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Aging-Associated Mental Impairment Protocol Recommended
Products: Numerous published studies indicate that brain aging can be controlled, at least in part. Some of these research findings demonstrate a preventive effect, whereas others show a benefit in reversing the neurological impairment caused by normal aging or by an age-related condition such as having had a stroke. Conventional medicine has little to offer for people who notice a small decline in their memory or mental abilities. Often these changes are attributed to being a natural or inevitable part of growing old. Alternative physicians advocate that people should take responsibility for their own intellectual health as soon as possible, certainly before minor symptoms progress to a pathological illness. This protocol has been designed specifically for persons who are experiencing age-associated mental impairment due either to aging itself or to an age-related disease. Fortunately, there are easy-to-follow lifestyle changes that can significantly help. Younger people, or parents who are concerned about possible cognitive deficits in their children, should consult the Attention-Deficit Disorder protocol.
Cognitive impairment has a variety of forms, including short-term memory loss, senility, and dementia. Dementia is a general term for diseases involving nerve cell deterioration. It is defined as a loss in at least two areas of complex behavior such as language, memory, visual and spatial abilities, and judgment that are severe enough to interfere with a person's daily living. Dementia, the most serious form of age-associated mental impairment, is often a slow, gradual process that may take months or even years to become noticeable. Symptoms vary depending on which areas of the brain are affected. It is important to make a distinction between normal, age-associated mental impairment and conditions such as dementia that signal a disease process. Not all memory difficulties or cognitive complaints indicate the presence of Alzheimer's disease or other mental disorders. Many memory changes are temporary and are linked to environmental factors such as stress rather than to physiological (bodily) processes. Neurological diseases such as dementia manifest most commonly in the elderly. The good news is that many of the underlying reasons for why people experience memory loss and other neurological disturbances are correctable. Any one or a combination of the following factors can cause age-associated cognitive dysfunction: The damaging effects
of chronic inflammation causing injury to both cerebral blood vessels
and neurons (brain cells). Take Steps to Preserve Your Mental Function You do not have to remain helpless while your mental acuity deteriorates. Even taking relatively simple steps can help protect your brain cells from the negative effects of aging. If you already have a significant decline in cognitive function, there are still ways that may partially reverse these effects. For instance, a study in the Proceedings of the National Academy of Sciences evaluated the effects of supplemental acetyl-L-carnitine and lipoic acid on the brains of old rats (Liu et al. 2002). Supplementation with acetyl-L-carnitine and lipoic acid resulted in improved memory. Electron microscopic studies in the hippocampus region of the brain showed that acetyl-L-carnitine and lipoic acid reversed age-associated mitochondrial structural decay. The conclusion of the scientists who conducted this study was that "these results suggest that feeding acetyl-L-carnitine and lipoic acid to old rats improves performance on memory tasks by lowering oxidative damage and improving mitochondrial function." This study, published in one of the world's most respected scientific journals, confirms that age-associated cognitive impairment and mitochondrial structural dysfunction can be reversed. Acetyl-L-carnitine and lipoic acid are sold as expensive drugs in Europe, but are available as dietary supplements in the United States at a relatively low cost.
An extensive review concerning the multiple effects of glyceryl-phosphorylcholine (GPC) appeared in the journal Mechanisms of Ageing and Development (Parnetti et al. 2001). The analysis covered 13 published clinical trials, which examined 4054 patients with various forms of brain disorders, including adult-onset cognitive dysfunction; Alzheimer's disease; stroke; and transient ischemic attack (TIA). Overall, the consistent finding was that "administration of GPC significantly improved patient clinical condition." According to Parnetti et al. (2001), the effects of glyceryl-phosphorylcholine (GPC) were superior to the results observed in the placebo groups, especially with regard to cognitive disorders related to memory loss and attention deficit. They noted that the therapeutic benefits of GPC were superior to those of acetylcholine precursors used in the past, such as choline and lecithin. However, what most impressed the researchers were data indicating that GPC helps facilitate the functional recovery of patients who have experienced a stroke. Brain aging is partially characterized by neurotransmitter deficiency, along with a structural deterioration of neurons and their connective transmission lines (axons and dendrites). Because research indicates that GPC may be of benefit in helping to prevent these pathological events, it may thus be possible to protect against underlying causes of brain aging while partially restoring cognitive function. Although sold as a prescription drug in European countries, GPC is available in the United States as a dietary supplement. Typical daily doses of GPC range from 600-1200 mg.
About 95% of cellular energy production occurs in the mitochondria, the cell's energy powerhouses. Many diseases of aging are increasingly being referred to as "mitochondrial disorders." Brain cells require a high level of energy metabolism to properly function. Acetyl-L-carnitine is a biologically active amino acid involved in the transport of fatty acids into the cell's mitochondria for the purpose of producing energy. Studies indicate that acetyl-L-carnitine can slow neurological aging. As discussed earlier in this protocol, supplemental acetyl-L-carnitine and lipoic acid have been shown to reverse certain parameters of brain aging in rats. One of the most potent mitochondrial energizers is coenzyme Q10 (CoQ10). When CoQ10 is orally administered, it is incorporated into the mitochondria of cells throughout the body where it facilitates and regulates the oxidation of fats and sugars into energy. Scientists have researched the effects of CoQ10, discovering exciting findings. The following are highlights from a study in the Proceedings of the National Academy of Sciences (Matthews et al. 1998): When CoQ10 was administered
to middle-aged and old rats, the level of CoQ10 increased by 10-40%
in the cerebral cortex region of the brain. This increase was sufficient
to restore the levels of CoQ10 to those seen in young animals. Based on the types of brain cell injury that CoQ10 can provide protection from, the scientists suggested that CoQ10 might also be useful in the prevention or treatment of Huntington's disease and ALS. It was noted that, while vitamin E delays the onset of ALS in mice, it does not increase survival time. CoQ10 was suggested as a more effective treatment strategy for neurodegenerative disease than vitamin E because survival time was increased in mice treated with CoQ10 (Matthews et al. 1998). CoQ10 might also be effective in the prevention and treatment of Parkinson's disease. One study reported that the brain cells of Parkinson's patients have a specific impairment that causes the disruption of healthy mitochondrial function. It is known that a "mitochondrial disorder" causes cells in the substantia nigra region of the brain to malfunction and die, thus creating a shortage of dopamine (Shults et al. 1997). Another interesting finding was that CoQ10 levels in Parkinson's patients were 35% lower than age-matched controls. This deficit of CoQ10 caused a significant reduction in the activity of enzyme complexes that are critical to the mitochondrial function of brain cells affected by Parkinson's disease. An impressive study showed that high-dose CoQ10 supplementation slows the progression of Parkinson's disease by 44% (Shults et al. 2002). The ramifications of these studies are significant. Parkinson's disease is becoming more prevalent as the human lifespan lengthens. The study by Shults et al. (2002) confirms the results of previous studies that Parkinson's disease may be related to CoQ10 deficiency. The conclusion of the scientists was that "the causes of Parkinson's disease are unknown. Evidence suggests that mitochondrial dysfunction and oxygen free radicals may be involved in its pathogenesis. The dual function of CoQ10 as a constituent of the mitochondrial electron transport chain and a potent antioxidant suggest that it has the potential to slow the progression of Parkinson's disease" (Shults et al. 2002). (See the Parkinson's Disease protocol for more information about this study.) Levels of CoQ10 decrease with aging. This depletion is caused by reduced synthesis of CoQ10 in the human body along with increased oxidation of CoQ10 in the mitochondria. Therefore, a CoQ10 deficit results in the inactivation of enzymes needed for mitochondrial energy production, whereas supplementation with CoQ10 preserves mitochondrial function. Compared to the levels of CoQ10 present in young human adults, CoQ10 levels in older individuals are at only 50% of that of young adults, thus making CoQ10 an important nutrient supplement for aging persons.
When it comes to providing protection for the brain and encouraging overall brain health, DHA may be the more important fatty acid. Studies found that DHA supplementation significantly decreased the number of reference memory errors and working memory errors in aged male rats as well as in young rats (Gamoh et al. 1999, 2001). Fish has long been referred to as "brain food," and scientific studies reveal that the oil of cold-water fish (high in omega-3 fatty acids such as DHA) functions via a variety of mechanisms to protect against common neurological impairments. Hormone Deficiency Impairs Memory The brain requires youthful levels of certain hormones to facilitate cell energy metabolism, maintain proper levels of acetylcholine, and protect brain cell membrane function. As a result, aging persons often require some hormone replacement to achieve the requisite levels. DHEA improves brain
cell activity and enhances memory. The daily production of DHEA drops
from 30 mg at age 20 to less than 6 mg at age 80. DHEA is naturally
synthesized in abundance in young people from pregnenolone in the brain
and the adrenal glands. Current findings suggest that DHEA enhances memory by facilitating the induction of neural plasticity, a condition that permits the neurons (nerve cells of the brain) to change in order to record new memories. Studies have shown that DHEA not only improves memory deficits, but also relieves depression in older people and increases their perceived physical and psychological well-being. DHEA has been shown to help preserve youthful neurological function. DHEA also helps to maintain the ability of brain cells to store and retrieve information involved in short-term memory. (Note: Some persons should not take supplemental DHEA. For complete information about DHEA, refer to the DHEA Replacement Therapy and Precautions protocol.) A thyroid hormone deficiency can also cause neurological disturbances that physicians often attribute to other health problems. Some symptoms caused by low thyroid hormone are poor concentration, memory disturbances, and depression. Many cases of thyroid deficiency are not diagnosed because of faulty laboratory blood reference ranges. For updated information about how to determine if you are thyroid hormone deficient, see the Thyroid Deficiency protocol elsewhere in this volume.
Another article in the journal Brain Research described an experiment using mice with surgically removed ovaries. The administration of both 17-beta-estradiol and estrone improved retention in a test of foot-shock avoidance in a T-maze. The authors concluded that these findings support the concept that estrogen improves memory by potentiating the activity of the cholinergic and glutamatergic systems (Farr et al. 2000). The benefits of estrogen to the brain have long been known. However, the increased risk of breast cancer, heart attack, and other diseases associated with using estrogen drugs is motivating some women to change to DHEA (which converts to estrogen in the body) and, when necessary, to safer forms of estrogen such as estriol. For information about the optimal modulation of estrogen levels in aging women, refer to the Female Hormone Replacement Therapy protocol in this book.
One protective mechanism provided by testosterone is against Alzheimer's disease: brain cells are protected from a toxic peptide called beta-amyloid, which can accumulate in certain regions of an aging brain. Beta-amyloid has been implicated in the development of Alzheimer's disease. An article in Brain Research describes a study in which cultured neurons were exposed to beta-amyloid in the presence of tes-tosterone. The resulting toxicity from beta-amyloid was significantly reduced by testosterone (Pike 2001). Other researchers have discovered that testosterone decreases the secretion of harmful beta-amyloid and increases the secretion protective cell substances, indicating that testosterone supplementation in elderly men may be beneficial in the treatment of Alz-heimer's (Godenough et al. 2000; Gouras et al. 2000). Researchers in Oxford (England) found that lower levels of testosterone were present in men with Alz-heimer's disease as opposed to controls (Hogervorst et al. 2001). The authors recommended further studies to determine whether low levels of total testosterone precede or follow the onset of Alzheimer's disease. A consistent finding in the scientific literature is that testosterone replacement therapy produces an increased feeling of well-being. Low testosterone correlates with symptoms of depression and other psychological disorders (Moger 1980; Barrett-Connor et al. 1999; Rabkin et al. 1999; Schweiger et al. 1999; Seidman et al. 1999). Physicians can prescribe natural testosterone replacement therapies. A 12-month clinical trial using an FDA-approved natural testosterone drug resulted in a statistically significant reduction in the depression score (6.9 before versus 3.9 after). Also noted were highly significant decreases in fatigue: from 79% before the patch to only 10% after 12 months (Androderm Testertosterone Transdermal System 1997). An article by Cherrier et al. (2001) described a randomized, double-blind, placebo-controlled study of 25 healthy volunteers aged 50-80 years. Participants received weekly intramuscular injections of either 100 mg testosterone enanthate or placebo (saline) for 6 weeks. Circulating total testosterone was raised an average of 130% from baseline at week 3 and 116% at week 6 in the treatment group. Estradiol increased an average of 77% at week 3 and 73% at week 6 in the treatment group. The treatment group had significant improvements in cognition for spatial memory (recall of a walking route); spatial ability (block construction); and verbal memory (recall of a short story) compared with baseline and the placebo group. The results suggest that short-term testosterone administration enhances cognitive function in healthy older men (Cherrier et al. 2001). However, it should be noted that sharp increases in estradiol are not good for men. What happens is that in response to the testosterone increase, the body converts (aromatizes) excess testosterone into estradiol (an estrogen). When a blood test reveals excess estradiol, the use of an aromatase-inhibiting drug such as Arimidex can block the rise in estradiol and thus enable the dose of testosterone to be reduced. Life Extension does not recommend testosterone injections. Natural testosterone patches, gels, or creams provide a consistent supply of testosterone through the skin and avoid the "spike" associated with testosterone injections. (For a complete explanation, refer to the Male Hormone Modulation protocol.) According to Jonathan Wright, M.D. (co-author of Maximize Your Vitality & Potency) , these effects have been reported in response to low testosterone levels (Wright et al. 1999): Loss of ability
to concentrate
Melatonin supplements easily enter the brain from the bloodstream. Melatonin is the primary regulator of brain cell synchronization (the body's internal clock) and is being researched as a possible treatment for various psychological conditions. Abnormally low levels of melatonin have also been discovered in patients who experience certain types of depression. The suggested level of melatonin supplementation for enhancing neurological function in those over age 35 is 300 micrograms to 3 milligrams a night, taken a half hour before going to bed (melatonin has a sedative effect). Those over age 50 can take up to 6 milligrams before bedtime.
One study determined that low folate levels (a B vitamin) are not only associated with cognitive deficits, but that patients treated with folic acid for 60 days showed a significant improvement in both memory and attention efficiency (Fioravanti et al. 1997). In a 6-year study to determine the relationship between nutritional status and cognitive performance in 137 elderly people, several significant associations were observed between cognition and vitamin status. Higher present and past intake of vitamins A, C, E, and B complex were significantly related to better performance on abstraction and visio-spatial tests (La Rue et al. 1997). In addition to a direct effect, vitamins indirectly impact mental function by altering the levels of harmful or beneficial substances in the body. For instance, elevated homocysteine levels have been linked to heart disease and poorer cognitive function. Studies show that vitamin B6 and folate taken at higher than recommended dosages reduced blood levels of homocysteine. One study revealed that less-than-optimal levels of vitamin B6, B12, and folic acid lead to a deficiency of S-adenosylmethionine (SAMe). SAMe deficiency can cause depression, dementia, or demyelinating myelopathy (a degeneration of the nerves) (Abou-Saleh et al. 1986). A typical American diet does not always provide enough essential vitamins. Because vitamin C and the B complex are water soluble and are rapidly excreted from the body, they must be replenished daily. Older persons are at greater risk for vitamin deficiency because they tend to not eat a variety of foods, although their requirements for certain vitamins such as B6 are actually higher. Older persons may also have problems with efficient absorption of nutrients from food. Often even healthy older persons exhibit deficiencies in vitamin B6, vitamin B12, and folate, as well as zinc. An article in the journal Psychopharmacology described a study of 76 elderly males who were given vitamin B6 versus placebo in relation to memory function. The authors concluded that vitamin B6 improves the storage and retrieval of information in the elderly patient (Deijen et al 1992). Another article that appeared in the Annals of Internal Medicine reviewed vitamin B12 deficiency in the elderly population relative to memory impairment and neuropathy. The authors concluded that both memory problems and neuropathy have been treated successfully with vitamin B12 injections or supplementation. (Carmel 1996) Additionally, an article in the New England Journal of Medicine reviewed subclinical vitamin B12 deficiency and the resulting neurological symptoms. The author stated that many common difficulties, such as memory loss, muscle weakness, and parasthesias, might well be a product of vitamin B12 deficiency without accompanying macrocytosis or other clinical indicators (Lindenbaum et al. 1988). Methylcobalamin is a coenzyme form of vitamin B that has been identified to protect against neurological disease associated with aging. The sublingual form of methylcobalamin is better absorbed because it does not become bound to food. Because most sources of B12 are from protein (meat products), vegetarian diets may be lacking in this vitamin.
A study in the Journal of the American Geriatric Society compared groups of older people over time and at a given time with regard to antioxidant intake and memory performance. The study found that free recall, recognition, and vocabulary were significantly related to vitamin C and beta-carotene levels. The levels of these antioxidants were found to be significant predictors of cognitive function even after adjusting for possible confounding variables (Perrig et al. 1997). For protection from the many types of free radicals to which it is vulnerable, the brain needs a wide variety of antioxidants. To Protect the Cerebral Blood Flow Vinpocetine Vinpocetine, an extract from the periwinkle plant, was introduced 24 years ago in Europe for the treatment of cerebrovascular disorders and symptoms related to senility. Since then, throughout the world, vinpocetine has been increasingly used in the treatment of cognitive deficits that are related to normal aging. The biological actions of vinpocetine initially demonstrated that vinpocetine enhanced circulation and oxygen utilization in the brain; increased tolerance of the brain toward diminished blood flow; and inhibited abnormal platelet aggregation that can interfere with circulation or cause a stroke. Vinpocetine also enhances cyclic GMP levels in the vascular smooth muscle, leading to reduced resistance of cerebral vessels and increased cerebral blood flow. The effect of vinpocetine on memory functions was studied in 50 patients with disturbances of cerebral circulation. Improvement of cerebral circulation was observed after vinpocetine was administered. Blood flow was increased most markedly in the gray matter of the brain. After 1 month of vinpocetine treatment, improvement of memorizing capacity evaluated by psychological tests was recorded. Longer-term use was associated with alleviation or complete disappearance of symptoms of neurological deficit. No side effects attributable to the drug were observed. The physicians stated that vinpocetine was indicated in the treatment of ischemic disorders of the cerebral circulation, particularly in chronic vascular insufficiency (Hadjiev 1976). Other studies also demonstrate that vinpocetine functions via several mechanisms to protect against the effects of brain aging. In a study to ascertain how vinpocetine boosts cognition, scientists measured the electrical firing effects in the neurons of anesthetized rats. The administration of vinpocetine produced a significant increase in the firing rate of neurons. The scientists also noted that the dose of vinpocetine used to increase electrical firing corresponded to the dose range that produced memory-enhancing effects. These results provided direct electrophysiological evidence that vinpocetine increases the activity of ascending noradrenergic pathways and that this effect can be related to the cognitive-enhancing characteristics of the compound (Gaal et al. 1990). Additionally, vinpocetine has been shown to protect against oxidative damage from beta-amyloid, which may make it clinically useful for Alzheimer's disease (Pereira et al. 2000). Another study suggests that the antioxidant effect of vinpocetine might contribute to the protective role exerted by the drug in reducing neuronal damage (Santos et al. 2000). The molecular evidence indicates that the neuroprotective action of vinpocetine is related to the ability to maintain brain cell electrical conductivity and to protect against damage caused by excessive intra-cellular release of calcium and sodium (Bonoczk et al. 2000; Solntseva et al. 2001). In a double-blind
clinical trial, vinpocetine was shown to effect significant improvement
in elderly patients with chronic cerebral dysfunction: 42 patients received
10 mg of vinpocetine, three times a day for 30 days, and then they received
5 mg of vinpocetine, three times a day for 60 days. Placebo tablets
were given to another 42 patients for the 90-day trial period. Patients
taking vinpocetine scored consistently better in all evaluations of
the effectiveness of treatment, including measurements on the Clinical
Global Impression (CGI) scale, the Sandoz Clinical Assessment-Geriatric
(SCAG) scale, and the Mini-Mental Status Questionnaire (MMSQ). There
were no serious side effects related to the treatment drug (Balestreri
et al. 1987).
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These statements have not been evaluated by the FDA. These products are not intended to diagnose, treat, cure, or prevent any disease
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