Showing posts with label aging. Show all posts
Showing posts with label aging. Show all posts

Friday, February 6, 2015

Exercise in the Elderly: BDNF and Executive Function



Exercise promotes cognitive function in children, adults and elderly individuals.

The mechanism for this effect is unclear. Some of the effect may be due to a general improvement in vascular function and health.

Another potential mechanism is via increased neuroplasticity mediated by neurotrophic factors.

Brain-derived neurotrophic factor (BNDF) is a known contributor to brain neuroplasticity. Levels of BNDF can be determined with serum assays.

RL Leckie and colleagues recently found support for BNDF mediation in an exercise in an interventional study with an elderly population.

The key elements of the design for their study included the following elements.

  • Participants: Adults between the ages of 55 and 80
  • Exercise intervention: Daily supervised walking sessions beginning with 10 minutes increasing to 40 minutes. Control intervention included stretching and toning sessions lead by an exercise professional
  • Cognitive assessment: Task-switching paradigm commonly used to assess executive function
  • Blood assay: Serum brain-derived neurotropic factor (BNDF) levels and BDNF genotype
  • Statistical analysis: Multivariate linear regression analysis with key dependent variable being cognitive performance after one year of intervention

The main findings from the study included:

  • Serum BDNF increased in the exercise group
  • This effect was limited to primarily the participants over 70 years of age
  • Enhanced executive function following exercise was demonstrated in those over 70
  • BDNF level increases in the over 70 age group correlated with cognitive performance

The authors note their does not mean exercise is not important for cognitive function in the younger age group (55-70 years of age). Their study only highlights the age interaction with BDNF in moderating a single executive function task.

BDNF levels decrease with age and the level of decrease in BDNF correlates with reduction in volume of the brain hippocampus. The hippocampus plays a key role in memory function and in decline in memory associated with aging.

It is quite possible that regular exercise after age 70 reduces the age related effect on cognition moderated by BDNF.

Readers with more interest in this study can access the free full text manuscript by clicking on the PMID link in the citation below.

Photo of ring kingfisher is from the author's files.

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Leckie RL, Oberlin LE, Voss MW, Prakash RS, Szabo-Reed A, Chaddock-Heyman L, Phillips SM, Gothe NP, Mailey E, Vieira-Potter VJ, Martin SA, Pence BD, Lin M, Parasuraman R, Greenwood PM, Fryxell KJ, Woods JA, McAuley E, Kramer AF, & Erickson KI (2014). BDNF mediates improvements in executive function following a 1-year exercise intervention. Frontiers in human neuroscience, 8 PMID: 25566019

Monday, February 2, 2015

Exercise in the Prevention of Alzheimer's Disease

Growing evidence links physical activity to improved cognitive outcome in elderly individuals.

Few studies have examined effects of exercise on those at highest risk for Alzheimer's disease.

J Carson Smith and colleagues recently published a prospective study of a cohort of older adults using structural magnetic resonance imaging.

The key elements of the design of their study included the following elements:
Participants: 97 adults between the ages of 65 and 89
Physical activity level: Frequency and intensity of leisure activity was assessed using the Stanford Brief Activity Survey
Alzheimer's risk status: Assessed using APOE genotype
Brain scanning protocol: Magnetic resonance imaging of brain using a 3T scanner at baseline and 18 months later. The brain hippocampal volume was identified as a key structure involved in APOE-related atrophy and memory decline
Statistical analysis: Participants were grouped in low and high physical activity groups and those with and without high-risk APOE Alzheimer's risk

The research team identified a statistically significant interaction between high-risk Alzheimer's participant and physical activity:
"Hippocampal volume decreased 3% in the High Risk/Low PA (physical activity) group whereas the volumetric changes in the remaining three groups were negligible."
The high-risk Alzheimer's group that participated in higher levels of physical activity appeared to have significant protection against hippocampal atrophy. To reach the higher levels of physical activity in the study they had to endorse one of the following levels:
  • Brisk walking 15 minutes daily three or more days per week
  • Jogging 15 minutes daily three or more days per week
  • Swimming 15 minutes daily three or more days per week
  • Moderately difficult chores 45 minutes daily three or more days per week
  • Regular jogging, running, bicycling or swimming 30 minutes or more
  • Playing sports such as handball or tennis an hour or more 

The authors examine the potential mechanisms for physical activity to reduce hippocampal atrophy in those with the high risk APOE genotype.

They note the beneficial effect of exercise may be through effects on cholinergic function, brain lipid metabolism or reduced neuroinflammation.

If this study is replicated it is an important finding with several implications.

One implication is that it may be one of the first research findings to support routine genetic testing for APOE and Alzheimer's risk. Those identified as high risk by APOE status could be targeted for aggressive behavioral interventions to increase physical activity along with increased surveillance of cognitive function.

Readers with more interest in this research can access the free full-text manuscript by clicking on the PMID link in the citation below.

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Photo of roseate spoonbill at sunset is from the author's files.

Smith JC, Nielson KA, Woodard JL, Seidenberg M, Durgerian S, Hazlett KE, Figueroa CM, Kandah CC, Kay CD, Matthews MA, & Rao SM (2014). Physical activity reduces hippocampal atrophy in elders at genetic risk for Alzheimer's disease. Frontiers in aging neuroscience, 6 PMID: 24795624

Monday, January 19, 2015

Mediterranean Diet and Aging

There is a growing research body of evidence to support beneficial effects of a Mediterranean diet on brain health.

In previous posts I have reviewed research on the Mediterranean diet and:

Cognitive Decline

Alzheimer's Disease Prevention

A recent study adds an important element in potential mechanisms for the beneficial effects of the Mediterranean diet.

Marta Crous-Bou and colleauges from Harvard University and the University of Washington published a study of the Mediterranean diet and chromosome telomere length.

This analysis used the large Nurses' Health Study cohort, blood samples and dietary questionnaires. Blood samples were analyzed for chromosome telomere length.

Chromosome telomere length has emerged as a biomarker of aging. DNA chromosome telomere lengths decline with age and shortened telomere lengths are associated with shortened life expectancy. 

The natural process of telomere shortening appears accelerated by inflammation and may be modified by lifestyle behaviors including dietary composition.

In the current study, subjects regularly completed dietary questionnaires. These questionnaires were rated on compliance with the Mediterranean diet on nine variables:

  1. Vegetables
  2. Fruits
  3. Nuts
  4. Whole grains
  5. Legumes
  6. Fish
  7. Monounsaturated fat to saturated fat ratio
  8. Red meat consumption
  9. Alcohol intake

Median values for variables 1-8 were identified and subjects received a score of 1 if they were above the median (below median for red meat consumption). One point was awarded for consuming between 5 and 15 grams of alcohol per day.

Telomere length shortening was associated with older age and heavier cigarette consumption history.

Subjects were grouped into quintiles (20%) groups from lowest to highest Mediterranean diet score.

After adjusting for confounding variables, telomere length was statistically linked to Mediterranean diet score. Those with higher ratings on Mediterranean diet had longer telomeres indicating better aging.

The highest quintile group reported the following mean daily servings for each category: Vegetables (4.3 servings per day), fruits (3.2), whole grains (2.1), fish (0.5), red meat (0.5), legumes (0.6) and nuts (0.5).

The authors note they were unable to identify any single variable that had a strong independent effect. The effect appeared to be a combined global effect of the Mediterranean diet score.

This is an important study because it adds evidence for a biological mechanism for some of the previously reported clinical advantages associated with a Mediterranean diet. 

However, this study is limited by being primarily cross-sectional in design. It does not inform on whether changing diet to a Mediterranean type reduces rate of telomere shortening. 

Readers with more interest in this research can access the free full-text manuscript by clicking on the citation link below.

Photo of foods highlighted in the Mediterranean diet is an original photo from my files.

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Crous-Bou M, Fung TT, Prescott J, Julin B, Du M, Sun Q, Rexrode KM, Hu FB, & De Vivo I (2014). Mediterranean diet and telomere length in Nurses' Health Study: population based cohort study. BMJ (Clinical research ed.), 349 PMID: 25467028

Sunday, June 22, 2014

Health Benefits of Resveratrol: New Plaudits

Joe: My doctor told me to give up drinking, smoking, and fatty foods.
Sam: What will you do?
Joe: I think I’ll give up my doctor.

I try not to get too excited about memory benefits of supplements, because too often the claims are not substantiated by studies that are well controlled and peer reviewed. I now think resveratrol may be one of the few supplements that benefits brain function.

When I wrote my first blog on research on resveratrol benefits for brain function and memory, there were over 2,000 scientific papers.[1]Don't worry; I am only going to tell you about a few studies.

Resveratrol is an active ingredient in red wine. This compound has been credited for explaining why red-wine drinkers in France, who drink more wine than most people, are healthier than would be predicted by their lifestyle of little exercise and eating lots of cheese. The problem is most studies suggest you would have to drink a 100 or more glasses of red wine a day to get much resveratrol effect (and that effect would obviously be negated by a toxic dose of alcohol). An obviously more healthful choice is the highly concentrated pill forms of resveratrol that are now on the market.

Most of the protective biological actions associated with resveratrol have been associated with its scavenger properties for free radicals and the protective effects that it confers on the heart and diabetes. 

One important study comes from a diabetes research group in Brazil recently who reported a beneficial effect of resveratrol on diabetic rats.[2]Resveratrol (in a modest rat dose of 10 and 20 mg per kilogram per day for 30 days) prevented the impairment of memory induced by diabetes. An earlier study by another group showed resveratrol improved glucose metabolism and promoted longevity in diabetic mice.

Another benefit of resveratrol is the anti-oxidant property. The brain produces more free-radical damage than other organs, and compared with other organs the brain has especially low levels of antioxidant defense enzymes. 

One recent study has revealed resveratrol had protective effects against brain damage caused by a chemical that kills acetylcholine neurons. Injection of this toxin into the brain of rats impaired their memory performance in two kinds of maze tasks. The impairment was significantly reduced by repeated injection of resveratrol (10 and 20 mg/kg) per day for 25 days, beginning four days before the toxin injection.[3]

Another recent study examined effects on working memory in mice fed a resveratrol-supplemented diet for four weeks before being injected with a cytokine to induce inflammation and accelerate aging. Resveratrol significantly reduced memory impairment in the aged group, but not in the young adults[4]. The lack of benefit in young adults was a little misleading, in that there was a "ceiling effect" in that the young adults were not impaired by the cytokine injection.

 The practical issue for us is whether resveratrol will help cognitive function in humans, especially healthy humans. It seems likely because other substances that have strong anti-oxidant properties seem to improve memory capability. Because animal studies have shown promise for resveratrol in preventing or treatment several different conditions associated with aging, several human clinical trials have been initiated.[5]

 An impressive new study of older humans, male and female, has just been reported.[6]Twenty-three healthy, but overweight people completed 6 months of daily resveratrol intake (200 mg ― the commercial brand I take has 300 mg/capsule). A paired control group got placebo pills. A double-blind design assured that neither the subjects nor the experimenters knew which individuals were in each group during data processing.

Memory tests of word recall revealed significant improvement in the resveratrol group. Resveratrol also increased brain-scan measures of functional connectivity, which identified  linked neural activity between the hippocampus and several areas of cerebral cortex.

Because others had shown that resveratrol increased insulin sensitivity in humans, these authors examine several markers important to diabetes. Resveratrol decreased the standing levels of sugar-bound hemoglobin, a standard marker for glucose control.  

What foods besides red grapes have resveratrol? The most likely other sources you would eat or drink are blueberries, cranberries, and peanuts. It is not likely that you could drink or eat enough of such substances to get enough resveratrol to do much good. Because of the scientifically documented benefits of resveratrol, highly concentrated supplements are now on the market (I have been taking it for a couple of years) I haven't given up my two glasses of red wine each day, but I have started taking one of the supplements. I haven't seen any reports that high doses of resveratrol are toxic.



[2] Schmatz R, et al. (2009). Resveratrol prevents memory deficits and the increase in acetylcholinesterase activity in streptozotocin-induced diabetic rats. Eur J Pharmacol. 2009 May 21;610(1-3):42-8. Epub 2009 Mar 19.
[3] Kumar, A. et al. 2007. Neuroprotective effects of resveratrol against intracerebroventricular colchicine-induced cognitive impairment and oxidative stress in rats. Pharmacology.79 (1): 17-26. DOI: 10.1159/000097511
[4] Abraham, J., and Johnson, R. W. 2009. Consuming a diet supplemented with resveratrol reduced infection-related neuroinflammation and deficits in working memory in aged mice. Rejuvenation research. 12 (6): 445-453.  DOI: 10.1089/rej.2009.0888
[5]Smoliga, J. M. et al. (2011). Resveratrol and health – a comprehensive review of human clinical trials. Mol. Nutrition Food Res. 55: 1129-1141
[6] Witte, A. V., et al. (2014) Effects of resveratrol on memory performance, hippocampal functional connectivity, and glucose metabolism in healthy older adults. J. Neuroscience. 34 23): 7862-7870.