Diagnosis Without Treatment: The Perils of New Tests for Early Alzheimer’s Disease

 In April, an independent panel established by the National
Institutes of Health came to the disheartening conclusion that currently, there
is nothing to prevent or delay the progress of Alzheimer’s disease in those of
us who are destined to join the 5 million Americans currently suffering from
this dreaded ailment.

The panel 
found that: “Although numerous interventions have been suggested to
delay Alzheimer’s disease, the evidence is inadequate to conclude that any are
effective.” Members rejected scientific evidence supporting the influence of
nutritional supplements, herbal products, dietary factors, pharmaceuticals,
medical conditions or even environmental exposures on the risk of contracting Alzheimer’s.

Now, just three months later, it turns out that there are
big developments in the Alzheimer’s field—just not in new treatments. At a conference
in Honolulu sponsored earlier this month by the National Institute on Aging and
the Alzheimer’s Disease Association, researchers from three working groups announced
that by using new imaging technologies, genetic testing, and tests of blood and cerebrospinal fluid, it will soon be far easier to diagnose
Alzheimer’s— in some cases decades before symptoms have even appeared. These
new tests are able to identify so-called biomarkers—amyloid plaques in the
brain, genetic variants, proteins and other substances in body fluids—that signal
a newly defined "pre-clinical" stage of Alzheimer's, when an individual has no symptoms but has positive
biomarkers for the disease.  

 The chair of the working group charged with creating this pre-clinical
definition was Reisa Sperling, assistant professor of neurology at Harvard
Medical School
In a MedScape article about the conference, Sperling said that the group struggled with the terminology
for pre-clinical Alzheimer’s disease (AD) and admitted that they knew it would
provoke controversy. If these new tests for biomarkers—including a PET scan
that can for the first time reveal amyloid plaques in a living brain—are
used in the general public, it could double or triple the number of people
diagnosed with Alzheimer's—at potentially great public and psychic expense.

But Sperling reminds critics that there are other medical
conditions that are diagnosed before symptoms are apparent; including carcinoma
in situ, asymptomatic coronary artery disease and kidney disease. What’s
important is that “not all individuals who have these risk factors or early
stages of these other diseases ever go on to manifest symptoms." Still,
the MedScape article adds, “treating high cholesterol has prevented many overt
cardiac and stroke events.”

Currently, doctors diagnose Alzheimer’s disease based on criteria
developed 26 years ago; mainly by using neurological tests that track the progressive
memory and cognitive deficits that characterize the disease trajectory. A
little over a decade ago, researchers began to recognize “mild cognitive impairment;”
as a condition that is strongly linked with later development of full-blown Alzheimer’s.
They’ve also increasingly been using imaging techniques like MRIs and PET scans
that reveal structural or functional changes in the brain associated with the
disease. There is a gene variant, APOE4, which is also associated with AD: It occurs in about 40 percent of all people
who develop late-onset AD and is present in about 25 to 30 percent of the general
population. But AD dementia can only be definitively determined once a patient
has died and an autopsy reveals the telltale amyloid plaques that are the
hallmark of this disease.

It’s been an inexact diagnostic practice. According to Gina
, writing in The New York Times 
last month, “Even at the best medical centers, doctors
often are wrong. Twenty percent of people with dementia — a loss of memory and
intellectual functions — who received a diagnosis of Alzheimer’s, did not have
it. There was no plaque when their brains were biopsied. Half with milder
memory loss, thought to be on their way to Alzheimer’s, do not get the disease.”

The goal of the new imaging techniques and other biomarker
tests is to make diagnosis far less ambiguous. They would also help better
identify risk factors (gene variants, environmental factors, etc.) that can be
strong predictors of who gets AD. Finally, the tests would also greatly help in
clinical research by identifying a larger pool of subjects who have an earlier
stage of the disease to test whether promising drugs might prevent progression
of AD. The initial emphasis, according to Creighton Phelps, director of the
Alzheimer's Disease Center's program at the National Institute on Aging, will
be on using these new tests in clinical research and validating the predictive
value of the biomarkers.

But what happens when (as it inevitably will) diagnosis of
pre-clinical Alzheimer’s becomes more widely available? Dr. Ronald Pies, a professor
of psychiatry at both SUNY Upstate Medical University and at Tufts University
School of Medicine, writes in Psychiatric Times, “the term ‘preclinical Alzheimer’s Disease’ may be adopted—but can ‘disease’
as we ordinarily understand the term really be ‘pre-clinical’? And what will be
the psychological effect of telling an asymptomatic patient, ‘You have
preclinical Alzheimer’s Disease’?

“Given that, at present, we have no treatments that can halt
or reverse the progression of AD neuropathology, will we not create unnecessary
anxiety in thousands of otherwise ‘normal’ individuals, by carrying out
widespread PET scanning for minor memory impairment? Furthermore, what if
large-scale testing reveals that 20% or 40% of the general population over age
65 years have abnormal plaques on their PET scans? Will we be doing more harm
than good by telling such individuals, as one expert suggested, ‘you are on the
Alzheimer road’?”

Nortin Hadler, writing in The Healthcare Blog , is more direct in stating the downside of pre-clinical testing for AD: “there
is a great public health danger in jumping the gun and prematurely using
biomarkers in clinical practice for diagnosis or prognosis.”

“[I]t offers no advantage to our patients today. Rather it
is far more likely to engulf the patient in spurious inferences at great
personal expense. Biomarkers have been tested only in small and highly selected
groups of patients where they have impressive rates of false positive results.
That portends a great deal of over-diagnosis in less selected patients.
Furthermore, all biomarker tests are expensive, some very expensive, and some
have medical risks. None is near ready to be used in routine clinical practice.”

Handler and Pies, along with others who are urging caution
are right. Beyond financial planning and a jump on “putting affairs in order,” there is
little benefit to knowing you are going to get a degenerative and untreatable
disease before you even have symptoms. Drug companies claim that they have
plenty of promising AD drugs in their pipelines. But they have had scant
success so far in developing effective Alzheimer’s drugs—with some 30 failures
occurring as far downstream as Phase 3 trials, according to a 2009 article in the journal Current
Alzheimer’s Research
. “[A] formidable barrier to drug development is that we know very little about
Alzheimer's disease, its pathogenesis, diagnosis, genetics and struggle with
its clinical heterogeneity; we do not have full pre-clinical models on which to
develop advanced therapeutic targets,” according to the authors.

Here is where the new imaging techniques and other tests for
biomarkers hold promise—in aiding in a deeper understanding of what actually causes
Alzheimer’s disease and as a method for identifying advanced therapeutic
targets. But these tests must be used carefully only in research settings—well-designed,
fully-considered and, ultimately, humane clinical trials. The technology is
clearly not ready for public consumption.

16 thoughts on “Diagnosis Without Treatment: The Perils of New Tests for Early Alzheimer’s Disease

  1. Perhaps if more people were diagnosed (accurately, of course), some of the stigma involved with the disease could be exposed. It’s important to talk about what’s going on and not run from it. By exposing it and talking about it, people can prepare for what’s happening and approach the disease in the best way possible. Fear of it is probably one of the worst things to do whether you have it or not.
    There are many books out there devoted to Alzheimer’s caretakers and many emphasize “living in the moment,” versus “trying to remember the past.”
    There are so many groups and programs available that even if people don’t necessarily need at the moment, could learn from and learn to respect and try to understand patients.

  2. Hopefully these early detection procedures will allow doctors to further study treatment methods over a longer period of time.
    Jane – The HBO original movie “Grandpa” is a great look into living with a relative who has Alzheimers if your interested.

  3. Thanks! I heard the movie ‘Iris’ is a good one as well, it’s waiting for me at the library. I think the disease is not being seen as so terrible in the mainstream media now because of all the early detection. I’ll be definitely sure to check out ‘Grandpa.’

  4. I can go for sceening for in situ cancers, even if some wouldn’t become invasive others can be averted.
    But I don’t think I’ll be volunteering for the Alzheimer’s disease screening. I would like to help research into the origins of the disease, but I feel like knowing it’s on the way would degrade the reamining higher-functioning years.
    Once people know they’ve got it then they’re medicalized. Check-ups, special diets, every little quack remedy will assume new importance. Bleah. I don’t want to spent my remaining good years being a billing event for some imagining center.

  5. As one affected by Alzheimer’s (my mom), I am thrilled with any positive news related to the disease. It happens far too infrequently.
    It’s my understanding though, that a concern of genetic testing is the expense. But I’m sure the availability and cost will only get better in the years to come.
    An exciting point about this research is how it may become refined to enable an accurate early diagnosis so treatments can be started ASAP, that is, once treatments are developed. Because Alzheimer’s is a disease that kind of sneaks up on you. Currently, by the time you’ve got a potential diagnosis, you’re often times already 2-3 years into the disease.
    For those beginning this journey, my heart goes out to them. I would suggest making the most out of life while it can still be enjoyed. And to tag this to another post on Maggie’s blog, talk about end of life issues with your family and physician.

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