New Blood Test Offers Early Warning for Alzheimer's Onset

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.

Comments

As a neurologist.

[MPAB]

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.

[tsotha]

He can get away with "propability" as long as he's not writing.

Re:As a neurologist.

[ljw1004]

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 from Lilly
* BACE1 inhibitor from Merck
* LMTX from TauRx

Disclaimer: I have family working on LMTX.

Re:As a neurologist.

[pepty]

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.

Re:As a neurologist.

[Wycliffe]

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. Then again,
if the average person only has alzheimers for the last 20 years of their life maybe a stopgap is all we need.

The "false positives" thing really does matter

[Dr. Spork]

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?)

Re:The "false positives" thing really does matter

[raynet]

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 accurate)

Re: What would I do?

[kayaker01]

Format a few drives.

If it were me

[transporter_ii]

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

Is Alzheimer’s Type 3 Diabetes?
http://opinionator.blogs.nytim...

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/...

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.

Re:If it were me

[flyingsquid]

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.

Coffee

[dalias]

Increase my coffee intake from 1-3 cups per day to 10+ cups per day: http://www.ncbi.nlm.nih.gov/pu...

Re:Coffee

[sinij]

IAmTryingThisDietRightNowButWhyIAmHereAgain?!
 
*Furiously shuffles away with his walker*

Re:What would I do?

[akozakie]

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.

Re:What would I do?

[Ol Olsoc]

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.

Re:What would I do?

[ColdWetDog]

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

That would be a horrible way to go.

Knowing could be Useful

[Roger W Moore]

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.

Re:What would I do?

[Wycliffe]

This is better than carbon monoxide, because nitrogen is completely inert and doesn't leave a hazardous scene for those who are present/recovering your corpse.

Wouldn't a room full of pure nitrogen be just as dangerous to the person recovering you if they also will continue to breath normally
until they black out and die as well?