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DHA and Alzheimer's Disease
Docosahezaenoic acid (DHA), an omega-3 fatty acid, could be a significant preventative supplement or treatment for neurodegenerative disorders in the aging population. It is accurate to say that DHA is beneficial for the development of the human brain during its formation and throughout infancy (1). It may be deduced then, that DHA may also provide some benefit to the brain at all stages of life. As the brain ages, it begins to deteriorate, reversing the cerebral-genesis of infancy. It has been proven that the addition of DHA to the diet "can improve the cognitive dysfunction due to aging or organic brain damages" (2). It is also possible that DHA can be added as a prophylactic before aging or the onset of neurodegenerative diseases, specifically, Alzheimer's Dementia (AD) (1,3). DHA has been proven to produce significant improvements in immediate memory and attention scores in clinical tests (2). However, DHA is not a cure for the aging or Alzheimer's brain. Because Alzheimer's disease is rarely diagnosed early enough in its progression to delay rapid progression, it may be advisable to add the consumption of adequate sources of DHA to a healthy diet or to consume it in a supplement. "It is also projected that omega -3 fatty acids could be useful in the prevention of deferent pathologies, such as cardiovascular, psychiatric, neurological, dermatological, and rheumatological disorders, as well as inflammatory and autoimmune and neurodegenerative diseases" (3). DHA is a very long unsaturated fatty acid chain. The fatty acid, DHA, makes up the phospholipid layer of neural cells in the human brain (3). DHA performs several
Rebecca Hodges 3/6/08 NRT 320 Research Paper other important functions in the brain including monitoring synaptic firing and monitoring all parts of the ion channel needed for signal transfer (3). Because of DHA's impact on neural signaling, research shows that neural membrane fluidity is directly related to the concentration of unsaturated fatty acids present in the brain (3,5,7). Although necessary, the human body cannot manufacture DHA, nor can humans sufficiently synthesize it from α-linolenic acid (ALA) or eicosapentaenoic acid (EPA); it must come from diet or supplementation (1,4). Further, "National studies suggest that the Western diet is deficient in long-chain omega-3 fatty acids" (3). It is found mainly in fatty fish like salmon, herring, and tuna (3,5). Because the fish do not make the DHA, it can also be found in the plankton and algae that the fish consume (3). The population of most concern in regards to DHA consumption is infants. Infants' brains are constantly growing and developing (1,3,5). Since 2002, DHA has been deemed vital enough for infant neural development, that most formula companies now fortify their products with it (3,4). This rise in fortification resulted from many research studies confirming that DHA is positively linked to the brain development of fetuses and infants (3,5). In stark contrast to the rapidly growing brain of an infant, aging adults with Alzheimer's disease suffer extreme deterioration of the brain. It can be assumed, then, that DHA is beneficial for the maintenance of those neural cell membrane phospholipids that it helped form initially (1). The elderly are particularly susceptible to malnutrition (6). They tend to eat less and consume a smaller variety of foods (6). Many factors contribute to the development of poor nutritional habits in later adulthood (6). Physical problems such as illness, weakness, and the effect of medications negatively affect the desire to eat (6). Also,
Rebecca Hodges 3/6/08 NRT 320 Research Paper factors like low income, little person to person interaction, or restricted diets that require extra energy to prepare, deter the elderly from cooking nutritious meals for themselves (6). An elderly person's poor nutritional status is directly related to his or her health status, including mental health. A particularly important factor in healthy aging is the maintenance of cognitive function (1). In the past several years, research has been conducted regarding the benefits of DHA for the aging brain. Further, DHA has been proven to benefit AD brains as well. Alzheimer's disease is a progressive neurodegenerative disease effecting "approximately 10% of the population over the age of 65 y and 47% of the population over 80 y of age in Western countries as the leading cause of dementia" (5). This disease is "characterized by progressive loss of memory, intellectual decline, and eventually global cognitive impartment" (5). These symptoms result from "massive neuronal cell loss in the association, hippocampus and limbic regions of the human brain, and progressive loss of synaptic proteins and contacts and diminution of inter-neuronal signaling" (7). AD may begin, in some cases, as many as twenty years before diagnosis (8). During that time, nerve cell death and tissue loss begins, eventually causing the brain to shrink significantly and fluid filled spaces to increase in size (8). Researchers do not know the exact cause of AD but many are led to believe that the formation of plaques and tangles could be causes (5,8). Plaques are "abnormal clusters of protein fragments, built up between nerve cells that block cell to cell signaling at the synapses" (8). These plaques are made up a beta-amyloid, which are pieces of protein that collect and stick together, blocking synaptic transmission and the delivery of nutrients to the cell (3,8).
Rebecca Hodges 3/6/08 NRT 320 Research Paper Tangles are "twisted strands of protein of dead and dying nerve cells" (8). They are formed when the track-like structures that transport food, cell parts and other necessary materials collapse (8). Therefore, they also deprive nerve cells of needed energy and eventually kill them (1,8). This places the brain into a cycle of potentially exponential cell death. The disruption of synaptic transmission, especially in the cortex, "damages thinking, planning, and long term memory" (8). These symptoms are usually evident in the second or mid-phase of AD progression. AD is usually diagnosed during this time and may last for 2-10 years. The last stage may increasingly affect the hippocampus, and impair the "formation of new memories" (8). In addition, AD deterioration leads to decline in "language and speech, as well as of abstract reasoning and visual-spatial perception" (5). This usually marks the final and most sever stage of AD progression where the victim may have difficulty with activities of daily living. Therefore, the protection of neural connections is paramount, particularly in the aging population In many studies, "Low intake of omega-3 fatty acids is becoming increasingly associated with several forms of cognitive decline in the elderly, particularly Alzheimer's disease" (1). Pharmaceuticals are available that treat the symptoms of Alzheimer's disease like NSAID (non-steroidal anti-inflammatory drug), but do not protect the brain from further deterioration (7). Further, AD is usually diagnosed in the second or third stage of the disease. At that point, there is much damage to the brain (8). Therefore, it may be concluded that supplementation will be most effective if administered before the onset of AD (1,3). The most recent pharmaceutical research is being done on targeting bata-amyloid (3). Studies have also revealed that there is a positive link between brain function in
Rebecca Hodges 3/6/08 NRT 320 Research Paper aging adults and a decline in DHA concentration in the brain (2). Research on AD model rats has revealed that DHA consumption before the onset of AD has a "beneficial effect on the decline on avoidance learning ability associated with the increase in the corticohoppocampal DHA and ALA rats and a decrease in bata-amyloid production" (3). As previously mentioned, tangles and plaques in an AD brain cause disruptions in signal transmission between synapses (8). If beta-amyloids were effectively targeted, as DHA has been proven to do, it reduces the amount of plaque buildup, and the blockage on neural traffic pathways. More energy reaching the living cells will greatly reduce the rate of neural deterioration. Moreover, memory, attention, and learning ability improves or at the very least, slows in its rate of decline (2,7). DHA is best used as a prophylactic because neural cells, once they have lost their connections, cannot be repaired (1,3). In a study conducted by Conquer, researchers tested "DHA serum concentrations in AD patients in comparison to those with other dementias (OD), cognitively impaired but not demented (CIND), and group of elderly control subjects with normal cognitive function" (5). Conquer and her associates determined that the "DHA levels of AD patients are 17-18% lower than those of normal elderly individuals, suggesting that they have lower dietary intake of the n-3 fatty acids" (5). Researchers discovered that low fatty acid concentrations, which cause the cell membranes in the brain to destabilize, are not a result of aging but are rather due to low intake (5). Conquer concluded that low intake of DHA is a risk factor for the development of AD. Further support from resent research indicated that intake of fatty fish is "inversely correlated with the development of dementia, and in particular Alzheimer's disease, in Western countries" (5). Along with
Rebecca Hodges 3/6/08 NRT 320 Research Paper the cell membrane damage that accompanies AD, they suggested that oxidative damage could also be a possibility (5). Another study focusing on omega-3 fatty acids and exploring their complementary roles in brain function and the function of nutrition in cognitive decline was conducted by Fremantle (1). He began by informing the reader that a main function of omega-3 fatty acids, which include DHA, is to supply energy to the brain (1). That function is impaired in AD patients, as revealed by Positron Emission Tomography (PET) scans (1). In a study that researchers conducted on rats, when the rats received 8090% less DHA it resulted in lower brain DHA and a decrease in glucose uptake by 3040% (1). Impaired glucose uptake leads to brain energy starvation and cell death. Thus, impaired glucose uptake is also a risk factor for AD (1). Finally, in this study, Freemantle briefly mentions that elderly populations have difficulty converting ALA to DHA and are particularly susceptible to DHA depletion (1). An article compiled by Mazza, was an overview of the roles of fatty acids and other antioxidants and their possible therapeutic value for neurological disorders. She and her associates sighted several research studies that determined that "Omega-3 fatty acids are useful in the prevention of different pathologies including neurological disorders"(3). Two separate studies, one done by McGahon in 1999 and one conducted by Mirnikjoo in 2001, "suggest neuroprotective consequences of diets enriched in omega3 fatty acids" (3). Many other studies suggested that "High DHA consumption is associated with reduced AD risk and that DHA could represent a possible prophylactic mean for preventing the learning deficiencies of AD" (3). Further, a study by Barberger-
Rebecca Hodges 3/6/08 NRT 320 Research Paper Gateau, conducted in 2002, provided evidence to support taking fish oil supplements to slow cognitive decline and decrease one's risk of developing dementia. (3). DHA is beneficial for the maintenance of phospholipids in the human brain at all stages of life, specifically the aging population (1,2,3,7). It is proven that there is a strong link between low concentrations of DHA in the brain and the onset of AD (1,2,3,5,7). While it is not a cure for AD, DHA has been proven effective in increasing brain fluidity and supporting the transportation of nutrients to neural cells (3,5,7). Many studies, even outside the ones sighted, document the importance of DHA for the mental health of aging populations. Some studies have been unable to provide a positive a correlation between DHA and AD brains, but the positive reports far outweigh reports with less conclusive findings. "The health benefits of DHA involve learning and memory, in the protection, regeneration and repair of neurons, in reducing the effects of neuronal injury" (7). The benefits of DHA support healthy aging and can be integrated into one's lifestyle by increasing the amount of fatty fish and DHA enriched foods one eats or by supplementation (2,5). Finally, it is recommended that those taking omega-3 fatty acids to improve cognitive fluidity and function should also take antioxidants like "Vitamins E, A, and C, flavonoids, plyhenol, carotenoids, lipoic acid and co-enzyme Q," to avoid over consumption of DHA and for basic neurological health (3).
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