Introducting Verax, chapter one

Newcomer introductions, personal anecdotes, caregiver issues, lab results, and n=1 experimentation.
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Verax
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Introducting Verax, chapter one

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Hi, I'm Verax, here because a few weeks ago 23andme informed me I had one ApoeE4 allele and heightened risk for LOAD. I am a computer geek and it didn't take me long to disover the other allele ApoE3. This surprised me because based on my medical history I expected bad LRRK2 and GBA genes to forecast some alpha-synucleopathy such as Parkinson Disease, Lewy Body Dementia, or Mutiple System Atrophy (MSA). Good news, LRRK2 and GBA ok. Of course, I also found out there are some 75 genes affecting AD risk, not reported by 23andme. And I didn't get any counseling of course.

I expected PD risk because several years ago I started having (probable) RBD. Rapid Eye Movement Sleep Behavior Disorder is a parasomnia usually involving both REM Sleep Without Atonia (lack of normal paralysis during dreams) (RWA) and Dream Enactment Behavior (DEB, stereotypically fighting off shadowy attackers during dreams, then awakening with clear recollection of dream). RBD is not common but has frightening implications. In my case, my bed partner complained of black and blue marks from my kicking her and after a second episode that I could no longer laugh off I went on Google and we went to the doctor. I saw that more than 81% of patients with RBD went on to a neurodegenerative disease (the risk has been assessed recently at a steady 6.3% each year even after decades). As I was on a Medicare Advantage Plan I had to go to a neighborhood sleep study center. I asked them to video the study to look for RBD but they couldn't and I didn't wake up early. The results were that I had obstructive sleep apnea and should use CPAP at a low level. About that time Robin Williams killed himself and his widow revealed his RBD premonitory of LBD. I dropped the insurance plan (had to move out of the county) and returned to Original Medicare with a Supplement so I could get referred to a neurologist at a teaching hospital with experience of RBD and sleep. RBD patients should be followed as their symptoms precede active PD or other disease many decades before motor or other symptoms. I volunteered for any long-term study but didn't qualify. In my case I have never shown RBD, RWA, or DEB in a follow-up sleep study (I have to sleep alone now.) Religious CPAP and a ketogenic calorie-restricted diet has evidently reduced my AHI (apnea-hypoxia index) and parasomnia. Although almost all RBD leads to alpha-synucleopathy, I saw a recent review that noted some go on to AD and some resolve after CPAP. I do have some symptoms of MSA but no hallucinations or delusions (yet). This experience and my conscientious personality made me eager to find any clinical trial to prevent AD once I knew my ApoE4 status, and my experience working in a hospital and with computers makes me grateful for this group. I'll break off the introduction here and add more later.
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Julie G
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Re: Introducting Verax, chapter one

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A very warm welcome, Verax. I share your heightened concern about PD as it runs in my family. This is the first that I've learned about the REM sleep behavior disorder (RBD) connection. Thank you for sharing. I've always been on the lookout for the "pill-rolling" behavior. Dr. Bredesen also recently mentioned a very early symptom of one arm not swinging freely during walk. I find myself studying everyone now. He's doing quite a bit of work with PD and believes the underlying drivers to be both an exposure to toxins and a perturbed gut. He's developing a protocol specific to PD which I hope will be revealed soon. I look forward to your next installment and congratulate you for identifying and addressing problem areas. Keep up the great work, my friend.
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Re: Introducting Verax, chapter one

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Julie, thanks for your kindness. Well, Chapter One has suddenly ended with bad news and very good news, and more to come in later chapters yet unwritten. Plot summary: I learned from 23andMe that I was Apoe 3/4 and confirmed that with two independent DNA tests. I intensified life style changes, lost more weight on a low-calorie, low-carbohydrate, low saturated fat diet with lots of fiber and complex resistant starch carbohydrates and extra-virgin olive oil. I increased high-intensity interval stationary biking and rowing and walking somewhat. I shifted from lisinopril to lovasartan and blood pressure dropped to below 120/60 without orthostatic hypotension. With weight loss and the same 6cm H20 CPAP my apnea-hypoxia index fell to normal levels around 1/hr, nocturia decreased to 0-1/night. Sleep efficiency and length improved with timed caffeine and melatonin. Hashimoto's thyroiditis was confirmed on antibody tests and I got TSH to optimal levels around 1 by shifting to taking it at bedtime with 500mg ascorbic acid. LDL fell to below 70 by shifting from pravastatin to rosuvastatin and HDL rose to 40. I started volunteering at a local soup kitchen. I felt (and feel) great.

Since Medicare wouldn't pay for expensive tests such as the Bredesen protocol, I voluneered for the Generation Study 2 clinical trial run by Novartis/Amgen/Banner at a nearby research unit. They did extensive memory tests, all normal for my age. Intact memory is necessary to enroll in this prevention study. Then they did an MRI and PET scan with CT, and I volunteered for the lumbar puncture for CSF tests. Yesterday my study partner and I learned the results. Bad news, I don't qualify for the study, no amyloid found on PET scan, only minor, stable, atherosclerotic lesions. They told me the CSF was normal too, but gave me a printout of lab results that included everything else. CMS fast tracked this study for Apoe e4 carriers and to further develop the PET scans (IDEAS trial is part of GS2), but doesn't want to pay for such expensive medical tests or approve drugs unless there is some physical evidence of change in biomarkers, I didn't have anything to improve at baseline, and probably won't in the next eight years of the trial.

The investigating doc told us I have a 17% change now of developing late-onset Alzheimer's in the next 10 years (I am a white male 75 years old). A recent article in Canadian Medical Journal refined that estimate and corrected for a bunch of confounding variables, concluding maybe 2-3x normal risk of say 10%. (There is also a risk of vasular and other dementia, and some 30% of AD patients are wrongly diagnosed.) The interesting point is that the incidence curve is sigmoid, leveling off after a certain age (around age 80--maybe because some die?). And the recent European Alzheimer's conference featured some news that maybe LOAD staging is possible, with detectible changes occurring in the CSF fluid and eyes, before amyloid detected in brain areas on PET, and then another 10 to 15 years later cognitive and psychiatric changes observed.

So the very good news is that as Apoe e3/e4 if I have LOAD it must be Stage -1 and will probably die of something else in the 15 years before I have a small chance of diagnosis of losing my mind. I am grateful for the baseline tests that can be used in the future to measure changes if retests needed. I have no evidence, however, that my lifestyle and drug changes have influenced that baseline, and the normal tests don't prove or disprove that I should continue or change them. However, I might slack off a little and try to enjoy life more without worrying about such matters.

The one thing that bothers me is the bad news that being excluded from the trial removes me from helping others such as you guys who are at risk just like me, and you might have less information to go on. So I encourage all to volunteer for clinicaltrials.gov as I had only good experience myself. Those of us who are normal (some of you are probably better than normal!), I believe, should be followed by researchers to learn more about the natural history of AD and what happens with interventions such as diet in the long term. I hope that biomarkers such as a simpler and cheaper blood test or eye exam will help that (Bill Gates is financing that research). I'm looking for other trials on clinicaltrials.gov and will periodically return here to this excellent and helpful site. God bless all.
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Re: Introducting Verax, chapter one

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Verax wrote:Julie, thanks for your kindness. Well, Chapter One has suddenly ended with bad news and very good news, and more to come in later chapters yet unwritten.
I have to think that it's better to be kicked out for being too well versus too sick! Do I understand correctly that you feel great, but also felt great before the changes that you made? More good news.

Having a better apnea-hypoxia score after interventions sounds like an improvement in "bio-marker" to me. Congratulations! Have you compared the blood work drawn by the Generation Study and the tests recommended by Dr Bredesen? I suspect there are a lot of Bredesen labs not included in the Generation Study. And appreciate that cost is often an issue. We all need to prioritize.

It's hard to keep up with lifestyle changes when we don't see or feel noticeable differences. Everything you've done so far will most likely pay good dividends as you move forward in your life. As you probably know, poorly controlled sleep apnea alone can cause multiple health problems, including cognitive decline. I encourage you to try to keep up with as much as you can, and continue to enjoy life.
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Re: Introducting Verax, chapter one

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Thanks, Slacker, I wish you good luck with your burden. I appreciate your comment about AHI being a biomarker. I looked into this and it seems it is not clear if sleep disruptions and desaturation from sleep apnea cause neurodegeneration, or the other way around (or maybe it is circular). To be clear, I have been using CPAP for years (I think most drop out, masks are uncomfortable, results slow) and I started lifestyle changes from fear of Parkinson Disease before learning my Apoe status.

As I learned more about sleep, I noticed some papers about biomarkers for AD in the eyes. We know that the optic nerves are really brain tissues extending outside the skull and so we can predict similar changes, and indeed retinal fiber layer thinning and optical coherence tomography has predicted and indicated AD both in the eyes and brain.

Moreover, the body's circadian rhythm is largely reset each day by blue light seen by specialized cells in the retina (recently discovered, not rods or cones) that are connected to the suprachiasmatic nucleus and then to the pituitary gland to regulate hormones such as melatonin. Some special retinal scans can pick up defects in those light-sensing cells indicating AD before cognitive changes. So ophthalmic examinations and tests hold promise for cheaper and non-invasive biomarkers to replace or augment expensive PET scans or lumbar punctures. Some of these eye scans use turmeric/curcumin tracers that bind to amyloid in the eye (I started to take Theracurmin HP, currently in clinical trial). Since such changes precede cognitive changes by many years, perhaps they can aid prevention or delay of this dreadful disease. I saw my eye doctor the other day and they are not ready for this quite yet.
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Re: Introducting Verax, chapter one

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Congrats, Verax! Amazing news; kinda like a "Get out of Jail Free" card :D. Pop in to wave once in a while.
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