National Geographic News
A photo of a woman surrounded by old photos.

According to researchers, patients with Alzheimer's may be affected by the disease long before symptoms like memory loss appear. Early diagnosis could slow its progression and improve treatments.

PHOTOGRAPH BY MARGHERITA VITAGLIANO, NATIONAL GEOGRAPHIC YOUR SHOT

Diane Cole

National Geographic

Published April 7, 2014

Can Alzheimer's disease be predicted? And if it could, would you want to take the test?

Those questions are being sparked by three new studies, each of which presents a potential method for foretelling, years in advance, the memory loss and cognitive impairment that are the hallmarks of the debilitating brain disease.

Researchers have already identified genetic risk factors that give some people higher odds of one day contracting Alzheimer's. The new studies are different: They propose that certain "biomarkers" of the disease may be detectable after it has begun to affect the brain, but before symptoms have become apparent.

The three studies target different biomarkers in different places: one in the blood, one in the cerebrospinal fluid, and one in the brain itself, as seen in PET scans. None of the tests are close to being available in doctors' offices and clinics. All will require more years of research.

What they share is the potential to "help us understand the early stages of the disease," says Dean Hartley, director of science initiatives for the Alzheimer's Association—and to improve treatment.

A Slow, Invisible Progression

Researchers believe that for perhaps as long as two decades before symptoms appear, the disease follows a steady, damaging course. It's characterized by a buildup in the brain of clumps, or plaques, of beta-amyloid protein and somewhat later by twisted tangles of another protein called tau protein. By the time the Alzheimer's diagnosis is made, the brain damage is already extensive.

The hope is that findings gleaned from earlier detection and diagnosis will also help encourage and speed the development of new therapies that can intervene that much earlier. "The earlier you are able to treat, the more you will be able to do to help, and the prognosis will probably be much better," Hartley says.

For now, however, the options for treating Alzheimer's are limited. The Food and Drug Administration has approved five drugs. All offer temporary relief for some people from the symptoms of Alzheimer's, but none treat the underlying disease.

That's the rub with the idea of earlier diagnosis. On the one hand, the possibility of a test for a disease that currently affects about 35 million people worldwide, including some five million Americans—numbers that are expected to grow larger as the population ages—heralds hope for even more research breakthroughs. On the other hand, with treatment options so limited, potential patients may be leery of foreseeing their future.

"If someone told me that there is a great test for someone like me, I wouldn't want it," says Jason Karlawish, professor of medicine, medical ethics, and health policy at the University of Pennsylvania Perelman School of Medicine. "It would be knowledge that would add to my level of existential anxiety."

Harbinger in the Blood

Perhaps the simplest and least invasive test would be the blood test currently under development by researchers led by Howard Federoff, professor of neurology and executive dean of the Georgetown University School of Medicine. Federoff and his colleagues from six other medical institutions collected blood samples and administered cognitive and memory tests to 525 people aged 70 and over. They then repeated the tests annually.

At the start of the study, 46 participants had some cognitive impairment; by the third year, another 28 had developed symptoms. The researchers discovered that the people with impairment had lower levels of ten blood lipids, even at the beginning of the study, than those who had remained cognitively healthy. The blood lipid levels could distinguish, with an accuracy of over 90 percent, who would remain cognitively normal and who would develop symptoms of Alzheimer's or of mild cognitive impairment over the next few years.

Blood lipids might predict Alzheimer's even farther in advance than that, Federoff says; to find out, he and his team are hoping to get access to archival blood samples from an older longitudinal study.

The researchers don't fully understand why blood lipids would be such good predictors of Alzheimer's. They'll need to understand more, and their study will need to be replicated, before there's any chance of a blood test for Alzheimer's becoming publicly available.

Spinal Taps and PET Scans

The other two potential tests are more involved. Claudio Soto, director of the Mitchell Center for Alzheimer's Disease and Related Brain Disorders at the University of Texas Medical School at Houston, has developed a test that detects misfolded beta-amyloid protein in tiny quantities in the cerebrospinal fluid of Alzheimer's patients—but not in patients with other neurological diseases.

"What we have shown so far is that we can find these particles and you can differentiate" Alzheimer's from non-Alzheimer's patients, Soto says. His study suggests these tiny beta-amyloid particles may be precursors of the plaques in the brain that are characteristic of Alzheimer's. He also wants to see if his technology can be applied to blood and urine samples—much easier to collect than cerebrospinal fluid, which requires a painful spinal tap.

PET scans can already detect beta-amyloid plaque in the brains of Alzheimer's patients. In the third new study, Murali Doraiswamy, professor of psychiatry and director of the neurocognitive disorders program at Duke University, showed that PET scans using the radioactive dye Amyvid can predict a high risk for developing Alzheimer's symptoms in patients that don't yet have them.

"If there are no plaques, the dye has nothing to stick to, so the PET scan is negative," Doraiswamy explains. "But if there are a lot of plaques," they will show up on the scan.

At the start of the study, 152 adults aged 50 and over were given PET scans as well as cognitive tests. Three years later they repeated the cognitive tests. Those with positive PET scans had a much greater rate of cognitive decline and were more likely to have been diagnosed with dementia than those whose scans had been negative.

But even a positive scan is not a perfect predictor, Doraiswamy cautions: "It does not mean you're going to get Alzheimer's."

To Know or Not To Know?

Once such tests become available, how do you decide whether to get one? "Counseling would be in order," says Federoff. It would focus, he says, on establishing whether the patient is ready for the potential results of a test—and also prepared to act on them. Getting treatment is only one possible action; planning financially and for the care that will be needed are others.

Soto sees the development of reliable diagnostic tools as essential for the development of effective treatments. "The main reason there is not good treatment is that there is not good early diagnosis," he says. "When you start [treatment] when the brain is destroyed, the treatment is less likely to work."

19 comments
Jen Gardner
Jen Gardner

I think if you knew then (possibly) you wouldn't be in denial when the inevitable happened.. the biggest problem with my grandparents are that they are in complete denial.. my nan refuses our help and when we try she takes it the wrong way.. perhaps if she knew this was coming she would know that we are really helping her because of her disease and not just trying to be patronizing. 

Carolina GI
Carolina GI

I recommend to try Ab test from Araclon Biotech (Spain). This kit measures Ab40-42

Jordan Lidgey
Jordan Lidgey

I would want to know. Because  if theres ways to try slow it down when someone  already has it. I rather start those before I am diagnosed with it. 

s. cesareo
s. cesareo

I am taking care of my Dad who has A.  I am an only child and have no family of my own.  I am not just living the agony of watching my dad decline (as Lynne says), but also taking care of all the practicalities.  If I should ever get this illness, having no family to take care of me as I do with my dad, I would definitely want to know.  I see what goes on in some places where patients with these illnesses are unless there is someone to look over you, and I would rather die.

Melinda Mills
Melinda Mills

My mother and some other females in her family had it so I would wish to know. Hope they make a breakthrough soon.


Lynne MacIntosh
Lynne MacIntosh

My mother had dementia caused by Alzheimer's and strokes. I would definitely want to know. I would want to plan to terminate my life before the disease robbed me of the ability to do so. I do not want my family to go through the agony of watching me decline when there's no hope I'll get better. Worse, the only future is going downhill. I don't want to go through that.

Sana Janakat
Sana Janakat

What are these lipids? Would you please add the reference.

Marie T.
Marie T.

My nan has Alzhimer's yes I'd want to be tested, knowing what my family and myself have been through with my nan I would want to know well in advance so I could make plans while I was still able to think for myself.
I know it so well that if there was a test freely available I would be happy to be checked regularly, there are drugs that help slow the progression of the disease and if diagnosed early enough can even reverse the symptoms it doesn't reverse the damage though, my nan wouldn't take the drugs I tell you now I certainly would, and even if they didn't work at all I would feel better knowing I made the most of my time left with the people I love and sort things out so they wouldn't have to do so much for me.
I don't understand what you guys are saying down there V
I know some of you are comparing it to incurable diseases... and that you wouldn't want to know unless there was a cure, excuse me I think that's a little selfish I would want to know if I was going to contract cancer too if it was detectable YEARS in advance, why? My family and loved ones that's why. If you're going to get it, you're going to get it regardless whether there is a cure or not, best to be prepared in my opinion.

rupa joshi
rupa joshi

i too have a mother who is 14 years into her alzhiemers. and yes, even i would not want to be tested until i knew there's a cure too!

Gary Robinette
Gary Robinette

Having a parent who is suffering through Alzheimer's I can sympathize. But I would not want to know in advance that I was going to get it unless there was a cure and there is none.  


That would be like having a test that told you that you were going to get a form of incurable cancer. What good would it be to know that?

Tessa Simpson
Tessa Simpson

I think a test would be great if there were new treatments to go with the knowledge.  Any amount of time with your memory would be great.  It's heartbreaking to see my grandmother lose more and more of her memory and not know who anyone is and see her so confused and scared at times.  

robert clapp
robert clapp

Without the capacity to cure such horrors, I have NO need to know of them.

Rodolfo Alonzo
Rodolfo Alonzo

Dean relax keep them comments coming in with facts and humility. The last time my mother called me her baby was 8 years ago. She was a living vegetable the last 3 years. Instead of coming up with a test. Could somebody construct a device that can terminate me quickly. I always fell asleep at school, found tests boring. Also I am concerned I may forget to take the test. My body mass is at 20 percent, I took good care of myself. But I can see though I read all the time. My memory is well like a wheel....slipping a little. Now on the device to construct you will not need many creature comforts. Because vegetables do not need high definition tv, sound systems, etc, etc. One things for sure when you die from Alzheimer's naturally. At least you do not know it.

Dean Schaff
Dean Schaff

Alzheimer's formerly was called senility, or your body outliving your brain.
It's part of what we used to call natural causes. All forms of mortality can't be cured, nor should they be.
I hope I don't get banned for this, I just registered today. 

Kieran Gregory
Kieran Gregory

Having a Grandad who passed away due to Picks disease, a form of Alzheimer's, it would be amazing if they could bring in such a thing. Hope this can happen.

Georgia Lesser
Georgia Lesser

We learn in med school that ApoE4 on chromosome 19 is a/w late onset Alzheimer's. This is an apolipoprotein that helps in fat metabolism. I'm not sure if the study relates to that or not, but it may help answer your question

David Seabaugh
David Seabaugh

@Dean Schaff. "Senility" has been replaced in the literature by "dementia", not Alzheimer's. Dementia is a series of cognitive changes that manifest as memory loss and one other change such as language difficulties. Dementia is a symptom and Alzheimer's is one of many possible causes of the symptom.

David Seabaugh
David Seabaugh

Dementia and Alzheimer's are not interchangeable words. Dementia is a symptom and Alzheimer's disease is a cause of the symptom.

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