New here? Some Best Practices

[abalboa]

Welcome Welcomeaboard,
Thank you for joining our site and posting in the forum. I am sure other members will provide you with some feedback as well but there are a number of ways you can get tested for APoE4. My personal preference would be a blood test through your doctor. Additionally- you can access a number of tests to get an idea if you might be experiencing cognitive impairment. Your doctor may be able to administer a simple MoCa test or you might go to Apollo Health and take a free assessment or even a CNS vital signs test. These could provide some baseline information that could provide additional guidance on what path forward you'd like to take in addressing any concerns.

Additionally, as a Support Team Intern, I can share several tools & resources to help you get the most out of your experience if you would like to explore the site in more detail. The Primer is a detailed and informative resource written by a practicing M.D. with ApoE4/4. It includes information about the biochemistry of the ApoE4 gene and offers a variety of research-based prevention strategies.

Some helpful tips to navigate the site include the How-To Guide. It includes topics such as navigating the forum, private messaging, and searching. One great tip is using the quote (") button when replying to a post. Using the button will automatically alert the member of your response.

If you are interested in learning more about other members check out Our Stories.

Again, I am so glad you joined our forum. I look forward to hearing from you in the future. Please feel free to reach out anytime.

Warmly,
Angie

[NF52]

Newbie question, I’m 83, plenty of walking, swimming, pretty good cognitive reserve, I think, yet my ST memory is failing. I haven’t been tested but believe I’m on track to cognitive impairment of some kind, brain fog, insomnia, rely on gabapentin to help sleep. I’ve read most of the orientation information here.
What is best most cost effective test to determine APOE, 4/4 or whatever? Following Dr Bredesen, Hyman, Daniel Amen, Peter Attia. Many thanks.

Another option, in addition to the good ones Tincup offered, is Life Extension's ApoE Genetic Test for Alzheimer’s and Cardiac Risk Cheek Swab which is currently $ 149. I've done many tests using Life Extension and once I've paid online, I get an email with an order, similar to what your doctor might provide a lab. I can either print it out, or just bring my phone with the email that. shows a code and have six months to take it to my local Lab Corp (or other lab).For most tests get results back within a few days. ApoE testing may take a bit longer--l did that at age 61 through 23& me and discovered I was ApoE 4/4.

If you want some good news: having watched, read and listened to smart people studying ApoE4, you may be like 25% or so of people with one copy of ApoE4 and doing fine. With what seems like your great cognitive reserve, lots of exercise, and finding our forum at age 83, you'd also be one very healthy ApoE 4/4 if you were one of the 2% of us with that. Being aware of mild short-term memory issues, especially if they don't interfere with your daily life, may also be due to reduced inefficiencies in our processing speed and attention span as we get older (I'm 71), which is why people still often use skills in reasoning, problem solving and expertise to make their brain networks compensate for the short-term changes. (Post-it notes work well also, as do calendar reminders!)

If you haven't had a sleep study, that might be something to consider. I had a loved one who slept alone and didn't realize they had severe sleep apnea until we were stuck in a hotel room during an ice storm and I got to hear about 50 interruptions per hour!

Nancy

[Tincup]

If you haven't had a sleep study, that might be something to consider. I had a loved one who slept alone and didn't realize they had severe sleep apnea until we were stuck in a hotel room during an ice storm and I got to hear about 50 interruptions per hour!

In some mild to moderate sleep apnea, taping your mouth shut at night can solve the apnea. I've used this tape for many (~10) years. There are others. Author of the book, "Breath" talks about mouth taping here. In his book, Nestor talks about how he and another subject had their noses plugged by a Stanford researcher for 10? or so days to test the impact of mouth breathing. It was quite dramatic.

In this post, you can see the impact of the post author's heart rate with and without mouth tape in the same night. The graphs are beat to beat heart rate vs time and without tape the heart rate shows apnea heart rate patterns.

In this book, breathing coach, Patrick McKeown describes how nasal breathing is much preferred over mouth breathing. He has many more resources on his site, including many books and a free app.

[Dannyjr]

My wife was diagnosed with MCI 5 years ago, they told us to return in a year. We thought whats the point, her father passed away at 73 from alzheimer's ...was there hope. Eighteen months ago I contacted a neurologist and Lauren went through extensive testing at which point I first heard of APOE4/4. Neurology said she was a perfect candidate for a Drug Protocol by Eli Lily Pharmaceutical. She qualified for the drug and in June she had her first infusion and subsequent ones since up to last week, Im now questioning the validity of this. Sunday a friend informed me to read Dale Bredesen's book "The End of Alzheimers" I had no idea there was so much information out there. One really has to take control of their own destiny. We are very active and already follow the primer to a T. Lots of research to do.
Should we stop the protocol?
Dan

[NF52]

My wife was diagnosed with MCI 5 years ago, they told us to return in a year. We thought whats the point, her father passed away at 73 from alzheimer's ...was there hope. Eighteen months ago I contacted a neurologist and Lauren went through extensive testing at which point I first heard of APOE4/4. Neurology said she was a perfect candidate for a Drug Protocol by Eli Lily Pharmaceutical. She qualified for the drug and in June she had her first infusion and subsequent ones since up to last week, Im now questioning the validity of this. Sunday a friend informed me to read Dale Bredesen's book "The End of Alzheimers" I had no idea there was so much information out there. One really has to take control of their own destiny. We are very active and already follow the primer to a T. Lots of research to do.
Should we stop the protocol?
Dan

Hi Dan,

Lauren is so lucky to have a husband who helped her to get an early diagnosis of MCI, which I hope helped both of you value the last 5 years and learn together how to "live alongside Alzheimer's", as I heard someone from Wales describe it this summer--wth about the same history as Lauren. I'm assuming that Lauren is in the TRAILBLAZER 6, trial, with the official title: Investigating the Effect of Different Donanemab Dosing Regimens on ARIA-E and Amyloid Lowering in Adults With Early Symptomatic Alzheimer's Disease For those interested, here is the description and a list of locations and contacts on
ClinicalTrials.gov

I'm 71 and also have Apoe 4/4 and know that deciding what to do to gain time is a very personal decision, with risks and benefits weighed by both individual factors and preferences. So there is no clear Yes/No answer to your question. but here are my thoughts.

Full disclosure: I happen to be in the AHEAD trial of lecanemab, a drug very similar to donanemab, Eli Lilly's anti-amyloid drug. My trial is for people with elevated amyloid who have normal cognition, and the drug's mechanism of action is to remove amyloid oligomers (toxic forms of amyloid beta) and clear out amyloid plaques. Both anti-amyloid immunotherapies (Donanemab and lecanemab) appear to also remove some toxic tau tangles that appear to be more damaging to neurons. Lecanemab recently received full FDA approval under the name Leqembi for people with MCI/Mild AD, with "appropriate use recommendations" including some "black box warnings". Donanemab is viewed as likely to received full FDA approval late this year or early in 2024, with similar labels and cautions. These drugs are controversial, because they have not been used in widely diverse populations and because they comes with known--and possibly unknown-- side effects for some people. Right now, Lauren might qualify for Leqembi with Medicare coverage, but it appears that she is likely getting a similar dose and drug in her current trial, with very careful monitoring.

Since she's been on the infusions for about 5 months, she's past the first few months when the highest risk of the side effect of ARIA-E (edema, or small pockets of fluid) have been seen in about 39% of people with ApoE 4/4 in the previous Trailblazer 3 trial in MCI/mild AD, most of whom had no symptoms and recovered with a pause in dosing. She's also past the time period when ARIA-H (micro-hemorrhages of about 5mm) are seen in some people. She has probably had several MRIs to check for both ARIA-E and ARIA-H, which will decrease in frequency after 6 months. Only about 1.6% of people had severe ARIA-E, which is treated with IV steroids. Mild cases of ARIA-E or ARIA-H are treated by pausing the dosing and doing repeat MRIs at about monthly intervals until the edema is gone or no additional micro-hemorrhages are seen.

People with ApoE 4/4 on both the placebo and the drug lecanemab in that trial (CLARITY) showed a similar rate of "isolated ARIA-H"--meaning they had a micro-hemorrhage without edema and it just happened sporadically. That's because people with APOE 4/4 are more likely to also have amyloid in the walls of their cerebral arteries, a condition called cerebral amyloid angioiopathy (CAA), which makes the tiny capillaries more prone to being "leaky".

Now for the possible benefits: People on donanemab have to show both elevated amyloid and a "positive" tau PET scan, which suggests they are further along in the development of the disease, since amyloid become elevated well before tau. The people in the TRAILBLAZER trial who were in the MCI and "early-mild" AD range with low-medium levels of tau had a 61% slowing of cognitive and functional skills over 18 months, compared to similar people on the placebo. Their care partners also reported high levels of maintenance or slowing of changes in functional daily living skills of about 45%. The changes in trajectories of line graphs between placebo and the drug appeared at about 12 weeks and continued throughout the trial--even in people who reached "amyloid negative" status on their 12-month PET scan and were switched to the placebo. In other words: donanemab appears to show that removing amyloid can happen between 12-18 months for most people with MCI/mild AD and they show benefits of about 5-6 months of "saved time" compared to when those on the placebo reached certain levels. About half of those on donanemab showed no decline after 12 months, compared with about 29% on the placebo.

I couldn't find how long TRAILBLAZER 6 lasts, but assume it's about 24 months of treatment, with a final assessment at about month 26. For what it's worth, I'm in month 22 of the AHEAD trial and will have my last biweekly infusion next week (Visit 96) along with a whole bunch of cognitive and blood tests. Today I have a Tau PET scan, to go along with the Amyloid PET scan I had Monday, and the MRI I had last Thursday. I don't know if I am on the placebo or the drug (50/50 chance), but if I'm on the drug, I am likely clear of amyloid that has been building up for more than 15 years and has been "elevated" since at least 2017 when I had my first PET scan. I feel fortunate to have had no serious side effects and to have wonderful people at my study site. Along with others I know of in these trials, I think that even if I don't benefit, the research is building on each trial to make it less likely that my Apoe 3/4 adult children will have to dread the disease that made the last years of life difficult for their two grandmothers and many of their great aunts and uncles.

I don't follow Dr. Bredesen's protocol "to a T", but I do follow many of his recommendations and have kept careful record of lots of biomarkers (Vitamin B-12, A1C, LDL-P, insulin resistance, glucose, C-reactive protein, etc). I've always been told that nothing in my trial would prevent me from following great lifestyle recommendations--which every researcher I hear believes may be of most benefit to those of us with ApoE 4/4.

Whatever you decide, please know you and Lauren are in our thoughts--and hearts!

Nancy

[JennyR]

My wife was diagnosed with MCI 5 years ago, they told us to return in a year. We thought whats the point, her father passed away at 73 from alzheimer's ...was there hope. Eighteen months ago I contacted a neurologist and Lauren went through extensive testing at which point I first heard of APOE4/4. Neurology said she was a perfect candidate for a Drug Protocol by Eli Lily Pharmaceutical. She qualified for the drug and in June she had her first infusion and subsequent ones since up to last week, Im now questioning the validity of this. Sunday a friend informed me to read Dale Bredesen's book "The End of Alzheimers" I had no idea there was so much information out there. One really has to take control of their own destiny. We are very active and already follow the primer to a T. Lots of research to do.
Should we stop the protocol?
Dan

Hi Dan-
I can't answer your specific question with regard to your wife's protocol and path forward but I did want to chime in to echo Nancy in welcoming you here and applauding your courage in being such a supportive caregiver and being open to new ideas. You will find so much information here on the Forum!

It sounds like you already found the Primer which has a plethora of information about the biochemistry of the ApoE4 gene and a variety of research-based prevention strategies.

If you're interested in finding an ApoE4 aware practitioner to join Lauren's care team and/or to support your Neurology team, we have a Directory of ApoE4-Aware Healthcare Practitioners that may be a helpful starting point.

Above, Nancy so generously shared her own personal experience which I hope is helpful for you and your wife. Although everyone's story is unique, there's something to learn from the experience of others. You're probably realizing that everyone here is asking many of the same questions that you all are--we're all in this together and you and Lauren are not alone!

I am so glad you found our forum. Please feel free to reach out anytime with additional questions and do please keep us updated on your journey!

With love, in health,
Jenny

[Dannyjr]

Nancy,
Thank you for your reply. I know it took a lot of time follow up with me and I appreciate it.
We do know Lauren is getting the drug and not a placebo. All MRI's have come back positive with no edema.
We lead a healthy active lifestyle but I do see decline in Lauren. Lauren has always had stomach issues which we have yet to get a diagnosis on. I believe this inflammation is hindering or attributing to the issue of cognitive issues.
I have so much to learn...
Dan

[TheresaB]

My wife was diagnosed with MCI 5 years ago, they told us to return in a year. We thought whats the point, her father passed away at 73 from alzheimer's ...was there hope. Eighteen months ago I contacted a neurologist and Lauren went through extensive testing at which point I first heard of APOE4/4. Neurology said she was a perfect candidate for a Drug Protocol by Eli Lily Pharmaceutical. She qualified for the drug and in June she had her first infusion and subsequent ones since up to last week, Im now questioning the validity of this. Sunday a friend informed me to read Dale Bredesen's book "The End of Alzheimers" I had no idea there was so much information out there. One really has to take control of their own destiny. We are very active and already follow the primer to a T. Lots of research to do.

Should we stop the protocol?

That question is one only you and your wife can answer.

However, the causes of Alzheimer’s are still poorly understood, and the mechanisms of its development have not been completely clarified. There are several hypotheses, of which the amyloid hypothesis has dominated but of late seems to be questioned more. Many drugs have tried to address Alzheimer's, the vast majority have failed. Until recently the only drugs that were approved only offered temporary relief, if any. The recently approved drugs still have many associated unknowns.

I believe some day drugs will provide benefit, but Alzheimer’s is a complicated disease. This slide illustrates just what the perfect Alzheimer’s drug would need to do.

Dr Bredesen perfect Alzheimer's drug.jpg

Like the less complicated (compared to Alzheimer's) disease, AIDS, there will likely someday be a drug “cocktail” but that day still seems to be far in the future.

I do know that of the drugs recently approved or currently in the pipeline, there’s only one that to me seems to offer potential benefit to 4 carriers, and it isn’t an Eli Lily drug (it’s ALZ-801 by Alzheon). I know of the recent six “mab” drugs, only 3 have had some form of success. The 3 that failed were gantenerumab, solanezumab, and crenezumab. The two that were approved by the FDA were: aducanumab (aduhelm) and lecanemab (leqembi). And the last one, donanemab is likely to be approved. But the “successful” drugs only slow the decline, everyone’s cognition still got worse.

Plus, the two approved drugs are not without controversy, especially for ApoE4s. With the first drug Aducanumab/Aduhelm, the FDA’s independent advisory committee cited insufficient evidence that demonstrated that the drug actually slowed cognitive decline and recommended disapproving it. The FDA approved it anyway. Three committee members resigned over that decision. Plus there was a scathing Congressional investigation into the approval process citing the FDA's conduct as "rife with irregularities" that the agency's actions "raise serious concerns about FDA's lapses in protocol" in its "atypical collaboration" with the drug maker. Specifically with regard to our genotype, initially the FDA cited no cautions for ApoE4 carriers but subsequently the updated its safety-related labeling for ApoE ε4/4 carriers to better characterize the risk of potential bleeding in the brain while on the therapy.

With respect to lecanemab/lequembi, all six advisers on the panel voted in favor of approval, however, the FDA advisory committee recommended that the Leqembi’s label require ApoE4 testing, however, the agency did not want to be too restrictive. The labeling does recommend genotyping. Clinical trials for Leqembi found that, compared to non-carriers and heterozygotes, ApoE ε4/4s experienced higher rates of amyloid-related imaging abnormalities (ARIA).

ApoE4s are more susceptible to brain arterial disorders such as cerebral atherosclerosis, small vessel disease, and cerebral amyloid angiopathy (CAA). All three disorders can lead to bleeding in the brain, thus ApoE4s need to be especially mindful when evaluating risks vs benefit when considering drug side effects. Additionally, as addressed in this thread, viewtopic.php?p=90134#p90134 the results in ApoEε4/4s and women taking Lecanemab/leqembi were not statistically significant.

But your wife is on an Eli-Lily drug, neither aducanemab or lecanemab, I just bring up those examples in the event your wife is being infused with the third apparently "successful" "mab" drug developed by Eli-Lily, donamemab. All "mabs" require monitoring for ARIA and the exact mechanism of these abnormalities is unknown, but what is known is the risk is higher for us ApoE4s. Although the FDA has not yet approved donememab, it's likely to be approved. From this article on the presentation of the Phase 3 Trial results given at the Alzheimer’s Association Conference in Amsterdam this past summer Alzheimer’s trial shows clear benefits and significant risks of Eli Lilly antibody the positive results showed that donanemab modestly slowed cognitive decline at a rate that was slightly better than lecanemab, however on the negative side,

Donanemab appears to come with higher risks than lecanemab. As a class, antiamyloid antibodies carry a chance of brain swelling and bleeding—known collectively as amyloid-related imaging abnormalities (ARIA)—whose severity can range from asymptomatic to fatal. In the donanemab trial, almost 37% of people getting the antibody developed ARIA, although many had no symptoms—the condition only being detected by brain imaging. One-quarter of participants on donanemab had brain swelling, the more common form of ARIA, and about one-quarter of these patients had symptoms, which included headaches and confusion. Three people died from brain swelling or bleeding attributed to the treatment.

So, everyone in the successful “mab” trials got worse, some on the drug just got worse more slowly while a good percentage experienced ARIA side effects. In comparison, the Bredesen protocol, known as ReCode, has been successful in reversing cognitive decline, people got better! Granted, results are not 100% effective, but in clinical trials, 84% improved. Additionally, I am not aware of any negative side-effects of pursuing the protocol. You can read more on the Apollo Health website: https://www.apollohealthco.com/

You can also read a sort of “cliff notes” in our ApoE4.info wiki: Bredesen Protocol

With respect to your suspicion of inflammation being at the basis of your wife's issue, that is very possible, ApoE4s are pro-inflammatory and of the 6 types of Alzheimer's Dr Bredesen has identified, Type 1 is Inflammatory. From Dr Bredesen’s 2nd book, The End of Alzheimer’s Program (a sort of "how to" manual for those who want to implement what he discusses in his first book, The End of Alzheimer’s, the book you were advised to read).

So as long as there is ongoing inflammation, you can expect ongoing amyloid production and Alzheimer’s. What we want to do, therefore, is to remove the cause of the inflammation, resolve the inflammation, then prevent future inflammation. The most common cause of chronic inflammation is leaky gut (increased permeability of the small intestine to bacteria, bacterial fragments, and food particles), which can be caused by stress, sugar, alcohol, processed foods, aspirin and related anti-inflammatories (e.g., ibuprofen), soft drinks, PPIs (proton-pump inhibitors used to treat acid reflux, or heartburn), and other damaging agents,…

You can read more about leaky gut in our ApoE4.info wiki: Gut-Brain Connection: Leaky Gut/Leaky Brain, Microbiome (gut bugs)

That you and your wife are following the recommendations of our primer is excellent to hear, but Dr Bredesen’s emphasis is to target the greatest drivers to the individual. In the book, The End of Alzheimer’s Dr Bredesen uses the analogy of Alzheimer’s as a roof with many holes in it. Patching one hole won’t stop the rain from leaking in, but close enough of the holes and significant improvement can be made. But not every patient has the same holes, so there is no set of rules that applies to everyone, the protocol should be individually customized to the issues that are the “low hanging fruit.”

Okay, I've hit you with more than enough. Whatever you decide to do, I wish you and your wife the best.

[Dannyjr]

Theresa,
I noticed you live on the front range, we reside in Colorado Springs. Have you found a Dr that specializes in Apoe4/4 locally that we could get further testing on inflammation.?
Dan

[TheresaB]

Theresa,
I noticed you live on the front range, we reside in Colorado Springs. Have you found a Dr that specializes in Apoe4/4 locally that we could get further testing on inflammation.?
Dan

Years ago, my husband identified a knowledgeable doctor who we connected with, but he was not local. We'd get blood drawn locally and then discuss the results over the phone. He tested for inflammatory markers and leaky gut (identified certain food sensitivities that I had no idea I was reacting to), as well as cardiovascular health, kidney health, liver health, etc, it's all connected. I followed his dietary advice, which happened to mirror Dr Bredesen's with respect to reducing inflammation: eliminating gluten, dairy, lectins (nightshades, legumes, squash or pressure cook them to eliminate the lectins), simple carbs and high in Omega-6 industrial seed oils (so called "vegetable oils" -- soybean oil, corn oil, coconut oil, etc). But I added lots of quality Extra Virgin Olive Oil, high in polyphenols and inflammation lowering. Among its benefits, olive oil enhances the blood brain barrier and showed greater cognitive benefit than lecanemab per CDR-SB (Clinical Dementia Rating- Sum of Boxes) testing.