New paper suggests that statins may be beneficial for E4 homozygotes

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Stavia
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Re: New paper suggests that statins may be beneficial for E4 homozygotes

Post by Stavia »

John wrote:
Stavia wrote:I'm still intruiged about the ability of the word "statin" to create an emotional reaction!
I'll bet any positive effect is related to inflammation not the lipid lowering effect. But it's just a guess.
Exactly!

Hi John. Welcome to our community.
There's always social and emotional factors at play huh! So interesting :)
Fc1345linville
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Re: New paper suggests that statins may be beneficial for E4 homozygotes

Post by Fc1345linville »

(For context, I'm 75, 4/4, no family history of AD, eat smart, sleep 8+, exercise daily, symptom-free so far)

I just checked my TOMM40 at 23andme.
rs2075650 is G/G
rs157580 is A/A

What does this tell me?

Fc
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Julie G
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Re: New paper suggests that statins may be beneficial for E4 homozygotes

Post by Julie G »

I just checked my TOMM40 at 23andme.
rs2075650 is G/G
rs157580 is A/A

What does this tell me?
I've got the same results, Fc. From what I understand, we have the "bad" version of the first snip giving us a 4 times higher risk of AD, but (good news!) recent work suggests, that the linkage disequilibrium between rs2075650 and the ApoE ε4 defining SNP rs429358 means that there may be little, if any, independent effect of rs2075650 on Alzheimer's risk. We have the "good version of the second snip.
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Re: New paper suggests that statins may be beneficial for E4 homozygotes

Post by NewRon »

Can anyone tell me the percentage of statin patients that get diabetes from the drug?

My doctor mentioned this to me recently, when I mentioned that I was trying to reduce my LDL.
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Re: New paper suggests that statins may be beneficial for E4 homozygotes

Post by DesertRaven »

NewRon wrote:Can anyone tell me the percentage of statin patients that get diabetes from the drug?

My doctor mentioned this to me recently, when I mentioned that I was trying to reduce my LDL.
Low. But it's definitely there, and dose related. Studies show that it reduces CV events even in diabetics with no other risk factors, so the main consideration for you is, what's your risk profile aside from high LDL?


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Re: New paper suggests that statins may be beneficial for E4 homozygotes

Post by Ski »

Ive posted this info in the past. but Ive been on a statin since the end of 2014, started very low dose and now on 10mg Crestor. I used in a combination with ezetimibe. On the topic of cognitive issues, my belief, not only from speaking with neuroligists about it and my own experience is that those that cause issues are due to it crossing the BBB and messing with the brains cholesterol synthesis.

Before being on a statin, I used Bergamot that behaved like a statin in combo with ezetemibe and experienced horrible brain fog. Cleared up after stopping Bergamot. My cholesterol was around 160 with an LDL around 90-95. Then upped my statin and on a combo of Crestor (least likely to cross BBB) and ezetimibe Ive had a total cholesterol of 110 and LDL of 43 with zero cognitive issues. Ive since come off ezetimibe. This is why I do not buy into the whole theory of using blood cholesterol as some measure for brain cholesterol. My .02 cents.

On the topic of diabetes, my doc also said incidence is low and dose dependent. I thought it was affecting me as I was beginning to have my readings increase. Turned out it was the Niacin as it restored to normal after stopping the Niacin.
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Re: New paper suggests that statins may be beneficial for E4 homozygotes

Post by DesertRaven »

Ski, your experience is similar to that of many patients. It's been shown that LDL can get very low without affecting cognitive ability. Not to say that a few patients can't have trouble, but in double blind controlled studies, statins don't pop up as being different from control. For diabetes or IR tendencies, it's harder; niacin a big offender as you found out, but careful dose management is key.


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Re: New paper suggests that statins may be beneficial for E4 homozygotes

Post by NewRon »

20170615_095827.jpg
Hmmm...20%-40% might have been mentioned by him but I can't remember because I was so shocked, as I hadn't hear of this up till he'd mentioned it to me. I wasn't asking for a statin but this came up in conversation.

Risk profile? Dunno really, I suppose high LDL of 3.5/135, HDL a bit low at 1.35/52, TG middling at 0.97/86. I did get the HDL up to 1.65/64 by eating a couple of kilos of mussels each week, maybe I should start again but LDL stayed at 3.5/135. My hsCRP usually 0.5 or less. My White blood cells and RBC's and neutrophils always a bit below minimums but nobody seems to worry about that (3.24 vs 4, 4.29 vs 4.5 and 1.56 vs 2). Vit D3 is 143nmol/57ng and TSH at 1.9. My other stats are all in the Prolon thread here:

viewtopic.php?f=4&t=3470&start=40#p41902

I did manage to get a particle size thingy done a while back but it took ages to organize (not common here) and had many delays with the result that I ended up doing it after I came back from a week of gourmet overeating and drinking, so it's value was questionable. It's attached. There was also a big discrepancy between the HDL shown on the graph 49mg and the Apo A1 of 1.88g/L. I asked them to explain and they said:

“of course, Apolipoprotein A1 is the major protein component of HDL particles and therefore Apo A1- and HDL-levels strongly correlate with each other.
However correlation means statistics and statistics doesn’t tell you much on an individual case. You must consider biological variation of HDL- and Apo A1-levels between individuals in addition to the variation coefficients of the two methods (each approx. 10 %).
To give an example: an HDL of 50 mg/dl doesn’t mean exactly an Apo A1 of 1.5 g/l, these levels only roughly correlate. Rather it is like this: with an HDL of 50 mg/dl the Apo A1 is between “x” and “y” with a probability of “z” %. Sorry, but I don’t have true numbers “x”, “y” and “z” available now. But because “z” is always less than 100, the individual case may still be the jackpot.”


Sound like waffle to me but I'm not an expert.

Parents died in mid eighties of old age really, possibly cancer.

Diet is good but some here think I eat a bit too much bread, at 30g a day of spelt sourdough. Some days 60g.
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Re: New paper suggests that statins may be beneficial for E4 homozygotes

Post by chrissyr »

back to this research:

Evidence for benefit of statins to modify cognitive decline and risk in Alzheimer’s disease
https://alzres.biomedcentral.com/articl ... 017-0237-y
In a Cox proportional hazards model (of 2570 subjects from the ROS/MAP dataset, after excluding those with a diagnosis of AD at baseline), statin use was associated with lower risk of AD (HR = 0.8; 95% CI 0.68, 0.95; p < 0.01). At the end of follow-up, the prevalence of AD in subjects using statins was 24.8% while in subjects with no known use of statins (at start or throughout follow-up) the prevalence of AD was 30.7% (p < 0.0005). Comparison between all AD statin users and nonusers revealed no statistically significant differences in cognitive function over time. However, in ApoE4/ApoE4 AD subjects (n = 24), those who were treated with statins had significantly better cognitive function over the course of 10-year follow-up, demonstrating significantly slower decline in MMSE and global cognitive scores over time (p < 0.01; Fig. 4). The use of nonstatin lipid-lowering drugs had no significant effect on either cognitive measure; however, there were only three subjects in the ApoE4/ApoE4 AD nonstatin lipid-lowering drug user group.
Right under this it shows pretty clearly the charts of Global Cognitive Score and MMSE for APOE4 carriers over 10 years, with much less decline in statin group. Sorry if this was highlighted earlier, I just wanted to revisit it after what Julie posted about LDL earlier.
(I'm still not on a stain but haven't ruled it out!)
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Re: New paper suggests that statins may be beneficial for E4 homozygotes

Post by SusanJ »

I always thought statin protection might be possible due to it's anti-inflammatory effects (like in CVD). As I've been working on the lipids wiki, I stumbled across some research suggesting how statins might work in preventing AD.

This 2003 human study found:

Correlation of statin-increased platelet APP ratios and reduced blood lipids in AD patients.
Platelets, like neurons, contain 120- to 130- and 110-kd amyloid precursor proteins (APPs). Their ratio is reduced in AD, further reductions correlating with reduced Mini-Mental Status Examination scores [r(11) = 0.69, p < 0.05]. As statins alter APP processing, platelet APPs were analyzed in patients with AD given anticholesterol drugs for 6 weeks. APP ratios increased [t(37) = -3.888, p = 0.0004], proportionally with reduced cholesterol [r(36) = -0.45, p = 0.005]. Longer trials may reveal slowed cognitive loss, validating this index.
https://www.ncbi.nlm.nih.gov/pubmed/12821755

A 2012 mouse study suggests this mechanism:

Dual effects of statins on Aβ metabolism: upregulation of the degradation of APP-CTF and Aβ clearance.
Statins might prevent the onset of AD through reduced Aβ production by enhancement of APP-CTF degradation and/or upregulation of Aβ clearance. We also showed that promotion of APP-CTF degradation and upregulation of Aβ clearance could be modified by a drug, suggesting possible mechanistic targets for disease-modifying drugs.
https://www.ncbi.nlm.nih.gov/pubmed/22301944

Haven't had time to dig any deeper than this.
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