This recent study looked at the effect of long term exercise on blood levels of brain derived neurotrophic factor in those who carry apoE4. BDNF normally goes up after habitual exercise and is suspected as being at least part of the story in how exercise improves cognitive function.
This study is disturbing in that those who are apoe4 did not have a rise in BDNF.
I wouldn't get depressed over this, but it is surprising. And it should not lead to the conclusion that being sedentary is just as good as being active. The implications of this single small study will take a long time to sort out.
Here is the study.
APOEε4 impacts up-regulation of brain-derived neurotrophic factor after a six-month stretch and aerobic exercise intervention in mild cognitively impaired elderly African Americans: A pilot study
• Joanne S. Allarda,
• Oyonumo Ntekimb,
• Steven P. Johnsonc,
• Julius S. Ngwad,
• Vernon Bondc,
• Dynell Pindera,
• Richard F. Gillumd,
• Thomas V. Fungweb,
• John Kwagyane,
• Thomas O. Obisesanc, ,
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http://dx.doi.org/10.1016/j.exger.2016.11.001
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Under a Creative Commons license
Open Access
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Highlights
•
Older adult men but not women demonstrate exercise-induced increases in VO2Max.
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Exercise-induced up-regulation of BDNF varies by APOE genotype.
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Muted BDNF response to physiological adaptations may explain ε4-related AD risk.
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Abstract
Possession of the Apolipoprotein E (APOE) gene ε4 allele is the most prevalent genetic risk factor for late onset Alzheimer's disease (AD). Recent evidence suggests that APOE genotype differentially affects the expression of brain-derived neurotrophic factor (BDNF). Notably, aerobic exercise-induced upregulation of BDNF is well documented; and exercise has been shown to improve cognitive function. As BDNF is known for its role in neuroplasticity and survival, its upregulation is a proposed mechanism for the neuroprotective effects of physical exercise. In this pilot study designed to analyze exercise-induced BDNF upregulation in an understudied population, we examined the effects of APOEε4 (ε4) carrier status on changes in BDNF expression after a standardized exercise program. African Americans, age 55 years and older, diagnosed with mild cognitive impairment participated in a six-month, supervised program of either stretch (control treatment) or aerobic (experimental treatment) exercise. An exercise-induced increase in VO2Max was detected only in male participants. BDNF levels in serum were measured using ELISA. Age, screening MMSE scores and baseline measures of BMI, VO2Max, and BDNF did not differ between ε4 carriers and non-ε4 carriers. A significant association between ε4 status and serum BDNF levels was detected. Non-ε4 carriers showed a significant increase in BDNF levels at the 6 month time point while ε4 carriers did not. We believe we have identified a relationship between the ε4 allele and BDNF response to physiologic adaptation which likely impacts the extent of neuroprotective benefit gained from engagement in physical exercise. Replication of our results with inclusion of diverse racial cohorts, and a no-exercise control group will be necessary to determine the scope of this association in the general population.
http://dx.doi.org/10.1016/j.exger.2016.11.001
apoE4, exercise and BDNF
Re: apoE4, exercise and BDNF
Slightly depressing, Marty. So many interventions (when isolated) show positive associations for non-E4 carriers, but not us . We have hints from FINGER, ADEX, MAPT, and even Dr. Bredesen's case studies that E4 carriers need to combine multiple synergistic strategies to get the same impact.
FWIW, Dr. Bredesen is very excited about the whole coffee fruit extract to increase BDNF. I don't think it's available commercially yet. You read read about the science here.
FWIW, Dr. Bredesen is very excited about the whole coffee fruit extract to increase BDNF. I don't think it's available commercially yet. You read read about the science here.
Re: apoE4, exercise and BDNF
Marty, anything in the full text that says how much excercise exactly? Maybe the dose was too low and e4s need more....
Re: apoE4, exercise and BDNF
Stavia wrote:Marty, anything in the full text that says how much excercise exactly? Maybe the dose was too low and e4s need more....
Aerobic exercise-training protocol:
Each subject's maximum heart rate was inferred from baseline VO2Max tests. Both aerobic exercise and stretch exercise group subjects participated in supervised training 3 days/ week. The aerobic exercise protocol complied with the American College of Sports Medicine Guidelines (ACSM) (American College of Sports Medicine Position Stand, 1998a), and included treadmill walking or jogging, stair-stepping, and elliptical training. Subjects underwent a warm up period, followed by intensity targeted-training and an appropriate cool-down period. Initial training sessions lasted 20 min at an intensity targeted at 50% VO2Max. Recordings of exercise heart rate and duration were used to monitor and ensure protocol compliance. Training duration increased by 5 min. each week until subjects attained 40 min. of exercise at 50% VO2Max. Subsequently, training intensity was increased by 5% VO2Max weekly until achieving 70% VO2Max. Aerobic group participants were asked to include an unsupervised 45–60 min. lower intensity walk during the weekend after the first 4–6 weeks of exercise in order to ensure maintenance of acquired fitness levels as well as to maintain motivation and interest.
Re: apoE4, exercise and BDNF
Stavia, I already know you well enough to know that you would push yourself harder than these subjects.Stavia wrote:Marty, anything in the full text that says how much excercise exactly? Maybe the dose was too low and e4s need more....
There certainly a lot of other benefits to fitness training beside just BDNF. Maybe the most important is the sense of well being. You can't bottle and sell that.
A different study from about two years ago showed that high intensity training did not improve cardiovascular fitness in a minority of subjects. While I don't recall the fitness protocol, it was intense and supervised. After several months maybe 10% of the participants showed no progress. All participants underwent needle muscle biopsy. The non-responders had DNA differences in their mitochondria. The point is, not everyone can become "fitter" in the traditional cardiovascular sense (max O2 consumption) even when putting the effort in. Nonetheless, I'll bet some enjoyed it.
Personally, I don't like "aerobic" exercise and never have. My desk is a treadmill (Treaddesk), which I've used for over a decade. I don't notice it since it's only going at 1.5 - 2 mph, so that works for me. Strength training has been much more to my liking and I continue that. If I were prescribed serious jogging or endurance biking, I'd get another opinion. The only way I'd put up with distance running is under immediate physical threat, which is exactly what my sergeants used to motivate me in the military.
We are all built differently. Some are better engineered physically for speed efficiency and some for strength based on muscle fiber patterns and mitochondrial (maternal) DNA. Maybe it isn't that surprising that we don't all push up our blood BDNF with aerobics.
Re: apoE4, exercise and BDNF
Thanks for the post, Marty. At first look the study is a bit disconcerting, but I agree w/you that it will take some time (and addt'l studies) to sort this out.
Noticed that of the 21 genotyped participants completing the 6 months exercise program, 14 were women (>55 years old) of which 6 were E4 carriers. Since hormone replacement therapy was a disqualifier, can't help but wonder if HRT might have impacted the results we see here.
I just read the abstract (full txt not available to me) of an older 2005 study out of the Depts of Pharmacology and Neurology at Columbia University, referring to evidence that estradiol can induce BDNF expression. If that is the case (no time to do at search atm), that would make me feel a bit more optimistic! Link below.
http://www.sciencedirect.com/science/ar ... 3604003728
Noticed that of the 21 genotyped participants completing the 6 months exercise program, 14 were women (>55 years old) of which 6 were E4 carriers. Since hormone replacement therapy was a disqualifier, can't help but wonder if HRT might have impacted the results we see here.
I just read the abstract (full txt not available to me) of an older 2005 study out of the Depts of Pharmacology and Neurology at Columbia University, referring to evidence that estradiol can induce BDNF expression. If that is the case (no time to do at search atm), that would make me feel a bit more optimistic! Link below.
http://www.sciencedirect.com/science/ar ... 3604003728
Re: apoE4, exercise and BDNF
Perhaps it's a matter of answering, did the cohort do any exercising prior to the study? Just reposting something MAC put out in another thread.
So, if this cohort did not exercise much in middle age, perhaps it's too late to reap exercise-BDNF benefit?
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4066890/For example, whereas mid-life exercise generally reduces the risk of developing AD or dementia in all subjects, carriers of the ε4 allele who participated in higher amounts of mid-life leisure-time exercise had greater protection against dementia or AD approximately 20 years later compared with ε4 noncarriers [16,71].
So, if this cohort did not exercise much in middle age, perhaps it's too late to reap exercise-BDNF benefit?