Exercise EVEN BETTER for 4/4s

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Gilgamesh
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Exercise EVEN BETTER for 4/4s

Post by Gilgamesh »

... according to one study, which I'm amazed I missed in my previous searches.

But first, a new study on exercise and APOE in general:

http://journal.frontiersin.org/Journal/ ... 00061/full

In it, there was this tidbit about exercise and homozygotes (finally!):
Etnier and colleagues reported that greater cardiorespiratory fitness was associated with better neurocognitive test performance in healthy older women who were APOE-ε4 homozygotes, but the same relationship was not observed in APOE-ε4 heterozygotes or non-carriers.
Here's the study:

Med Sci Sports Exerc. 2007 Jan;39(1):199-207.
Cognitive performance in older women relative to ApoE-epsilon4 genotype and aerobic fitness.
Etnier JL1, Caselli RJ, Reiman EM, Alexander GE, Sibley BA, Tessier D, McLemore EC.
http://www.ncbi.nlm.nih.gov/pubmed/?term=Etnier+apoe

And see this:

https://www.facebook.com/PaadStudy

OK, back to work. (I'm so behind..., but it's hard to stop thinking about APOE -- and this great community we have!)

GB
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Re: Exercise EVEN BETTER for 4/4s

Post by pal »

Thanks. Etnier is a great study because they actually tested people for fitness rather than merely relying on self reporting of physical activities, as in many studies. Small number of E4/E4s, but still larger than some other studies. Here's some more info. on the study from a Review article:

"Etnier et al. [49] measured cardiorespiratory fitness using indirect calorimetry (measured from a
maximal graded exercise test) in 94 women aged 51 to 81 (mean age = 62 years). They found that
greater cardiorespiratory fitness was associated with better performance on the Rey Auditory Verbal
Learning Test (Trial 5 performance) [55], the Rey-Osterreith Complex Figure Test [56], and Paced
Auditory Serial Addition Task [57] only in healthy older women who were APOE-ε4 homozygotes,
but not APOE-ε4 heterozygotes or non-carriers. The interaction effects were based on only eight
APOE-ε4 homozygotes, so these effects need to be replicated with a larger sample to rule out a
spurious or sample specific effect. Also, this study did not have a prospective design, did not assess
clinical outcomes, and included fewer subjects than the population based studies described above.
However, it is noteworthy for its rigorous characterization of cardiorespiratory fitness and use of a
battery of standardized neuropsychological outcomes."
http://www.mdpi.com/2076-3425/3/1/54
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Re: Exercise EVEN BETTER for 4/4s

Post by James »

Checking into this paper led to the discovery of this, hot off the press!, which cites the original (as ref #78). I've got the full-text for anyone interested. I haven't read it yet but it looks like it covers some very interesting topics.

------------------
http://www.ncbi.nlm.nih.gov/pubmed/24690272

Exercise, APOE genotype, and the evolution of the human lifespan.
Raichlen DA1, Alexander GE2.
Trends Neurosci. 2014 May;37(5):247-255. doi: 10.1016/j.tins.2014.03.001. Epub 2014 Mar 30.

Abstract
Humans have exceptionally long lifespans compared with other mammals. However, our longevity evolved when our ancestors had two copies of the apolipoprotein E (APOE) ɛ4 allele, a genotype that leads to a high risk of Alzheimer's disease (AD), cardiovascular disease, and increased mortality. How did human aging evolve within this genetic constraint? Drawing from neuroscience, anthropology, and brain-imaging research, we propose the hypothesis that the evolution of increased physical activity approximately 2 million years ago served to reduce the amyloid plaque and vascular burden of APOE ɛ4, relaxing genetic constraints on aging. This multidisciplinary approach links human evolution with health and provides a complementary perspective on aging and neurodegenerative disease that may help identify key mechanisms and targets for intervention.
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Julie G
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Re: Exercise EVEN BETTER for 4/4s

Post by Julie G »

Nice to see you posting, James. Or, should we call you Dr. Cain? I'd greatly appreciate a copy of that paper. It looks amazing. May explain why E4 carriers in developing countries don't develop AD. Thanks :D
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Re: Exercise EVEN BETTER for 4/4s

Post by James »

I won't be Dr. Cain for another three weeks. It's so close!

I'm starting to have more free time and I want to put pursue more personal writing interests and forums, so hopefully you'll see me around more often.

It seems I can't PM file attachments so here's a Dropbox link that I'll leave active for a while.
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Julie G
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Re: Exercise EVEN BETTER for 4/4s

Post by Julie G »

An early congratulations to you, James!

I got the paper- thanks. I haven't read through all of it yet, but was struck by the inconsistency in Table 1 between the increased rate of developing AD between 4/4 Asians and Caucasians- so DRAMATIC. Japanese 4/4s (living in Japan) develop AD at a rate of 21.8% compared to their 3/3 peers. For Korean 4/4s in Korea their rate is 24.7%. Juxtapose that with Caucasians living in the US, with an increased rate between 12.5-14.9%. Or, French and Norwegian 4/4s living in their respective countries with rates of 11.2% and 12.9%. Why do Asians have such a dramatically increased rate?

Wow, some of the 4/4 populations with very low rates are also startling. I expected the Africans in Africa to have very low rates...but the Africans in the US too? And Hispanics in the US? The stats for those two groups contradict other reports we've seen. Hmmmm. I'll try to find other data to resolve that inconsistency. Maybe African Americans and Hispanic Americans as a whole (both E4 and non-E4 carriers) develop high rates of AD, but 4/4s have some protection? THAT would be worth exploring. I look forward to hearing any theories.

Thanks for sharing, James :D
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Julie G
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Re: Exercise EVEN BETTER for 4/4s

Post by Julie G »

Pondering my questions...I think the increased rate for Asians MAY be based on the extremely low rate of AD (and E4 carriers) overall in their countries. For instance, the rate of AD in Japan is around 2.5%. For 3/3s, it is lower- hence the dramatically increased percentage for 4/4s :idea: Or, am I misunderstanding?
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Re: Exercise EVEN BETTER for 4/4s

Post by LillyBritches »

I think you're right, Jul - and, actually - I've always wondered if the low incidence of AD in India is more that 4/4 is pretty uncommon there, and not so much their using curcumin (tumeric)...probably synergistic, right?
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Re: Exercise EVEN BETTER for 4/4s

Post by pal »

Wow, interesting article. Thanks Dr. Cain; it doesn't hurt to practice your new name since it's only a few weeks away -- congrats. :D This article provides an excellent review of the exercise studies and seems to support the position that for E4s the fitter you are, the better:
"Thus, there is growing evidence that physical activity, exercise, and aerobic fitness significantly reduce CAD risk and improve cognitive aging and biomarkers of AD pathology in APOE e4 carriers."
"Thus, in studies with high-quality measures of physical activity, there is clear and growing support that engagement in physical exercise has a protective effect for APOE e4 carriers."

If you have access to the original study (Etnier), I would be super interested in seeing it as I've been looking for the full text for a while; I previously checked all the co-authors' websites to no avail.

P.S. Really enjoyed listening to you on the radio show. Great job!
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Re: Exercise EVEN BETTER for 4/4s

Post by LillyBritches »

Wait. We have a doctor in this house (okay, a three-week-to-be-MD)???

My spidey senses are getting all tingly...from excitement! :lol:
I'm just a oily slick in a windup world with a nervous tick.
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