A news item crossed my radar screen a couple weeks ago. This actually goes all the way back to August 2019, and was published in the Neurology, which is an academic journal, and subsequently was picked up by various news outlets.
I saw this through a press release from Washington University School of Medicine which is located in St. Louis, Missouri. The report focused on a new blood test that’s available for Alzheimer’s Disease.
Currently, it’s in testing phases. But, it has been developed, and researchers think that it holds great promise, and let me explain why that is.
So, first of all:
What does the test do?
I have both an ARTICLE and a YouTube VIDEO on some of the possible causes for Alzheimer’s disease. One of the causes that’s often referenced is the accumulation, in the brain, of various protein “gunk.”
There are two different types of protein that are implicated in this. The first is called beta-amyloid and the second is called tau. The two of these, together, account for the various “plaques and tangles” that Alzheimer’s patients’ brains seem to be riddled with.
The 100% definitive test for this is going to be an autopsy. (For these assortment of Alzheimer’s “tests,” see – again – either my other written work, e.g., HERE, or the companion, video presentation, HERE.)
There is very little use, obviously, for an autopsy to play in terms of preventative medicine or even in treatment, while somebody’s alive. It can give you the accurate cause of death only after the fact. But it’s not going to be too good for medicinal purposes.
Now comes a blood test that promises, or at leads holds the promise, of being able to detect levels of beta-amyloid in the blood during a person’s life.
Two kinds of beta-amyloid protein are being focused upon. And those are designated “Number 40” and “Number 42.”
My layman’s “take” on this is that there is an array of these beta-amyloid’s, but that 40 and 42 somehow play particularly important roles in the pathological accumulation of these deposits in an Alzheimer’s-afflicted brain.
I should say the test has actually been going on for couple years.
What researchers have hypothesized, and has since been borne out – at least, in early stages – is that levels of beta-amyloid in the blood suggest an accumulation of the beta-amyloid in the brain.
Why is the test important?
I mentioned that autopsies are the definitive test for Alzheimer’s. But, of course, autopsies are no good for diagnostic purposes so long as the patient is alive.
So, the most accurate test a living person can get right now is a so-called “Pet Scan,” which is shorthand for the more forbidding “positron-emission-tomography scan.”
A pet scan is essentially the best test that’s available.
But… pet scans are both expensive and time-consuming to perform. Therefore, this blood test holds out the hope for being able to be administered on a much wider scale and at far less of a cost.
Those are two points in its favor.
In theory, a blood test of this kind would be able to be given in a doctor’s office – instead of, for example, having to send the patient to an imaging center.
How Accurate Is the Blood Test?
What researchers discovered, when they compared the blood-test results against the pet-scan results, was that the blood test was 88% correlated with the pet scan.
What this seems to suggest is that, if for every 100 pet scans displaying evidence of Alzheimer’s, a blood test would detect Alzheimer’s in 88 of those cases.
At least… that’s the way I’m reading the article. (Disclaimer: I am not a medical professional! This is simply my untutored commentary on the situation. For advice, seek a healthcare expert who is familiar with your personal history.)
So, the test was (provisionally) determined to be 88% effective, in the above respect.
What Other Risk Factors Were Considered?
It’s worth pointing out that when they coupled the blood test with a couple of other risk factors – for example, age – the effectiveness increased.
It’s widely accepted that a person’s Alzheimer’s risk goes up with age. In fact, it’s said that your risk actually doubles every five years after age 65.[1]
Also, they factored in genetic predisposition. So, if you have the APO-E4 variant gene in your genetic makeup – as I myself do (see my video testimony, HERE) – then you have a higher (3 to 5 times higher actually!) chance of developing Alzheimer’s sometime in your life.[2]
Another risk factor – believe it or not – is sex. We talked about this in other places. (My AlzheimersProof.com post is HERE and my video is HERE.) Sex may not be its own risk factor. It may simply be that women live longer and therefore are more likely to manifest symptoms of Alzheimer’s and other dementias because of their longevity. But it is sometimes said that two out of three Alzheimer’s sufferers are female.[3]
When researchers incorporated age and genetic predisposition, they found that the test was 94% effective in terms of matching up to the pet scan.
What’s the Practical Benefit of an Alzheimer’s Blood Test?
But what they found, in addition to that, was that when some of the blood tests came up positive for people who had not yest been pet scanned, those people eventually came up positive on the pet scan as well.
This suggested to researchers that the test might actually be even more accurate than the pet scan, and able to detect Alzheimer’s in its very earliest stages.
Recall, also, that Alzheimer’s disease manifests in symptoms. But researchers believe that the underlying brain changes may take place as far back as a decade or more prior to the onset of symptoms.
One of the benefits obviously of early detection is they want to be able to treat people in presymptomatic stages. They feel like once memory changes, and other changes manifest in the brain, then that brain is already so damaged that it is basically beyond help.
In possibly being able to find people in the earliest stages of Alzheimer’s, another potential benefit of the blood test is that it might help with constructing clinical trials for developing interventions.
An early version of this test goes back to 2017 or even 2016. At that time, some of the articles referenced “autoimmune antibodies,” also called “autoantibodies.” The idea was that the immune system’s response to the accumulation of beta-amyloid protein might be able to be gauged. But, upon closer inspection of these articles now, in retrospect, they also seem to be describing a blood test that focuses on some of these beta-amyloid protein variants.
The fundamental idea is to try to catch Alzheimer’s disease in its very earliest stages.
Sometimes this “preclinical” stage is referred to variously as Very Mild Cognitive Impairment (especially on the so-called 7-Stage-Dementia view – about which, see HERE and HERE) or Mild Cognitive Impairment, often better known simply by the abbreviation “MCI.”
Note, however, that not all cases of MCI develop into Alzheimer’s disease. For one thing, there are other sorts of dementia (e.g., Lewy-Body Dementia, Multi-Infarct Dementia, Parkinson’s Disease, etc.) and there are traumatic brain injuries and other conditions that also might be prefaced by mild cognitive impairment. (For the difference between “Alzheimer’s Disease” and “dementia,” see my video, HERE.)
“Mild Cognitive Impairment” is, in a sense, just a catchall phrase for a certain level of mental diminishment as well as for the impoverishment of other perceptual and reasoning capabilities.
Concluding Reflection
There’s little doubt, though, that this blood test is fascinating. Even though it still has some way to go before you can expect it at a physician’s office near you, it holds promise.
Number one, it’s less expensive than the pet scan. Number two, it is able to be administered more widely, and in more environments – like doctors’ offices, and other places (such as out-patient clinics and “urgent-care” centers) – whereas the pet scan is obviously limited to an imaging center. Number three, it’s possibly more accurate than the pet scan. And, number four, it’s certainly superior to the autopsy in the sense that it holds out promise for being able to help treat and diagnose people while they are still alive – which is, quite obviously, advantageous.
How to Detect Alzheimer’s: 10 Tests of Varying Accuracy
There are a number of things that can be meant by “detecting Alzheimer’s Disease.”
For one, Alzheimer’s progresses (or regresses) in stages. It may not take much to “detect” the condition once it is sufficiently advanced. A series of simple questions might ferret out the truth. (For more on the utility of such widely employed tests, read further on.) However, by the time the patient is far-gone enough to fail such a “mini-cognitive” test, the result could be of little use in terms of intervention and treatment – except perhaps as an official, doctor’s confirmation of an already obvious diagnosis.
On the other hand, a diagnosis in an early stage of Alzheimer’s could be quite important, therapeutically speaking (albeit emotionally devastating and unwelcomed). Such a diagnosis could serve as a warning and encourage the implementation of lifestyle (for example, to diet [see HERE] and sleep [see HERE and HERE]) and medical changes that could potentially slow down the degenerative process.[1]
At present, though, there simply is no one test that can definitively establish that a person is in early stages of Alzheimer’s.[2] Unfortunately, only an autopsy can confirm, 100%, that a person has Alzheimer’s telltale “amyloid plaques.” Once again, however, by the time an autopsy is relevant, the patient has presumably already succumbed to the disease.[3]
Nevertheless, there are a several tests available. Although they may or may not detect Alzheimer’s in any given instance, they are (collectively and individually) they best that we have for the time being.
Here is my list of ten such tests, in no particular order.[4]
Olfactory: “Peanut-Butter Smell” Test
This particular item came across my desk in late 2015. Numerous news sources ran with phrases like “peanut-butter smell test.” Designed by one Jennifer Stamps,[5] a graduate student in neurology at the University of Florida, the test requires only a dollop of peanut butter and a ruler. It is motivated by the thought that Alzheimer’s patients typically have lost or severely compromised senses of smell.
This point was made vividly for me during one family get-together years ago. At the time, I dabbled in making home-made, flavored liqueurs. I passed around a few samples for some relatives to smell (and, yes, taste!). I recall that my dad, Jim, literally ended up with one of his nostrils pressed firmly around the rim of a bottle. We knew his condition. But I just thought that the culprit was lost motor skills or messed-up spatial awareness. Heck, I even entertained the notion that he might have just lacked the requisite tact for the occasion. In hindsight, I feel confident saying that he simply couldn’t smell the concoction, and so he kept trying to get his nose closer and closer.
The test is administered one nostril at a time. The subject is instructed to close his or her eyes, mouth, and one nostril. The tester then opens and raises a jar (or other container) of peanut butter, positions a ruler vertically under the open nostril, and tracks the peanut butter upwards along the ruler. The test ends when the subject declares that he or she can smell the peanut butter.
It is not entirely clear to me whether how researchers interpret their results. Presumably, they hope eventually to hash out a range of measurements to wield for diagnostic purposes.
Some articles applaud the test and suggest that fine points, like alleged differences in a single patient’s nostril sensitivity, may be explained in virtue of which side of the brain is Alzheimer’s-affected. Other articles are thoroughly skeptical. Still others advise that while the “smell test” might serve a purpose in confirming a diagnosis of Alzheimer’s, it is not well-evidenced enough to be relied upon by itself.
So…can Alzheimer’s be detected by such a crude test? Let’s say that the jury is still out.
It certainly seems possible to approximate this test yourself. Peanut and measuring sticks are easily obtained. The downside, however, is that you will likely have trouble interpreting your results. It’s probably best to stick (no pun intended) with the experts.
Proprioceptive: “One-Leg” Balance Test
In 2009, Science Daily published an article titled “Simple Balance Test May Predict Cognitive Decline in Alzheimer’s Disease.”[6] In it, the author unpacked a somewhat quirky test in which the subject was instructed to try to maintain his or her balance for as long as possible, while standing on one leg.
From grade-school anatomy classes, I recall that the cerebellum is the brain structure credited with the primary role in regulating balance. Indeed, there is evidence that “frontotemporal” dementia affects the cerebellum. (What areas of the brain are affected? See HERE.)
Five seconds seems to be the important threshold. If a person is unable to hold themselves up on one leg for at least five seconds, then their balance is labeled “abnormal.” Although this test is even easier than the previous one to replicate at home, it is possible that balance can be negatively affected by causes other than Alzheimer’s Disease.
Intuitively, certain earaches and headaches might throw your balance off kilter. Additionally, the low blood-sugar conditions experienced periodically by diabetics may render a person unable to maintain his or her balance. Finally, leg or join pains of various sorts might make you physically (or mechanically) incapable of standing on one leg, even if you would be capable from a “mental” (or “proprioceptive”) perspective.
Spatial Acuity: The “Four Mountains” Test
Simply put, the Four Mountains or 4MT test is a test of spatial memory. During the examination, testers present a subject with a digital topographical map that looks like it is a snapshot from an environment in a video game. As the name implies, this landscape sports four “mountain” formations. The subject is then shown four additional images. One of these subsequent images represents the same four-mountain terrain – albeit from a slightly different point of view. The other three images are simply representations of different computer-generated mountain clusters.
According to test creators, 4MT is dependent upon this core idea. “Allocentric spatial memory is a key function of the hippocampus, one of the earliest brain regions to be affected in Alzheimer’s disease (AD) and impairment of hippocampal function predates the onset of dementia.”[7]
Designers maintain, therefore, that the 4MT test is capable of distinguishing “mild cognitive impairment” (MCI) due to Alzheimer’s, from MCI that is caused by other forms of dementia.
Mental Status: Six-Item Cognitive-Impairment Test, “Mini-cog” (Mini Mental-State Examination), and Other Short-Term Memory Tests
These tests are commonly administered by doctors’ offices, insurance companies, and the like. For the former, the objective may be to evaluate a patient’s memory and reasoning abilities without having to be physically invasive.[8] Similarly, insurers are looking to estimate an individual’s risk for needing long-term care due to cognitive issues.
In employing tests of this sort, administrators are looking to gauge a person’s cognitive abilities by asking a series of simple questions.
In one version of the test, a person is given a short list of words (3 to 10) and is then asked to perform a simple task, such as positioning clocks to a certain position. Once the task is complete, the interviewer asks the subject to repeat the list of words. There are numerous variations of this test.
In another permutation, published by the British newspaper Daily Mail, an individual is asked a handful of questions. Example questions include: What is the year? What’s the month? What time is it? (With or without looking at a clock face.) Can you count down from [n]? (N is some number, say 25.) Can you name the months of the year – in reverse?
Such tests also include some component designed to test short-term memory. For instance, a name or address might be given to the target at the beginning of the test. At the end, the administrator would ask the person if he or she recalls the given information.
Commonly, incorrect answers are awarded points. The number of points is then tallied and, if it exceeds some (presumably experimentally established) threshold, then it is deemed to be clinically significant.
Visual: Eye Tests
There are a couple of options when it comes to eye tests. One basic test has to do with changes in visual acuity. Specifically, some researchers believe that early stages of Alzheimer’s might be detectable by tracking certain perceptual “color changes” using a device called a hyperspectral endoscope. The idea is that amyloid deposits will change the way the eye receives and processes light, resulting in measurable wavelength shifts that may be an early indicator of Alzheimer’s.
A second sort of test relies upon techniques for assessing the thickness of a cluster of neurons termed “macula.” It turns out that thinning macula are correlated with diminishing cognition. State-of-the-art optometric imaging machines may therefore be able to warn of impending Alzheimer’s by peering into a subject’s eyes.
Hematologic: A Blood Test for MCI
Mild cognitive impairment, or MCI, is a condition that attends early-stage Alzheimer’s Disease. However, it is also associated with other sorts of dementia and with pathologies, including multiple sclerosis and Parkinson’s Disease. In 2016, news broke concerning the possibility that a blood test could both detect MCI and distinguish Alzheimer’s-related MCI from other types.
According to one of the test’s designers, “it is possible to use a small number of blood-borne autoantibodies to accurately diagnose early-stage Alzheimer’s.”[9] Researchers devised a panel of 50 “autoantibody biomarkers” that, they believed, were highly correlated with Alzheimer’s.
It appears that this test is still in an experimental phase. But it holds the promise of being able to detect Alzheimer’s Disease years before it manifests its giveaway symptoms.
For the latest on blood tests, see my video:
Genetic: DNA Test
The company 23AndMe offers a saliva-based genetics test for Alzheimer’s.
Whereas blood testing purports to reveal when a person has early-stage Alzheimer’s, genetic testing supposedly can disclose your risk before any clinical signposts are present. The California-based firm 23AndMe, already widely known for its ancestry analyses, has released a DNA test that predicts one’s risk level for Alzheimer’s dementia. At least, that is the claim.
Like its ethnicity test, the disease test begins with the collection of a person’s saliva. The company then tests the saliva for the “E4 variant” of the “Apolipoprotein E” (or APOE) gene.
Apparently, processing once took around two months. Now you frequently receive your results in about two to three weeks.
23AndMe acknowledges that environmental and lifestyle factors may affect a person’s overall Alzheimer’s risk. Furthermore, the test only looks at one specific genetic factor. There might even be other genetic factors that are relevant to overall risk, but that are ignored by the test.
It is important to note that the test does not “diagnose” a person with Alzheimer’s – it merely indicates one factor that is presently believed to increase a person’s genetic risk.
In fact, designers maintain that the test can disclose predispositions toward nine other diseases, in addition to Alzheimer’s, including coeliac disease, and Parkinson’s.
The price includes laboratory-testing fees. So, after you purchase your package, and receive a saliva-collection kit, all you have to do is send your sample back to the company. You will then get a stack of genetic reports – the company numbers them at “75+.”
Of all the tests covered in this post, this one is probably the best value, in terms of both accessibility and scientific credibility. It’s not invasive, and it gives genuinely important and pertinent information about your risk level. But it is certainly not the final word.
Although it is far from clear that health providers will be recommending this sort of test, I can tell you that I am interested enough to take it myself. I will be reporting on my own experience in a later post. (UPDATE: See the video, below, for a start.)
Cerebrospinal: Lumbar Puncture
The collection of cerebral-spinal fluid (CSF) begins another test with encouraging results when it comes to the early detection of Alzheimer’s dementia. Specifically, the relevant test evaluates two amyloid proteins, labeled beta and tau, that are prevalent in the brain deposits and plaques that are characteristic of an Alzheimer’s-riddled brain. Alzheimer’s patients customarily have elevated levels of these proteins in their CSF.[10]
Various CSF tests are commercially available. However, they are definitely “invasive.” The participant must submit to a collecting procedure that is variously termed “lumbar puncture” or the evocative (and, dare I say, heavy-metal-ly) “spinal tap.” A small needle is inserted into the spinal area and some fluid is removed for analysis.
There is a constellation of side effects that can accompany spinal-tap procedures. The most common of these is a bad headache. This is so widely experienced that numerous resources refer to this as a “post-lumbar puncture headache.” There can also be unspecified pains as well as dizziness, nausea, and vomiting.
Brain Imaging: Amyloid PET Scan
Just the facts: Positron Emission Tomography uses radioactive sugar (e.g., fluorodeoxyglucose, or FDG) to give doctors a peek at a person’s brain tissue.[11] PET scans, as they are called, “…[measure] important body functions, such as blood flow, oxygen use, and sugar (glucose) metabolism, to help doctors evaluate how well organs and tissues are functioning.”[12] Their benefit is that they reveal the amyloid plaques that announce the presence of Alzheimer’s Disease.
So, an upside is that this test is reliable.
A downside is that it radioactive.
My opinion: I am a bit leery. Healthcare workers typically insist that “low doses” of radiation have “no known” lasting negative (or adverse) effects.[13] But, as an article on MedLine Plus discloses: “…The risk of cancer depends on the dose and begins to build up even with very low doses. There is no ‘minimum threshold.’…”[14]
This makes sense when we consider the canonical description of how cancer originates. In the words of the editorial board at Cancer.net: “All cancers begin when one or more genes in a cell are mutated, or changed.”[15] One or more.
Of course, when we are considering a person who is suspected of having Alzheimer’s, it may well be worth the risk of cancer (however high or low it might be) to “risk” the radioactivity of the PET scan.[16]
On a personal note, my dad (read “Jim’s Story”), had two surgeries prior to reaching “advanced” stages of Alzheimer’s. He had a triple bypass for his heart and a colectomy to remove a cancerous portion of his bowel. In hindsight it is tempting to think that he may have had less miserable experience dying of cancer than of Alzheimer’s. But, as one instructor put it once (concerning counterfactual statements): There is no way to get an answer, and nothing to do with the answer even if you could get it.
Autopsy
A final “test” is not really a test in the same sense as the previous nine entrants on this list. An autopsy,[17] of course, is a port-mortem medical examination – that is, one performed on a deceased person’s body. According to the Alzheimer’s Association: “While the diagnosis of A[lzheimer’s] D[isease] can now be up to 90% accurate, it can only be positively confirmed through autopsy.”[18]
Apparently, some autopsies still collect brain material for purposes of scientific study. Others are performed to confirm the diagnosis of Alzheimer’s, which, since it enhances the detail of the medical record, can benefit other family members down the road.
The Alzheimer’s Association stresses the need to plan and to coordinate such an undertaking with the funeral home, hospital, primary-care doctor, and nursing home. (It’s morbid, but a brain autopsy must be performed prior to the embalming process.)
The next of kin (usually a surviving spouse or adult child) must sign a permit. Autopsies cost anywhere from $0 to a few thousand dollars, depending on the circumstances and facilities involved.
Notes:
[1] As one New York Times writer put it: “Alzheimer’s …starts a decade or more before people have symptoms. …[B]y the time there are symptoms, it may be too late to save the brain. …[T]he hope is to find good ways to identify people who are getting the disease, and use those people as subjects …in studies of drugs that may slow or stop the disease.” (Gina Kolata, “In Spinal-Fluid Test, an Early Warning on Alzheimer’s,” Aug. 9, 2010, <http://www.nytimes.com/2010/08/10/health/research/10spinal.html>.)
[2] Developing tests is tricky business. The tests have to meet various criteria, reliability perhaps foremost. But tests also have to be available – both to doctors and patients – and affordable (or at least “covered” by health insurance). The ten tests (or categories of test) surveyed herein are each at different developmental stages. Not all of them are equally accessible, affordable, or reliable.
[3] Of course, a person could die at any time from a variety of causes – both natural and non-natural. It is possible for a person’s Alzheimer’s to be detected during an autopsy that was performed after a death unrelated to dementia. But I am ignoring that possibility, here.
[4] Full disclosure: I had intended to try to “rank” the tests in terms of accuracy. But since I am neither a clinical researcher nor physician, I lack the requisite qualifications to carry out such a task. Moreover, a quick glance at the popular-level literature suggests that there may be no fact-of-the matter about this sort of hypothetical ranking. Alternatively, even if there is an answer, objectively speaking, it could be unknowable – at least given the current state of the relevant science. So, even though my list might look like a “ranking,” I’m sticking to my story: It isn’t!
[5] Stamps apparently worked at least partially under the direction of Professor Kenneth Heilman, in the University of Florida’s College of Medicine.
[7] Neil Burgess, Dennis Chan, Laura Marie Gallaher, Kuven Moodley, Ludovico Minati, and Tom Hartley, “The 4 Mountains Test: A Short Test of Spatial Memory with High Sensitivity for the Diagnosis of Pre-dementia Alzheimer’s Disease,” Journal of Visual Experiments, no. 116, 2016, <https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5092189/>.
[8] Several authors refer to these sort of cognitive tests as “invasive.” Surely, this is not true in a physical sense. Still, it is obvious sense that being unable to answer basic questions (like “what year is it?”) is embarrassing. There may be some sense, then, in which these tests are “emotionally invasive.”
[10] The New York Times cited a study in which 75% of people with MCI displayed increased amyloid levels in their CSF; while 33% of “normal” people did as well. The Times author added that researchers suspected the 33% were in a “pre-symptomatic” stage and would ultimately develop Alzheimer’s. Another study apparently found that the signature CSF elements were identified in 100% of Alzheimer’s patients tested. See Kolata, loc. cit.
[11] Other types of imaging are available. Writers at Alz.org remind that an important part of a doctor’s procedure in diagnosing Alzheimer’s (or any condition) is a general review of the patient’s case. This will include family and personal medical history as well as other facets of a “routine” examination. To this end, CT (computed tomography) and MRI (magnetic resonance imaging) may be employed “to rule out other conditions that may cause symptoms similar to Alzheimer’s…,” “Tests for Alzheimer’s Disease and Dementia,” <https://www.alz.org/alzheimers_disease_steps_to_diagnosis.asp>.
[16] There are hypothetical questions about the use of PET scans in routine-screening procedures. Maybe there is a fruitful comparison to be made with mammography. Again, I quote the New York Times: “A 17-year study has concluded that screening mammography — in which all women in certain age groups are routinely screened for breast cancer — does not reduce the incidence of advanced tumors, but does increase the diagnosis of lesions that would never have led to health problems.” Nicholas Bakalarian, “The Downside of Breast Cancer Screening,” Jan. 11, 2017, <https://www.nytimes.com/2017/01/11/well/live/the-downside-of-breast-cancer-screening.html>.
[17] The word “autopsy” is interesting. It has Greco-Roman roots and is basically has two components: autos, meaning “self,” and opteuō, meaning “I see.” The sense of autoptēs was “seeing with one’s own eyes” and sometimes conveys the idea of being an “eyewitness.” See William Arndt, Walter Bauer, Frederick Danker, and Felix Gingrich, A Greek-English Lexicon of the New Testament and Other Early Christian Literature, 3rd ed., Frederick Danker, ed., Chicago: Univ. of Chicago Press, 2000, p. 152. There is an intriguing quasi-religious angle. A similar etymology, tracing the word to autopsia, is given by Albert Mackey in “Autopsy,” Encyclopedia of Freemasonry, Robert Clegg, ed., vol. 1, Chicago: Masonic History Co., 1956, p. 113. The Online Etymology Dictionary concurs and adds: “Sense of ‘dissection of a body to determine cause of death’ is first recorded 1670s, probably from the same sense in French autopsie (1570s).” Douglas Harper, “Autopsy,” <https://www.etymonline.com/word/autopsy>.
