Lifestyle changes may not help Apoe4s

Insights and discussion from the cutting edge with reference to journal articles and other research papers.
mike
Senior Contributor
Senior Contributor
Posts: 664
Joined: Fri Mar 09, 2018 4:55 pm
Location: CA - Sonoma County

Lifestyle changes may not help Apoe4s

Postby mike » Tue Aug 27, 2019 11:08 am

New research suggests that better life style may not help those with Apoe4.

https://www.medpagetoday.com/neurology/ ... ate_Active

Modifying health and lifestyle factors lowered the risk of dementia in about 73% of people -- those already genetically predisposed to low or intermediate dementia risk -- but did not offset dementia risk in people who had high-risk apolipoprotein E (APOE) status


Not what most here want to read, but this study started at a later age than an earlier UK study which came to different conclusions. Could be that life style changes need to happen at an earlier age to be effective for Apoe4s. This actually makes sense if the damage is the result of CV problems decades prior to AD symptoms as recent research is showing...
Sonoma Mike
4/4

User avatar
Jmac
Contributor
Contributor
Posts: 137
Joined: Mon Aug 05, 2019 7:59 pm
Location: Georgia, USA

Re: Lifestyle changes may not help Apoe4s

Postby Jmac » Tue Aug 27, 2019 6:37 pm

mike wrote:New research suggests that better life style may not help those with Apoe4.

https://www.medpagetoday.com/neurology/ ... ate_Active

Modifying health and lifestyle factors lowered the risk of dementia in about 73% of people -- those already genetically predisposed to low or intermediate dementia risk -- but did not offset dementia risk in people who had high-risk apolipoprotein E (APOE) status


I read the article, then clicked to look at the study. I wasn't willing to spend $9 to read it. I would like to find out exactly what kind of lifestyle they considered healthy. I will go back and re-read the article closer but think the study is going to go into the kind of details I'm interested in seeing. I think many of us are following an ultra-ultra-healthy lifestyle :-) Could be the people in the study weren't doing a 12-16 hour fast most days, switching from bad oils to good oils, taking the supplements recommended by Bredesen or some of the others, etc., etc.

I hope someone has a subscription to the site with the study and will share some details. I'm guessing we'll be hearing more about it from those like Amen, Bredesen, etc.

Fiver
Senior Contributor
Senior Contributor
Posts: 597
Joined: Wed Feb 01, 2017 12:51 pm

Re: Lifestyle changes may not help Apoe4s

Postby Fiver » Wed Aug 28, 2019 11:10 am

This is counter to some of the other recent studies showing that lifestyle improvements helped E4s as much or more, compared to E3s/E2s. I suppose it would make sense that E4s would have a harder time "recovering" later in life, or maybe anytime in life. But I'll wait for more studies and a concensus to emerge.

If I got all healthy for nothing, I'm ok with that.
Four relatives with AD. Concerned, but hopeful. Introverted, but will talk about science.

TelopeaBlue
Contributor
Contributor
Posts: 12
Joined: Wed Aug 01, 2018 8:36 am

Re: Lifestyle changes may not help Apoe4s

Postby TelopeaBlue » Wed Aug 28, 2019 12:17 pm

Jmac wrote:I read the article, then clicked to look at the study. I wasn't willing to spend $9 to read it. I would like to find out exactly what kind of lifestyle they considered healthy. I will go back and re-read the article closer but think the study is going to go into the kind of details I'm interested in seeing. I think many of us are following an ultra-ultra-healthy lifestyle :-) Could be the people in the study weren't doing a 12-16 hour fast most days, switching from bad oils to good oils, taking the supplements recommended by Bredesen or some of the others, etc., etc.

I hope someone has a subscription to the site with the study and will share some details. I'm guessing we'll be hearing more about it from those like Amen, Bredesen, etc.


I have access to most of the biomedical literature, since I work at a Comprehensive Cancer Center. I'd be happy to provide you with some details, but due to our copyright agreements obviously can't provide the paper in its entirety.

A few points I immediately gleaned over and above the editorial article Mike linked were:
a) this study started in 1990 (with a new cohort added in 2000).
b) in addition to ApoE status, 27 other genes were taken into account in establishing a polygenic risk score. I can provide the genes, and snps if there is interest. There is nothing that jumped out at me that is out of the ordinary
c) Modifiable risk factors, as stated in the editorial were (1)abstaining from smoking, (2) absence of depression, (3) absence of diabetes [defined as HbA1c > 7.0], (4) regular physical activity, (5) avoiding social isolation and (6) adherence to a healthy diet, which included limited alcohol consumption.
d) Diet was self-reported and healthy was defined as "adher[ance] to at least half of the following dietary guidelines: consumption of a sufficient amount of fruits, nuts, vegetables, whole grains, fish and dairy products, and a limited amount of refined grains, processed meats, unprocessed red meats, sugar-sweetened beverages, trans fats, sodium and alcohol. Further details and cut-off values are described elsewhere." The linked article is open access.

That's it for starters (and until after Labor Day, when I will be back in the office and able to access the article again). Hope that helps.

DoubleBond
Contributor
Contributor
Posts: 14
Joined: Wed Feb 06, 2019 4:21 pm

Re: Lifestyle changes may not help Apoe4s

Postby DoubleBond » Wed Aug 28, 2019 1:22 pm

I think the message is not as discouraging as it may sound at first!

The study had 3 groups of APOE risk (high - at least one ε4, intermediate - ε3ε3, low risk - at least one ε2) with 1847, 3717, and 887 people, respectively. Each group was stratified according to lifestyle: favorable, intermittent, unfavorable.
In the APOE4 group, there was no difference in dementia cases between the favorable and unfavorable lifestyle groups; while in the 3/3 group there was about 30% decrease for the favorable lifestyle.

But how was the lifestyle defined?
We adapted six health and/or lifestyle factors shown to be important during later life to lower dementia risk, as set out by a recent meta-analysis and endorsed by the World Health Organization. Among these are: (1) abstaining from smoking, (2) absence of depression, (3) absence of diabetes, (4) regular physical activity, (5) avoiding social isolation and (6) adherence to a healthy diet, which included limited alcohol consumption. Using these six factors, we computed an overall profile of modifiable risk factors with a score ranging from zero to six, and we subsequently grouped participants into three categories of modifiable risk (unfavorable, ≤2 protective factors; intermediate, 3–4; and favorable, ≥5).


Physical activity was defined as 40 minutes per week with a MET intensity of ≥4. As for a healthy diet:
To have a healthy diet, a participant needed to adhere to at least half of the following dietary guidelines: consumption of a sufficient amount of fruits, nuts, vegetables, whole grains, fish and dairy products, and a limited amount of refined grains, processed meats, unprocessed red meats, sugar-sweetened beverages, trans fats, sodium and alcohol.


These criteria are not very specific. Under the criteria, 2/3 of all studied people across all different APOE groups were in the "favorable" lifestyle group (at most one risk factor). It is remarkable that for ε3ε3 and ε2 groups, these "easy" lifestyle choices were already enough to produce an association with a decreased dementia risk. It appears that these "easy" lifestyle choices are not enough for us in the ε4 group, but maybe if "harder" lifestyle choices were studied (more exercise, even healthier diet, incorporation of fasting, etc) there would be an association with less dementia?

Thus, we need not be discouraged - we need to work harder on our lifestyles!

Tincup
Mod
Mod
Posts: 2637
Joined: Fri Aug 08, 2014 2:57 pm
Location: Front Range, CO

Re: Lifestyle changes may not help Apoe4s

Postby Tincup » Wed Aug 28, 2019 1:46 pm

Jmac wrote:



"...we also measured several health and/or lifestyle factors that have been implicated in a lower risk of dementia11,14. These include: (1) abstaining from smoking, (2) absence of depression, (3) absence of diabetes, (4) regular physical activity, (5) avoiding social isolation and (6) adherence to a healthy diet, which included limited alcohol consumption (see Methods for additional information). Using these six factors, we computed an overall score based on modifiable risk factors, ranging from zero to six"

At baseline, the high risk group had fasting glucose of 6.0 mmol/L (108/mg/dL) vs the low risk group 5.6 mmol/L (101 mg/dL).

The DOI for the paper is 10.1038/s41591-019-0547-7 for those who have access to sci-hub.tw
Tincup
E3,E4

User avatar
Jmac
Contributor
Contributor
Posts: 137
Joined: Mon Aug 05, 2019 7:59 pm
Location: Georgia, USA

Re: Lifestyle changes may not help Apoe4s

Postby Jmac » Wed Aug 28, 2019 1:58 pm

TelopeaBlue wrote:A few points I immediately gleaned over and above the editorial article Mike linked were:
a) this study started in 1990 (with a new cohort added in 2000).
b) in addition to ApoE status, 27 other genes were taken into account in establishing a polygenic risk score. I can provide the genes, and snps if there is interest. There is nothing that jumped out at me that is out of the ordinary
c) Modifiable risk factors, as stated in the editorial were (1)abstaining from smoking, (2) absence of depression, (3) absence of diabetes [defined as HbA1c > 7.0], (4) regular physical activity, (5) avoiding social isolation and (6) adherence to a healthy diet, which included limited alcohol consumption.
d) Diet was self-reported and healthy was defined as "adher[ance] to at least half of the following dietary guidelines: consumption of a sufficient amount of fruits, nuts, vegetables, whole grains, fish and dairy products, and a limited amount of refined grains, processed meats, unprocessed red meats, sugar-sweetened beverages, trans fats, sodium and alcohol. Further details and cut-off values are described elsewhere." The linked article is open access.

That's it for starters (and until after Labor Day, when I will be back in the office and able to access the article again). Hope that helps.


Thank you --- that is enough to tell me that what they consider a healthy lifestyle and what I consider a health AD preventive lifestyle are far apart! Which is good news.

User avatar
ru442
Mod
Mod
Posts: 705
Joined: Sun Mar 20, 2016 8:52 am

Re: Lifestyle changes may not help Apoe4s

Postby ru442 » Wed Aug 28, 2019 2:51 pm

Jmac wrote:Thank you --- that is enough to tell me that what they consider a healthy lifestyle and what I consider a health AD preventive lifestyle are far apart! Which is good news.

Totally agree... that is definitely not how most of us diet!!
Male 4/4 56 yrs., "Live, Laugh, Love"

mike
Senior Contributor
Senior Contributor
Posts: 664
Joined: Fri Mar 09, 2018 4:55 pm
Location: CA - Sonoma County

Re: Lifestyle changes may not help Apoe4s

Postby mike » Wed Aug 28, 2019 5:24 pm

TelopeaBlue wrote:b) in addition to ApoE status, 27 other genes were taken into account in establishing a polygenic risk score. I can provide the genes, and snps if there is interest. There is nothing that jumped out at me that is out of the ordinary

I think you have this wrong - the earlier UK study that compared genetic risk and healthy lifestyle used the polygenic risk score, while this Rotterdam study just looked at ApoE - breaking them up into three categories with having E4 putting you in the high risk group.
With all genes thrown in, there was no difference with genetics, all seemed to improve with life style. With this study, which looked at only the ApoE gene, they found that only those without E4 improved.

Now, there are obvious issues with the study, and you can say that your lifestyle is better than that in the study, but it still brings up some disturbing news if true - E4s may not do as well as others with life style improvements. The other two lower risk groups (no E4s) both responded to lifestyle change. Small sample size is an issue, so more research needs to be done. Another difference was the age of subjects, with this study having older (69 instead of 65 ave age) subjects than the UK study.

This may suggest that these people need to be targeted earlier for preventative efforts to lower their dementia risk.
Sonoma Mike
4/4

DoubleBond
Contributor
Contributor
Posts: 14
Joined: Wed Feb 06, 2019 4:21 pm

Re: Lifestyle changes may not help Apoe4s

Postby DoubleBond » Wed Aug 28, 2019 5:42 pm

mike wrote:Now, there are obvious issues with the study, and you can say that your lifestyle is better than that in the study, but it still brings up some disturbing news if true - E4s may not do as well as others with life style improvements. The other two lower risk groups (no E4s) both responded to lifestyle change. Small sample size is an issue, so more research needs to be done. Another difference was the age of subjects, with this study having older (69 instead of 65 ave age) subjects than the UK study.

In my mind, this does not show that lifestyle changes are futile for E4s. Perhaps we need more and earlier lifestyle improvements than E3s for the same cognitive benefit, and E3s need more lifestyle improvements than E2s. Just like we require more omega-3s than E3s.


Return to “Science and Research”

Who is online

Users browsing this forum: No registered users and 34 guests

 

 

cron