A Suicidal Reader Seeks Advice:
A Cautionary Tale About Informed Consent
(and the Unintended Consequences of Authorship)
Letting the Genie out of the bottle . . .
THE (TRUE) STORY
(Anonymized and shared with permission)
A reader of my book, whom I’ll call A, is a 71-year-old successful professional who reached out to me via email. A family member had given them a copy of Aging or Alzheimer’s?. A shared their experience of “brain fog” for several years, blaming it on COVID until “a recent blood test showed I had high-ish markers of p-tau 217.”
[NOTE: This breakthrough blood test was first presented as a “Key Takeaway” from the September 2024 Alzheimer’s Association International Conference. A positive test is considered by both The National Institute on Aging (NIA) and the Alzheimer’s Association (AA) to be “sufficient to establish a diagnosis of Alzheimer’s disease.”1 A was in the long latent phase of the disease, referred to as “Preclinical” AD, that precedes the onset of symptoms by decades.2]
And A’s response to this news . . .
“I’m not sure I would have taken the test if I knew what it would find.
AD (Alzheimer’s disease) was completely off my radar.”
and,
“I am writing to you about “the end.”
[Not the sort of mail this new author was expecting.]
“The End”: As a consequence of an uninformed decision to submit to a blood test, this knowledgeable professional’s plan consisted of closing their office and laying the legal and personal groundwork for suicide by “VSED”, Voluntary Suspension of Eating and Drinking (i.e., starving oneself to death).
The remainder of the email consisted of five detailed and practical questions addressed to me as a physician. They were all about optimizing suicide by VSED: the best timing, minimizing pain, “a drug to hasten the process”, and how can Hospice get involved or physician-assisted suicide be accessed for a disease in which the requirement for less than six-months’ life expectancy cannot be predicted?
HOW THE HELL DID THIS HAPPEN?
A healthy and intelligent person went from seeking help for suspected COVID-19 brain fog to planning their death by starvation!
IT SEEMED LIKE A GOOD IDEA AT THE TIME . . .
A had joined an online physician-run program offering to “Optimize Brain Health and Prevent Cognitive Decline” for $75 monthly (plus the one-time “with labs option” for an additional $930). As a consequence of submitting a blood sample suggested to “Detect Cognitive Decline Before Symptoms Begin”, they were informed of an abnormal p-tau blood test, a result deemed “sufficient to establish a diagnosis of Alzheimer’s disease.1”
BUT ON SECOND THOUGHT . . .
A: “I’m not sure I would have taken the test if I knew what it would find. AD (Alzheimer’s disease) was completely off my radar.”
This feared and unwanted revelation happened because those promoting “the only Dr. _____-approved protocol for preventing, treating, and reversing Alzheimer’s disease” failed to follow a basic tenet that has been guiding the ethics of medical practice and research since the Nazi war crime tribunals in 1947: patients or research subjects are required to be told the risks and benefits of tests and procedures.
INFORMED CONSENT
Informed consent is a fundamental ethical and legal requirement in medical research and practice. It ensures that individuals fully understand and voluntarily agree to participate in a medical procedure, treatment, or research study after being provided with all relevant information.(ChatGPT)
In our daily lives, we most frequently encounter signed informed consent before an intervention where the skin is broken (major or minor surgery) or our accessible body cavities are violated (various scopes). Obtaining consent for diagnostic testing like x-rays and blood tests is most commonly utilized in research. The risks that doctors, hospitals and their lawyers choose to disclose to us when asking for our consent can range from common to exceedingly rare and from minimal to life-threatening. Everyday examples include scans with contrast dye, office biopsies, diagnostic scopes like colonoscopy, chemo or radiation Therapy, contraceptive device placement, and fertility treatments. Most often we have already had some discussion, prior experience, or a general idea of the risks, and our written consents is presented, signed without reading, filed, and forgotten. In my doctors’ offices I am most commonly presented with a digital signature pad, offered without explanation by front-desk personnel. Regardless, “Informed consent should always include a discussion of the purpose, the risks and benefits, and any alternative options.” (ChatGPT and I agree)
The biggest risk of these Alzheimer’s screening tests is making an uninformed choice that you can never take back.
Once the
Genie is Out of the Bottle . . .
LIFE-CHANGING ANXIETY, ALONG WITH SUICIDAL THOUGHTS OR ACTS, ARE PREDICTABLE RISKS OF LEARNING THAT ONE HAS “PRECLINICAL ALZHEIMER’S DISEASE” AND MERIT INFORMED DISCUSSION PRIOR TO TESTING
Up to 75% of those who test positive for biomarkers like p-tau will not develop dementia during their lifetimes, nor can progression be predicted for any individual worried senior. Yet the National Academies of Sciences notes that for everyone with a positive test “there are several ethical concerns with disclosing biomarkers status to patients, which include the risks of clinical Depression, Anxiety, and suicide”. 3 For example, a healthy neuroscientist who (fortunately) had a negative screening test for Alzheimer’s as a subject in a research study said that, had the test been positive, it would have changed his life forever: “I will wake up every morning and wonder whether . . . this is the day I am going to forget something.” 3
“On the individual level, this information can lead to psychological distress and irreversible decisions, even up to pre-emptive suicide, particularly when no efficacious therapies are available.”4 In fact, suicide is a cause of death that is uniquely associated with the diagnosis of dementia, with individuals identified with dementia having a 54% higher risk of suicide within the first year after their diagnosis. The risk was particularly high among those aged 74 years and younger5 and was not related to the presence of other mental disorders6.
OTHER UNDISCLOSED RISKS AND UNINTENDED CONSEQUENCES OF A POSITIVE TEST IN ASYMPTOMATIC INDIVIDUALS
The presence of what can be interpreted as inevitable Alzheimer’s disease confounds every aspect of life. In the absence of effective treatments, there appears no advantage to finding preclinical-AD patients for early intervention. Nor can one predict the time lapse between identifying an early stage of Alzheimer’s and the actual onset of dementia.
Even the 75% of those with positive tests who will not develop dementia in their lifetime are at risk for other dire consequences. Of all the ”preexisting conditions” in the world, this positive blood test has to be one of the worst. Many cancers can be cured or controlled. Dementia, not so much. Health insurance companies are often accused of using any excuse to deny care or raise rates. How are they going to respond to your abnormal result. While health insurers are prohibited by law from completely denying coverage for Alzheimer’s disease, there is nothing to prevent those writing long-term-care policies and life insurance from refusing to consider someone who is positive for an AD biomarker. Persons aware of their diagnostic label and its prognosis report a lower quality of life than those unaware of these facts about themself. The associated sense of loss is unrelated to the actual severity of the cognitive impairment.8
Families, in addition to concerns for their loved one and the personal risks and burdens of becoming long-term caregivers, are also affected by what a positive result may imply about their own potential Alzheimer’s disease risk.3 It is difficult to plan and allocate finite resources for an uncertain future of decline. It seems to me that since the risk of AD increases with age, someone with only subjective symptoms and an early positive biomarker is condemned to a cycle of near-continuous worry. The challenges presented to asymptomatic, but biomarker-positive, patients and their families in processing all that information are described as overwhelming—like drinking from a fire hose.
As is true with other serious neurodegenerative diseases (like Amyotrophic Lateral Sclerosis (ALS) a.k.a. “Lou Gehrig’s disease”) the benefit of presymptomatic biomarker testing is limited by the absence of preventative treatments to offer, and the inability to predict when (or even if) someone who is bio-marker positive will develop AD.
As the size of the population with “Preclinical” Alzheimer’s disease inflates as a result of the ease of blood testing, I have no doubt that insurance companies, employers, matchmakers, dating apps, the funeral industry, supplement purveyors and other inventive souls will find additional ways to further complicate the lives of those carrying this knowledge burden.
WHAT CAN (AND SHOULD) BE DONE?
A simple answer for my unfortunate reader would have been increased regulation and oversight of those online and for-profit “medical” websites offering testing without informed consent. Relevant agencies are the FDA and the Centers for Medicare & Medicaid Services (CMS). Let them keep selling their “brain-healthy, fully-prepared chef-curated cuisine”, but be required to properly inform their online patients about the risks of their ”gentle alternative” blood tests (recently discounted from $1299 to $799).
Licensing boards should police bullshit claims like: (a) “Routine cognitive testing is advised for individuals 30 and older.” [ACTUALLY, THIS IS NOT ADVISED BY ANYONE WHO IS NOT SELLING BLOOD TESTS.], and (b) “For those aged 30 and above, the p-Tau 217, GFAP, and NfL blood tests offer early detection of cognitive decline and help guide prevention and treatment strategies. . . . It combines three blood tests to help you avoid Alzheimer’s disease by “scanning for it” before any problems arise.” [NO!, THERE ARE ZERO “GENERALLY ACCEPTED PREVENTION AND TREATMENT STRATEGIES THAT CAN ”HELP YOU AVOID ALZHEIMER’S DISEASE.”]
Discussing the availability of blood biomarkers in their 2024 “Revised criteria for the diagnosis and staging of Alzheimer’s disease”, the NIA and Alzheimer’s Association said: “First, the clinical use of AD biomarkers is presently intended for the evaluation of symptomatic individuals, not cognitively unimpaired individuals. We highlight the distinction between can and should. AD can be diagnosed in asymptomatic individuals, but we do not believe this should be done for clinical purposes at this time.”
UNFORTUNATELY, CONCERNS FOR ADEQUATE INFORMED CONSENT FOR ALZHEIMER’S BLOOD BIOMARKER TESTING EXTEND BEYOND MEDICAL ENTREPRENEURS TO
THE ESTABLISHED SCIENTIFIC COMMUNITY
Many point out that in individuals without symptoms of dementia, the most appropriate use for definitive blood tests for Alzheimer’s disease is to identify subjects for research on disease-modifying therapies or for early interventions for prevention or delay. On that point, again from the two major Alzheimer’s organizations: “Although it is expected that clinicians will use AD biomarkers to determine potential eligibility for recently approved Aβ-specific therapies, clinical applications also include counseling and tailoring medications for symptomatic treatment.”1
If any research subjects deserve a thorough explanation of the risks of blood-test positivity, it is those who are Volunteering to help others. Unfortunately, the academic medical community can be as opaque as its for-profit counterparts in revealing the risks of testing to potential research subjects. For example, a published study of “Informed Consent (IC) in Two Alzheimer’s Disease Research Centers” concluded:
“Obtaining IC in AD research is challenging. . . . The traditional paper-based consent isn’t particularly adapted to the needs of vulnerable participants with memory deficit. Consent forms are often too long and complicated, making it difficult to stay engaged. In addition, although the forms contain important information meant to support participant’s decision, the information presented isn’t always relevant to participants in longitudinal AD research.”7
The latest example is the recently completed ALZ-Match Pilot Study sponsored by the National Institute on Aging and conducted by the University of Southern California (USC) Alzheimer’s Therapeutic Research Institute.8
Who wouldn’t trust those two institutions to protect them?
The stated purpose was to use blood biomarkers to identify individuals with preclinical AD to then be offered the opportunity to enroll in upcoming treatment or prevention studies.
The (very worthwhile) goal was to take advantage of recently available blood biomarkers to recruit individuals over age 49 with no self-reported dementia diagnosis to take the blood test after “electronic consent”. The nine-page “e-consent” document never indicated that, if positive, the test they were taking would identify them as having unequivocal biochemical evidence of pre-clinical Alzheimer disease. The only test results the subjects were to receive was whether or not they would “qualify” for subsequent studies.
“The ALZ-Match Study is looking to learn if we can use blood tests to help determine if a person is more likely to qualify to join a research study. Participants in this study will learn if they are likely to be “eligible” or “not eligible” to join a research study. . . We cannot provide you with a specific result associated with your blood test. We can only use the result to help us better understand if you may be eligible or not eligible. . . . At the end of the study, we will share the results of the study, but we will still not be able to provide your individual results.”
Thank goodness that the life-saving hematoma-awareness teams of USC and NIA did join forces and were able to fully inform all participants of the risks associated with having their blood drawn!
“Possible side effects include feeling light-headed, vein swelling, pain, bruising, bleeding in the spot where your blood is drawn, and/or a slight possibility of infection”
Protection of research subjects against such (to me) totally unsatisfactory and even potentially deadly ”(un)informed consent” is the responsibility of Institutional Review Boards (IRBs). They operate under Federal Regulation 45 CFR 46 “Protection of Human Subjects” and rules set by the U.S. Department of Health and Human Services (HHS) and the Food and Drug Administration (FDA). IRB review and approval of a research study is intended to ensure ethical standards and regulatory compliance, with the primary purpose of protecting the rights, welfare, and well-being of participants.( ChatGPT) Although the consent notes that “This research study is being conducted by the University of Southern California (USC) Alzheimer’s Therapeutic Research Institute (ATRI),” to then assume USC’s IRB had any role in reviewing or approving the consent form would be unsubstantiated. Like many other studies, approval came from a for-profit private commercial IRB. The described deficiencies in their “IRB Approved Version 4 Oct 2023” of the consent strongly suggest a need for better oversight of that industry by the agencies charged with human subject protection. It is not unreasonable to ask how the employees of a busy commercial IRB could know or learn enough about a blood test that was not presented to the Alzheimer’s Association International Conference until 10 months after they approved the protocol. Of interest, I can find no physicians or PhD’s on that commercial IRB’s list of “Thought Leaders”, nor anywhere else on their website.
REFERENCES
- Jack CR Jr, et al. Revised criteria for diagnosis and staging of Alzheimer’s disease: Alzheimer’s Association Workgroup. Alzheimers Dement. 2024 Jun 27. https://alz-journals.onlinelibrary.wiley.com/doi/10.1002/alz.13859),
- Dubois et al. Proceedings of the Meeting of the International Working Group (IWG) and the American Alzheimer’s Association on “The Preclinical State of AD”; July 23, 2015; Washington DC, USA. Preclinical Alzheimer’s disease: Definition, natural history, and diagnostic criteria. Alzheimers Dement. 2016 Mar;12(3):292-323. https://pmc.ncbi.nlm.nih.gov/articles/PMC6417794/
- National Academies of Sciences E, Medicine, Division of B, et al. The National Academies Collection: Reports funded by National Institutes of Health. In: Forstag EH, ed. Implications for Behavioral and Social Research of Preclinical Markers of Alzheimer’s Disease and Related Dementias: Proceedings of a Workshop—in Brief. National Academies Press (US), 2021. https://nap.nationalacademies.org/catalog/26295/implications-for-behavioral-and-social-research-of-preclinical-markers-of-alzheimers-disease-and-related-dementias
- Schicktanz S, Schweda M, Ballenger JF, Fox PJ, Halpern J, Kramer JH, Micco G, Post SG, Thompson C, Knight RT, Jagust WJ. Before it is too late: professional responsibilities in late-onset Alzheimer’s research and pre-symptomatic prediction. Front Hum Neurosci. 2014 Nov 20;8:921. https://pmc.ncbi.nlm.nih.gov/articles/PMC4238325/
6. Schmutte T, Olfson M, Maust DT, Xie M, Marcus SC. Suicide risk in first year after dementia diagnosis in older adults. Alzheimers Dement. 2022 Feb;18(2):262-271. https://pmc.ncbi.nlm.nih.gov/articles/PMC8613307/
7. Choi JW, Lee KS, Han E. Suicide risk within 1 year of dementia diagnosis in older adults: a nationwide retrospective cohort study. J Psychiatry Neurosci. Jan 4 2021;46(1):E119-e127. https://pmc.ncbi.nlm.nih.gov/articles/PMC7955848/
8. Suver CM, Hamann JK, Chin EM, Goldstein FC, Blazel HM, Manzanares CM, Doerr MJ, Asthana SJ, Mangravite LM, Levey AI, Lah JJ, Edwards DF. Informed Consent in Two Alzheimer’s Disease Research Centers: Insights From Research Coordinators. AJOB Empir Bioeth. 2020 Apr-Jun;11(2):114-124. https://pmc.ncbi.nlm.nih.gov/articles/PMC7266429/
9. Stites SD, Karlawish J, Harkins K, Rubright JD, Wolk D. Awareness of Mild Cognitive Impairment and Mild Alzheimer’s Disease Dementia Diagnoses Associated With Lower Self-Ratings of Quality of Life in Older Adults. J Gerontol B Psychol Sci Soc Sci. Oct 1 2017;72(6):974-985. https://pmc.ncbi.nlm.nih.gov/articles/PMC5927082/
See also: https://ouragingbrains.com/im-worried-about-alzheimers-should-i-undergo-biomarker-testing/
Comments Welcome
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