Currently, more than six and a half million Americans suffer from Alzheimer’s Dementia. The number is projected to increase to between ten million and fifteen million, mostly among those over 65, by 2050. At more than 20% of the population, that means that about 15%-20% of Americans over 65 are expected to suffer. [1]
The cause is unknown. Presenting with profound memory loss, Alzheimer's is the most common cause of dementia, a brain disorder that worsens over time. Resulting in gradually increasing declines in memory, thinking, behavior, and social skills, the disease ultimately thwarts a person's functioning ability.
Probably worse than the effects of the disease on the patient is the impact on caretakers and loved ones who watch the person they once knew disintegrate into a two-dimensional caricature, a painful and constant reminder of what once was.
As my colleague and friend Dr. Chuck Dinerstein wrote:
“Alzheimer’s Disease (AD) is a devastating illness that robs one of their “self” long before the end of life. “
Demand and desire for a cure drives the need to find an underlying cause - so far, none has been proven. However, changes in the brain that involve the onset of amyloid plaques and tau (neurofibrillary) tangles are usually noted. There is no proof that these plaques or tangles cause the disease, just that they are present in roughly 75% of people with clinical Alzheimer’s -- meaning over 25% of those diagnosed – don’t have them
The curious presence of these plaques (normally produced proteins that abnormally clump together in the brain and accumulate for years before thinking or memory issues arise) – is that they can also exist without brain disturbance.
Outside clinical evaluation, the most objective diagnostic test includes a spinal tap to identify the abnormal proteins and brain imaging, most often Positron Emission Tomography or PET. [2] . These must be done in a hospital and read by a physician. However, physicians don’t always get the reading right, and the imaging material may cause side effects, although other safer tests, involving “markers” in the blood now exist.
Despite the lack of a causal connection between plaques, tangles, and Alzheimer’s, the pharmaceutical industry is developing medications to reduce plaque formation, necessitating these invasive tests before, during, and after drug administration to measure the drugs’ effectiveness. Two such drugs, Adulhelm and Leqembi, were recently approved by the FDA for mild cognitive impairment in the early stages of the disease. Regarding Aduhlem, the FDA overruled its advisory board, which recommended against approval, prompting several resignations according to my ACSH colleagues, Dr. Josh Bloom, Dr. Chuck Dinerstein, and Dr. Henry Miller, who condemned the decisions. Leqembi comes with serious side effects, including death. Other drugs, like Eli Lilly's donanemab, are in the testing stages and supposedly showing promise.
As Dr Bloom writes:
“Aduhelm, an antibody drug, did accomplish what many experimental AD drugs could not – a measurable decrease in beta-amyloid plaque – a hallmark of the disease. It is indisputable that these plaques go hand-in-hand with AD, but it is far from clear whether the plaques are a cause of the disease or a result of it. If it's the latter, the potential utility of aducanumab will be limited; the damage will have been done. “
Although Aduhelm appeared to reduce the incidence of plaques, it had little effect on disease progression or clinical manifestations. While Leqembi has shown some clinical impact [3], it’s unclear whether they are clinically significant (even assuming the serious side-effect issue can be resolved). Meaning - currently, we’re not sure there is an effective drug available.
“My view is we need to be cautious about what we think of as disease modifying,... To say the monoclonal antibodies are disease modifying because they remove plaques is primarily true if the plaques are causing the disease. What if the plaques are not primarily responsible for the disease?”
Russell Swerdlow, MD, director of the University of Kansas Alzheimer Disease Research Center.
Do It Yourself (DIY) Diagnostics
This hasn’t stopped Quest Diagnostics from marketing a “simple,” DIY at-home blood test to determine your risk of disease, or so they claim - for a mere $399 plus a doctor’s referral fee of $13.00. And because the test is marketed as a Laboratory Developed Test (LDT) - it doesn’t need FDA approval!
“Exclusively available at Quest. This screening test provides an amyloid ratio, which is a risk factor of Alzheimer’s disease. This ratio is based on two biomarkers … reported as helping to detect early signs associated with the risk of developing Alzheimer’s disease. This can potentially help you and your doctor design interventions and a management plan that is most beneficial to you.” [emphasis added].
Quest initially marketed the test (AD-Detect) to physicians, but a mere month after the FDA’s latest approval, it was featured as “direct to consumers.”
Not everyone is eligible for the test, though. You have to certify you have at least one Alzheimer-related risk, including:
- Acknowledging you have mild cognitive impairment or decline (and who over 50 doesn’t or won’t say they do if they want the test?), and
- Another risk factor, e.g., trouble remembering, concentrating, making decisions, a history of brain injury or head trauma, or a suspicion of this.
The test measures the amyloid plaque ratios, those abnormal proteins we aren’t sure are even causally related to the disease. Its “success” or accuracy rate isn’t pretty, either
What exactly does the test tell you?
Compared to a PET scan (which has its own levels of inaccuracy), Quest’s blood test will provide:
- A sensitivity of 89%, meaning 11% of the time, people getting a negative report will have the plaques, i.e., the test will produce- a false negative result. Sensitivity measures the accuracy of the positive result finding.
- A specificity of 79%, meaning 21% of the time, people getting a positive report will not have the plaques, i.e., the test will produce a false positive result. This result translates into unnecessary concern and further testing in that population [4]. The public health community considers specificity, which measures the accuracy of a negative finding, as of greater importance in screening.
These numbers assume Quest’s laboratories are providing accurate results. Given that they are producing a non-FDA-regulated product, there is no oversight on their lab results. While a move is underway to compel this type of inspection, “the laboratory industry argues that FDA regulation would stifle their ability to quickly innovate and develop new tests.”
Will the consumer understand the flimsiness of the results?
Given that 500,000 will be diagnosed in America this year, and assuming all are tested, that means 50,000 people will have plaques and be falsely assured that they don’t, while 100,000 will have false positive findings - and undergo needless worry and further invasive tests to rule out the possibility they may develop Alzheimer’s, when there is no real evidence they do.
“This Quest announcement makes me very nervous. It hints that there are treatments and that’s a reason to get [the AD-Direct] test.”
Professor Caplan’s objection is not the only reason not to get the test. More important reasons include the facts that the significance of plaques is poorly understood, the reliability of the tests is subpar, the accuracy of the results is questionable in a significant population, and that further, more invasive testing would be required before the medication, with its own side-effects, is prescribed.
The pressure on the FDA to approve the drug is understandable, given that even an ineffective drug provides “hope in a bottle.” However, the FDA’s purpose is to provide assurances of effectiveness, not provide an imprimatur for placebo marketing.
The Quest test latches on to the false hope generated by the drugs’ approval. Now that there is the appearance of effective therapy, people are more likely to want to find out if they are affected or likely will be. That the test gives no such assurance, and coupled with the questionable effectiveness of the drugs and serious side effects, it seems to me to be an exercise of what the FDA is charged with preventing: fraud and harm to the public.
[1] Significant government initiatives to address the problem began about five years ago with the passage of the BOLD National Alzheimer's Project Act (NAPA) and the Alzheimer's Accountability Act
[2] Positron emission tomography involves the injection of a slightly radioactive material that can identify changes in our physiology, like blood flow, or in our metabolism, like the use of glucose. This signal from the radioactive “tracer” is combined with brain images to identify areas of concern.
[3] It delayed progression by about five months of memory loss in patients followed for 18 months. More importantly, this effect was far less for women, at 12%, than for men, at 43%. Women are far more likely to experience Alzheimer’s Disease than men.
[4] Screening tests must balance sensitivity against specificity; no test can provide both to the same degree.
