If your argument is ‘crappy tests in a world where we have no effective remedies are a bad idea” then yes, they clearly are. But you’d have to be an idiot to think otherwise. Sensible people in the uk, where I’m based, are saying that effective early testing combined with effective treatments might be the way forward, but we’re not there yet.
This is one of the clearest explanations I’ve seen of the real problem in Alzheimer’s care: it’s not that pathology is impossible to detect; it’s that pathology doesn’t map neatly onto symptoms, prognosis, or what we should do next. A biomarker is most useful when it answers a specific clinical question, not when it creates one in the absence of context. 
As a clinician, the “sequencing” point feels exactly right: phenotype + trajectory + function first; then imaging to understand pattern and competing etiologies; then biology as an adjudicator. Reversing that order turns a blood test into interpretive debt, especially in older adults where mixed pathology is common and incidental amyloid positivity is not rare. 
And the post is also realistic about downstream consequences. Even in the era of anti-amyloid monoclonals, treatment isn’t triggered by a screening blood test, but it requires confirmation of brain amyloid (PET or CSF), MRI review and surveillance for ARIA risk, and a values-forward conversation about modest benefit vs real harms and monitoring burden. 
Lastly, this fits neatly with the broader screening principle: for asymptomatic community-dwelling older adults, the USPSTF has found insufficient evidence to recommend routine cognitive impairment screening, because “detecting something” only helps if it reliably leads to better outcomes without disproportionate harms. 
Blood biomarkers are exciting tools, including p-tau217 and related markers are improving fast, but your central message is the one that will protect patients: testing should serve understanding, not replace it.
The point of early testing, and it's clear that the tests aren't very good at the moment, is to identify a cohort at risk to enter into trials of possible preventative strategies. That's a reasonable goal of a test, we just need better ones.
Great post. In particular, I like the emphasis on global clinical assessment prior to testing.
Simply identifying abnormal cognition isn’t enough to always warrant a ptau217. It’s a little like getting an MRI for suspected radiculopathy: there are potentially lots of irrelevant positives, but it can be helpful when it clearly correlates with the clinical picture.
It seems less helpful when the probability of co-pathology is high (e.g., in those with a high burden of small vessel disease, or in those who have an atypical/non-amnestic pattern).
Counseling about a positive ptau217 in MCI can be tricky. In common parlance, Alzheimer disease = dementia. To a patient and his/her family, mild cognitive impairment from Alzheimer’s disease (but not Alzheimer’s dementia) often doesn’t compute.
In my geriatrics practice, I’ve gone from caution with testing (because I wasn’t comfortable with it) to frequent testing (because I became comfortable) to I hope more judicious testing (because I learned).
Respectfully, I think there is a lack of discussion around the lifestyle changes that can be made with early detection. Peer-reviewed studies are increasingly showing benefits of slowing Alzheimer’s (exercise, sleep pattern changes, socialization, annual vaccinations, treatment for herpesvirus reactivations, etc), much more than suggesting anti-amyloid as the default intervention at time of screening. It’s also becoming clear that many individuals think they live a healthy lifestyle and exercise efficiently but objectively this is not the case and a consultation with a physician after a real detection can dramatically shape changes in individuals. I say this as a dementia researcher and professor of neurology that studies risk factors.
Thank you for the thoughtful comment — I agree that lifestyle factors matter, and we have made modest but real strides in treating early symptomatic disease. The harder question is what screening adds. Most of the interventions you mention—exercise, sleep optimization, vascular risk control—are broadly advisable regardless of biomarker status. A positive result increases probabilistic risk, but it doesn’t tell us who will progress, on what timeline, or whether that trajectory can be meaningfully altered. In older adults especially, time horizon and competing mortality become central.
We are making strides in the treatment of Alzheimer’s disease??? Not true. Alzheimer's is on the rise and getting worse. I agree with your premise not to attempt to diagnose a disease for which there is no cure. But we know what causes Alzheimer's in the majority of cases. And you are right. We need to address the causes early on in life: Processed food, sugar, sedentary lifestyle, lack of exercise, lack of social connections and purpose, avoidance of the sun, lack of omega 3, statins, metabolic diseases, toxins in the environment etc. How can an elusive pill of the future ever rebuild brain tissue that has been destroyed by years of assault and neglect? Once symptoms emerge, it is too late.
This may be a case study n=1, so take it as anecdotal evidence. I have a former patient who was diagnosed with Alzheimer's. So much so that he retired, moved his home to be close to others and looked for strong medical guidance. He was lucky enough to join clinical research that follows patients along the course of their life after being diagnosed. He took up more exercise, decided to move to a ketogenic diet, stopped all alcohol, and adhered to a strict sleep program (if I recall was at least 9 hours a night, his wife wasn't happy with this early 8pm bed time that he is religious about). And he got all the blood tests and brain scans because of this research program. He is 6 years in and has had no changes in his cognitive function. He attributes this to the lifestyle changes preventing further loss. I know this man and he definitely has cognitive loss/changes. So I would not say he was misdiagnosed. I would say the changes have halted further decline. He has taken no other meds for the diagnosis. He declined all of that and decided he would make positive changes to how he lives. It seems to be working well. But this doesn't make pharma money, so maybe it is less popular with the medical community!? Again, this is just 1 guy. I also know lots of patients with metabolic dysfunction and they seem fuzzier and fuzzier every time I see them. They have not made lifestyle changes and it shows on the outside and the inside.
Excellent observation. I, likewise, have witnessed many of my patients responding to the positive brain efforts, I mentioned previously. In addition, I have 2 patients that have actually improved dramatically in cognitive abilities. While $Billions are being spent on a cure, we are neglecting the cause, which can make all the difference for most patients.
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.
Can Ivermectin reverse or prevent Alzheimers?
Well said!
If your argument is ‘crappy tests in a world where we have no effective remedies are a bad idea” then yes, they clearly are. But you’d have to be an idiot to think otherwise. Sensible people in the uk, where I’m based, are saying that effective early testing combined with effective treatments might be the way forward, but we’re not there yet.
What an amazing clear and succinct assessment of the unfortunate paradigm shift in medicine today whereby Occam's razor no longer applies.
This is one of the clearest explanations I’ve seen of the real problem in Alzheimer’s care: it’s not that pathology is impossible to detect; it’s that pathology doesn’t map neatly onto symptoms, prognosis, or what we should do next. A biomarker is most useful when it answers a specific clinical question, not when it creates one in the absence of context. 
As a clinician, the “sequencing” point feels exactly right: phenotype + trajectory + function first; then imaging to understand pattern and competing etiologies; then biology as an adjudicator. Reversing that order turns a blood test into interpretive debt, especially in older adults where mixed pathology is common and incidental amyloid positivity is not rare. 
And the post is also realistic about downstream consequences. Even in the era of anti-amyloid monoclonals, treatment isn’t triggered by a screening blood test, but it requires confirmation of brain amyloid (PET or CSF), MRI review and surveillance for ARIA risk, and a values-forward conversation about modest benefit vs real harms and monitoring burden. 
Lastly, this fits neatly with the broader screening principle: for asymptomatic community-dwelling older adults, the USPSTF has found insufficient evidence to recommend routine cognitive impairment screening, because “detecting something” only helps if it reliably leads to better outcomes without disproportionate harms. 
Blood biomarkers are exciting tools, including p-tau217 and related markers are improving fast, but your central message is the one that will protect patients: testing should serve understanding, not replace it.
I for one do not want to be diagnosed with anything that does not have a clear action plan attached to it. Ignorance may be bliss sometimes.
The point of early testing, and it's clear that the tests aren't very good at the moment, is to identify a cohort at risk to enter into trials of possible preventative strategies. That's a reasonable goal of a test, we just need better ones.
Great post. In particular, I like the emphasis on global clinical assessment prior to testing.
Simply identifying abnormal cognition isn’t enough to always warrant a ptau217. It’s a little like getting an MRI for suspected radiculopathy: there are potentially lots of irrelevant positives, but it can be helpful when it clearly correlates with the clinical picture.
It seems less helpful when the probability of co-pathology is high (e.g., in those with a high burden of small vessel disease, or in those who have an atypical/non-amnestic pattern).
Counseling about a positive ptau217 in MCI can be tricky. In common parlance, Alzheimer disease = dementia. To a patient and his/her family, mild cognitive impairment from Alzheimer’s disease (but not Alzheimer’s dementia) often doesn’t compute.
In my geriatrics practice, I’ve gone from caution with testing (because I wasn’t comfortable with it) to frequent testing (because I became comfortable) to I hope more judicious testing (because I learned).
Nice post. Harkens back to some fundamental clinical first principles.
You do a test to investigate symptoms. And not as a random fishing expedition.
You do a test when the results will change management.
This current test seems to fail on both those fronts. But no doubt they will do good business among the worried well.
Respectfully, I think there is a lack of discussion around the lifestyle changes that can be made with early detection. Peer-reviewed studies are increasingly showing benefits of slowing Alzheimer’s (exercise, sleep pattern changes, socialization, annual vaccinations, treatment for herpesvirus reactivations, etc), much more than suggesting anti-amyloid as the default intervention at time of screening. It’s also becoming clear that many individuals think they live a healthy lifestyle and exercise efficiently but objectively this is not the case and a consultation with a physician after a real detection can dramatically shape changes in individuals. I say this as a dementia researcher and professor of neurology that studies risk factors.
Thank you for the thoughtful comment — I agree that lifestyle factors matter, and we have made modest but real strides in treating early symptomatic disease. The harder question is what screening adds. Most of the interventions you mention—exercise, sleep optimization, vascular risk control—are broadly advisable regardless of biomarker status. A positive result increases probabilistic risk, but it doesn’t tell us who will progress, on what timeline, or whether that trajectory can be meaningfully altered. In older adults especially, time horizon and competing mortality become central.
We are making strides in the treatment of Alzheimer’s disease??? Not true. Alzheimer's is on the rise and getting worse. I agree with your premise not to attempt to diagnose a disease for which there is no cure. But we know what causes Alzheimer's in the majority of cases. And you are right. We need to address the causes early on in life: Processed food, sugar, sedentary lifestyle, lack of exercise, lack of social connections and purpose, avoidance of the sun, lack of omega 3, statins, metabolic diseases, toxins in the environment etc. How can an elusive pill of the future ever rebuild brain tissue that has been destroyed by years of assault and neglect? Once symptoms emerge, it is too late.
This may be a case study n=1, so take it as anecdotal evidence. I have a former patient who was diagnosed with Alzheimer's. So much so that he retired, moved his home to be close to others and looked for strong medical guidance. He was lucky enough to join clinical research that follows patients along the course of their life after being diagnosed. He took up more exercise, decided to move to a ketogenic diet, stopped all alcohol, and adhered to a strict sleep program (if I recall was at least 9 hours a night, his wife wasn't happy with this early 8pm bed time that he is religious about). And he got all the blood tests and brain scans because of this research program. He is 6 years in and has had no changes in his cognitive function. He attributes this to the lifestyle changes preventing further loss. I know this man and he definitely has cognitive loss/changes. So I would not say he was misdiagnosed. I would say the changes have halted further decline. He has taken no other meds for the diagnosis. He declined all of that and decided he would make positive changes to how he lives. It seems to be working well. But this doesn't make pharma money, so maybe it is less popular with the medical community!? Again, this is just 1 guy. I also know lots of patients with metabolic dysfunction and they seem fuzzier and fuzzier every time I see them. They have not made lifestyle changes and it shows on the outside and the inside.
Excellent observation. I, likewise, have witnessed many of my patients responding to the positive brain efforts, I mentioned previously. In addition, I have 2 patients that have actually improved dramatically in cognitive abilities. While $Billions are being spent on a cure, we are neglecting the cause, which can make all the difference for most patients.
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.