Against exaggerating genetic risk

Insights and discussion from the cutting edge with reference to journal articles and other research papers.
Post Reply
theocurt
New User
New User
Posts: 1
Joined: Sun May 26, 2024 4:34 am

Against exaggerating genetic risk

Post by theocurt »

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5360223/

A very interesting study by Qiang et al 2017 suggests that lifetime Alzheimer’s risk for Apoe-4 genotypes may be overstated, including by genetic testing companies like 23andMe:

"The risk that an individual with APOE-e4/e4 will develop Alzheimer disease dementia has been reported to be as high as 50%–67%, but these estimates come from statistical modeling, not direct observation… Lifetime risk was more consistent across the two samples in which it could be estimated, and did not vary as much with age, ranging from 31% to 40% for those with APOE-e4/e4."

The study did not discuss environmental and lifestyle factors, which of course can reduce significantly, even for APOE-4 genotypes. This calculator:
https://github.com/MelisAnaturk/dementi ... lator.xlsx
created by the British Medical Journal shows that someone with one APOE-4 gene can have just <10% chance of developing Alzheimer’s by 84 with the right environmental factors.

APOE-4 is obviously a hugely important risk factor, but it is important to remember that with the right lifestyle choices risk of developing Alzheimer’s can likely be kept well below 50% even for APOE-4 homozygotes.
NF52
Support Team
Support Team
Posts: 2953
Joined: Tue Oct 25, 2016 9:41 am
Location: Eastern U.S.

Re: Against exaggerating genetic risk

Post by NF52 »

theocurt wrote: Sun May 26, 2024 5:23 am A very interesting study by Qiang et al 2017 suggests that lifetime Alzheimer’s risk for Apoe-4 genotypes may be overstated, including by genetic testing companies like 23andMe:

"The risk that an individual with APOE-e4/e4 will develop Alzheimer disease dementia has been reported to be as high as 50%–67%, but these estimates come from statistical modeling, not direct observation… Lifetime risk was more consistent across the two samples in which it could be estimated, and did not vary as much with age, ranging from 31% to 40% for those with APOE-e4/e4."

The study did not discuss environmental and lifestyle factors, which of course can reduce significantly, even for APOE-4 genotypes. This calculator:
https://github.com/MelisAnaturk/dementi ... lator.xlsx
created by the British Medical Journal shows that someone with one APOE-4 gene can have just <10% chance of developing Alzheimer’s by 84 with the right environmental factors.

APOE-4 is obviously a hugely important risk factor, but it is important to remember that with the right lifestyle choices risk of developing Alzheimer’s can likely be kept well below 50% even for APOE-4 homozygotes.
Welcome to the forum!

You are absolutely correct to note that environment, lifestyle, as well as other genetic and epigenetic factors can dramatically reduce the risk of Alzheimer's. It sounds like you're personally and/or professionally familiar with some of the well-designed observational studies of Alzheimer's risk. For our members who might not be, the Qiang et al study, which included three population cohorts, one of them in a Latino group, and one multi-site cohort with family history of AD is available here: APOE-related risk of mild cognitive impairment and dementia for prevention trials: An analysis of four cohorts.

I was given the information from that study in 2017 when I was enrolled in the Generations 1 study of a BACE inhibitor in ApoE 4/4 carriers. It was the first time I realized that my 23&me prediction of a median age of Alzheimer's dementia diagnosis of 68 might be wrong. [I'm 72 and doing just fine. And in another study.] Here are quotes you're probably very familiar with, but they still are likely to be valid:
The four cohorts also differed markedly...NACC also had a 58.3% fraction with a family history of dementia, compared to 18.6% in the Rotterdam Study, the only other site that assessed it....Similarly, viewing the cumulative incidence for APOE-e4/e4 genotype across the three age strata, cumulative incidence ranged from 5.60% to 20.58% in the three population-based cohorts versus from 23.06% to 38.34% in NACC...The difference between the population-based cohort studies and NACC, on the other hand, is striking... Individuals join this cohort for a variety of reasons, but concerns about family history and their own memory are likely to play a role. This probably contributes to the relatively high APOE-e4 allele frequency and reported family history of dementia in this cohort seen in Table 1...

...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.
We always welcome people like you, who can highlight the limitations of articles which may be based on well-characterized cohorts, but rely on data from different generations, with different lifestyles and environment. Studies from group recruited in the 1990's or early 2000's were often unintentionally skewed towards people with strong family history, which before 23&me and other recruiting efforts was the easiest way to find participants.

You may not need any overview of ApoE4, but the Primer is written by Stavia, a practicing M.D. with ApoE4/4 offers everything from strategies to an appendix of suggested biomarkers.

The How-To Guide shows how to quote members (use the " icon in the upper right of any post) so they get an email notification of your post. It also shows how to use the Search function for topics, and how to subscribe to topics of interest.

Our Stories is a great place to share your own path to "downsizing" any ApoE4 risk.

Hope to see more great articles shared by you!

Nancy
4/4 and still an optimist!
User avatar
TheresaB
Mod
Mod
Posts: 1676
Joined: Wed Feb 03, 2016 9:46 am
Location: Front Range, CO

Re: Against exaggerating genetic risk

Post by TheresaB »

theocurt wrote: Sun May 26, 2024 5:23 am https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5360223/

A very interesting study by Qiang et al 2017 suggests that lifetime Alzheimer’s risk for Apoe-4 genotypes may be overstated, including by genetic testing companies like 23andMe:

"The risk that an individual with APOE-e4/e4 will develop Alzheimer disease dementia has been reported to be as high as 50%–67%, but these estimates come from statistical modeling, not direct observation… Lifetime risk was more consistent across the two samples in which it could be estimated, and did not vary as much with age, ranging from 31% to 40% for those with APOE-e4/e4."

The study did not discuss environmental and lifestyle factors, which of course can reduce significantly, even for APOE-4 genotypes. This calculator:
https://github.com/MelisAnaturk/dementi ... lator.xlsx
created by the British Medical Journal shows that someone with one APOE-4 gene can have just <10% chance of developing Alzheimer’s by 84 with the right environmental factors.

APOE-4 is obviously a hugely important risk factor, but it is important to remember that with the right lifestyle choices risk of developing Alzheimer’s can likely be kept well below 50% even for APOE-4 homozygotes.

Thank you for sharing this, and welcome.

Your emphasis that generalized odds are inexact on an individual basis is spot on. In addition to controllable lifestyle factors, there are also many uncontrollable variables that factor in to the equation such as other genes, gender, age, race, geographic ancestral history, environmental exposures, family environmental/trauma history, etc.

And to add to the pile of studies that show lifestyle makes a difference, the ApoE4.info facebook page https://www.facebook.com/apoe4.info just posted this article Lifestyle-Dementia Links Persist Regardless of Risk Genes, French Study Shows published by Medpage Today, of a French study published a few days ago which had this quote:
The findings show that a "combination of lifestyle and other modifiable risk factors is associated with a lower risk of dementia, regardless of genetic susceptibility, including among those most at risk of Alzheimer's disease -- carriers of the APOE4 gene and other genetic variants as well,"
If interested,here's the actual French study: Association of Lifestyle for BRAin health risk score (LIBRA) and genetic susceptibility with incident dementia and cognitive decline (Jeanne Neuffer et al, 22 May 2024)
-Theresa
ApoE 4/4
Post Reply