diabetes, but exactly how is unclear. Recent research suggests that inflammation inside the body plays a role in the development of type 2 diabetes.

    The good news: An "anti-inflammatory" diet and exercise plan can help prevent and treat type 2 diabetes.

    The effects of inflammation are familiar to anyone who has experienced a bug bite, rash, skin infection, or ankle sprain. In those situations, you will see swelling in the affected area.

    With type 2 diabetes, inflammation is internal.

    • by LaZZaR ( 216092 )

      I second everything mentioned above, and also recommend the book "Grain Brain" (look it up on Amazon). It is written by a neurosurgeon who makes a very compelling, leading edge (and medically unpopular) case against grains and gluten, its relationship to inflammation and its effects on Alzheimer's, and the uncanny links with other first world epidemics like diabetes, obesity, heart disease, etc. Its very easy to read and there is lots of research referenced throughout.

      At 33 I recently went through a cardiac

    • Re:If it were me (Score:4, Informative)

      by flyingsquid ( 813711 ) on Sunday March 09, 2014 @08:38PM (#46442559)

      Diet can have a profound effect on brain health. One example of this is epilepsy. It turns out that fasting can reduce epileptic seizures- in fact this was originally documented by the Greek physician Hippocrates, in the 5th century BC- but obviously that's not a viable long-term treatment, since eventually you have to eat or you starve. However, it's possible to mimic the state of fasting if you cut your carbohydrate consumption- the body burns fat, instead of sugar, just as it does in a fast. Using low carbohydrate diets- either a fat-heavy ketogenic diet or the induction phase of the Atkins diet- it's possible to reduce seizure frequency in most people with epilepsy. Often it's effective where drugs fail, and a small percentage of people- around 15% actually see seizures eliminated, sometimes permanently, even after they discontinue the diet. In other words, in a small number of patients, diet can actually cure a severe neurological disease like epilepsy.

      A few years ago some psychiatrists speculated that it might work for bipolar disorder as well. The thing is, drugs that work for epilepsy also work for bipolar, suggesting they are somehow related. This was purely speculation at the time, but there are now a couple of documented cases of people suffering from bipolar who have been successfully treated with low-carbohydrate diets- and they claim it works better than the drugs.

      The implications are profound. Some psychiatric and neurological disorders may in fact be metabolic disorders, perhaps in part caused by diet. There's been a big push in the past few decades to focus on DNA as the answer to everything, but there's a huge environmental component to these disorders. Twin studies show that if one twin has epilepsy, the odds of the other getting it are only around 50%. So even with identical DNA, and being raised in a similar environment, they only have about a fifty-fifty chance of getting the disorder... clearly genetics aren't destiny. What we really need is a better understanding of the environmental effects that cause one person to get a neurological disease, while the another stays healthy. Throwing drugs with severe side effects at people after they get sick is a good business model for pharmaceutical manufacturers, but what we really need to do is prevent people from getting these disorders in the first place.

      Last, the observation that low-carbohydrate diets can be effective in treating severe neurological and psyhicatric diseases... well, it has disturbing implications for modern, high-carbohydrate diets.

    • by Anonymous Coward

      My grandfather (born in 1909) was the healthiest man I have ever known. He was a fitness and health enthusiast. He always ate healthy foods and was extremely active. He developed Alzheimer's at age 75. His mother had dementia (probably Alzheimers). My mother is now showing signs. Genetics seems like a more of a factor.

  • by dalias ( 1978986 ) on Sunday March 09, 2014 @07:29PM (#46442227)
    Increase my coffee intake from 1-3 cups per day to 10+ cups per day: http://www.ncbi.nlm.nih.gov/pu... [nih.gov]
    • by sinij ( 911942 )

      IAmTryingThisDietRightNowButWhyIAmHereAgain?!
       
      *Furiously shuffles away with his walker*

  • Oh wow, what a useful breakthrough...considering there's no cure or prevention.
  • ... with the stipulation that it cannot be further modified by me at any time after I have been diagnosed as having such dementia.
  • Now that I have your attention with my crude joke*, here's the real tip -- coconut oil. virgin. cold pressed.

    Greenie article:
    http://undergroundhealthreport... [undergroun...porter.com]

    Clinical trial:
    http://health.usf.edu/NR/rdonl... [usf.edu]

    (*My get out of jail card - a family history of dementia)

  • I would volunteer for that one-way mission to Mars!

    Of course the trip better not take too long, because of the Alzheimer's progression. If I get there too late, I might make a fool out of myself on the mission:

    "Hi, Mars, Bob Flemstein, big fan! I know you're crazy busy with us suicidal visitors and everything, but...could you sign? I don't wanna be that guy, but..."
  • Who wants to know earlier they have a horrible fatal disease? And who wants their insurance company to know that as well?

  • Professor Bob Nagele (from the med school I'm attending now) has had a blood-based Alzheimer's test since 2011 [webmd.com]: http://www.plosone.org/article... [plosone.org]

    Using human protein microarrays to characterize the differential expression of serum autoantibodies in AD and non-demented control (NDC) groups, we identified potential diagnostic biomarkers for AD. The differential significance of each biomarker was evaluated, resulting in the selection of only 10 autoantibody biomarkers that can effectively differentiate AD sera from NDC sera with a sensitivity of 96.0% and specificity of 92.5%.

  • From the author's research page [georgetown.edu]: "His research has received support from the National Science Foundation, the National Institutes of Health (NIH), and the U.S. Department of Defense, among other sources." Irritating, no?

  • There is a free 10 minute test that was developed at the UW which has a higher accuracy rate and can be administered by any physician.

    Without a blood draw.

    I guess if you don't pay for it, you don't realize the cheaper one is the better one.

    And the reason for using a physician is that they can follow up with treatment after confirming the diagnosis.

  • Precautions: Do not consume alcohol, do not smoke.Do not eat tinned food or packaged food.Learn new things; stay busy in writing, reading and other things.Engage yourself in activities. Home remedies: Diet plays a very important role in slowing the progress of an Alzheimer patient [completehealthnews.com]. Almonds, hazelnuts, vegetable oils, egg yolk, whole grain products and avocado are rich sources of Vitamin E, which plays a role of deterrent to Alzheimer.Various Natural Herbs have medicinal properties that can fight Alzheimer.

Mater artium necessitas. [Necessity is the mother of invention].

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