Vitetta
Luis Vitetta, B.Sc. (Hons), Ph.D.
offers
Professional Medicinal Suggestions
relative to Brain Aging and Medicinal Applications for
Alzheimer’s Disease
The implementation of a regime of nutrients
is found to be of vital importance
in the fight against Alzheimer’s Disease.
DISCLAIMER: This information is offered purely as a prompt suggesting the reader take whatever appropriate steps he or she deems necessary in order to acquire more complete education pertinent to Alzheimer’s Disease. To the best of my knowledge, any and all statements throughout this website have not been evaluated by the Food and Drug Administration, the AMA or any medical professional other than the author of the piece you might read or watch. Any suggestions made or product identified on this website are not intended to diagnose, treat, cure or prevent any disease.
Article Furnished by…
Literature Review 2009
Compiled by Dr. Ronald Klatz, M.D., D.O., President
and
Dr. Robert Goldman, M.D., Ph.D., D.O., FAASP, Chairman -
The American Academy of Anti-Aging Medicine (A4M)
As a Public Information Service
Nutritional Factors
Including
Antioxidants in Dementia and Anti-Aging
ABSTRACT
Both normal cognitive aging and diseases that cause dementia, such as Alzheimer’s disease (AD) and vascular dementia, can impair vital cognition in old age. Although the cognitive impairments associated with normal aging have been defined and may impair quality of life, cognitive decline with aging is believed not to be inevitable. Recent research has resulted in data identifying clinical risk factors for cognitive aging that are potentially modifiable. These new data support an emerging basis for primary and secondary prevention efforts that could achieve and maintain a vital cognitive brain in late life.
Strategies that would promote this vitality in cognition with aging include lifelong learning, social engagement, and occupational complexity. Within this framework, lifestyle modifications that include nutritional factors and antioxidant supplementation with a mind-body medicine approach to health could significantly prevent and possibly stop further cognitive decline in adults.
Keywords: Alzheimer’s Disease; vascular dementia; essential fatty acids; antioxidants; B-vitamins; folate; vitamin C; dietary macronutrients; mind-body connection.
INTRODUCTION
The longevity revolution has increased the focus on many aspects of health in aging. The older population is growing rapidly, and individuals are typically living longer with more active lives. Nevertheless, many older individuals still face late life with cognitive function changes that affect quality of life and increase mortality. Both normal cognitive aging and diseases that cause dementia, such as Alzheimer’s disease (AD) and vascular dementia, can impair vital cognition in old age. Although the cognitive impairments associated with normal aging have been defined and may impair quality of life, cognitive decline with aging is believed not to be inevitable. However, many older adults, including some centenarians, appear to avoid cognitive decline even into the eleventh decade of life. Recent research has resulted in data identifying clinical risk factors for cognitive aging that are potentially modifiable. These new data support an emerging basis for primary and secondary prevention efforts that could achieve and maintain a vital cognitive brain in late life. Strategies that would promote this vitality in cognition with aging include lifelong learning, social engagement, and occupational complexity. Within this framework, lifestyle modifications that include nutritional factors and antioxidant supplementation with a mind-body medicine approach to health could significantly prevent and possibly stop further cognitive decline in adults.
In this paper we shall discuss the aging brain and examine trends in cognitive decline, in particular, the increasing incidence of cognitively impaired people, most notably the aged. We will also consider the link between nutrition, brain function and cognitive performance, and discuss whether nutrition may play a role in the causation of cognitive decline in the elderly.
DEMENTIA AND THE BRAIN
Cognitive function is a chronic disease. We all recognize that dementia in its most chronic form, AD, is associated with multiple domains on different chromosomes, as well as the amyloid precursor protein (APP). We can actually see changes in the general level anatomy of the brain, and these are exemplified by cellular disruption mechanisms. What is particularly interesting for us, in terms of the study and the epidemiology evidence that we have, is the oxidative stress that is actually a primer of the disease.
If you think about lifestyle factors that may influence the risk of an illness like AD, you may consider high blood pressure that remains undetected, or high cholesterol that remains unmanaged. Other things that need to be considered are the increase in body mass index that persists throughout the adult life, high blood sugar, and also the most important: sedentary lifestyle. Sedentary lifestyle is an overall factor that is basically associated with mind/body medicine attitudes within the community.
Cognitive impairment is a major component of dementia syndromes, and this is what we understand is influencing the ability to function in a community. As the population ages, cognitive impairment is actually expected to increase, and when you establish an early diagnosis the benefit of that is that you have additional treatment options for that particular patient.
Clinical definitions are important because we need to identify those in the community that are suffering from a true frank dementia, from those that actually have a dementia that is associated with an increasing aging process. When cognitive impairment is greater than that found in normal aging a person will be diagnosed as having dementia, whereas normal age-associated cognitive impairment is classed as mild cognitive impairment (MCI), which is actually the most widely used term in psychiatry and in neurology. In terms of the common causes of dementia, the two overwhelming reported conditions are AD, which accounts for about 70% of cases, and vascular dementia, which comprises around 30% of the cases.
Recent data shows that the risk of dementia increases with age, and projected figures from the United States National Institutes on Health (NIH) and from a recent publication in the Journal of Neurology suggest that within two decades the baby boomers will be the predominant group in our community, and that within the next four or five decades the number of people with AD will be into the tens of millions. If these estimates prove to be true we will have a significant clinical and community problem.
Now if you look at depression and dementia, depression is significantly associated with dementia. Depression is a risk for dementia, and dementia is a mind/body medicine factor: a very important factor in terms of the lives of individuals that are in the community. Depression may be a prodrome of dementia. There is a question mark on this at the moment, however, depression could play a causal role in dementia, and dementia has numerous attenuants associated with chronic disease. The link between depression and dementia is thought to be via a glucocorticoid cascade type mechanism that affects the hippocampus.
The adult brain weighs about 3 pounds. It looks like a medium cauliflower in terms of size. The brain contains billions of neurons and trillions connections, and consumes more oxygen than any other organ in the body. It has a high concentration of easily oxidizable lipids, and a relative deficiency of antioxidant enzymes when you compare it with other tissues. It also consists of 50% of essential fatty acids. Iron and copper have been getting a lot of publicity in the last few years, and rightly so. It is though that the two minerals could play an important role in free radical generation, and free radicals have been found in high concentration in the brains of those suffering from AD.
In a study of centenarians, Thomas Perls and his study group at Boston University found that healthy cognitive function is actually a better predictor of independent functioning than physical health. This is an extremely important clue as to the fact that it is independent function at late age that may show us the factors that are required to prevent dementia. In a follow-up study on the centenarians, Perls found that a third did not have dementia, and that those with no dementia were cognitively intact. Furthermore, neuropathologic examination of the participants brains after death revealed that the brains of those with no dementia looked like the brains of 60 year olds.
Further evidence tends to show that some people are able to escape age associated disease such as AD and cerebrovascular disease by virtue of the lifestyle that they lead. Lifestyle choices associated with a reduced risk of dementia include: good nutrition, maintaining an active life, and proper anti-oxidant supplementation. There is also evidence to suggest that the brain may possess a cognitive reserve that offers people who keep their brains’ active some sort of protection from cognitive decline. Perls et al also found that dementia-free centenarians tended to weigh less, and therefore have a lower body mass index. This suggests that fat metabolism may have an important role to play as a marker for achieving a long-life without any form of dementia.
THE EFFECT OF NUTRITION
AND MACRONUTRIENTS ON
DEMENTIA AND COGNITIVE DECLINE
Fats
In an Italian study by Solfrizzi et al, it was suggested that diet plays a significant role in age related cognitive decline. This study was concerned with a Mediterranean diet, which is associated with a high consumption of fresh produce, olive oil, and essential fatty acids. Results showed that a high consumption of monounsaturated fatty acids was associated with a significant reduction in cognitive decline.
Other studies of macronutrients suggest that a high consumption of monounsaturated fats, a low saturated fat intake, and a high plant food intake, are all beneficial. Meanwhile, results of a study by Kalminj et al linked high linoleic acid intake with increased risk for cognitive impairment, and high fish consumption with reduced risk of cognitive impairment. Both linoleic acid and fish are rich sources of polyunsaturated fatty acids, however linoleic acid contains high levels of n-6 poyunsaturated acids, while fish oils are a rich source of n-3 polyunsaturated acids. Additional nutritional epidemiological data from longitudinal studies actually clouds the issue with respect to which type of essential fatty acid or which type of fat is actually protective and minimizes the risk of cognitive impairment and which type increases the risk. There are studies that have found that consuming high levels of saturated fat improves cognitive function. However, However, in those particular studies, participants were also being given supplementary antioxidants, vitamins, and minerals, so the evidence then becomes somewhat controversial.
There is a mechanistic hypothesis going around that looks at polyunsaturated fatty acids and maintains that their consumption is associated with maintaining the structural integrity of neuronal membranes, which then leads to a fluidity of synaptic membranes between neurons as well as regulation of neuronal transmission. Some neurologists doing research in this particular area think that essential fatty acids may actually be initiating neuronal transmission.
In terms of unsaturated fat consumption, that unsaturated fat consumption is probably a marker for other dietary factors, for example polyphenols. So if it really is the high consumption of olive oils that is the preventative nutrient with respect to reducing the risk of age-related cognitive decline and AD, it is probably something to do with the polyphenols present in the olive oil, and the oil itself if just a marker for that.
Epidemiological investigations actually show that there is a significant correlation between the consumption of n-3 polyunsaturated fatty acid, which are obtained from eating fish, and the development of dementia problems like AD. The Japanese are renowned for living long, healthy lives. These people meditate every day and consume fish twice a day, and many of the oldest people in the World live in Japan.
Studies of the link between AD and n-3 consumption have shown that regular fish eaters are significantly less likely to develop AD: people who ate fish just once a week were found to have a 60% lower risk of AD in a study by Morris et al; people with AD tend to have significantly lower plasma n-3 fatty acids levels than age-matched people who do not have AD or any other type of dementia. So, the evidence suggests that essential fatty acids of the type found in fish are primarily important in preventing some sort of cognitive deficit in later life.
As the all the evidence suggests that fish is good for the brain, doctors often recommend that their patients should eat fish regularly. However, it is important to remember that many types of fish are contaminated with mercury to such a degree that it may be deleterious to health. Therefore, with respect to consumption of fish, it may be prudent to advise patients that the essential fatty acids in fish can also be obtained from other sources, such as oil in salad dressings and nuts. If fish is not an option with respect to the mercury content, as it is in the North American content, it may also be worthwhile to advise patients that they need to be taking essential fatty acids in capsule form if there is any clinical sign that they are in a minor cognitive impairment state with no dementia.
Antioxidants, Vitamins & Minerals
Antioxidant supplementation often improves memory performance in aged individuals. In terms of the epidemiology, it has been shown that low serum levels of a number of B vitamins and vitamin C and folate are correlated with cognitive decline in older people. Decreasing levels of serum vitamin A have also shown the same trend.
Poor cognition has actually joined the list of adverse outcomes that are associated with hyperhomocysteinemia. With respect to this, the homocysteine/folate relationship as shown in Seshadri et al’s study of participants from the Framingham Heart Study, is actually the proof of the evidence. Results of this study showed that over the follow-up period of eight years, 10% of participants developed dementia, and 75% of these participants were diagnosed with AD. Increased plasma homocysteine levels were found to be strongly linked to dementia risk, and individuals who were found to have a plasma homocysteine level greater than 14 micromol per liter were nearly twice as likely to develop AD than those with normal levels. With today’s evidence, it appears that increased homocysteine levels are a strong independent risk factor for the development of AD or some form of minor dementia.
Some very interesting results have been obtained from studies on blueberry supplementation in rodents. Joseph et al found that blueberry supplementation led to a reversal of the effects of aging on motor behavior and neuronal signaling in senescent rodents. This is a very interesting result as blueberries are loaded with phytochemicals, and we still do not fully understand what it is that they do. Joseph found that blueberry fed mice models of AD showed no deficits in Y-maze performance and had no alterations in amyloid-beta burden. They concluded that these protective benefits appear to be derived from blueberry-induced enhancement of memory-associated neuronal signaling and alterations in neutral sphingomyelin-specific phospholipase C activity. Thus, suggesting that it may be possible to overcome genetic predispositions to Alzheimer disease through diet.
The Importance of a Healthy Diet
and Other Factors
Pharmaceutical medicine has a place in treating any form of dementia but the physician needs to be involved in an overall integrative approach for management that can enhance the medical care of that patient with dementia. Thus, it is important to discuss micronutrients, macronutrients, herbal therapies, the use of ginkgo biloba, the use of DHEA and other hormonal treatments, and more, with patients. Encourage them to eat healthily, that is try to make sure that they eat plenty of complex carbohydrates, fibers, cereals, red wine, fresh fruit and vegetables, and try to keep animal fat consumption as low as possible, as this is the type of diet that is thought to offer protection against age-related cognitive decline. This kind of a diet is also independently aging stopping, as shown by the epidemiological data of those people that actually live a long life; and by the way, only one person in two billion lives to 114, and only a handful actually die from old age. Most people actually die from a chronic disease or the complications thereof. The diet should also include a high intake of monounsaturated fatty acids from olive oil, and vitamin supplementation to correct minor deficiencies that could have an effect upon cognitive impairment. Foods containing large amounts of aluminum-containing additives should be avoided, as should aluminum from drinking water, and anything else that might add a risk to an aberrant process. So, a healthy diet, antioxidant supplements, and the prevention of nutritional deficiencies, could be considered the first line of defense against the development and progression of any form of dementia.
OXIDATIVE STRESS AND DEMENTIA
If the number of reactive oxygen species (ROS) present in a cell exceeds the antioxidant capacity of the cell, it is in a deleterious state of condition known as oxidative stress. The evidence tends to suggest that oxidative stress in the brain is a source of neuronal damage. In terms of oxidative damage and oxidative reactions, what is actually going on is that the ROS are actually damaging the cellular membrane in terms of reacting with that cell membrane through lipid peroxides. Mitochondria have been touted as being at the center of aging, and at the center of chronic diseases like dementia and AD. Just 1% of the mitochondrial electron flow leads to free radical formation, and this 1% produces the superoxide radical, or 02-, as a result of the process of converting oxygen to energy. If you interfere with that electron process, you skyrocket the amount of free radicals that are actually being produced.
Cells actually possess quite a few mechanisms that actually balance this reaction out and the superoxide radical is actually converted to hydrogen peroxide. However, hydrogen peroxide can actually give rise to the hydroxyl radical, which is a much more potent free radical, and it can cause havoc for DNA, RNA, proteins, and carbohydrates, as well as lipid membranes. If you look at free radical formation with respect to the risk of producing an abnormal cell, you are looking at DNA damage, and there are the biological antioxidants that we recognize, such as glutathione, and the vitamins and carotenoides, that can actually limit the harm caused by oxidative damage. There are a number of different systems that are associated with free radicals and oxidative stress. The body itself has numerous mechanisms to mop up the free radical activity that is actually being produced. What is significant though is that if you are under an excessive amount of physical stress, you could actually exceed the capacity of these antioxidants to balance the free radicals and be in a synthetic state of oxidative stress. An unchecked excess of ROS species can actually lead to the destruction of cellular components, and this can then lead to cell death and necrosis.
In vitro studies implicate the ROS in neuronal death; however, we do not really have any clear in vivo evidence, although, markers for oxidative stress have been found in neurofibrillary tangles (NFTs) and senile plaques present in the brains of AD sufferers. Furthermore, significantly increased levels of 8- hydroxyguanine (8-OHG), the most prominent marker of DNA oxidation, have been found in the cerebrospinal fluid (CSF) of patients with AD.
Changes in the cellular balance of certain transition metals, in particular iron and copper, have also been implicated in the etiology of AD and other neurodegenerative diseases. Researchers are currently studying clioquinol, an old antibiotic that actually sequesters iron and copper from the brain as an alternative treatment for patients with AD.
So the questions that we ask in terms of our research domain, are: Can antioxidants actually prevent wear and tear on human cells? And if so, can this affect aging of the brain? Furthermore, are we able to actually show that we are displaying an age-related deficit if we don’t have the adequate amounts of antioxidants, and is this actually manifested as a cognitive and minor performance aberration in those patients that have got an underlying disease?
MIND-BODY MEDICINE
You cannot improve dementia, and you cannot improve chronic disease until you talk about the mind-body medicine approach. The mind-body medicine approach is associated with the stresses in life, and there are very few, if any, people out there who can honestly say that they have not got any stress. The major stressors in life are associated with doing your job, changing jobs, moving house, breaking up a relationship, and the death of a loved one: all of these are major stress factors. In terms of mind-body medicine this is really interesting because it is not just about what you eat; and with respect to actually eating all the right food, there is always somebody out there that is going to stress you, that is going to cause to actually get something. So, when you look at mind-body medicine, what is the definitive point?
It is the brain. The brain is at the center of health. It is the conductor of the body orchestra. If the brain is happy, the rest of the body is happy as well. There are enormous amounts of data to show that stress and certain forms of minor cognitive impairment associated dementia are associated with a bidirectional flow of information between the brain, the nervous system, the hormonal system, and the immune system. When we look at the cause of disease, it is a balance between stress and pleasure. Obviously, there are other factors associated with it: whether you smoke or you don’t smoke; whether you are overweigh or not; whether you have got the genetic background; and so on. So, there are multiple factors.
The critical one to associate in terms of a mind-body medicine approach is that balance between the stressors in life and the pleasures in life. A good example is cancer. A number of studies have shown that there is an increased cancer incidence in those that are depressed and those that have multiple life stressors on a continuous basis. Osteoporosis is something else that is associated with that, as is platelet function. Platelet function is associated with stress as well as numerous other factors, but stress is up at the top. In terms of heart disease, the epidemiological data says that if you are a stressful person, you are at increased risk of heart attack. Stress is also a predetermining significant factor for AD. It alters brain structures. It affects dendrites. It atrophies the areas in the hippocampus. There is some evidence to suggest that stress can actually kill neurons.
So what can be done to solve this problem? With regards to heart disease or a minor cognitive impairment there is a sort of reversal program that patients can actually partake in. This includes going to stress management classes, taking up meditation and yoga, taking regular exercise, and eating a low-stress diet: that is a diet that is low in saturated fats, low in animal fats, and high in vegetables and fish.
CONCLUDING REMARKS
Mind-body medicine is at the center of health. It is what determines what we do with the hand. The hamburger that we pick up and put to the mouth is not an automatic action. This is a conditioned action. The cigarette that you put in your mouth is a conditioned action. As a matter of fact, some great research in the US showed that if you give depressed patients an antidepressant, they actually stop smoking quicker. So the mind is hugely important.
Get some sunlight in your life. That does not mean go out and burn your skin, just get some sunlight. It improves serotonin levels. Exercise and walk rather than go up the escalator. Go up the stairs. Drink red wine with meals, red wine contains potent phytochemicals. Eat non-mercury-polluted fish daily. Eat dark chocolate: it’s an antidepressant. Last year a group from Australia published an article, a leading article in the American Journal of Psychiatry where they showed that actually dark chocolate was more effective at treating depression than Zoloft®. This probably has something to do with the antioxidant effect of the cocoa and extra phytochemicals. Take supplementary folic acid, as well as other antioxidants. Folic acid is a potent genetic corrective agent, and is hugely important in health and maintaining health in order to prevent disease rather than actually cure it. None of these things are cures. These are all preventative approaches that can help to thwart the adverse outcome. If you want to talk anti-aging, and you want to talk about stunting dementia indefinitely, one needs to be thinking out of the box, not within it.
REFERENCES
Conquer JA, Tierney MC, Zecevic J, Bettger WJ, Fisher RH. Fatty acid analysis of blood plasma of patients with Alzheimer’s disease, other types of dementia, and cognitive impairment. Lipids. 2000;35:1305-1312. ABOUT THE AUTHOR Dr. Luis Vitetta is the Director of Research for the Swinburne University Graduate School of Integrative Medicine, Melbourne, Australia. Dr. Vitetta is an Honors Graduate from Monash University (1981) in the Department of Biochemistry/Faculty of Medicine, and a PhD Graduate from the University of Melbourne (1985) and the Faculty of Medicine’s Department of Surgery (Austin & Repatriation Medical Centre) where he studied the epidemiological and etiological factors of biliary disease. He was a Senior Research Associate with the University of Melbourne’s Faculty of Medicine/Centre for Palliative Care at Caritas Christi Hospital and St Vincent’s Hospital. Prior to that, he was a University of Melbourne Research Fellow with the Faculty of Medicine and the Department of Surgery at the Austin & Repatriation Medical Centre. His interests are predominantly in clinical epidemiology. He has collaborated extensively in numerous epidemiological projects related to chronic diseases, such as large bowel cancer, breast cancer, and skin cancer. His interests include nutrition, immune system function, and mind/body medicine. You may wish to return to…
Joseph JA, Denisova NA, Arendash G, Gordon M, Diamond D, Shukitt-Hale B, Morgan D. Blueberry supplementation enhances signaling and prevents behavioral deficits in an Alzheimer disease model. Nutr Neurosci. 2003;6:153-162.
Kalmijn S, Feskens EJ, Launer LJ, Kromhout D. Polyunsaturated fatty acids, antioxidants, and cognitive function in very old men. Am J Epidemiol. 1997;145:33-41.
Morris MC, Evans DA, Bienias JL, Tangney CC, Bennett DA, Wilson RS, Aggarwal N, Schneider J. Consumption of fish and n-3 fatty acids and risk of incident Alzheimer disease. Arch Neurol. 2003;60:940-946.
Solfrizzi V, Panza F, Torres F, Mastroianni F, Del Parigi A, Venezia A, Capurso A. High
monounsaturated fatty acids intake protects against age-related cognitive decline. Neurology. 1999;52:1563-1569.
