One study shows that physical activity and diet health exert some control over Alzheimer's risk. Scientists have found possible mechanisms between physical activity and Alzheimer's risk.
Alzheimer's disease is a brain disease that causes loss of memory and cognitive function. The disease is caused by the build up of toxins in the brain leading to deterioration of brain tissue. The hippocampus, our brain's memory center, deteriorates as the disease progresses. The National Institute of Health estimates that 5.1 million Americans suffer from Alzheimer's.
In 2009 a study found negative correlations between the risk of developing Alzheimer's disease and physical activity and diet health (Physical Activity, Diet, and Risk of Alzheimer Disease, 2009, Nikolaos Scarmeas, et al.). The study looked at 1880 elderly individuals from New York City over an average period of 5.4 years. Individuals diet score and physical activity score was collected. The study participants were screened to ensure that they were not suffering from dementia before participating in the study. Those reporting significant physical activity had a 37-50% lower risk of developing Alzheimer's disease. Those in the highest Mediterranean-style diet adherence tertile had a 32-40% reduced risk of developing Alzheimer's disease.
Good physical activity and a healthy diet were both found to independently reduce risk of developing Alzheimer's disease. The Godin leisure time questionnaire was administered to determine physical activity. The questionnaire looked at physical activity over a two-week interval. Diet was determine with the 61-item version of the Willett Semiquantitative Food Frequency Questionnaire to determine adherence to a mediterean-type diet (points for fruits, vegetables, fish, grains and lost for meats, dairy, fats). Subsequent questionnaires were administered every 1.5 years to ensure the validity of the initial questionnaire.
The participants were all 77+/-1 years old; as is the case with elderly populations physically activity was not prevalent in the study participants. Therefore, the high physical activity corresponded to 1.3 hours of vigorous physical activity, 2.4 hours of moderate physical activity or 4 hours of light physical activity. This demonstrates that even a small amount of physical activity can lead to significant benefits in reducing Alzheimer's.
How does exercise protect the brain?
The mechanism that exercise influences Alzheimer's Disease risk may be through various toxins and neuro-factors. Research has shown that brain-derived neurotrophic factor (BDNF) protects against synapse deterioration and may be able to treat Alzheimer’s. Moderate to vigorous physical activity increases BDNF. Low levels of Nerve Growth Factor (NGF) has been shown to be a risk factor for Alzheimer's. Like BDNF, exercise increases the brain's NGF. Reactive oxygen species in the brain may be another risk factor for Alzheimer's. Exercise takes care of reactive oxygen species via two pathways: exercise reduces their production and exercise raises antioxidant levels, which detoxify reactive oxygen species. Exercise has been shown in mice models to reduce expression of several genes that have been found to correlate with Alzheimer risk.
Another mechanism exercise may influence Alzheimer's risk is through cerebral blood flow and metabolism. Both cerebral blood flow and metabolism decrease with the onset of Alzheimer's. Exercise significantly increases both. Exercise increases vascular endothelial growth factor (VEGF) in the brain. VEGF spurs the development of nigral microvessels, countering the decrease in nigral micro vessel density, an effect of aging. Exercise, especially high intensity exercise, at a young age has been shown to have a tremendous impact on the the promotion of VEGF.
For more information about the biological mechanisms behind exercises reduction in Alzheimer's risk read Exercise Plays a Preventive Role Against Alzheimer's Disease (Z. Radak, et al., 2010).
In summary, physical activity and diet exert significant influence on Alzheimer's Disease risk. Although the mechanism is not exactly known, researchers speculate that it may be through neuro-factors, toxins, cerebral blood flow and cerebral metabolism, all of which are controlled by some extend through exercise. Please share your thoughts!
Physical activity leads to significant improvements in the quality of life of ovarian cancer survivors. In addition, studies are looking at the best ways to get cancer survivors to follow a healthy lifestyle.
Physical activity is recommended all cancer survivors by the American Cancer Society. A study published in 2007 found that ovarian cancer survivors showed significant increases in quality of life through physical activity, (Associations between physical activity and quality of life in ovarian cancer survivors, 2007, Clare Stevinson, et al.) Ovarian cancer ranks fourth in cancer-related deaths among women. Unfortunately, the current five-year survival rate among ovarian cancer patients is less than 50%. A major focus of the treatment of ovarian cancer patients is on improving quality of life.
The study was published in Gynecologic Oncology and used ovarian cancer survivors from Alberta, Canada. The study categorized participants based on recommendations set forth by the American Cancer Society (150 to 300 weekly minutes of moderate exercise or 60 to 120 weekly minutes of strenuous exercise). Four groups were established: sedentary, below guidelines, meeting guidelines and above guidelines. Quality of life was measured with the Functional Assessment of Cancer Treatment-Ovarion (FACT-O) scale. Physical activity was self-reported using a mail-in questionnaire. Of the respondents only 31.1% were meeting or exceeding American Cancer Society recommendations. The author's suggested that this number is probably even lower because physical activity tends to be slightly inflated when self-reported and survivors in poor health were excluded from the study. As the figure below shows, quality of life among those below the guidelines was significantly lower than those meeting or exceeding physical activity guidelines. However, no significance was established between the sedentary group and below guideline group or between the within the guidelines group and exceeding guideline group.
Quality of life of ovarian cancer survivors across the four physical activity categories.
In addition, FACT-O scores were compared between ovarian cancer survivors currently fighting the disease and those with the disease in intermission. The figure below shows that the rise in FACT-O score from being in the physical activity group was three times higher among those currently fighting the cancer. Surprisingly, quality of life as measured by FACT-O score was found to be higher among those currently with the ovarian cancer, but meeting the guidelines of physical activity, than those in remission regardless of whether or not they met the guidelines.
Exercise may increase quality of life through two paths. A study found that physical and functional well-being, but not emotional or social well-being, was improved by exercise in cancer survivors participating in group psychotherapy classes (The group psychotherapy and home-based physical exercise trial in cancer survivors: physical fitness and quality of life outcomes, 2003, K.S. Courneya, et al.). Exercise controls obesity. Obesity has been shown to dramatically decrease ovarian cancer survival rate (Effect of obesity on survival in epithelial ovarian cancer, 2006, J.C. Pavelka, R.S. Brown, B.Y. Karlan, I. Cass, R.S. Leuchter, L.D. Lagasse et al.).
If physical activity increases quality of life in ovarian cancer survivors, how can patient adherence to physician prescribed exercise treatment be increased?
A recent study looked at moderate to vigorous physical activity in breast and prostrate cancer survivors receiving two types of mailed print intervention for ten months (Long-term physical activity outcomes of home-based lifestyle interventions among breast and prostate cancer survivors, 2012, Allison J. Ottenbacher, et al.). One group received publicly-available lifestyle brochures (attention control) and another received tailored brochures (tail intervention). As the figure below demonstrates, both groups (who were initially sedentary) showed significant increases in physical activity. Although the tailor intervention group had higher physical activity rates after a year, the gains in the tailor intervention group became somewhat diminished in a two-year follow-up.
Trajectory of median minutes of moderate to vigorous physical activity over time, by intervention assignment.
Another recent study found that quality of life in ovarian cancer survivors was significantly improved through lifestyle counseling (Feasibility of a lifestyle intervention for ovarian cancer patients receiving adjust chemotherapy, 2011, V. Gruenigen, et al.). The study found that patients enrolled in physical activity and nutritional counseling with every chemotherapy visit increased nutritional dietary intake and physical activity. In addition, quality of life as measured with the Functional Assessment of Cancer Therapy and symptom severity measured by the Memorial Symptom Assessment Scale also showed improvement in ovarian cancer patients receiving the lifestyle counseling.
In summary, participating in 150 minutes of moderate exercise a week has been shown to improve quality of life in ovarian cancer survivors. However, getting patients to follow physical activity guidelines poses a significant hurdle. Studies have found that tailored intervention mailings and lifestyle counseling increase adherence to prescribed physical activity, but more measures may be needed to reach higher levels of participation. Please share your thoughts!
Two studies suggest exercise may reduce risk of Parkinson's Disease and reduce the behavioral effects after onset.
Parkinson's disease affects over a million Americans is the second most prevalent neurodegenerative disease following Alzheimers disease. Parkinson's disease is a dopaminergic brain disorder that leads to slow movements (bradykinesia), rigidity, tremor and postural instability. Parkinsons patients often develop problems with speech, memory, general cognition and smell. As a result of these symptoms, Parkinson's disease is a dehibilating disease burdening life for both patient and family. However, patients can remain functional with treatment for over 30 years after diagnosis, it is a slowly progressing disease unlike some other neurodegenerative diseases. Parkinson’s disease results from a loss of dopaminergic neurons in the substantia nigra (a region in the midbrain of the brainstem). An etiology is not known, although several genes have been implicated including alpha-synuclein (which forms lewy bodies in neurons, a pathologic characteristic of Parkinsons) and DJ1 (related to mitochondria function). Reactive oxygen species, calcium signaling, proteinaupathy, and viruses have all been discussed as possible etiologies. Several different treatments are available to mask the symptoms, but there is currently no cure. These treatments include dopamine (prescribed as Levodopa), dopamine agonists (Mirapex) and deep brain stimulation (DBS).
In 2010, a study was published finding that adults who participated in physical activity had a reduced risk of developing parkinson's disease in the next four to ten years (Physical Activities and Future Risk of Parkinson Disease, 2010, Q. Xu, Y. Park, et al.). This study looked at the physical activity of 200,000 plus participants in a NIH-AARP study. Doctor diagnosed Parkinson's disease rates were collected ten years later. Those who were diagnosed with Parkinson's in the four years immediately following the initial physical activity survey were left out of the statistical analysis. The study found that adults who reported participating in physical activity over each of the two survey periods had a 40% lower risk of being diagnosed with Parkinson's disease ten years later. Interestingly, the study found that physical activity at early ages had no link to risk of developing Parkinson's. Exactly why physical activity is correlated with a reduced risk of developing Parkinson's is not exactly known. Most likely, exercise was delaying onset of symptoms and progression of disease, rather than fully preventing diagnosis. However, several studies provide some light on possible explanations.
A study published in 2003 found that mice forced to run on a treadmill after being injected with a dopamine toxin, 6-hydroxydopamine, showed less loss of motor control and better retention of neurochemicals that play a role in the dopamine pathway (Exercise induces behavioral recovery and attenuates neurochemical deficits in rodent models of Parkinson's disease, 2003, J.L. Tillerson, et al.).
The study looked at the levels of DAT, VMAT2 (vesicular monamine transporter) and TH (tyrosine hydoxalase). DAT is responsible for dopamine re-uptake in the synapse. VMAT2 is responsible for the vesicle that transports dopamine between the synapses. TH is the rate-limiting enzyme in the synthesis of dopamine. Studies have shown that people with Parkinson's have reduced levels of VMAT2. When mice were treated with the toxin MPTP significant decreases in VMAT2, DAT and TH were observed. However, as figure A shows, mice forced to run on a treadmill showed a reduced drop in DAT, VMAT2 and TH.
In addition, motor function was measured in the neurotoxin-treated mice using a forepaw test. Parkinsons-model mice running on a treadmill showed significantly better performance in motor function than sedentary mice. This suggests that exercise could be used to reduce the behavioral consequences of Parkinson's disease.
In summary, a large human study demonstrated exercise reduces risk of being diagnosed with Parkinson's disease over the next ten years. In addition, a study of mice treated with a parkinsons-inducing neurotoxin found that exercise reduced dopamine neurochemical drop and motor function. Researchers will find a cure for parkinson’s disease, but in the meantime exercise may be the only option for delaying the progression.
Men who work full time have higher levels of physical activity than healthy men who are unemployed or are employed part time. Women's physical activity and employment status are not as strongly correlated.
According to a cross sectional study published in August of 2011, employment status correlates to physical activity level. The paper, entitled Employment and Physical Activity in the U.S. (Tamara Harris, et al.), found that full-time employed men were most active.
The study broke participants into groups based on gender, employment status, and employment activity level. Employment status was defined as full time (35+ hours a week), part time (1-35 hours a week) and unemployed (excluding those who were disabled or unable to work do to health reasons). Employment activity level was broken down into active and sedentary positions. A hip accelerometer was used to determine activity level and time at which activity was performed for study participants.
The study found surprising gender differences in physical activity level. In general, men were found to have higher levels of physical activity than their female counterparts. Physical activity and employment status in men was positively correlated. Full-time employed men were the most physically active. In fact, men with full-time jobs classified as sedentary were found to have greater physical activity levels, even on weekdays, than healthy, unemployed men. Men who were part-time employed were found to have a physical activity level that was lower than full-time employed men, but higher than healthy, unemployed men.
Women, on the other hand, showed little difference between physical activity level as a function of employment status. Women employed full-time with sedentary jobs demonstrated the least amount of mean physical activity when compared to women employed part-time in sedentary jobs and healthy, unemployed women. Part-time working women, regardless of job classification, tended to be the most physically active by measurements of mean activity level and percent of time spent doing moderate to vigorous physical activity. However, differences in activity level for women tended to be minor and did not follow any overarching trends based on employment level.
Not surprisingly, both men and women with active jobs showed significantly higher physical activity levels. Employed men had higher activity levels during weekdays whereas employed women showed more consistent activity levels throughout the week. The results for the study are shown below.
In an earlier post (Stress and Telomere Length) it was mentioned that women employed full-time were found to have shorter telomeres, a sign of premature aging. In addition, exercise has been shown to activate telomerase, an enzyme that extends shortened telomeres (see Physical Activity, Stress and Telomere Length). Could shorter telomeres in women employed full-time be the result of the working women's tendency to get less physical activity, or is it a direct link to stress as the study's author's hypothesized (Employment and work schedule are related to telomerase length in Women, CG Parks, et al.)?
In summary, physical activity increases as employment increases in men, but the trend, although not as pronounced, is the opposite in women. Significant increases in physical activity are observed in people of both genders employed in active jobs.
Exercise has been shown to be comparable in remission rate and adherence rate to anti-depressant medication. However, exercise does not have the social stigma that prevents many from seeking anti-depressant medication.
Mild to moderate major depressive disorder (MDD) is a serious illness that affects many Americans. According to the Global Burden of Disease, MDD ranks second globally, only behind heart disease, in responsibility for years of life lost due to disability or premature death. According to a 1999 report from the US Surgeon General, only 23% of people inflicted with MDD seek treatment. Unfortunately, the social stigma around depression, and psychological problems in general, prevents many people from seeking treatment. This stigma is a major hurdle to getting proven pharmaceutical anti-depressant treatments out to those who need them. A small, carefully controlled study found that exercise, an activity viewed positively by society, may work as well as anti-depressant pharmaceuticals and better than cognitive therapy in curing mild to moderate major depressive disorder (Exercise treatment for depression: Efficacy and dose response, 2004).
The study, published in 2005 in the American Journal of Preventive Medicine, divided study participants with MDD into 4 experimental groups and a control group. The experimental group was separated by dosage of exercise and frequency by which that dosage was administered. The exercise dosages were the public health recommended 17.5 Cal/kg/week and a low dosage of exercise at 7.0 Cal/kg/week. The frequency by which these dosages were administered was 3 times a week and 5 times a week. The control group participated in flexibility exercise 3 days a week.
Interestingly, the frequency of exercise per a week did not affect the success of the treatment. However, dosage of exercise did. Although the public health recommended dosage of 17.5 Cal/kg/week had a success rate (47% reduction in 17-item Hamilton Rating Scale for Depression-HRSD) comparable to pharmaceutical anti-depressants, the low exercise dosage of 7.0 Cal/kg/week resulted in a success rate (30% HRSD reduction) only slightly better than the placebo (29% HRSD reduction). The results of the different dosages are shown in the figure below.
The study administered exercise dosage in a clinically controlled, individual setting to ensure validity of dosage and exclude social benefits of exercising with others. The treatments were administered for 12 weeks.
Remission rate of depression symptoms by the public health recommended exercise dose was 42%. This compares to a 42% remission rate of anti-depressant medication imipramine hydrochloride and a 36% rate of remission for cognitive behavioral therapy (R.R. Pate, M. Pratt, S.N. Blair et al. Physical activity and public health. 1995). In addition, exercise treatment has been criticized for treatment adherence. However, in this study the exercise treatment adherence (72%) compares favorably to adherence rates found in medication trials.
In summary, the public health recommended dosage of exercise treats depression as well as anti-depressant medication. However, low dosage of exercise did little better than the placebo control group. Frequency did not affect the results. Adherence rate was comparable to medication trials suggesting it could provide a viable, stigma-free alternate treatment. This study was small by many standards, 80 participants, but more research should be done to explore the alternate treatment of mild or moderate major depression disorder with exercise.
Telomeres (highlighted red in the photo to the left) are protective stretches of DNA and the end of a chromosome. Their length has been shown to shorten as a result of both age and stress. Physical activity has been shown to act as a buffer against stress-induced shortening.
In a previous post the affect of stress on telomere length was discussed. As explained in that post, telomeres are stretches of DNA at the end of chromosomes responsible for protecting the chromosome. Every time a cell divides its telomeres are shortened. In some cells an enzyme named telomerase replenishes the lost telomerase, but in other cells the telomeres gets continually shorter. Therefore, telomere length can be a good predictor of aging. Eventually, the telomere protection disappears and unprotected genetic material would get cut with each division. Usually, at this point the cell dies.
Individuals scoring high on a stress test have been shown by many studies to have shorter telomeres. For a more in depth look at the stress-telomere length studies visit this the Stress and Telomere Length post.
In 2010, a study (The Power of Exercise: Buffering the Effect of Chronic Stress on Telomere Length, Puterman E, Lin J, Blackburn E, O'Donovan, Adler N, et al.) found that the negative effect of stress on telomere length disappeared when the subject was deemed to be physically active.
The study broke subjects into groups based on physical activity reported: sedentary and physically active. Each subject completed a Perceived Stress Scale. Subjects categorized as sedentary tended to score higher on the Perceived Stress Scale. Sedentary subjects showed an inverse correlation between stress score and telomere length, confirming results found in previous studies. Surprisingly, subjects categorized as physically active (equal or more than 75 minutes of exercise per week) did not show a decrease in telomere length when stress level was increased. The relationships are shown below. Notice that the sedentary group shows a noticeably negative relationship between telomere length and perceived stress; conversely, the active group shows no relationship.
Interestingly, 75 minutes of exercise per a week is the recommendation of the Center of Disease Control and Preventions. Shorter telomeres have been shown by many studies to correlate with an increased risk of developing chronic illnesses like cancer and heart disease. Therefore, 75 minutes of weekly exercise may decrease risk of developing a chronic illness through telomere length. Although a relationship has been found between exercise and risk of developing many chronic diseases, telomere length has not been established as the pathway for exercise's effect on chronic illness risk.
The authors of the study theorized that the pathway by which exercise buffers against stress-induced telomere shortening is through telomerase activity. As mentioned above, telomerase is an enzyme that lengthens telomeres shortened by cell division. Stress has been shown to inhibit telomerase activity (Accelerated telomere shortening in response to life stress, 2004, Elissa S. Epel, Elizabeth H. Blackburn, et al.). Exercise has been shown to increase telomerase activity in mononuclear cells from rats and human leukocytes ( 2009, Physical Exercise Prevents Cellular Senescence in Circulating Leukocytes and in the Vessel Wall).
In summary, physical activity acts a buffer against the telomere shortening effects of stress. The biological pathway this may occur is through the exercise proliferation of telomerase, an enzyme responsible for extending telomeres.
Please leave any thoughts you have on this study!
Recent studies show that telomere length, a measure of cellular aging, is strongly influenced by stress.
Telomeres are stretches of DNA at the end of chromosomes responsible for protecting the chromosome. Every time a cell divides its telomeres are shortened. In some cells an enzyme named telomerase replenishes the lost telomerase, but in other cells the telomeres gets continually shorter. Therefore, telomere length can be a good predictor of aging. Eventually, the telomere protection disappears and unprotected genetic material would get cut with each division. Usually, at this point the cell dies.
Elizabeth H. Blackburn, a researcher at the University of California, San Francisco, shared the 2009 Nobel Prize in Physiology or Medicine for her work on the process of telomere shortening. Blackburn's current research is looking at telomere length and its association with risk of developing chronic diseases like cancer, heart disease and other illnesses. In addition, Blackburn's work has contributed to a growing plethora of research showing that various lifestyle decisions influence telomere length.
In the Science Talk section of the October 2011 Scientific American, Blackburn says that unpublished research shows that people with higher blood levels of omega-3 fatty acid had much less telomere shortening.
Stress has been shown to accelerate telomere shortening. A study published in August 2011 found that women who worked full-time had significantly shorter telomeres than those who were not employed (Employment and work schedule are related to telomerase length in Women, CG Parks, et al.). A study published in 2004 found a negative correlation between the number of years a woman spends raising a chronically ill child and that woman's telomere length (Accelerated telomere shortening in response to life stress, Elissa S. Epel, Elizabeth H. Blackburn, et al.). In addition, women who perceived them to be under greater stress were found to have shorter telomeres. In fact, a person under high stress could expect to see on average a 550 base pair loss in telomere length. Telomere length correlates linearly with age. This study found that the average person sees a 31-63 base pair reduction in telomere length per a year. Therefore, someone with high stress ages the equivalent of 9-17 years more than their equivalent with low stress! The results of the study are shown below:
Telomere Length v. Stress (Years Caring for Terminally Ill Child)
As the studies mentioned in this article demonstrate, a low-stress lifestyle is important for controlling cellular aging and the chronic illnesses that have been shown to be associated with shortened telomeres: cancer, heart disease. However, all hope is not lost if you are in a situation where stress cannot be controlled. In my next post on this blog I will previewing a 2010 study that found that physical activity may control the shortening effect on telomeres in people with stress.
Open window theory explains why athletes find themselves sick after a taxing bout of exercise. Let’s take a look at how open window theory was developed.
It started with a notable study led by Dr. David C. Nieman, a professor in the Department of Health, Leisure, and Exercise Science at Appalachian State University, that found 12.2% runners who participated in the 1987 Los Angeles Marathon reported an infectious episode in the week following the marathon versus 2.2% of similarly experienced runners who did not participate in the marathon. The study also found a positive correlation between weekly running mileage and infectious episodes in the two months prior to the marathon.
Dr. Nieman published the aforementioned study looking at infectious rates of Los Angeles Marathon participants and many other studies focusing on the relation between strenuous exercise and infectious disease. In 1994, Dr. Nieman offered a theoretical model for the relationship between exercise and risk of upper respiratory tract infection. The model (see inset) revealed a J-curve relationship between exercise and risk of upper respiratory tract infection. While this model provides a simplified relationship between exercise and risk of contracting an infectious disease, it did not explain biologically why such a relationship exists.
In 2000, Nieman published a follow-up paper in Immunology and Cell Biology that explained how exercise affects the human immune system. The open window theory says that the immune system is weakened for 3-72 hours following extended, strenuous exercise. Monocytes and neutrophils invade the inflamed area that results from muscle injury during exercise. Despite this neutrophilic invasion, the ability of neutrophils to phagocyte foreign invaders has been shown to be reduced following exercise in athletes (Müns 1993). In addition, salivary excretion is reduced up to 18 hours after intense exercise (Steerenberg 1997) demonstrating disruption to the body’s physiology. A 1997 study by Neiman found that natural killer cell activity is reduced after exercise. Cytokine concentration is altered by intense exercise, disturbing the body’s ability to react to and target foreign invaders. Exercise resulting in muscle soreness is linked to a stronger anti-inflammatory response. The alterations in the immune system may be an etiology for the overtraining syndrome, which is responsible for underperformance and mood distrubances in overtrained elite athletes. Nonetheless, exercise has been shown to enhance the immune system's ability to target tumors.
To prevent infectious disease around a taxing athletic event, Dr. Neiman recommends athletes take the following precautionary steps:
- Keep other life stresses to a minimum (mental stress in and of itself has been linked to increased URTI risk).
- Eat a well-balanced diet to keep vitamin and mineral pools in the body at optimal levels.
- Avoid overtraining and chronic fatigue.
- Obtain adequate sleep on a regular schedule (disruption is linked to suppressed immunity).
- Avoid rapid weight loss (linked to adverse immune changes).
- Avoid putting the hands to the eyes and nose (a major route of viral self-inoculation).
- Before important race events, avoid sick people and large crowds when possible.
- For athletes competing during the winter months, influenza vaccination is recommended.