Understanding your risk of Alzheimer's, including the ApoE4 allele

[SusanJ]

We get many questions from newcomers, who have just found out their ApoE4 status, about the risk of developing Alzheimer's.

I wanted to post a link to some information that will help you understand the big picture about the issue of risk.

https://wiki.apoe4.info/wiki/Main_Page# ... he_disease

The important take-away is that we have so many other risks, which can be mitigated, when it comes to our personal risk to developing AD. As you read through the forum, you'll find most of us end up viewing the knowledge of our E4 status as the motivation to live our healthiest life possible.

[Orangeblossom]

Thanks Susan, this is so helpful!

From the Wiki link-

"Here's some background on the idea of modifiable risk. According to the Lancet Journal (2017):

Alzheimer's includes about 65% non-modifiable risk (meaning genetic) including only 7% contributed by the ApoE4 allele, so about 58% of your AD risk is attributable to OTHER genes."

I find this so helpful to know. Some of the articles we see online make out APOE4 to be the be all and end all, but it's not, and this helps get that in context.

[Orangeblossom]

https://www.alzheimers.org.uk/DementiaRisk

I noticed this estimates how many people with APOE4 will get dementia by a certain age, alongside other risk factors. I found it quite helpful (mainly as the risk seemed better than I thought!)

Sharing as I thought it may help others, too.

[circular]

That's a very effective tool, although it's worth noting that they seem to be talking about all cause dementia, not just Alzheimer's. On the APOE risk slide, if they mean to narrow that risk to Alzheimer's specifically, they should be more clear about it. I did read a paper some years ago about how ApoE4 raises risk of dementia in other neurological illnesses like Parkinsons, so they may in fact mean to show the risk of all cause dementia for APOE4. While that website section is about dementias plural, if all the slides, or even just the APOE one, are intended to reflect Alzheimer's risk specifically it should be made more clear. 23andMe uses the image of all the people with some darkened to illustrate risk too, but they way this site has enhanced that approach is really good.

[Orangeblossom]

Yes, it is a bit confusing isn't it, especially as they are called Alzheimers UK. Also another thing, they just look at age 75 and not older ages. I just felt it gave a bit of perspective into how it affects us compared to other things. Also I guess it is important to remember there is a lot more risk from other genes than APOE as well. (not mentioned much on the site).

[Fiver]

Thanks! Very interesting.

[RJones]

Thank you for the link -- I also found it kind of reassuring.

I believe all the slides, including the one about variation with APOE4, are about dementia in general rather than Alzheimer's specifically.

The reason is that their percentage for "everyone" at age 75 is 6%.

The table below, from another publication ("NCBI"), shows an Alzheimer's incidence for ages 70-79 as only 2.3%, and the incidence for all dementia as 5.0%. It is the "all dementia" number that is closest to the 6% number shown in the UK link.

https://www.ncbi.nlm.nih.gov/pmc/articl ... /table/T3/

It's interesting that at age 75, the UK link shows the dementia difference for both "everyone" and "0 APOE4" people to be 6%. Obviously you'd think the "0 APOE4" would have less dementia than the population as a whole, but I guess they must be the same within a rounding error.

It probably makes more sense to be concerned about dementia in general rather than Alzheimer's dementia specifically, so I think it's good that that's what they plotted.

[alangreenmd]

These type statistic which discuss total dementia with AD included and general population with E4 are extremely misleading and very much underestimate risk for E4 carriers. Example is Diabetes. they give 6/100 at age 75 and 10/100 with diabetes. Looking at specific data (from Peila, Honolulu-Asia Aging study) get very different picture. Diabetes was associated with total dementia RR 1.5, and AD RR 1.8...Individuals with both type 2 diabetes APOE e4 allele had an RR 5.5 for AD compared to those with neither risk factor. In this study RR for AD with only E4 was 2.0.
The actual jump in RR from 2.0 to 5.5 shows great need to avoid diabetes. The real understanding of risk is lost when lump dementia with AD and general population with E4.

[Della66]

Thanks Susan, this is so helpful!

From the Wiki link-

"Here's some background on the idea of modifiable risk. According to the Lancet Journal (2017):

Alzheimer's includes about 65% non-modifiable risk (meaning genetic) including only 7% contributed by the ApoE4 allele, so about 58% of your AD risk is attributable to OTHER genes."

I find this so helpful to know. Some of the articles we see online make out APOE4 to be the be all and end all, but it's not, and this helps get that in context.

This is the main problem I'm having reading about APOE4. I'm so tired of reading articles that say it is "the greatest genetic risk factor that we know of"; I find it all to be terribly upsetting. Even Dr. Bredesen writes in his book that the presence of even one APOE4 causes your risk for Alzheimer's to "soar". I just find reading these types of things counterproductive to my health efforts. Makes me just want to give up.

[Della66]

Are there any statistics that estimate what percentage of total APOE3/4 and 4/4 carriers never go on to develop Alzheimer's by age group?