Prevention of Alzheimer's Disease (AD) and Possibly Other Dementias

Prevention of Alzheimer's Disease (AD)

What May Help Prevent AD and possibly other dementias?

Continued Education

Given the reduced risk of AD for persons with at least 8 years of education, it is reasonable to recommend active, regular use of thinking skills such as reading, writing and arithmetic. For example, research in the area of use-dependent plasticity has shown that persons who use language skills have larger, more elaborate connections in the areas of the brain related to language function. Also, we routinely see, clinically, patients with AD who have particular talents that are well preserved until moderately demented. A partial list of these preserved talents includes singing, sewing, reading, calculating, playing bridge, playing jazz piano, drawing cartoons, golf and tennis. The mechanism for such relative preservation of a skill even in the face of progressing AD pathology may relate to the regional activation of neuroprotective factors by the performance of the talent itself, which promotes resistance in these regions to the damage incurred by the pathological processes of AD.

Cardiovascular Exercise

The Macarthur foundation has shown that persons over 75 who do regular cardiovascular exercise for about 30 minutes daily, such as briskly walking five miles a week, perform better on a variety of measures of cognitive function. The mechanism may be related to animal models of exercise in which rats which run the most on a treadmill show the highest levels of growth factors in their brains. Growth factors generally act to protect brain cells and their processes from damage.

Estrogen Replacement Therapy

After menopause, women who are deficient in estrogen have increased risks for stroke, heart disease, osteoporosis, AD and possibly other dementias. Estrogen replacement therapy reduces the risks of stroke, heart disease, and osteoporosis. Whether such therapy also reduces the risk for developing AD and possibly other dementias is being evaluated nationally by the Women's Health Initiative. Whether estrogen use slows the rate of progression or improves some functions in AD is also being evaluated nationally by the Alzheimer's Disease Cooperative Study Unit.

Although endometrial cancer is not an issue for hysterectomized women, it is for women with a uterus. Postmenopausal women with a uterus who take estrogen have a slightly increased risk for endometrial cancer that can be reduced by concomitantly taking progesterone. There may also be an increased risk for breast cancer, but this is less clear. The benefits of estrogen replacement therapy in postmenopausal women appear to outweigh the risks when they have estrogen deficiency. Research over the past 10 years has shown that doses of up to 1.25 ug of estrogen are safe in postmenopausal women unless such doses of estrogen are specifically contraindicated.

Antioxidants

The generation of free radicals which can oxidatively damage brain cells is a response to a variety of insults which occur throughout life, and has been implicated as one of the mechanisms by which AD damages brain. In vitro studies show that neurons pretreated with free radical scavengers such as vitamins C or E are not damaged by exposure to free radicals. Clinically, antioxidants limit the amount of ischemic damage occurring during stroke. Antioxidants have also been tried in Parkinson's disease without success. The doses and types of antioxidants that may help reduce the risk of developing AD are not known, but it is known that for most people, antioxidants are safe and inexpensive. Some of the more widely known antioxidants are Vitamins C, E, and beta-carotene, gingko biloba extract, selegiline, antagonic stress, and coenzyme Q. Given current knowledge, a reasonable, inexpensive, and large dose that is safe for most people (unless there is a specific contraindication) is:

Use of anti-inflammatory Agents Plus H2-blockers

Twin studies have shown a reduced risk of developing AD in those taking anti-inflammatory medicine. This has been followed by a series of short-term anti-inflammatory therapies in AD patients suggesting some benefit. Some further recent epidemiologic studies of the association between anti-inflammatory medicine and lowered risk of developing AD have found even greater risk reduction for persons taking anti-inflammatory agents and type 2 histamine receptor blockers ( anti-ulcer medicine). The mechanism for the additive risk reduction may be that AD has an immune-mediated component of neuron damage potentially suppressible by anti-inflammatory agents, and that H2 receptor blockers reduce glutamate-mediated excitotoxic cell damage which is also postulated to be involved in AD neuropathology. The optimal doses and specific agents which best reduce risk for AD are not known, but are being investigated in clinical AD trials. Since anti-inflammatory agents can have significant side effects such as ulcer and gastrointestinal bleeding, they must be taken under physician supervision. Given the present state of knowledge, the safest dose for most people would be a single, 325 mg aspirin daily with food.

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