#1

There is als/parkinsons/etc in my family, so I took the APOE test.

It came back E3/E4

I know E4/E4 is the worst, but out of lesser risk, average risk, moderate risk, and high risk, this puts me at moderate risk.

If you were me, in addition to a healthy lifestyle, what interventions would you consider?

Interestingly, it did ‘know’ that I have cholesterol issues.

Thank you!

PS
If there is a good place to move this topic to, please do!

5 Likes
#2

@DrFraser has a good blog article that addresses this a bit. I’ll try to find it for you. The only advice I have from a fellow longevity enthusiast is stay calm! Hahaha

4 Likes
#3

https://mailchi.mp/grantfrasermd/the-months-blog-neurocognitive-decline-series-17221816?e=7f0eed5c05

3 Likes
#4

Amor @DrFraser, so thank you!

I am calm!!! I realize a heart attack will get me waaaay before PD does!

Oh, is that not what you meant by calm :slight_smile:

Seriously, thank you for the info!!!

5 Likes
#5

Hi Beth–I too carry APOE3/4 and first-degree relative with AD. Good for you for investigating your risk factors!

My research-based advice:

  1. If you’re in menopause, consider HRT, which is particularly beneficial for AD prevention in APOE4 women. At my request, my doctor prescribed .0375 mg estradiol patch + 100mg oral micronized progesterone. Check out Dr. Ann Hathaway.

  2. Monitor lab markers in the Bredesen protocol. Most are included in routine lab work your doctor can order. (If you can afford it, you might consider the much more expensive Appollo Health route.) I find this Google Cognoscopy spreadsheet very helpful for tracking biomarkers over time, including cholesterol: Cognoscopy spreadsheet - ApoE4.Info

  3. Exercise: I’ve done yoga for decades but needed to step up exercise after a diagnosis of osteopenia/osteoporosis. Together w/ HRT, strength training reversed my osteoporosis, with DEXA scans showing 4.5% increase after initiating HRT and a further 2.2% after one year of strength training. I’m now doing 4 days/week of consistent strength training using the program described in the book Built from Broken. I’ve started adding more HIIT. Exercise is crucial for bone health but also for addressing inflammation that is at the heart of APOE4’s elevated AD risk.

  4. Diet: Keto and intermittent fasting show promise for APOE4. My current focus is plant-based whole foods with fish and a little poultry. No red meat. Watch saturated fats, which are not good for APOE4. Love coffee!

  5. Rapamycin: I’ve just started a weekly 4mg protocol. This seems to be of particular benefit for APOE4. See Dr. Alan Green.

  6. Reduce stress: Easier said than done, but exercise and meditation help. I love the free Plum Village apps’ Deep Relaxation tracks.

Hope this helps!

Bridget

6 Likes
#6

Biologist Rhonda Patrick is e4/e4. She was on episode 252 of the Peter Attia podcast. They discuss Alzheimers and her prevention regimen in detail. Certainly worth a listen.

6 Likes
#7

Welcome Bridget!

Well, you certainly over-delivered for your first post! This is chock full of good info, so thank you for well thought out list.

@hitch Thanks for that reference! I will listen to that podcast today. I respect Patrick.

3 Likes
#8

@Beth, I just think you’re probably doing more right/positive things than you might give yourself credit for. Sorry to insinuate that you weren’t calm. I was imagining how I initially get when I have new information due to my tendency towards health anxiety but obviously mirroring that onto you is wrong! Sometimes online communication gets tricky. My apologies ma’am.

2 Likes
#9

OH NOOOO, no need to apologize!!! It was just my east coast sense of humor that didn’t land!!

I didn’t feel you were insinuating anything!!!

So, MY apologies right back at YOU for making you feel you did anything wrong!!!

2 Likes
#10

I think there is evidence that Parkinsons is another thing linked to mitochondrial function. Hence I would concentrate on things that are good for mitochondria. We have a long list of these. (including Rapamycin).

4 Likes
#11

That’s helpful. I’ll search this site to find and I will most likely come back w a list of questions. Thx!

#13
3 Likes
#14

There is no FDA approved treatment that can prevent Alzheimer’s disease.

#15

Thx! I didn’t think there was, but was wondering about some prescriptions or supplements that have promise to help. For example, I know some have talked about glp-1s…

#16

Numerous factors predispose to the progression of cognitive impairment to Alzheimer’s disease and related dementias (ADRD), most notably age, APOE (ε4) alleles, traumatic brain injury, heart disease (HtD), hypertension, obesity/diabetes, and Down’s syndrome. Protein aggregation is diagnostic for neurodegenerative diseases and may be causal through the promotion of chronic neuroinflammation. We isolated aggregates from postmortem hippocampi of ADRD patients, HtD patients, and age-matched controls. Aggregates, characterized by high-resolution proteomics (with or without cross-linking), were significantly elevated in HtD and ADRD hippocampi. Hexokinase-1 (HK1) and 14-3-3G/γ proteins, previously implicated in neuronal signaling and neurodegeneration, are especially enriched in ADRD and HtD aggregates versus controls (each P < 0.008), and their interaction was implied by extensive cross-linking in both disease groups. Screening the HK1::14-3-3G interface with structures of drugs approved by the U.S. Food and Drug Administration (FDA) predicted strong affinity for ezetimibe, a benign cholesterol-lowering medication. Diverse cultured human-cell and whole-nematode models of ADRD aggregation showed that this drug potently disrupts HK1::14-3-3G adhesion, reduces disease-associated aggregation, and activates autophagy. Mining clinical databases supports drug reduction of ADRD risk, decreasing it to 0.14 overall (P < 0.0001; 95% C.I. 0.06–0.34) and <0.12 in high-risk HtD subjects (P < 0.006). These results suggest that drug disruption of the 14-3-3G::HK1 interface blocks an early “lynchpin” adhesion, prospectively reducing aggregate accrual and progression of ADRD.

#17

Thanks for the welcome, Beth. I hope “over-delivered” doesn’t mean “over-shared,” though I can see it may have been a bit much for my first message.

I’ve been lurking for a while and was seeking the opportunity to introduce myself to others with similar interests. I hope I shared something of value.

Perhaps I should have prefaced my first message with:

Hi everyone! I’m Bridget, and my interest in this topic borders on obsession. Thanks for making this space available. I’ve benefited from your collective knowledge and experience.

4 Likes
#18

@Bridget_O Thanks for joining us. We welcome those who are obsessed with improving their health and the health of others. :slight_smile:

Welcome!

3 Likes
#19

With failures of most AD trials to satisfy efficacy criteria in mixed AD populations, exploratory analyses of existing trial data are justified and necessary to understand lack of efficacy and to identify sub-populations that may have benefited from interventions. The NILVAD trial was designed for the analysis of a mixed mild and moderate AD population and further stratification of the study population into very mild, mild and moderate AD was unplanned and therefore exploratory. As such, these subgroup analyses were underpowered, particularly when considering the confounding effects of gender and APOE. Nevertheless, analyses adjusted for these factors continue to suggest that very mild AD subjects responded positively to nilvadipine on both the ADAS-Cog 12 and the ADCOMS. Furthermore, analyses of the ADAS-Cog 12 sub-scales demonstrate that beneficial effects on memory and language traits were associated with nilvadipine treatment in very mild and mild AD patients, respectively. Together, findings from this clinical study and CSF biomarker analyses suggest a differential response to nilvadipine treatment in AD related to the severity of the disease at treatment initiation.

APOE4 interactions:

A 2018 paper discussed the outcomes of a trial of 511 patients with mild to moderate dementia treated with placebo or nilvadipine, a CCB available in the EU and Japan. Nilvadipine did not slow progression, as measured by progression on ADAS-Cog 12 and CDR-sb. In a sub-analysis, the authors found that APOE4 carriers had less decline than non-carriers when treated with nilvadipine. However, the authors did not test for significance in their subgroup analyses (Lawlor et al., 2018).

Some preclinical evidence indicates that APOE4 may disrupt calcium homeostasis and increase calcium influx compared to other APOE genotypes; thus, calcium channel blockers may have a theoretical therapeutic mechanism of action (Ramakrishna et al., 2021, Jiang et al., 2015). One case cohort study examined 274 patients in an aging study who were diagnosed with dementia over the course of the study, and created a regression model to compare progression to dementia in patients who had used anti-hypertensives compared to those who did not. They also collected information about APOE genotype. The regression model indicated that CCB use was protective in both APOE4 carriers and non-carriers, and that CCB use in APOE4 carriers restored their progression to dementia to the levels of non-carriers who did not use CCBs (Lovell et al, 2015). These data are too sparse to draw any firm conclusion beyond a possibility of a useful effect in APOE4 carriers.

2 Likes
#20

Definitely did not mean over shared!! I meant you exceeded expectations. Your first post was excellent and you provided a lot of useful information!!!

1 Like
#21

So far, I’ve found the following list of things to investigate further. Because I don’t have a diagnosis, my goal would be to try things that can do no harm but might possibly help.

And now to go listen to the two Attia podcasts that were shared.

Trulicity

SGLT2

Ecklonia cava

Proline

Rapa

Glp1

Ezetimibe