Nice article. Before doing a screening for AD the patient should know
Early diagnosis does not improve the natural course of the illness
Those things that do improve the natural course are lifestyle changes which apply to everyone
If positive you will likely not be able to get disability or long term care or even life insurance (APOE4 might be protected as it is a genetic test)
If positive you will be labeled as sick
There is some evidence that APOE4 might change certain lifestyle recommendations but it is unethical IMHO to order it without going through the downstream repercussions of it with the patient. I would not discuss it with a patient unless the patient first brings it up
“…confusing detection with understanding.” This says it all. The excellent writing and comprehensive understanding belies the writer’s level of training.
That’s a thoughtful distinction. I was primarily referring to plasma biomarkers such as p-tau and Aβ42/40 that are being used to infer the presence of Alzheimer’s pathology. ApoE genotyping is different — it identifies genetic risk rather than current pathology.
That said, ApoE4 status is a probabilistic risk marker, not a diagnostic tool. Many carriers never develop dementia, and many patients with Alzheimer’s do not carry ApoE4. For that reason, I think genetic testing can be reasonable in select circumstances, particularly with appropriate counseling, but I would hesitate to frame it as something “everyone should know” in the absence of clear implications for management.
I completed a fellowship with Dr. Marshal Folstein at Jonhs Hopkins in the early 90s. Perhaps the most important clinical pearl I learned was his admonition “The diagnosis of Alzheimer’s comes from the history.” I spent the next 30 years in academics and clinical practice telling medical students, residents , and colleagues that an appropriate diagnosis depended upon a careful history of symptoms, progression, and functional impact. Your comments are very helpful.
Really good cut for someone so young. I’d say he’s going to be an excellent clinician. Only one thing I’d add. The real reason to do imaging is to rule out other causes like hydrocephalus, tumors, etc.
among the conoscenti screening has a very weak evidence base, even in those diseases for which early diagnosis helps. Colon cancer example. Do you know an American study showing improvement in all cause and disease specific mortality? Good luck. The AGA only allows as an end point “advanced neoplasia” as an endpoint. Hey, we found a 10 mm polyp! But we don’t want to know if that will add a minute to your life. The NORDICC study showed no benefit from colonoscopy screening.
The hubris of medicine overflows when addressing "the masses". All neural pathways are not alike, but those who think they know better, seem to continue to put us in "one size fits all" category. Have you ever worn a "one size fits all" garment?
"Alzheimer’s disease resembles conditions that require staged subspecialty evaluation—oncology, epilepsy surgery, movement disorder phenotyping—far more than diseases amenable to broad screening." Question: is Alzheimer's in fact like these? Is there anything evidence-based to do, or are we at the stage where we're assuming there COULD be a treatment and looking for human lab rats to test on? For the question below that pointed to the relief of a negative test, my father had consistently good hearing tests from his doctor as he clearly lost his ability to participate in family conversations which just gave him good cover for not getting hearing aids until he was very impaired. If you have cognitive issues, the neg blood test doesn't change that.
My analogy to oncology or epilepsy surgery was meant to highlight that diagnosis and management require careful staging and clinical calibration, not that Alzheimer’s has comparable therapeutic leverage or curative options. We do have evidence-based therapies in early symptomatic disease, but their benefits are modest and their risks real, which makes precision important.
I also agree that a negative test does not resolve cognitive symptoms. A biomarker result — positive or negative — does not replace clinical evaluation. That’s part of the concern: tests can create false reassurance or false certainty if divorced from context. Clinical judgment still has to lead. Appreciate your comment.
My wife was diagnosed with FTD by a top neurologist at Columbia about 14 years ago. All kinds of scans and other tests all for nothing IMO. We were told that typical patients can live about 11 years from initial diagnosis. And that's pretty much what happened as she died 3 years ago. There was no treatment then and while I've stopped the amount of reading I do on the subject, it seems little if anything has changed. So at 80, the next time my PCP wants to do the clock or count backwards or 3 words tests, I'll ask why. Should it be discovered I'm cognitively impaired, what's our next steps? I already eat and exercise well. I see no personal ROI in going down this rathole. Just my non medical opinion
I’m very sorry for your loss. Frontotemporal dementia is a particularly difficult diagnosis, and for many years there have been few meaningful treatment options.
The purpose of brief cognitive screening in primary care isn’t to create a label for its own sake. It’s meant to identify change early enough to evaluate potentially reversible causes, plan appropriately, and support safety and function. That said, the value of testing depends on what would be done differently with the information.
There isn’t a single right answer — it depends on goals, preferences, and how the results would change management. Shared decision-making matters here.
In general a good logical assessment and opinion. However, this is an example in the real world of medicine of some inflexible thinking.
Sometimes the screening binaries are quite helpful in certain patients and scenarios. As a negative result can , which is more common than the positive, allay fears and allow continue cognitive monitoring. False negatives may be far less common than subjective testing, and tech testing of mri and per scans. All modalities in primary care should be used and tailored to individual patient needs and risks. Awareness that there are tools like Cognivue to screen and monitor over time. Removes the subjective bias. Psychosocial assessments for cause, nutritional assessments, and family risk factors, along with a detailed and regularly scheduled Hx & PE that often are all not done enough and adequately in Primary care in particular and medicine in general. Yes, it is key in these cases to have primary care have continuity with patients and the lead in care
Keep flexibility in thinking. Avoid the conclusions to defend this and that screening or assessment as the only approach in medicine.
I appreciate the thoughtful comment. My concern was not that screening tools are categorically harmful or that negative results cannot be reassuring. In fact, individualized assessment and continuity in primary care are essential. The point I was trying to make is narrower: when biological tests are used in a screening mindset without clear anchoring to clinical context and downstream management decisions, they can create interpretive ambiguity rather than clarity. A negative result may reduce anxiety, but a positive result does not reliably predict trajectory, nor does it automatically justify intervention.
I agree that flexibility and individualized use of tools are important. My argument was less about eliminating screening and more about being cautious about how we translate biological signals into diagnostic labels and treatment decisions. That calibration, rather than rigidity, is what I was advocating for.
I would recommend beginning with exploring the work of Dr. Dale Bredesen, whose Apollo Health program and books provide actionable roadmaps and resources. Oftentimes correlations with metabolic health and /or toxicity markers can be detected and treated with good results if detected early. www.apollohealthco.com is the website to find out more information on his Recode for reversal and Precode for prevention programs, in addition to a link to a free cognitive assessment test that may provide valuable insights.
Certainly. If you’re noticing memory changes, document specific examples and patterns — repetition, missed bills, getting lost, personality shifts. Then schedule a focused visit specifically to address cognition and bring someone who can provide collateral history. Establishing a baseline and following changes over the next several months is often the most important step. If there’s clear progression or functional decline, that’s when further evaluation becomes appropriate.
It is very encouraging to see such good sense and perspective from a young physician.
Nice article. Before doing a screening for AD the patient should know
Early diagnosis does not improve the natural course of the illness
Those things that do improve the natural course are lifestyle changes which apply to everyone
If positive you will likely not be able to get disability or long term care or even life insurance (APOE4 might be protected as it is a genetic test)
If positive you will be labeled as sick
There is some evidence that APOE4 might change certain lifestyle recommendations but it is unethical IMHO to order it without going through the downstream repercussions of it with the patient. I would not discuss it with a patient unless the patient first brings it up
Brilliant! Thank you for this, very well articulated. My language was perhaps less gentle in last year's "The New Alzheimer's Test Is A Billion Dollar Scam" (https://researchtranslation.substack.com/p/the-new-alzheimers-test-is-part-of).
Great read. I will need to read it a few more times as it is a level above and beyond where I’m at. Thanks for your time.
“…confusing detection with understanding.” This says it all. The excellent writing and comprehensive understanding belies the writer’s level of training.
Dr. Allen,
Are you lumping ApoE4 testing in with other "blood tests" that you would advise against obtaining in those without clinical evidence for Alzheimer's?
It is the biggest genetic risk factor for AD and I think arguments can be made that everyone should know their ApoE4 carrier status.
Just as everyone should know their Lipoprotein (a) status for full understanding of coronary heart disease risk.
That’s a thoughtful distinction. I was primarily referring to plasma biomarkers such as p-tau and Aβ42/40 that are being used to infer the presence of Alzheimer’s pathology. ApoE genotyping is different — it identifies genetic risk rather than current pathology.
That said, ApoE4 status is a probabilistic risk marker, not a diagnostic tool. Many carriers never develop dementia, and many patients with Alzheimer’s do not carry ApoE4. For that reason, I think genetic testing can be reasonable in select circumstances, particularly with appropriate counseling, but I would hesitate to frame it as something “everyone should know” in the absence of clear implications for management.
agree completely
I completed a fellowship with Dr. Marshal Folstein at Jonhs Hopkins in the early 90s. Perhaps the most important clinical pearl I learned was his admonition “The diagnosis of Alzheimer’s comes from the history.” I spent the next 30 years in academics and clinical practice telling medical students, residents , and colleagues that an appropriate diagnosis depended upon a careful history of symptoms, progression, and functional impact. Your comments are very helpful.
Dr BJ
Really good cut for someone so young. I’d say he’s going to be an excellent clinician. Only one thing I’d add. The real reason to do imaging is to rule out other causes like hydrocephalus, tumors, etc.
among the conoscenti screening has a very weak evidence base, even in those diseases for which early diagnosis helps. Colon cancer example. Do you know an American study showing improvement in all cause and disease specific mortality? Good luck. The AGA only allows as an end point “advanced neoplasia” as an endpoint. Hey, we found a 10 mm polyp! But we don’t want to know if that will add a minute to your life. The NORDICC study showed no benefit from colonoscopy screening.
The hubris of medicine overflows when addressing "the masses". All neural pathways are not alike, but those who think they know better, seem to continue to put us in "one size fits all" category. Have you ever worn a "one size fits all" garment?
"Alzheimer’s disease resembles conditions that require staged subspecialty evaluation—oncology, epilepsy surgery, movement disorder phenotyping—far more than diseases amenable to broad screening." Question: is Alzheimer's in fact like these? Is there anything evidence-based to do, or are we at the stage where we're assuming there COULD be a treatment and looking for human lab rats to test on? For the question below that pointed to the relief of a negative test, my father had consistently good hearing tests from his doctor as he clearly lost his ability to participate in family conversations which just gave him good cover for not getting hearing aids until he was very impaired. If you have cognitive issues, the neg blood test doesn't change that.
My analogy to oncology or epilepsy surgery was meant to highlight that diagnosis and management require careful staging and clinical calibration, not that Alzheimer’s has comparable therapeutic leverage or curative options. We do have evidence-based therapies in early symptomatic disease, but their benefits are modest and their risks real, which makes precision important.
I also agree that a negative test does not resolve cognitive symptoms. A biomarker result — positive or negative — does not replace clinical evaluation. That’s part of the concern: tests can create false reassurance or false certainty if divorced from context. Clinical judgment still has to lead. Appreciate your comment.
My wife was diagnosed with FTD by a top neurologist at Columbia about 14 years ago. All kinds of scans and other tests all for nothing IMO. We were told that typical patients can live about 11 years from initial diagnosis. And that's pretty much what happened as she died 3 years ago. There was no treatment then and while I've stopped the amount of reading I do on the subject, it seems little if anything has changed. So at 80, the next time my PCP wants to do the clock or count backwards or 3 words tests, I'll ask why. Should it be discovered I'm cognitively impaired, what's our next steps? I already eat and exercise well. I see no personal ROI in going down this rathole. Just my non medical opinion
I’m very sorry for your loss. Frontotemporal dementia is a particularly difficult diagnosis, and for many years there have been few meaningful treatment options.
The purpose of brief cognitive screening in primary care isn’t to create a label for its own sake. It’s meant to identify change early enough to evaluate potentially reversible causes, plan appropriately, and support safety and function. That said, the value of testing depends on what would be done differently with the information.
There isn’t a single right answer — it depends on goals, preferences, and how the results would change management. Shared decision-making matters here.
In general a good logical assessment and opinion. However, this is an example in the real world of medicine of some inflexible thinking.
Sometimes the screening binaries are quite helpful in certain patients and scenarios. As a negative result can , which is more common than the positive, allay fears and allow continue cognitive monitoring. False negatives may be far less common than subjective testing, and tech testing of mri and per scans. All modalities in primary care should be used and tailored to individual patient needs and risks. Awareness that there are tools like Cognivue to screen and monitor over time. Removes the subjective bias. Psychosocial assessments for cause, nutritional assessments, and family risk factors, along with a detailed and regularly scheduled Hx & PE that often are all not done enough and adequately in Primary care in particular and medicine in general. Yes, it is key in these cases to have primary care have continuity with patients and the lead in care
Keep flexibility in thinking. Avoid the conclusions to defend this and that screening or assessment as the only approach in medicine.
I appreciate the thoughtful comment. My concern was not that screening tools are categorically harmful or that negative results cannot be reassuring. In fact, individualized assessment and continuity in primary care are essential. The point I was trying to make is narrower: when biological tests are used in a screening mindset without clear anchoring to clinical context and downstream management decisions, they can create interpretive ambiguity rather than clarity. A negative result may reduce anxiety, but a positive result does not reliably predict trajectory, nor does it automatically justify intervention.
I agree that flexibility and individualized use of tools are important. My argument was less about eliminating screening and more about being cautious about how we translate biological signals into diagnostic labels and treatment decisions. That calibration, rather than rigidity, is what I was advocating for.
For those of us with aging parents, do you have a recommendation for next steps if we fear we are noticing memory problems in them?
I would recommend beginning with exploring the work of Dr. Dale Bredesen, whose Apollo Health program and books provide actionable roadmaps and resources. Oftentimes correlations with metabolic health and /or toxicity markers can be detected and treated with good results if detected early. www.apollohealthco.com is the website to find out more information on his Recode for reversal and Precode for prevention programs, in addition to a link to a free cognitive assessment test that may provide valuable insights.
Certainly. If you’re noticing memory changes, document specific examples and patterns — repetition, missed bills, getting lost, personality shifts. Then schedule a focused visit specifically to address cognition and bring someone who can provide collateral history. Establishing a baseline and following changes over the next several months is often the most important step. If there’s clear progression or functional decline, that’s when further evaluation becomes appropriate.