Earlier menopause and poor synaptic health could raise Alzheimer’s risk: Study

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I guess this would be one more reason to use rapamycin - as prolonging time to menopause might have significant benefits.

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I would say [aging mechanism] = [development mechanism]

If you slow development you slow aging.

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@adssx @DrFraser based on your extensive research which currently available intervention do you think is the best to prevent Alzheimer’s before it develops?

Is Dementia Incidence Still Dropping? Birth Cohort Data Say Yes.

As the baby boom generation reaches its hopefully golden years, scientists have been projecting a doubling of dementia cases in the U.S. by 2050, alarming health care agencies, the public, and health economists. Now, a new editorial argues this “tsunami” could be more of a gentle wave. In the March 12 JAMA, Eric Stallard, Svetlana Ukraintseva, and Murali Doraiswamy at Duke University, Durham, North Carolina, explain that tsunami predictions assume that dementia prevalence in each age range remains constant over time. That is not the case, they say.

Their analysis of three large population studies found that age-adjusted prevalence has dropped by a whopping two-thirds over the last 40 years. In other words, every successive birth cohort has a lower risk of dementia than did its predecessor. Extrapolated forward, these rates would predict only a 25 percent bump in dementia cases by 2050. This would challenge conventional wisdom. “I feel a bit like Copernicus,” Stallard quipped.

Other scientists agreed this analysis is reasonable, and said it highlights the potential for people and societies to modify dementia risk through health and lifestyle interventions.

https://www.alzforum.org/news/research-news/dementia-incidence-still-dropping-birth-cohort-data-say-yes

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You can add to this list: amlodipine (if BP still too high with telmisartan 80 mg), selegiline low dose (especially if depressed), vaccines, GLP-1RAs (if overweight or obese), vitamin D (if deficient, otherwise probably useless). Rapamycin looks great but it’s unclear what is best for neuroprotection: 1 mg/day or larger intermittent dose?

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I think Prostate issues are pretty well pure splicing issues and hence anything that deals with splicing issues will help with the prostate (this is all about how much acetyl-CoA is in the cytosol/nucleus).

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I like @adssx 's answer on this.

Assess risk - check an ApoE and then the other genes that FIDALabUS.com has on their AD advanced gene panel (which doesn’t include ApoE). Check for HSV, P. gingivalis …

First step is lifestyle, activity, optimal metabolic health. Brain activity in a variety of things, including continually learning new skills outside of the domains that you are already expert.

Test and treat chronic infections. Optimize periodontal health. Avoid toxic chemical/mold/metal exposures and if suspected test and if present treat.

I’d add GLP1’s, Omega 3 index to 8% if no ApoE4 and 10% if present. 40 Hz Gamma devices like Koushicare or Symbyx. Vagus nerve stimulator like Pulsetto.

Possibly intranasal rifampin.

Those would be my low hanging fruit.

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I’m very skeptical about this. APOE4 carriers don’t seem to be able to transfer supplemental DHA into the brain. And DHA supplementation can cause depression. So I’m not sure supplementation is effective in people with APOE4. That’s why I stopped it.

Other than that I agree with you.

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Is valacyclovir itself to prevent the risk of dementia/alzheimers/etc if one has hsv1, or is it to prevent an outbreak which is actually the risk? Meaning, if your outbreak is controlled, is there benefit to the valacyclovir

I ask because I assume I have HSV1 because I can get a cold sore, but I probably only get one every 5 years or so. Lysine alone will nip anything in bud for me.

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Risk of Afib as well, is there any trial showing short term benefits of supplementation on cognition anyway? MR study of Omega-3 index?

It feels heavily marketed. But I might be wrong.

Nowhere near as convinced as for lipids, BP, etc.

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So a few things - there is plenty of literature out there on DHA and depression - essentially showing no link and many psychiatrists actually using Omega 3 fatty acids for mood disorders (of which I’m not convinced has evidence). However, there is a relationship between having a high fish diet and decreased mood disorders. However, there will always be individuals who get adverse effects with these, but on a population basis, it seems to promote better mental health).

The Afib stuff is far from clear - especially at typical doses of EPA+DHA at ~1000 mg/day. If the relationship exists at all, it is dose related, and there is an approximate 30% symptomatic vascular disease reduction with optimization of Omega 3’s.

Now in regard to the defective transport into the brain @adssx with those with ApoE4’s - this is why I’ve now gone over to the NatureBell Product that is krill based and loaded with phospholipids, which significantly gets around that issue. A double dose (4 capsules) is required to get up the 1000 mg of EPA/DHA. This supplies 800 mg of phospholipids.

@Beth My best assessment on HSV-1 is that it is likely doing low grade damage to the brain and causing neuroinflammation. So suppressing that would be the rational. This is a separate issue than treating an episode where it comes down the nerve to cause a visible outbreak.

This is what Vera-Health says on this:
Recent studies suggest that valacyclovir and acyclovir, both antiviral medications, may have a role in reducing the risk of Alzheimer’s disease (AD). The VALAD trial is investigating the use of valacyclovir in patients with mild AD who are seropositive for HSV1 or HSV2. This trial hypothesizes that valacyclovir could slow cognitive and functional decline by reducing amyloid and tau accumulation in the brain 2.

Further supporting this, a study found that valacyclovir and acyclovir could reverse transposable element dysregulation in HHV-positive AD brains, potentially reducing tau-associated neuropathology 3. Additionally, a systematic review and meta-analysis demonstrated that antiherpetic medications, including valacyclovir and acyclovir, significantly reduced the risk of dementia, particularly in individuals with severe herpesvirus infections 4.

Moreover, computational docking studies and animal models have shown that valacyclovir may improve neurobehavioral markers and reduce neuroinflammation, suggesting a potential disease-modifying effect in AD 5.

The mechanism by which these antivirals may exert their effects involves inhibiting HSV1, which has been implicated in AD pathogenesis, particularly in individuals carrying the APOE-ε4 allele. HSV1 reactivation in the brain can lead to amyloid beta and tau formation, contributing to AD pathology 6.

In summary, current evidence suggests that valacyclovir and acyclovir may decrease the risk of Alzheimer’s dementia by targeting HSV1-related mechanisms. However, further clinical trials are needed to confirm these findings and establish definitive treatment guidelines. These drugs are primarily used for treating herpes infections by interfering with DNA polymerase to inhibit DNA replication (ASHP).

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WOW, thanks for that and I had no idea.

I’ll reach out to your personally on this, but for everyone’s benefit…

If one gets cold sores, does it mean you have HSV1 or does one still need to test to confirm … meaning, is it always the cause?

(it looks like I’m going to be consuming 1000 calories a day in pills!!!)

ApoE4 brings an impairment to the transporters of DHA into the brain. To circumvent the problem a phospholipid form is called for. I get mine from Nordic Naturals, the only problem being the dosage needed is much higher as a percentage of the product is phospholipid. If anything the implication from the data is that apoE4 people need MORE DHA than others so the seeming non response is from dose insufficiency. However I’ve seen that to have a protective effect a high omega 3 index needs to go hand in hand with high Vit 12 and Vit D levels. Otherwise the benefits are largely mooted.

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FWIW, Rhonda Patrick (who has ApoE4) stated in a podcast with Huberman, that she’s personally has given up on krill oil because 100% of commercially available product that she has come across is significantly rancid, which turns supplementation with it from a positive to a health negative.

I read somewhere that when it comes to fish oil, the human nose is pretty sensitive detecting rancidity, because rancidity has such dire health effects that we have evolved to have a strong aversion to it and good ability to detect it. So unless masking agents are used (and I’ve seen fish oil with lemon scent added!), you should be able to tell if a given oil “passes the smell test”.

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The naturebell isn’t, I routinely cut open a capsule with each bottle of omega 3 products I start and assess.
So interesting claim, but not an issue with my latest bottle.

On the HSV question prior - generally best to get an IgG level for HSV1/2 to confirm. This is an inexpensive blood test.

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Wondering if a woman* (*c’est moi) who went through early menopause (age 42) but took estradiol and progesterone from that time to age 70 would be protected from negative effects of early menopause.

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Unfortunately, @medaura @DrFraser , I’m afraid this is totally wrong: neither lysophosphatidylcholine-bound omega-3 fatty acids nor krill oil increase brain DHA in APOE4 mice:

I emailed these papers to Rhonda Patrick and she never got back to me. The archetype of the bullshit health influencer.

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No. The largest trial, VITAL-DEP, n=18,353 with 465 mg EPA + 375 mg DHA (so 55% EPA and 45% DHA) over a median treatment duration of 5.3 years (!!!) found that “Depression risk was significantly higher comparing omega-3 (651 events, 13.9 per 1000 person-years) with placebo (583 events, 12.3 per 1000 person-years; hazard ratio [HR], 1.13; 95% CI, 1.01-1.26; P = .03).”: Effect of Long-term Supplementation With Marine Omega-3 Fatty Acids vs Placebo on Risk of Depression or Clinically Relevant Depressive Symptoms and on Change in Mood Scores: A Randomized Clinical Trial 2021

Is there a single better trial that found that omega 3 could lower depression? Most trials are small, short, and of low quality. VITAL-DEP is the definite answer to the question: EPA + DHA CAUSES depression.

Meta-reviews and analyses only found that EPA only or EPA > 60% could lower depression: Omega 3 makes me depressed: why? - #39 by adssx

So EPA alone improves depression while EPA + DHA makes it worse. Conclusion: DHA causes depression?

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Being ApoE3/4, I’ll definitely be getting the AD panel, however I wonder if there is any test that either tests directly for FN1, or is strongly associated with the existence of the protective FN1 variant: