Research on the Hazda and exercise

[circular]

... a next phase is to find something fundamentally very difficult cognitively that I find interesting and sustainable. I have a technical/analytical background and profession, but I don't have the challenges of the earlier part of my career.

Maybe for you the real neurogenic brain changer is to try things that are creative expression oriented, bypass the analytical? (I could say the same for me.)

[Tincup]

If I'm not huffing and puffing and soaked...I haven't done my proper exercise: I must do YUCK. Others will achieve with resistance although I feel aerobic may be more ancestrally beneficial.

Though still active, earlier in my life I was chronically fit. A lot of endurance exercise. Competing in high altitude races & etc. At 49 (now 61) this chronic fitness brought me to atrial fibrillation. While most afibbers have metabolic dysfunction, those who get it younger in life got it because they are chronically fit (look at the percentage of pro basketball players like Larry Bird & Jerry West with afib). The risk for getting afib at a young age is almost nil in the sedentary. It is material (~20% is a guess) in those who exercise a lot. For more on this, see articles from bicyclist and electrophisiologist, John Mandrola here and here. From the second link, "As for electrical abnormalities, the data speaks for itself. Long-term endurance exercise results in a five-fold increase in the risk of developing AF."

I was blessed to be able to create a remission program that includes significant detraining and very material electrolyte supplementation (primarily magnesium to bowel tolerance). I now focus on minimum effective dose. I also look endurance exercise as depleting a capital account that is fixed, at least in the short term. I know I have a genetic risk for this, but just wanted to throw this out there - exercise can have significant costs for some.

[MAC]

Thanks for the reference info George, I have no plans to become a marathon runner or exercise much beyond my current limited regiment, especially not altitude racing or triathlons. I don't enjoy running that much...it's mainly the mental motivation to fight cognitive decline, and overall superior health attainment. I've been at it for about 4 months, feel no ill effects, and combined with my diet and elevated metabolism, loosing significant weight (something I've always wanted to do) and getting close to an ideal BMI, and excising any remnant IR!

I just want to get lean (no belly fat), muscularly strong, and maintain and much higher than average MVPA regiment. I believe there is tremendous vascular health benefit to relatively intense aerobic exercise, which again, I tie back to ancestral evolutionary programming.

[MAC]

I like the exercise theory but my own experience has been that sleep is the top factor in my daily well being, which is of course intertwined with stress and exercise.

This sounds a bit whiny, but I would like to include the concept of the joys/stresses of raising children. My two kids are now 12 and 14 so the sleep deprivation (and diaper duty) of their early years are over but I'm still doing the taxiing work of modern American life along with trying to cook nutritious meals after work. I recognize that many kids are over-programmed but just having one extracurricular activity can still include 3-4 trips out of the house per week. Granted - we all need to establish priorities but I wonder if the ~20 years of child-rearing means some short changing of our health needs with the reality of family commitments. A similar argument could be made about the first 5-10 years of a demanding career.

Chris, I find that with my daily strenuous exercise, I am pretty zonked at bed time...so I'd say exercise aids my sleep cycle.

No doubt early career and kids absolutely impacts the opportunity to take care of one's own health, but there are many people who do it...so I'm sorry to say, our western lifestyle allows us to EASILY rationalize away lack of exercise to our personal health needs. You hear it all the time, "I have no time between work/kids/other commitments" to take care of myself. Well, time waits for no one, and us E4's need to dispense with the rationalization and get on with the yucky hard slogging to thwart cognitive/CVD.

[Stavia]

@Mac : I'm almost 3 yrs post finding out, I've evolved my program - but I started the piano studies and meditation within a month. I'm so pleased you have found a direction that you can follow with passion.

@cdamaden : I so hear you. I couldn't have done this if my kids were still at home. I certainly compromised my health during those years and threw myself passionately into parenting plus I obviously worked full time. Dunno if they appreciate it. On the bad side, there were a lot of oven chips and pasta....

[circular]

You hear it all the time, "I have no time between work/kids/other commitments" to take care of myself. Well, time waits for no one, and us E4's need to dispense with the rationalization and get on with the yucky hard slogging to thwart cognitive/CVD.

As usual truth and beauty are somewhere in between. I don't think it's just about time in many people's cases. While we all can try harder to achieve better balance in one area or another by adjusting our schedules and priorities, I have come to feel that some people have some inherent physical advantages at the mitochondrial level allowing them to accomplish more with more ease. This probably depends on both genetics and/or early environments depending on the individual. One needs to have enough ATP on board, and good hormonal/adrenal reserves, to go whole hog parenting, career and fitness, to mention the usual big 3. I know some people who have plenty and more to spare, and others who simply don't. The ones who have plenty are often, not always, critical of those who don't, but those who don't first have to work on their energy capacity (mitochondrial health and other factors) and reserves, including gradual exercise to boost mitochondria but not so much as to get into adrenal deficit. It can be a long, long road while occasionally hearing we're just short on willpower and need to simply buck up and make better choices. So go easy on us, it may not be that simple with everyone. My lack of reserves is one of a number of reasons I never ever wanted to have children for two minutes and in my 50s have zero regrets about it. I'm glad you're flying higher. Then there are many in between. Alas, I'm typing too much and need to lift some weights, so there's also something to what you say

[SusanJ]

Although I don't plan on giving up exercise, this one will make us pause...

Genetics and lifestyle independently determine dementia risk, but the interaction is unclear. We assessed the interactive relationship of apolipoprotein E (APOE) genotype and physical exercise on dementia risk over a 5-year period in 1,646 older adults from the Canadian Study of Health and Aging who were dementia-free at baseline. Physical exercise moderated the relationship between genotype and dementia (p < 0.01). Specifically, for APOE ɛ4 non-carriers, the odds of developing dementia were higher in non-exercisers than exercisers (OR = 1.98, 95% CI = 1.44, 2.71, p < 0.001), whereas, for APOE ɛ4 carriers, the odds of developing dementia were not significantly different between non-exercisers and exercisers (OR = 0.71, 95% CI = 0.46, 1.31, p = 0.34). Given that most individuals are not at genetic risk, physical exercise may be an effective strategy for preventing dementia.

https://www.ncbi.nlm.nih.gov/pubmed/27911292

[MAC]

The full paper (DOI 10.3233/JAD-160424) is behind a paywall. Members in jurisdictions for which access to is legal may want to search http://sci-hub.bz/ for the paper there.

Thanks for the reference Susan, really helps continue a very important subject for us E4's. But as with all studies, the devil is in the details.

The median age was about 62 yrs old. As for the definition of "exercise" and experimental protocol of this study, it was a questionnaire, and not a rigorous controlled RCT with high MVPA and follow-up longitudinal study.

"To assess engagement in regular physical exercise, participants were asked, “Do you engage in regular exercise?” and provided a yes/no response. Thus, exercise was categorically coded as exercisers (0) or non-exercisers (1). Exercisers were asked two additional questions regarding the type and frequency of their exercise; the majority of exercisers walked (67%) or participated in exercises more strenuous than walking (26%) at a frequency of three times per week (75%). These physical exercise questions have been previously determined to be reliable and valid"

So only 26% did anything "more strenuous" (???) than walking only 3X/week Give the age of this cohort, I would hazard a guess that is a VERY LOW MVPA in the context of say the Hazda or highly metabolic stressing exercise which produces demonstrable cardio/metabolic enhancement. What if this study was done on similar age cohort of persons doing high MVPA aerobic or resistance exercise? Or as referenced below, is the exercise important BEFORE significant structural changes have already taken place?

The authors cite another study which DID show significant effect for E4 carriers:

"In contrast, studies using the CAIDE dataset [17–19] assessed a substantially younger cohort (Mean = 50 y) and yielded the opposite result, with APOE ε4 carriers benefitting the most from physical exercise. The large age differences across studies, confounded by the corresponding age-related accumulation of neural pathology associated with dementia, may account for these divergent findings [28]. In other words, there may be a potential threshold in disease progression above which the neural damage accumulation in APOE ε4 carriers may be too extensive to benefit from the therapeutic effects of physical exercise. Indeed, carriers of at least one APOE ε4 allele show metabolic and structural brain changes characteristic of dementia prior to the clinical manifestation of the disease [29], and those with two APOE ε4 alleles tend to experience greater accumulation of neural plaques and neurofibrillary tangles [30]. Although it remains unclear how physical exercise is changing the human brain to reduce dementia risk, rodent models demonstrate reduced plaque burden with regular aerobic exercise [31]. This may mean that there is a sensitive period during which physical exercise can benefit homozygous APOE ε4 carriers that occurs at an earlier stage of the disease before neural plaques and tangles can amass"

The last sentence is hugely important as it relates to an overall PREVENTION protocol.

[SusanJ]

Thanks for finding the details. I'm sure it's hard to get the money to do a long RCT when it comes to exercise, so no surprise it's like a lot of diet studies in having people fill out the form.

This may mean that there is a sensitive period during which physical exercise can benefit homozygous APOE ε4 carriers that occurs at an earlier stage of the disease before neural plaques and tangles can amass

I did wonder if there was a difference for those who have exercised over the long term, because we know the process for E4s starts early, well before our 60s. Looking forward to reading that second paper.

[MAC]

Like I said in a previous post "anything worth doing is hard".

Running a controlled RCT on the benefit of exercise in a large cohort to to assess MCI effect would be insanely "worthy" but yet (sadly) too yucky to do.

Cynically, of course, pharma would NEVER support such an RCT.

In the absence of such studies and watching the clock tick away waiting for pharma, we can only infer from pre-industrial high MVPA societies with low AD/CVD incidence that exercise IS supremely beneficial.

Why NOT make that bet in the context of high relevance epigenetics? No guesswork vs. zillion dietary iterations and EVERYONE can do without equivocation, except its yucky (hard).

We are all here thirsting for positive E4 epigenetics after all yes?

For me it's a no-brainer LOL!