Alzheimer's disease

Alzheimer's disease (AD), a neurodegenerative disorder, is the most common cause of dementia and characterised clinically by progressive intellectual deterioration together with declining activities of daily living and neuropsychiatric symptoms or behavioral changes. The most striking early symptom is memory loss (amnesia), usually manifest as minor forgetfulness that becomes steadily more dense with illness progression, with relative preservation of older memories. As the disorder progresses, cognitive (intellectual) impairment extends to the domains of language (aphasia), coordinated movement (apraxia), recognition (agnosia) and those functions (such as decision-making and planning) closely related to the frontal lobe of the brain, reflecting extension of the underlying pathological process. This consists principally of neuronal (cell) loss (or atrophy), together with deposition of amyloid plaques and neurofibrillary tangles. Genetic factors are known to be important, and polymorphisms (variations) in three different autosomal dominant genes - Presenilin 1, Presenilin 2, and A-Beta - have been identified that account for a small number of cases of familial, early-onset AD. For late onset AD (LOAD), only one susceptibility gene has so far been identitified - the epsilon 4 allele of the APOE gene. Age of onset itself has a heritability of around 40%.

Prevention

Efforts to find effective treatments for Alzheimer's after-the-fact have so far been disappointing. Age is the primary risk factor for Alzheimer's. The baby boom is approaching its golden years. Indeed, much of the concern about the solvency of governmental social safety nets is founded on estimates of the costs of caring for baby boomers, assuming that they develop Alzheimer's in the same proportions as earlier generations.

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Some studies have indicated that non-steroidal anti-inflammatory drugs (NSAIDs) like ibuprofen and aspirin may delay the onset, and lower the ultimate risk, of Alzheimer´s disease. According to population studies, low but consistent daily NSAID used over a period of years such as ibuprofen (Advil, Motrin) seems to slow the progress of Alzheimer's. It seems that NSAIDs may affect the onset of the disease but is of little use for treating it once it has progressed to early or full-blown Alzheimer's.

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It should be noted that some drugs such as acetaminophen, naproxen, and the 'COX-2 inhibitors' were found to have no demonstrated benefit (and some evidence of cardiac harm). This ineffectiveness and the increase in adverse cardiac events associated with these agents was reported in various studies in 2004 and highlights the key role of ibuprofen in the original studies showing moderated risk associated with NSAID use.

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A study (Archives of Neurology 2004; 61:82-88) has reported that the combination of vitamins E and C might, over time, sharply reduce the risk of Alzheimer's disease. Marked reduction (up to 80% risk reduction) was achieved after a period of more than five years, but only if dosage was 400 i.u. per day of vitamin E plus 500 mg or more per day of vitamin C. Lesser amounts, such as those found in multivitamin pills, appeared markedly less effective. Large doses of vitamin E without vitamin C had only a mild effect, while large doses of vitamin C without vitamin E had no benefit. However in one small study, 2000 i.u. per day of vitamin E did appear to delay the progression of early Alzheimer?s by several months. Other evidence suggests that vitamin E becomes a damaging pro-oxidant if given in isolation (without other antioxidants). In isolation vitamin E is not recharged after absorbing a free radical by another antioxidant such as vitamin C or Alpha-Lipoic Acid. Some studies suggest that a ratio of at least 1000 mg of vitamin C to 400 i.u. of vitamin E is ideal. Recent studies suggest that the most common forms of E sold in supplements, the dl-alpha or d-alpha tocopherol form, are of little value, and that the gamma form of vitamin E, or a mixture of all the tocopherols and tocotrienols that collectively make up vitamin E from food, provide the most benefit. Vitamin E is markedly less effective unless taken with oil.

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In a number of retrospective studies, regular physical exercise has appeared to be inversely related to the development of Alzheimer?s. The Alzheimer's risk of those exercising regularly was half that of the least active. This research is consistent with the observation that virtually all measures designed to promote cardiac fitness and reduce stroke risk also seem to reduce Alzheimer's risk. However in one study, dance appeared to be the only exercise effective in reducing risk. The presence of cardiovascular risk factors -- diabetes, hypertension, high cholesterol and smoking -- in middle age (ages 40 to 44) was found very strongly associated with late-life dementia, as reported in Neurology 2005;64:277-281.

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Improved nutritional status of the B vitamin folic acid was found to reduce Alzheimer's incidence in a study of an order of nuns, many of whom volunteered to have their mental status assessed and donated their brains for study after death. The "Nun's study" also revealed nuns who, in life, showed little or no dementia, but upon autopsy were found to have extensive Alzheimer?s plaques. The unimpaired nuns? brains were free of evidence of stroke, including micro-strokes. Nuns whose brains revealed both plaques and stroke damage, however, were severely impaired in functioning while alive. Thus avoidance of risk factors for stroke may be a key element in preventing final progression to being disabled by Alzheimer's dementia. The discovery of the co-founding role of stroke supports other research showing that quitting smoking, weight reduction, and avoidance of diabetes all reduce Alzheimer's risk. Diabetes greatly increases Alzheimer's risk, and one factor at work may be that the enzyme charged with removing excess insulin from the blood, the Insulin Degrading Enzyme (IDE), also has the responsibility for removing Beta-amyloid plaques from the brain. Perhaps the excess insulin involved in the pre-diabetic metabolic syndrome, as well as insulin used to treat existing diabetes, may demand more IDE than the body is able to produce, leaving none to remove accumulating beta amyloid plaques from the brain.

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Some evidence suggests that Alzheimer's risk may also be reduced by inclusion of certain kinds of fish in the weekly diet. Those that contain Omega 3 fatty acids are thought to most effective.

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The spice turmeric reduces Alzheimer's incidence in a mouse model and actually dissolves human senile plaques in the test tube. These factors suggest that inclusion of a bit of turmeric or curry spice in the diet may provide preventive value. Turmeric is a powerful antioxidant and a powerful anti-inflammatory. In India, where turmeric is commonly consumed in curry spices, Alzheimer's disease afflicts only approximately 1% of the elderly, whereas in the U.S. a much larger percentage are afflicted.

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There may be a connection between the cholesterol level inside the brain cells and the deposition of the toxic amyloid plaques which make the brain cells die. In addition to lowering cholesterol, the so-called statins, drugs like lovastatin, simvastatin etc., may have a beneficial role in reducing inflammation. However, retrospective studies into possible protective effects of statin drugs as a means of preventing or delaying Alzheimer´s have been inconclusive; no protective effect was found in one large prospective observational study. Arch Neurol. 2005;62:1047-1051.

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Prospective studies and well-analyzed retrospective studies show that smoking increases the risk of developing Alzheimer's. Biomed Pharmacother. 2004 Mar;58(2):95-9. The increased risk may be substantial. See, e.g., J Neurol Neurosurg Psychiatry 2000;68:622-626 (May). Cigarettes contain many substances in addition to nicotine, and the increased risks incurred by smokers are not to be confused with the controversial possible slowing of the progression of established Alzheimer's disease by administration of pure medical nicotine.

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