How frightened should I be?

[hairyfairy]

I know that apoe4 increases alzheimers risk, but by how much? & at what age does it usually strike? I an`t stop worrying about it. Iv`e enrolled in a study on alzheimers in London, but I may have to have a study buddy to continue. The trouble is that I don`t know anyone that I could trust with the knowledge of my apoe4 status. I don`t want it becoming common knowledge.

[TheresaB]

Probably depends on your lifestyle. Dr Bredesen has said Alzheimer's should be a rare disease. That was an all inclusive statement, he didn't say rare for 3's and 2's but not 4's. There are populations that are 4 dominant and Alzheimer's is rare. The ApoE4 allele has thrived for millions of years, there's a lot of good about it.

By how much? Well, if you eat the Western diet and live the western lifestyle, then your odds are a lot higher than if you followed many of Dr Bredesen's recommendations in his protocol and lived more like our ancestors did.

[NF52]

I know that apoe4 increases alzheimers risk, but by how much? & at what age does it usually strike? I an`t stop worrying about it. Iv`e enrolled in a study on alzheimers in London, but I may have to have a study buddy to continue. The trouble is that I don`t know anyone that I could trust with the knowledge of my apoe4 status. I don`t want it becoming common knowledge.

Hi again, my English friend,

"It all depends" isn't a very helpful answer, but it's the most accurate one. But if you're looking for ranges across populations, here's a large-scale analysis of several thousand people followed for decades and published in 2017: It found that the risk of being diagnosed with EITHER Mild Cognitive Impairment (MCI)--which allows most people to still function at home fairly well) or dementia of any type by the age of 85 was 20-25% for people in the US and Rotterdam with one copy of ApoE4 who are currently 60-75 years old. So if you're in that age group, the "odds" are 75-80% that if you survive to 85 (about the average life expectancy of women in the U.S.) you will still have a functioning brain!

That's pretty good odds by my estimation. Because people with NO ApoE 4 still have a 10-15% chance that they will have a diagnosis of MCI or dementia by the age of 85.

If you can keep your blood pressure in a good range, avoid diabetes, continue to get exercise, and eat a healthy diet (without a lot of added sugar or highly processed foods), your odds may even be better for a healthy lifespan.

Here's the source for that study: APOE-related risk of mild cognitive impairment and dementia for prevention trials: An analysis of four cohorts

More importantly, here's some very recent research on how you can do things now to improve your brain's resilience. Knowing you can do something NOW should help you feel less worried about the future:

Enhanced lifestyle counselling prevents cognitive decline even in people who are carriers of the APOE4 gene, a common risk factor of Alzheimer's disease, according to a new study published in JAMA Neurology.

The two-year FINGER trial involved 60-77 year-old people living in Finland and with risk factors for memory disorders. The study participants were divided into two groups: one of the groups was given regular lifestyle counselling and the other enhanced lifestyle counselling. Enhanced counselling involved nutrition counselling, physical and cognitive exercises, and support in managing the risk of cardiovascular diseases.... The analysis included 1,109 persons of whom 362 were carriers of the APOE4 gene. The findings show that enhanced lifestyle counselling prevented cognitive decline despite the presence of the risk gene. Analyses carried out within the groups also indicate that the intervention results might even be better in carriers of the APOE4 gene.

Lifestyle changes prevent cognitive decline even in genetically susceptible individuals

And as far as that study partner, please know that your friends can handle this news. I know of a wonderful woman who has a group of long-time friends who serve as a sort of collective "Study partner" since they all see her regularly. They are all of an age where they have dealt with family members with Alzheimer's, or other health issues, and are hopeful that research will lead to prevention treatments. They enjoy the chance to be there for her, and no one suddenly treated her as if she had announced she was carrying the plague! Please share the news with a close friend, maybe one who has been there for you through other ups and downs. And let us know how she reacts.

[TheresaB]

I just listened to the recently released interview with Dr Bredeson, https://www.peak-human.com/home/dr-dale ... XB_aJA51IU

A quote by him from the interview,

"For people who are APOE4 postitive, find out early, get on prevention, and you should have a very, very low chance of getting the disease.”

Bold font emphasis added. But very, very low chance of getting Alzheimer's, that's not frightening at all. I've repeatedly said I'd rather be an insulin sensitive 4/4 than an insulin resistant non 4. So much of our fate is in our own hands.

[Fiver]

Dr. Bredesen is an expert with years of experience. And that's a great outlook to have!

Personally, at the moment however, I have trouble being quite so optimistic. Quite a large number of studies show the myriad negative impacts of E4 (and the positive effects of replacing E4 with E3 or E2 genes, in cells or mice). It seems a lot to overcome to make one's risk "very, very low". Not that we can't lower (or raise) our risks substantially with good (or bad) health choices - we can! But my gut tells me that the regular risk, without health and lifestyle improvements that we are increasingly aware of, might be reflected in studies like this recent one:

APOE-related risk of mild cognitive impairment and dementia for prevention trials: An analysis of four cohorts
PLOS March 21, 2017
https://doi.org/10.1371/journal.pmed.1002254
https://journals.plos.org/plosmedicine/ ... ed.1002254

Five-year risk was highly variable across the four samples within each group; for APOE-e4/e4 individuals, it ranged from 0% to 23% in those entering the study at age 60–64 years, 9% to 35% in those entering at 65–69 years, and 19% to 38% in those entering at 70–75 years.

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.

I figure with some good decisions, made over many years, the risk would drop.

Just my opinion, however, and I am not an expert.

[TheresaB]

Not that we can't lower (or raise) our risks substantially with good (or bad) health choices - we can! But my gut tells me that the regular risk, without health and lifestyle improvements that we are increasingly aware of, might be reflected in studies like this recent one:

APOE-related risk of mild cognitive impairment and dementia for prevention trials: An analysis of four cohorts
PLOS March 21, 2017
https://doi.org/10.1371/journal.pmed.1002254
https://journals.plos.org/plosmedicine/ ... ed.1002254

Five-year risk was highly variable across the four samples within each group; for APOE-e4/e4 individuals, it ranged from 0% to 23% in those entering the study at age 60–64 years, 9% to 35% in those entering at 65–69 years, and 19% to 38% in those entering at 70–75 years.

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.

I think I'm going to say the same thing you just said, that is: without health and lifestyle improvements (which doesn't look like it's forthcoming on a population scale any time soon) APOEe4s will continue to experience high rates of Alzheimer's. But for the sake of beating a dead horse I'm going to elaborate.

The four cohorts from the referenced study -

• 1. National Alzheimer’s Coordinating Center (NACC) (n = 5,073, 158 APOE-e4/e4) –participants come from Alzheimer's Disease Centers (ADCs) across the United States
  2. The Rotterdam Study (n = 6,399, 156 APOE-e4/e4) – participants come from the City of Rotterdam in The Netherlands.
  3. the Framingham Heart Study (n = 4,078, 67 APOE-e4/e4) – the residents of the city of Framingham, Massachusetts.
  4. Sacramento Area Latino Study on Aging (SALSA) (n = 1,294, 11 APOE-e4/e4) -- elderly Latinos in the Sacramento, California, region.

The vast majority of those participants likely followed Western/Standard American Diet and lifestyle practices, meaning they were probably metabolically deranged to begin with. In other words: excess waist circumference, abnormal cholesterol and triglyceride levels, hypertension, and insulin resistance. So the APOEe4 incident rates of Alzheimer's cited in that study shouldn't apply to those of us who understand the peculiar sensitivities our allele holds and are being proactive at being metabolically healthy.

To back up my presumption about the metabolic health of those cohorts, I’ll cite this recent study Prevalence of Optimal Metabolic Health in American Adults: National Health and Nutrition Examination Survey 2009–2016. That study found that only 12.2% of adults are in optimal metabolic health with being younger tending to correlate more highly with metabolic health, and less than one third of normal weight adults were metabolically healthy. Holy Cow!!

The conclusions section of the paper said, "this has serious implications for public health." Indeed!

We are very fortunate to have this ApoE4.info website to become knowledgeable about the APOEe4 allele and hopefully we are all taking measures to lower our risk and improve overall health. We know Alzheimer’s doesn’t just magically appear. We know genes don’t predetermine outcomes, they predispose, but we know ultimately outcomes are significantly influenced by how we treat our genes (epigenetics). As APOEe4s we just have to work harder than our 2 or 3 brethren, those are just the cards we were dealt.

Unfortunately, until there's a sea change in health attitudes, we (all genotypes) will continue to see high rates of Alzheimer's, cardiovascular disease, Type 2 Diabetes, cancer, strokes, and other chronic diseases, which means APOEe4s will continue to experience higher rates of Alzheimer's and cardiovascular disease.

The operative question is what is the risk of developing Alzheimer's for APOEe4s who are proactive in addressing diet, lifestyle, and toxic exposures? That's where Dr Bredesen's risk assessment of "very, very low" is very motivating since putting those best practices to work can be daunting at times.

[Fiver]

Hi Theresa. Yep, I think we are agreeing. Those unmodified risks are from generation who lived without the benefit of our knowledge. We can do better now.

How much better is the question.

I'm reading some of the intervention studies, when health and lifestyle improvements were evaluated. There's no doubt they lowered the incidence, or individual risk. That's outstanding, and very encouraging.

Dr. Bredesen shows very impressive and encouraging results, first in a small study and then in one of moderate size.

But I just have not yet seen numbers I'd call very, very low in a large study.

To get there I think we're going to need health and lifestyle improvements AND medical diagnostics and treatments AND a change in the attitude of the medical / insurance system.

That will be a good day!!!

[hairyfairy]

The trial that I applied to go for was shut down, but I`ll try to get on any others that are on offer.