Best brain scan to detect pre-symptomatic Alzheimer's

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TeaAndGlasses
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Best brain scan to detect pre-symptomatic Alzheimer's

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I'm curious what the best brain scan is to see how you are doing (Alzheimer's wise, of course). Not something used in research studies, but something you might be able to get a doctor in the US to prescribe.

I don't have any symptoms, but I'm a 3/4 and am middle-aged, and I often wonder if I already have any signs of developing AD in my brain.

I've scanned the forums and it seems like maybe it is an amyloid PET scan or something looking for Tau. I'm not sure, so I thought I'd ask!
paulryan
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Re: Best brain scan to detect pre-symptomatic Alzheimer's

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There is no single brain scan that can definitively detect pre-symptomatic Alzheimer's disease. However, certain imaging techniques can provide valuable information and help in assessing the risk of developing Alzheimer's or identifying early signs of the disease.

It's important to note that these imaging techniques are typically used in research or specialized medical centers, and their availability and usage may vary. Additionally, while they can provide valuable information, they are not definitive diagnostic tools for Alzheimer's disease. A comprehensive evaluation by a healthcare professional specializing in neurology or dementia is necessary for a proper diagnosis and assessment of the risk of developing Alzheimer's disease.
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Re: Best brain scan to detect pre-symptomatic Alzheimer's

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paulryan wrote: Tue May 30, 2023 5:16 am There is no single brain scan that can definitively detect pre-symptomatic Alzheimer's disease. However, certain imaging techniques can provide valuable information and help in assessing the risk of developing Alzheimer's or identifying early signs of the disease.
Welcome paulryan! Thank you for posting in our forum and sharing your knowledge of brain scans. We are happy you found us and look forward to connecting with you.

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Re: Best brain scan to detect pre-symptomatic Alzheimer's

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TeaAndGlasses wrote: Mon May 29, 2023 11:56 am I'm curious what the best brain scan is to see how you are doing (Alzheimer's wise, of course). Not something used in research studies, but something you might be able to get a doctor in the US to prescribe.

I don't have any symptoms, but I'm a 3/4 and am middle-aged, and I often wonder if I already have any signs of developing AD in my brain.

I've scanned the forums and it seems like maybe it is an amyloid PET scan or something looking for Tau. I'm not sure, so I thought I'd ask!
Great question, since every scientist in the AD field wants to know how to track the slow development of changes that MAY eventually lead to a diagnosis of Mild Cognitive Impairment (MCI) or Alzheimer's dementia (or vascular dementia, Lewy body, etc).

The short answer is: PET scans are not yet available at your local doctor's office. But we're improving on early diagnosis, with a blood test still mostly reserved for people with symptoms but used to screen people for clinical trials of anti-amyloid drugs. Since you are in mid-life, with only one copy of ApoE 4, and have no symptoms and a healthy life, it's highly unlikely that the Precivity test (see below) would indicate a positive amyloid result. My advice, as someone with ApoE 4/4, who first tested positive for amyloid in 2017, at the age of 65 and is still doing fine on cognitive tests as recently as last month at age 71, is to keep doing what you're doing, and wait 10 years to see where the diagnostics are then.

The TL/DR answer is: PET scans are still in the province of research trials, mostly, and MRIs are mostly for people with clear symptoms, but unclear diagnosis of a specific type of impairment.

I have had MRIs, Amyloid PET and Tau Pet scans as a participant in clinical trials, and I don't get to hear what the results are, beyond "Your MRI hasn't changed" and "Your Amyloid PET scan shows amyloid".

Clinical drug trials for anti-amyloid drugs want people with a "positive" Amyloid and/or Tau PET scan, so participants have to be told the results of one or both tests, depending on the inclusion criteria. Studies show that most people in clinical trials want to be told more than they are already told, but for now the details- areas and levels of amyloid and tau on PET scans, changes on the MRI that are not indicative of a serious side effect or require medical intervention--- are not shared. The reasoning is that knowing your score (like knowing your IQ) may change your performance on testing without being valid.

This is a rapidly-evolving field, especially in people with no cognitive or behavioral changes, so researchers are using current trial participants to learn more. Disclosing results of a PET scan comes with a conversation and informed consent in clinical trials, since this represents information that people may find distressing, without any clear ability to predict whether it is linked to a diagnosis in 5 years, 20 years or never.

BUT: The FDA recently approved the Precivity™ blood test that uses a combination of amyloid in blood plasma and an algorithm that includes ApoE4 status to predict the likelihood of a "positive" amyloid score on a PET test and to help confirm a diagnosis of Alzheimer's when cognitive impairments are seen on testing. Here's a 2020 article excerpt from AlzForum:
To be clear, C2N’s Precivity plasma Aβ test is not intended as a stand-alone diagnostic, at least not yet. It has received breakthrough device designation from the FDA, and C2N is still working toward approval as an in vitro-diagnostic.

For now, C2N hopes the assay will help clinicians and scientists make a correct diagnosis. It is not intended as a screening test. “It is for individuals under care of a physician who present with complaint and evidence of cognitive decline and are being evaluated for dementia,” C2N CEO Joel Braunstein told Alzforum. “If we can boost physician confidence in their diagnosis from 55 or 60 percent to 85 percent or greater, then we have produced a useful diagnostic tool,” he said. That said, the company is marketing the test directly to consumers. It is available in 45 states, D.C., and Puerto Rico, and other states are expected to approve it soon.
Plasma Aβ Test Wins Approval—Are p-Tau Tests Far Behind?


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TeaAndGlasses
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Re: Best brain scan to detect pre-symptomatic Alzheimer's

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Thank you for that very thorough response, Nancy. I guess I'll just try to chill out and keep doing what I can to stay healthy. :)
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Re: Best brain scan to detect pre-symptomatic Alzheimer's

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TeaAndGlasses wrote: Mon May 29, 2023 11:56 am I'm curious what the best brain scan is to see how you are doing (Alzheimer's wise, of course). Not something used in research studies, but something you might be able to get a doctor in the US to prescribe.

I don't have any symptoms, but I'm a 3/4 and am middle-aged, and I often wonder if I already have any signs of developing AD in my brain.

I've scanned the forums and it seems like maybe it is an amyloid PET scan or something looking for Tau. I'm not sure, so I thought I'd ask!
One thing you can look for is brain shrinkage. An MRI with a supplemental Neuroquant analysis will show brain shrinkage. Brain shrinkage usually occurs in folks with AD decades prior to symptoms. The neuroquant gives you volumetric analysis of different parts of the brain by comparing your brain to the average for your age, adjusted to cranial size. I had an MRI in 2014 when I had a brainstem clot. I then went in and had another MRI in 2019 with the neuroquant. I then went in to UCSF and had a baseline AD analysis. In addition to various memory and speed tests, they compared the two MRIs to look for changes (volume, micro bleeds). If my insurance had not paid 80%, I would have had to pay around $650 in 2019. I had VERY little change between the two and there wasn't any abnormal shrinkage, meaning I probably have at least 10 years before symptoms might start. Even if I had to pay the full $650, the peace of mind that I got would have been worth it.
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Re: Best brain scan to detect pre-symptomatic Alzheimer's

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TeaAndGlasses wrote: Mon May 29, 2023 11:56 amI'm curious what the best brain scan is to see how you are doing (Alzheimer's wise, of course). Not something used in research studies, but something you might be able to get a doctor in the US to prescribe....
mike wrote: Wed Jun 07, 2023 11:30 amOne thing you can look for is brain shrinkage. An MRI with a supplemental Neuroquant analysis will show brain shrinkage. Brain shrinkage usually occurs in folks with AD decades prior to symptoms...I had an MRI in 2014 when I had a brainstem clot. I then went in and had another MRI in 2019 with the neuroquant. I then went in to UCSF and had a baseline AD analysis. In addition to various memory and speed tests, they compared the two MRIs to look for changes (volume, micro bleeds)....I had VERY little change between the two and there wasn't any abnormal shrinkage, meaning I probably have at least 10 years before symptoms might start...
Hi Mike and TeaAndGlasses,

Starting in 2013, teams of researchers identified three biomarkers of changes seen in people with a diagnosis of mild cognitive impairment (MCI) or dementia caused by Alzheimer's disease, and realized that other types of dementia (vascular, Lewy body, frontal temporal dementia, chronic traumatic encephalopathy [CTE], etc) had different patterns than Alzheimer's disease.

The three biomarkers were coded as A (amyloid), T (tau) and N (neurodegeneration or brain atrophy).

Using PET scans or CSF (spinal taps) and MRIs, people could be classified in these ways:

A-/T-/N- Negative for all 3 biomarkers. These people are highly likely to be cognitively unimpaired.

A+/T-/N- Amyloid positive; no tau or atrophy.
A+/T+/N- Amyloid and tau positive; no atrophy
A-/T+/N- Amyloid negative; tau positive; no atrophy
A-/T-/N+ Amyloid and tau negative; evidence of atrophy on MRI.

A+/T+/N+ Amyloid, tau and neurodegeneration all evident on brain imaging. These people are more likely to have a diagnosis of MCI or dementia of either Alzheimer's type or a mixed dementia (AD+ vascular; AD+Lewy body, etc.) than those with only one or two biomarkers. But even they may still be cognitively unimpaired if they have high levels of cognitive reserve (ex. high education) or cognitive resiliency (genetic or other factors which make their brain resilient to pathology.

Since then, many studies have looked at whether and how these biomarkers could to be useful to track changes in cognitively unimpaired (CU) people years before any symptoms, and whether the profiles would lead to better diagnoses of changes primarily caused by tauopathies (ex. frontal temporal dementia) rather than Alzheimer's, as well as to targets for prevention and treatment.

Here's the results from Exploring the ATN classification system using brain morphology published March 2023 by a collaboration between researchers in Germany, Scotland, London and Portugal looking specifically at whether amyloid beta comes before tau and neurodegenetaion on most cases. The arrows signify which biomarker was seen before another in progression. Their use of the term ACH refers to the amyloid cascade hypotheses; that amyloid positivity is seen on PET scans before Tau and before neurodegeneration on MRIs in those that progressed to actual diagnosis of Alzheimer's dementia:
Results: The ACH-based progression A-T-N-➔A+T-N-➔A+T+N-➔A+T+N+ was consistent with cognitive decline and clinical diagnosis. Using hippocampal volume for operationalization of neurodegeneration (N), ACH was most evident in 9% of gray matter predominantly in the medial temporal lobe. Many cortical regions suggested alternative non-monotonic volume progressions over ACH progression groups, which is compatible with an early amyloid-related tissue expansion or sampling effects, e.g., due to brain reserve. Volume decline in 65% of gray matter was consistent with a progression where A status converts before T or N status (i.e., ACH/ANT) when compared to alternative sequences (TAN/TNA/NAT/NTA). Brain regions earlier affected by tau tangle deposition (Braak stage I-IV, MTL, limbic system) present stronger evidence for volume decline than late Braak stage ROIs (V/VI, cortical regions). Similar findings were observed when using CSF total-tau for N instead.

Conclusion: Using the ATN classification system, early amyloid status conversion (before tau and neurodegeneration) is associated with brain volume loss observed during AD progression. The ATN system and the ACH are compatible with monotonic progression of MTL atrophy.
The clinical trials that I have been in, and the researchers I have talked to, all see amyloid as the first sign of changes, possibly as much as 15-20 years before a diagnosis--but only likely to lead to a diagnosis when tau comes along and kills neurons. It doesn't mean that atrophy can't happen in a healthy person; but that atrophy is probably not a prediction of Alzheimer's, per se.
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Re: Best brain scan to detect pre-symptomatic Alzheimer's

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NF52 wrote: Thu Jun 08, 2023 9:19 am Nancy,

What comes first - chicken or the egg... Are you 100% sure AB comes first?
https://www.aan.com/PressRoom/Home/PressRelease/940
For the study, researchers used MRI scans to measure areas of the brain in people with no memory problems or other signs of Alzheimer’s, then followed them for years to see who developed the disease. The researchers specifically focused their measurements on areas known to be involved in AD. Those with smaller brain size in the Alzheimer’s-related areas of the brain were much more likely to develop the disease than those with larger measurements.
https://alz-journals.onlinelibrary.wile ... dad2.12197
Some of the aforementioned imaging modalities are expensive, involve exposure to ionizing radiation, and are relatively scarce in many parts of the world. It is thus encouraging that baseline hippocampal volume and change in hippocampal volume over time, which can be measured from MRI, are both predictive of decline in DIAD-MC.12
http://appliedradiology.com/Articles/no ... -shrinkage
While traditional MRI is capable of showing where damaged areas of the brain have decreased in volume, the qGRE technique goes a step further, detecting the loss of neurons that precedes brain shrinkage and cognitive decline.
This last article agrees with your AB-Tau-Neuron loss, but proposes a new MRI method that can detect Neurons in poor health...before neuron loss

Until the current crop or blood biomarkers becomes available, MRI still seems useful
Sonoma Mike
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