Research on the Hazda and exercise

[circular]

Good on ya' MAC. You have my full support

[MAC]

Although I dove head 1st into exercise as previously referenced, I thought I'd poke around pubmed to see what studies have been published on AD/physical activity. I really do believe our evolutionary DNA is associated with high physical activity and shifting away to a more sedentary lifestyle is metabolically detrimental to our overall systemic health.

https://www.ncbi.nlm.nih.gov/pubmed/28049634
Physical Activity and Alzheimer's Disease: A Systematic Review

Physical activity was inversely associated with risk of AD in most studies (n = 18)

https://www.ncbi.nlm.nih.gov/pubmed/27138799
Physical activity delays hippocampal neurodegeneration and rescues memory deficits in an Alzheimer disease mouse model

We believe that we provide evidence for the first time that enhanced physical activity counteracts neuron loss and behavioral deficits in a transgenic AD mouse model. The present findings underscore the relevance of increased physical activity as a potential strategy in the prevention of dementia.

https://www.ncbi.nlm.nih.gov/pubmed/27889467
Treadmill exercise decreases amyloid-β burden possibly via activation of SIRT-1 signaling in a mouse model of Alzheimer's disease

Although treadmill exercise reduces Aβ levels, the molecular mechanisms underlying the effects are not fully understood. We hypothesize that treadmill exercise decreases Aβ production and alleviates cognitive deficits by activating the non-amyloidogenic pathway via SIRT-1 signalling. Treadmill exercise improved cognitive deficits and alleviated neurotoxicity. Most importantly, treadmill exercise increased SIRT-1 level, which subsequently resulted in increased ADAM-10 level by down-regulation of ROCK-1 and upregulation of RARβ, ultimately facilitating the non-amyloidogenic pathway. Treadmill exercise-induced activation in SIRT-1 level also elevated PGC-1α level and reduced BACE-1 and C-99 level, resulting in inhibition of the amyloidogenic pathway. Treadmill exercise may thus inhibit Aβ production via upregulation of SIRT-1, which biases amyloid precursor protein processing toward the non-amyloidogenic pathway. This study provides novel and valuable insight into the molecular mechanisms possibly by which treadmill exercise reduces Aβ production. In summary, our study is the first to report that treadmill exercise might reduce Aβ production and, improve cognitive deficits possibly by increasing ADAM-10 and decreasing BACE-1 via activation of SIRT-1/PGC-1α signaling, ultimately activating the non-amyloidogenic pathway and inhibiting the amyloidogenic pathway. This study provides new insight into the mechanisms of treadmill exercise-induced Aβ reduction, which represents a potential therapeutic strategy for AD Loss of SIRT-1 expression has been observed in patients with AD, resulting in elevated Aβ production whereas SIRT-1 over expression has been shown to decrease Aβ production indicating that activation of SIRT-1 by physical exercise may prevent Aβ production in AD brains. Several studies demonstrated that physical exercise increases SIRT-1 expression. Treadmill exercise remarkably increased SIRT-1 expression, which was associated with decreased Aβ accumulation. the forced treadmill exercise used in this study allows for precise regulation of physical exercise demands, which maintain a constant intensity of physical exercise. these results demonstrated that treadmill exercise reduced Aβ level by activating SIRT-1, strongly suggesting that treadmill exercise may prevent Aβ production through enhancement of the non-amyloidogenic pathway. (This is an amazing root cause study, albeit mice)

https://www.ncbi.nlm.nih.gov/pubmed/27328058
Physical Exercise and Brain Mitochondrial Fitness: The Possible Role Against Alzheimer's Disease

Exercise is one of the most effective strategies to maintain a healthy body and mind, with particular beneficial effects of exercise on promoting brain plasticity, increasing cognition and reducing the risk of cognitive decline and dementia in later life. Moreover, the beneficial effects resulting from increased physical activity occur at different levels of cellular organization, mitochondria being preferential target organelles.The relevance of this review article relies on the need to integrate the current knowledge of proposed mechanisms, focus mitochondria, to explain the protective effects of exercise that might underlie neuroplasticity and seeks to synthesize these data in the context of exploring exercise as a feasible intervention to delay cognitive impairment associated with neurodegenerative conditions, particularly Alzheimer disease.

https://www.ncbi.nlm.nih.gov/pubmed/27716670
BDNF Responses in Healthy Older Persons to 35 Minutes of Physical Exercise, Cognitive Training, and Mindfulness: Associations with Working Memory Function.

We show that a single bout of physical exercise has significantly larger impact on serum BDNF levels than either cognitive training or mindfulness practice in the same persons. This is the first study on immediate BDNF effects of physical activity in older healthy humans and also the first study to demonstrate an association between serum BDNF responsivity to acute physical exercise and working memory function.

https://www.ncbi.nlm.nih.gov/pubmed/27656623
Treadmill exercise ameliorates Alzheimer disease-associated memory loss through the Wnt signaling pathway in the streptozotocin-induced diabetic rats

The rats in the exercise groups were made to run on the treadmill for 30 min per one day, 5 times a week, during 12 weeks. Treadmill exercise improved short-term memory and spatial learning ability in the diabetic rats. The present study suggests that treadmill exercise alleviates Alzheimer disease-associated memory loss by increasing neurogenesis through activating Wnt signaling pathway in the diabetic rats

https://www.ncbi.nlm.nih.gov/pubmed/27978791
Exercise prevents cognitive function decline and demyelination in the white matter of APP/PS1 transgenic AD mice

In this study, 6-month-old male APP/PS1 double transgenic mice were exercised by running for 20 min/day for four months, and then the effects of exercise on cognitive function and white matter in these AD mice were investigated. In addition, the white matter, myelinated fiber and axon volumes in the white matter of the exercised group were significantly increased compared with those of the sedentary group. Our results suggest that exercise potentially improves cognitive function in AD and that the effects of exercise on the white matter in AD might represent a structural basis of its protective effects on cognitive function in this disease. The exercise-induced improvement in cognitive function may have occurred because exercise prevents the demyelination of myelinated fibers in the white matter in AD

http://www.arcmedres.com/article/S0188- ... 0277-9/pdf
Physical Activity, Brain Plasticity, and Alzheimer's Disease

In addition, randomized interventions using neuroimaging tools have reported that participation in physical activity increases the size of prefrontal and hippocampal brain areas, which may lead to a reduction in memory impairments. Consistent with these findings, longitudinal studies using neuroimaging tools also find that the volume of prefrontal and hippocampal brain areas are larger in individuals who engaged in more physical activity earlier in life. We conclude from this review that there is convincing evidence that physical activity has a consistent and robust association with brain regions implicated in age-related cognitive decline and Alzheimer's disease

https://www.ncbi.nlm.nih.gov/pubmed/27039886
Exercise as a pro-cognitive, pro-neurogenic and anti-inflammatory intervention in transgenic mouse models of Alzheimer's disease

There is now a growing body of evidence from the literature which highlights the contribution of exercise to ameliorating AD pathology, improving cognitive performance, enhancing adult hippocampal neurogenesis and reducing neuroinflammation in transgenic mouse models AD. Despite the many questions that remain to be debated, preclinical studies provide a strong basis for the consideration of adopting exercise as a non-pharmacological intervention in the human AD population.

https://www.ncbi.nlm.nih.gov/pubmed/27785416
Physical activity and long-term mortality risk in older adults: A prospective population based study (NEDICES)

Significant dose effects were observed between light versus the sedentary group and intense versus the moderate group. PA prevents long-term mortality in older Spanish adults, with the highest intensity levels being those related to the lowest risk of mortality. These findings indicate that health policies for old age care should include PA as one of the main targets.

[Stavia]

Mac, thank you for this very thorough summary. I will be adding a link to this thread in our intro. Very muchly appreciated

[MAC]

Hope it might be of some assistance Stavia.

I was actually sort of surprised to find so many STRONG causation studies on exercise (post review not surprised), which I reiterate is IMHO woefully lacking in this forum. Why aren't we offering up ALL scientific knowledge relating to cognitive enhancement/prevention? It is a scientific fact that exercise is a key element of an overall complete lifestyle altering approach to reduced AD, improved CVD/TCM, and enhanced longevity.

So I went back and counted all the individual presentations/posters of the past Ancestral Health Symposia. There have been approximately 262 (+/-) individual presentations on some ancestral subject (I think I missed/could not find ASH2015), and only 6 that referenced something about physical fitness/exercise, so about 2%. We are having raging debates about lipids, of course the bogey man cholesterol, LCHF, HFLC, , and every possible iteration in between, with arguably, similar or weaker correlative AD science than the effect of exercise on cognitive, yet only 2% of the past presentations at AHS touched on this subject? I'd be curious to run the same statistics on this forum re posted discussion subjects frequency...hmmm.

What am I missing re the front line professional medical community thinking on preventing AD? Too yucky?

[Julie G]

MAC, of course, we have no formal relationship with AHS other than we used their symposium as an opportunity to meet last year and arranged some excellent ApoE4 presentations. That being said, we DID have Dr. Raichlen, author of this paper, on the agenda, but he had to back out at the last minute. My guess is that he'd be thrilled to present this year if asked.

Thank you for chiding us for not talking more about exercise. For us old-timers, it's a given; far and away, the most proven, least controversial strategy we can employ within our individual parameters. Because of that, we tend to move onto more controversial topics... like diet mistakenly leading newcomers to think it's not important. It IS #2 in Stavia's primer. Perhaps we should switch it to #1?

[Stavia]

I thought long and hard about the hierarchy of strategies in my primer and have just looked again. I still think IR comes slightly higher. Of course exercise is part of reducing IR.

I'm personally intruiged why so many people are lipid obsessed. Media? I just don't get it.

Mac, I've tried to interest members in strategies other than lipids (and IR and supplements). There was a teeny bit of interest then nothing.
Julie is right - the old timers take it as given and move on.
As a doctor, I always discuss exercise with patients if appropriate. There are those who do it already and those that never will. I'm wasting my time with the latter.

[MAC]

Julie, re the AHS statistics, I was not making a direct association with this forum.

The AHS "about us/manifesto" asserts:

"AHS is motivated by a belief that evolution has much to teach us about healthful living and effective healing. Studying modern health from an evolutionary perspective to develop solutions to our current health challenges. We need health reform, ultimately, in order for any efforts at healthcare reform to succeed sustainably. Modern humans suffer from numerous diseases linked to the metabolic syndrome, such as diabetes, yet these health maladies were virtually nonexistent during most of our ancestry. In modern science, evolution is the default perspective for inquiry. In modern healthcare, however, evolution is almost nowhere to be seen. Neolithic and (especially) post-industrial diets combined with modern sedentary lifestyles have pushed our physiologies dangerously far from their adapted environments, and it is becoming exceedingly expensive and ineffective for medical practitioners to fix the resulting damage done to our bodies or halt the epidemic flood of illnesses collectively referred to as the diseases of civilization. In fact, the current generation of children may live shorter lifespans than do their parents—a startling reality that should shock health experts into creative, collaborative solution-searching"

From above "In modern healthcare, however, evolution is nowhere to be seen" They got that right! 2% of the symposium program is allotted to perhaps THE most important element of ancestral health..superb physical fitness, which we know, pretty much crushes most all metabolically self-induced diseases. (sort of hard to be super fit if you were eating poorly, so sort of trumps even a "good Apoe4 healthy diet"). Everyone that I know that is high physically engaged/fit, also eats very well, so I see fitness as sort of dragging everything else along (stress, sleep, diet) for the ride.

I repeat that I strongly believe we are also lacking as a community in more strongly promoting exercise as a key tenet of prevention. I believe dietary and exercise lifestyle changes are both very important epigenetic impact variables predisposed to AD prevention. We need to get that message out.

Stavia, as a doctor, I am sure you must be frustrated with the shear lack of motivation in patients to undertake exercise as part of daily lifestyle regiment at the level of diet, sleeping, stress, etc for optimal well being. Popping a pill is a lot easier than running 5 miles...

Stavia, not suggesting you make it a #1 in your primer, but as a doctor, imagine the impact if you did? The other stuff is so much easier to get compliance, but the exercise...very yucky!

[Stavia]

Mac, AHS had an exercise component every day at lunch and at the start of the day. Actually delegates physically exercising. Its taken as a given. George and I were seen balance-beaming!

I still stand by my hierarchy, as IR, if present is hugely dangerous to multiple organ systems, more so IMO than lack of exercise. Which is a very close second IMO.

And IR is very difficult to fix. People that get it are often inherently unable to do what is needed. Either for psychological or social or financial reasons.

[MAC]

Potential for primary prevention of Alzheimer's disease: an analysis of population-based data.
https://www.ncbi.nlm.nih.gov/pubmed/25030513

The full paper (doi.10.1016/S1474-4422(14)70136-X) 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

Summary

Recent estimates suggesting that over half of Alzheimer’s disease burden worldwide might be attributed to potentially modifiable risk factors do not take into account risk-factor non-independence. We aimed to provide specific estimates of preventive potential by accounting for the association between risk factors (see below)

Of the seven risk factors, the largest proportion of cases of Alzheimer’s disease in the USA, Europe, and the UK could be attributed to physical inactivity.

[SusanJ]

MAC, here's one to watch related to exercise. An upcoming study that is looking at the effect of exercise on n-3 fatty acids "to develop n-3 fatty acids-based prediction of cognitive responses to aerobic exercise treatment in Alzheimer's disease."

They note:

On the molecular level, exercise and fatty acids share some similar effects on cognition. Both act on dopaminergic pathways,8 9 and influence the expression of brain-derived neurotrophic factor, which promote synaptic plasticity, cell proliferation, and cell survival in humans and rodents.10 11 Because of the shared neurobiological and physiological effects, several human and animal studies have speculated about the benefits of higher, endogenous levels of n-3 fatty acids in plasma in contribution to the pro-cognitive effects of exercise.12 13

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5223628/