Prevention

Many companies are examining compounds that can contribute to a neuroprotection format. Forest and Lundbeck are expanding beyond memantine, and Ceregene, Allon Therapeutics, Johnson & Johnson, and Memory Pharma are all working on this. Somewhat overlapping are the efforts to find agents that enhance memory. There are a number of companies working in this area: Helicon, Sention, NeuroSearch, Memory Pharmaceuticals, Abbott, and Schering-Plough. However, as Bart De Strooper, a major plaque researcher in the Netherlands, said (2/1/05), "The main purpose of a medicine will be to salvage as many brain cells as you can by halting the progress of the disease in the areas of the brain where it has already developed, and by preventing plaque from forming in the parts of the brain they have not yet affected."

There isn't much that is powerful for prevention yet. No medications have consistently positive results for prevention of dementia in people who have Mild Cognitive Impairment, the most likely target group for intensive prevention efforts (Kirshner HS Mild cognitive impairment: to treat or not to treat. Current Neurology and Neuroscience Reports 2005 Nov;5(6):455-7).

Many people overlook the very basic prevention factor of protecting the brain. Wear your seatbelt (and a helmet for speed sports such as biking or skiing). Head injuries increase the risk of Alzheimer's. Make your living space safe with respect to the chance of falling down. As with many disease prevention regimes, you manage your diet and exercise. Regular physical exercise may be the most powerful risk-reduction correlate. S. Rovio, Kivipelto and others at the Aging Research Center's Division of Geriatric Epidemiology, in the Karolinska Institutet, Stockholm, Sweden concluded that "Regular physical activity [through mid-life, at least twice a week] may reduce the risk or delay the onset of dementia and AD, especially among genetically susceptible individuals." (Lancet Neurol. 2005 Nov;4(11):705-11.). Even if you don't have diabetes there may be good reason to limit the peaks of insulin so that they don't over-burden the insulin-degrading enzyme that might be involved in limiting the accumulation of beta-amyloid in the brain. Some people think that timing a bit of exercise with those peaks (such as after dinner) gives an extra advantage to exercise. It is possible that the relationship between physical exercise and risk reduction is mediated by the general (or other specific) habits, such as mental activity, that characterize the people who do a lot of physical exercise.
(Update: In their more recent work, published in Lancet Neurology, the Kivipelto group used logistic regression statistical methods to determine that the risk of dementia in middle aged people is related to 7 factors (age, male sex, low education level, obesity, hypertension, high cholesterol, and lack of exercise).

Recent research on the "Mediterranian diet" indicates some protective effect (See research by n. Scarmeas). That diet involves lots of fruits and vegetables, some fish, red wine, not much dairy or red meat. A substantial portion of dietary prevention of AD may come from prevention of circulatory problems. Eat foods that have lots of antioxidants (blueberries, broccoli, beets, spinach, raisins, red grapes, kale, oranges, almonds, curry). Get your protein from foods with good fatty acids (tuna, salmon - probably all the fish with fins that swim deep in the ocean, almonds). In a prospective study with a large sample (n=2273), a 3-year follow-up indicated that moderate alcohol consumption might be protective, particularly 3-4 glasses of wine a day. Orgogozo et al Rev Neurol, 153:185-192, 1997. Take folic acid and vitamin E (and, most recently reported, Niacin) but avoid excess. Vitamins mostly prevent vitamin deficiency, and that doesn't take much.

Develop your memory abilities by practicing mneumonics, word games, crossword puzzles. There are now many sets of special, supposedly specific mental training practice tools; these may be quite valuable, if you need the structure and don't get out socially (e.g. Keep Your Brain Alive: 83 Neurobic Exercises by Lawrence Katz or Reversing Memory Loss by Vernon Marks), but don't expect them to be better than any routine of very active mental activity. Have a lot of social conversation, read, learn new words, play mentally challenging games. Your connections to friends are more important to your brain health than you might think. Get out and talk to people, and this may also help manage any depression. Tell your doctor about any depression you experience and she/he can help you manage it better.

Watch for news about an Alzheimer's vaccine. Actually, such news will be hard to avoid. There are several efforts in progress to develop a vaccine.

Statins and good blood pressure management may have the most significant prevention effects for strokes and with mixed (partially vascular) dementia but also may, second to regular exercise, be the most powerful prevention agents available for Alzheimer's.

Non-steroidal antiinflammatory drugs These drugs include such common over-the-counter medications as aspirin, ibuprofen (Motrin, Advil), and naproxen (Naprosyn), but not acetaminophen (Tylenol). Inform your doctor about using any of these for Alzheimer's prevention, even if you get them without a prescription, because of the serious side effect risks (such as internal bleeding). They might have a symptom-delaying effect, if used regularly for at least a couple of years. Prednisone, however, doesn't seem to help.
Stewart et al, Neurology, 626-632, 1997.
Alsen et al, Neurology, 54, 588-593, 2000.

Vitamins/Antioxidants
Vitamin E, Vitamin C and Niacin may have usefulness in the delay or prevention of cognitive decline (Masaki et al, Neurology, 54, 1265-1272, 2000). However, the fads keep changing from folate to vitamin C to B-12. The extent to which a group study's results can be translated into a recommendation for an individual is a complicated matter. Vitamins basically prevent vitamin deficiency. The utility of vitamins is uncertain for other purposes, because the theory behind their use (free radicals, oxidation, and aging) is used to justify all kinds of hype and the very legitimate tests of its value have to be gleaned out of the mess of unjustified claims. We think the data show that vitamin E and C have a slight delaying effect upon the progression of Alzheimer's, maybe because of preventing heart disease.

Low calorie diet - In addition to the effects upon blood pressure and cholesterol levels, a low calorie diet may stimulate the production of neurotrophic factors (proteins that promote survival and growth of neurons). It may be worthwhile to follow research on how to suppress our "HPG axis" hormones. Richard Bowen seems to be an expert on that. Good control of your weight and of your diabetes are very important. Fish consumption appears to have a significant protective effect upon the risk of AD (Kalmijn et al, Ann Neurol, 42:776-782, 1997).

Estrogen replacement therapy
This is inconclusive despite a whole lot of research. There doesn't seem to be any consistent treatment benefit of estrogens (and substantial risks), but there might be a way in the future to engineer an estrogen protective effect. The type of estrogen or method of estrogen delivery might be improved to enhance the agent's usefulness. 2005: Raloxifene (actually for prevention of osteoporosis) and other selective estrogen receptor modulators might be useful for prevention of Alzheimer's. Kristine Yaffe's work at the San Francisco VA Medical Center is the most interesting.
Kawas et al, Neurology, 48, 1517-1521, 1997.
Mulnard et al, JAMA, 283, 1007-1015, 2000.

Memantine is another potential candidate for a prevention "cocktail" along with Vitamin E and Niacin. Memantine is the first "breakthrough" drug for the prevention of further deterioration among patients with moderate to severe Alzheimer's.

If you smoke marijuana, don't be too concerned; it may have a neuroprotective effect, unless you smoke enough to increase the risk of heart disease, in which case you don't give a rat's ass about any of this stuff.