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

[Searcher]

from https://jamanetwork.com/journals/jamane ... ct/2670443

"Question Are the cognitive benefits of a 2-year multidomain lifestyle intervention affected by the apolipoprotein E ε4 allele?

Findings In the Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability, a randomized clinical trial of 1260 at-risk elderly individuals from the general population, the cognitive benefits of a multidomain intervention (diet, exercise, cognitive training, and vascular risk management) were not significantly different between apolipoprotein E ε4 carriers and noncarriers (test of interaction). Within-group results by apolipoprotein E ε4 carrier status suggested beneficial effects, particularly among carriers.

Meaning Healthy lifestyle changes may be beneficial for cognition in older at-risk individuals even in the presence of apolipoprotein E–related genetic susceptibility to dementia."

[drae]

from https://jamanetwork.com/journals/jamane ... ct/2670443

"Question Are the cognitive benefits of a 2-year multidomain lifestyle intervention affected by the apolipoprotein E ε4 allele?

Findings In the Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability, a randomized clinical trial...

Meaning Healthy lifestyle changes may be beneficial for cognition in older at-risk individuals even in the presence of apolipoprotein E–related genetic susceptibility to dementia."

Searcher, and all you who are helping this way, I need to try to tell you how important it is that those of you who can "translate" the scientific language into simple statements for some of us. I cannot be the only one.

I used to read scientific studies and get alot out of them. Now, just reading the language in a paragraph can cause my brain to lock and my eyes to glaze, making me want to run the other way or at least just close my eyes.

But I find it so important to understand some of these things, and along comes someone like you who quotes a study and then says, meaning... and puts it in a form I can understand. Thank you! Sometimes, I might even think I could be understanding, but when I read the translation I know. This is a huge service to any of us who need it and I thank you for it.

Drae

[Searcher]

"Concordance rates for Alzheimer's disease were 59% for monozygotic twins, 32% for like-sexed, and 24% for unlike-sexed dizygotic twins. Among monozygotic twins where both twins had Alzheimer's disease, the within pair difference in age of onset ranged from both becoming demented in the same year to 7 years difference in onset."

From "complete ascertainment of all cases of Alzheimer's disease (AD) and other dementias in 14,435 individuals aged 65 and older from the national Swedish twin registry."

So, about 40% of the risk of Alzheimer's in this population was NOT attributable to genes. These were ordinary people, not known to be making any special efforts to stay healthy.

If you make a reasonable effort to stay healthy, genes are likely to play an even smaller role in your risk of Alzheimer's. Even if you have an identical twin who's developed Alzheimer's, your efforts to stay healthy could gain you as many as 7 years without Alzheimer's.

In everyday language: do what you can to stay healthy, make a fulfilling life, and don't let your genes oppress you.

[Fiver]

"don't let your genes oppress you"

My favorite quote from the forums.

[forestmoss]

Thank you, All for your comments.
Is there a good source on risk associated with heterozygous alleles:
ApoE4/ApoE2 or ApoE4/ApoE3?

[Jena S]

Thank you, All for your comments.
Is there a good source on risk associated with heterozygous alleles:
ApoE4/ApoE2 or ApoE4/ApoE3?

Welcome, forestmoss!

We are so glad to have you join our group. I hope you will find it as valuable and supportive as others have so far! May I suggest you take a look at the Primer (Home->Getting Started) which has a wealth of knowledge written by our moderator (and a physician)? This is a great place to start to find more information and research. The forums are an excellent place to browse various topics placed at the table by group members with supportive and research-based responses. Please do not hesitate to reach out if you need anything or have any further questions! Great to have you here!

[NF52]

Hi forestmoss (what a soothing name!)

I'm sure others will offer suggestions for your question, but here's a source I like: a meta-analysis of four large cohorts of people in the U.S and Rotterdam, Netherlands. This was done in preparation for a clinical study (Generation 1 and Generations 2) enrolling people with ApoE 3/4 and 4/4, to be able to give the best statistical risk prediction (not individual risk--that's unique to each of us!)

Three of the cohorts were what's called "population-based"--meaning they were not people specifically selected for an Alzheimer's study, or because they had a relative with Alzheimer's. Population-based studies are considered a better measure of how something naturally occurs. (For example, if you check the spelling ability of all the kids in the National Spelling Bee, it will be pretty high. If you check the spelling ability of people in my home town, it will range from low to high.) A population study of the risk of Alzheimer's is going to show lower risk than a study of people who were diagnosed with Alzheimer's, or people who signed up for an Alzheimer's study wondering about their genetic status. That's why you should look askance at articles that cite "9-12x the risk for 4/4"; the more accurate figure may be 3-5x the risk.

"Lifetime" here is designated as to age 85; there aren't good figures for people above that age, and the average expected lifespan is about 85. Note that the risk is for Mild Cognitive Impairment (MCI) or dementia-MCI is a much lower threshold than "Alzheiemer's".

Here's a quote with the info you asked for emphasized in bold, and the link to the complete article:

APOE-related risk of mild cognitive impairment and dementia for prevention trials: An analysis of four cohorts
The Generation Study elected to disclose the following “lifetime” risks of MCI or dementia to its potential participants: 30%–55% for individuals with APOE-e4/e4; 20%–25% for individuals with APOE-e3/e4 and -e2/e4 (with a note that risk might be lower for those with APOE-e2/e4); and 10%–15% for individuals with APOE-e3/e3, -e3/e2, and -e2/e2 (with a note that risk might be lower for those with APOE-e2/e3 and -e2/e2). These values are consistent with our findings, but use round numbers for intelligibility, and broader ranges to reflect statistical and other sources of uncertainty.

http://journals.plos.org/plosmedicine/a ... ed.1002254

Hope this helps! Feel free to share other questions.

[Jan]

Thank you, All for your comments.
Is there a good source on risk associated with heterozygous alleles:
ApoE4/ApoE2 or ApoE4/ApoE3?

Hi forestmoss, I add my welcome. Here's a clickable link to the Primer Jena S mentioned. In it, there is this section: viewtopic.php?f=33&t=1418&hilit=risk#p15616 which speaks about risk. Physician member Stavia's Primer is an excellent resource, and is particularly helpful at differentiating between topics that are more or less 'settled' and those which are still the subject of colliding discourse. I hasten to add, genetics are not destiny. Diet and lifestyle interventions have proven helpful to many at diverting from what was once an unquestioned outcome. Please allow me to mention Dr. Dale Bredesen's recent book, The End of Alzheimer's: the First Program to Prevent and Reverse Cognitive Decline, if you haven't already discovered it. Look forward to your continued participation!