514 - Vitamins and Memory, Alzheimer’s Blood Test? Being Pre-Paired

From the Literature

1)  Multivitamins and Memory?

Cognitive impairment and dementia have proven very difficult conditions to ameliorate with our usual pharmacologic tools. The promise of a simple answer is attractive and probably drove the authors of the COSMOS study (COcoa Supplement and Multivitamin Outcomes Study) was a large, internet-based pragmatic study that examined the effect of cocoa supplement (don’t get excited, it was extracted “cocoa flavanols” in tablet form) and multivitamins (Centrum Silver) on web-based scales and questionnaires about memory and executive function. The cocoa flavanol intervention was reported separately and the results were…underwhelming. This paper reported the multivitamin intervention. The trial was set up well but had fairly restrictive inclusion criteria – no ischemic vascular disease, no one aged < 65 for women and <60 for men, no active cancer, no other “serious illness”. The patients had a 2-month run-in period where adherence was measured, and the non-adherent were excluded.

The study medications were mailed to the patients. Adherence was self-reported, and outcome measure questionnaires and tests were taken on computer and submitted online. 3562 subjects were enrolled, and outcomes assessed in an intention-to-treat analysis. There was about 10% loss to follow up in both groups. The report trumpeted the positive effect of the multivitamins on memory, stating “the effect of the multivitamin intervention improved memory performance above placebo by the equivalent of 3.1 y of age-related memory change.”  The actual result was an improvement in immediate recall from an average of 7.10 words recalled initially to 7.81 words after one year in the intervention group (vs. 7.21 and 7.65 words respectively in the control group, mean difference 0.23 (+/- 0.10) words, p = 0.025). And there were NO other differences seen in the secondary outcomes – including delayed recall and measures of executive function. In the very brief safety analysis, there was a mention (with scant details in this report) of increased gastrointestinal bleeding in the intervention group, but lower rates of other side effects like rashes and abdominal pain.

John’s Comments:

As with trials of some recently approved and very expensive injectable medications, our attempts to treat dementia with pharmaceuticals have resulted in trivial improvements in outcomes. In our desperation, we over-emphasize these results. This example emphasizes the importance of looking past the abstract and the headlines and reading more deeply, which is only worth the time for articles that would change your practice if true. I won’t tell my patients not to take multivitamins if they want, but would caution those with increased GI bleeding risk, and will help them temper their expectations of its effectiveness.

Reference:

• Yeung LK, Alschuler DM, Wall M, et al. Multivitamin Supplementation Improves Memory in Older Adults: A Randomized Clinical Trial. The American Journal of Clinical Nutrition. Published online May 2023:S0002916523489046. Link

From the Literature (Sort of) and a Question From a Colleague

2)  New Blood Test For Alzheimer’s Disease (AD) Screening?

Question:

“I’ve had a few patients ask me about a new blood test for Alzheimer’s Disease that they can get directly from the company.  What’s the story?”

Answer:

Your patient is likely referencing the AD-Detect blood test from Quest Diagnostics.  In early 2022 this test was introduced for use by physicians and then in August of 2023 began being marketed directly to patients.  The test measures amyloid-beta 42 and amyloid-beta 40 in blood to provide an amyloid-beta 42/40 ratio. In theory, the ratio may help identify the risk of developing Alzheimer's Disease and this is how it is being marketed. 

While there is scant, non-peer reviewed evidence correlating this ratio to other potential markers for AD risk, such as the FDG-PET, Amyloid-PET and CSF biomarkers, there is no evidence that it can predict whether a cognitively unimpaired person will transition to being cognitively impaired.  As such, the Alzheimer’s Association does not endorse the use of the test by consumers.  In a statement from the Alzheimer’s Association in response to this new approach by Quest Diagnostics, Rebecca Edelmayer, PhD, senior director of scientific engagement at the Alzheimer's Association said, “We challenge Quest to pursue a path of FDA approval that demonstrates, rigorously, that this test is valuable to clinicians and patients as part of the diagnostic process."  It should be noted that Quest did not go through an FDA approval process for this test, which is not required if the test is ordered by a physician.   

The test is normally $399 (plus a $13 “Physician Service Fee”) but is presently on “sale” for $299.(through October 1^st).  According to Quest, anyone over the age of 18 can order the test, and anyone with a family history of Alzheimer's disease, mild cognitive decline (trouble remembering, concentrating, making decisions, etc.), brain trauma, or excessive alcohol consumption should consider getting the test, particularly if over the age of 50.  Once patients pay for the test, it is apparently reviewed and then ordered by a physician.  They can go to any local Quest lab for a blood draw.  Test results are available on line, and patients have the option to speak with a physician about their results at no additional cost.  According to the company, if the test is positive, patients will be automatically contacted by a physician from an independent network to discuss the next steps and potentially can share the results with other physicians.

Mark’s Comments:

Those of you who know me can likely guess that the more I researched this one, the more use my “Pause! Button” received.  Therefore, I decided to reach out to Brian Unwin, MD, our Section Chief for Geriatrics, to get his impression.  Brian replied: 

“I would not order the test on a patient unless:

• the patient/family had a clearly articulated concept of what they will do with the result.
• the patient (and clinician) should clearly understand that presence of amyloid does not equal progression or death from AD.
•  treatments now (mostly not impressive) do not portend what might be available in the future.
• addressing potentially modifiable risk factors (especially hearing loss, obesity, diabetes, etc.) can potentially modify trajectory.
•  understanding risk of something that classically is a late life (age 75+) phenomenon is a hypothetical when you are 40s-50s-60s. 
• the patient understands the result may have future implications for their ability to obtain long-term care insurance.

Even after all those concerns are addressed, we should still be careful what we screen for, especially if it is not treatable. Ultimately, I think this and tests like it will simply add to neurosis and overtreatment, and add unnecessarily to the “Big Lab” and “Big Pharma” bottom lines. 

It’s like he was reading my mind but expressing it in a much more diplomatic manner ….

References:

• Quest Diagnostics Press Release. Quest Introduces First-To-Market Consumer-Initiated Blood Test for Alzheimer's Disease Risk Assessment on questhealth.com.  31 July 2023  Link  Link for Test Ordering (just to see what’s being advertised) 
• Pérez-Grijalba, V., Romero, J., Pesini, P. et al. Plasma Aβ42/40 Ratio Detects Early Stages of Alzheimer’s Disease and Correlates with CSF and Neuroimaging Biomarkers in the AB255 Study. J Prev Alzheimers Dis 6, 34–41 (2019). Abstract

From PeerRxMed ( www.PeerRxMed.org )

3)  The Importance of Being Pre-Paired 

“Something I know about community is that you have to build it before you need to lean on it.”  Suleika Jaouad (Author and Blogger)

Where or to whom do you turn when you’re experiencing professional distress or perhaps even a professional crisis?  Hopefully, one of your go-to answers is “my PeerRx partner/s.”  Unfortunately, the most common answer for most of our colleagues is “nowhere and to no one.” 

Often in the context of my PeerRxMed work I am asked to give interviews or talks regarding the importance of health care professional peer support and how PeerRx is different from other peer support programs.  During these opportunities, I find it essential to make the distinction between “formal” and “informal” peer support and make the contrast between “reactive” and “proactive” support.

In the AMA STEPS Forward material on Peer Support Programs for physicians, formal peer support is defined as the process where formally trained non-mental health clinicians (“peers”) offer support to their colleagues after adverse clinical events or other professionally stressful circumstances.  In many organizations, these are known as "Second Victim" programs.  This is contrasted with “informal” peer support, where a well-meaning inquiry is made by a colleague after an adverse event, but without proper training there is a concern they might minimize, dismiss, justify, or try to fix the situation rather than simply being present and supportive. 

What is common about such “formal” peer support programs is that they are always “reactive” (after the fact), are activated by adverse circumstances, and usually involve interacting with someone who is relatively unfamiliar.  Because they also often exist within a culture that does not talk about peer support in any other context, they can seem punitive.  While such programs are a necessary (though generally underutilized) safety net when needed, they do nothing to address the emotional needs of the >50% of physicians and other healthcare professionals presently experiencing professional distress and burnout as well as the many who operate in “survival mode” as they try to navigate their daily professional demands while feeling isolated and alone.  

To even begin to address this, a proactive, relationally based, and less structured (“informal”) process is necessary.  Such a process should involve regular and intentional connection with a colleague or colleagues to share the entirety of our professional journey.  My experience as well as those of many others would indicate that in the busyness of our professional lives, this too often just doesn’t happen, even with “the best of intentions – at least not without a “nudge.”  The PeerRxMed process and platform has been my response to this need.  It is designed to be both “preventive” and “supportive” as well as to provide an obvious and ready resource in those times of crisis. 

I don’t know about you, but I’d much prefer to be “pre-paired” for the inevitable challenges that will come my way on this professional journey.  My PeerRx buddies have helped me navigate many difficult professional times, and have also celebrated and laughed with me in the good times.   Along the way, we’ve encouraged each other to be “better” versions of our professional, and personal, selves, and have greatly enjoyed doing it.  No one should care alone – ever.  Pass it on ….

______________

Mark and John

Carilion Clinic Department of Family and Community Medicine

Feel free to forward Take 3 to your colleagues. Glad to add them to the distribution list.

Email: mhgreenawald@carilionclinic.org