Top10alz.doc  2/13/02 


(under development)


J. Wesson Ashford, M.D., Ph.D.


The field of Alzheimer’s disease is rapidly uncovering information for the treatment and prevention of Alzheimer’s disease.  While much discussion about cause is still speculative, there is mounting evidence to support several ideas about how Alzheimer’s disease develops.  Though there is never enough evidence to prove any scientific theory, there is frequently enough evidence to discuss a particular idea with patients and to make practical recommendations.  In the field of Alzheimer’s disease, there are several such issues that can now be brought to the clinic setting.  There are some recommendations based on current experience with treating Alzheimer patients or the associations between Alzheimer’s disease and other dementing disorders.  Other suggestions are based on scientific hypotheses with only preliminary evidence. 

1)     Take your blood pressure regularly and be sure that the systolic pressure is always less than 130.  This recommendation is based on the association between stroke and Alzheimer’s disease and several articles relating high blood pressure to poor memory and a higher incidence of Alzheimer’s disease, particularly in association with certain genes.  There is also some evidence that patients taking diuretics for their elevated blood pressure get less Alzheimer’s disease.  So keep track of your blood pressure and, if necessary, make sure that it is well treated. 

2)     Watch your cholesterol; if your cholesterol is elevated, get treated with “statin” drugs and be sure your cholesterol is fully controlled.  First, cholesterol levels are related to arteriosclerotic vascular disease, which is in turn related to heart disease and stroke.  So, this is a good idea in any case.  There is recent evidence that that cholesterol plays an important role in memory in the brain and is controlled by Apolipoprotein E, which may be associated with 50% of the Alzheimer risk.  Two recent studies have suggested that individuals taking “statin” drugs are less likely to get Alzheimer’s disease.  While these findings cannot be considered to warrant prescription without cholesterol elevation, clearly these data give individuals with elevated cholesterol have another reason to take their prescribed medications.  There has been one epidemiological study associating animal fat intake with Alzheimer risk across many different countries, but this study is not convincing enough to ask everyone to take all animal fat out of their diet.  But, if the fatty chemicals in your blood are not good, you should discuss modification of your diet with your physician. 

3)     Exercise your body and mind regularly.  There are many studies extolling the virtues of exercise.  While there are no specific links between exercise and Alzheimer’s disease, there are links between exercise and health and cognition.  People can get smarter by exercising.  So, there is a logical recommendation to exercise to reduce the risk of Alzheimer’s disease.  But, beyond this, there are recent theories linking insulin to Alzheimer’s disease.  The blood insulin level peaks about an hour after you eat.  If you exercise about 30 minutes after you eat, even if just walking for about 15 minutes (that’s after each meal), you might reduce your peak insulin level and leave the insulin-degrading enzyme to do its other task of breaking down the harmful beta-amyloid that forms fibrils in the brains of Alzheimer patients.  There are also several studies linking education to delayed onset of Alzheimer’s disease and some recent evidence suggesting that keeping your mind active can also delay onset.  Though all of these studies can be criticized in various ways, it makes sense to stay in school as long as possible and continue seeking intellectual stimulation throughout your life. 

4)     Wear your seat belt; wear a helmet when you are riding a bicycle or participating in any activity where you might hit your head.  There have been many reports of a relationship between head injury and Alzheimer’s disease.  While head trauma probably accounts for less than 5% of the cases of Alzheimer’s disease, safety can help to reduce this factor. 

5)     If you have diabetes, make sure that your blood sugar is optimally controlled.  One of the greatest advances in medicine has been the ability to control diabetes.  Patients with diabetes have a tendency to get vascular disease, and this disease can injure the brain.  While there is not clear relation between diabetes and Alzheimer’s disease, patients who have had blood sugars that have gone too high or too low may lose memory and be at greater risk for suffering from dementia. 

6)     Consult your doctor about treatment for your arthritis pain.  There have been several studies indicating that arthritis patients who take NSAIDs (non-steroidal anti-inflammatory drugs) have a reduced risk of Alzheimer’s disease.  A recent study (t’Veldt et al., 2001, New England Journal of Medicine) suggested that arthritis patients who had taken NSAIDs for over 3 years had an 80% reduction in their risk of getting Alzheimer’s disease.  Because the risks of these drugs (especially internal bleeding) are so great, they cannot be recommended for routine prevention.  However, if you have arthritis, you should seek the advice of your doctor for treatment.  Of additional great interest is another suggestion (from the lab of E. Koo), that only certain NSAIDs may prevent the development of a toxic protein in the brain that may be a specific cause of Alzheimer’s disease (beta-amyloid-1-42).  The particular NSAIDs identified with this benefit so far are ibuprofen (Motrin, Advil), sulindac (Clinoril), and indomethacin (Indocin).  Indomethacin may be the most potent, and one study suggested that this drug does slow down the course of Alzheimer’s disease.  Ibuprofen is most readily available.  However, a good recommendation for pain patients at this time is for sulindac because it is the most easily administered and has the least side effects. 

7)     Take your vitamins.  There is little reason not to take supplemental vitamins after you turn 50 years of age, and they might even help if you have some transient deficiency in your diet (see Willett & Stampfer, 2001, New England Journal of Medicine).  There is general support to take extra supplements of Vitamin E (400 international units) and Vitamin C (500 milligrams) together (once per day for prevention, twice per day if memory problems are present, and three times per day if Alzheimer’s disease is diagnosed).  These recommendations are based on the oxidation/free-radical theory of aging and Alzheimer’s disease and one large study which suggested that Vitamin E delayed specific end-points for Alzheimer patients by as much as 6 months.  Though the free-radical theory of Alzheimer’s disease has not been shown to be causal and the Vitamin E study has not been replicated, this “neuroprotective regimen” has become a common treatment of Alzheimer’s disease and taken by many as a preventive. 

B12 and folate have also been advocated as brain protective agents.  B12 recommendations are complicated by the issue of intestinal uptake by intrinsic factor.  The RDA for folate is 400 mcg per day, but this dose can be increased to 1 mg per day if memory difficulty is a concern and B12 levels are not low.  Recent correlation between elevated homocysteine levels and Alzheimer’s disease (Sheshadri et al., 2002, New England Journal of Medicine) brings a focus on this substance and the associated intake of B12 (which is inadequate with a “vegan” diet) and folate.  B12 and folate supplementation can keep homocysteine levels in check.  Alcohol and caffeine intake and tobacco use increase homocysteine. 

8)     Discuss sex-hormone replacement therapy with your physician.  There are general recommendations to post-menopausal women to take hormone replacement therapy to reduce the risk of heart disease and improve life in a variety of ways.  There is also some evidence that these hormones might reduce the risk of Alzheimer’s disease.  However, one study has suggested that the treatment of female Alzheimer patients with hormone replacement therapy may have more risk than benefit.  The issue of sex-hormones is of interest because these chemicals seem to enhance the function of many brain cells.  This leads to another question, which is, would sex-hormone replacement help elderly males as well? 

9)     If you have difficulty getting to sleep, consider trying 6 milligrams of melatonin at bedtime.  Melatonin is a natural substance produced by the pineal gland in the brain.  This substance is produced only in the dark and may help to initiate and sustain sleep.  As you get older, the brain produces less melatonin, and older people sleep less.  Sleep is good for the body and brain in any case and may help to keep Alzheimer pathology from developing.  There is only scant scientific evidence that melatonin helps sleep, but there are many patients and their family members that claim that it helps a great deal.  A big problem is that melatonin is a health food, not regulated by the FDA, so potency is not monitored.  Also, it may help sleep only in those individuals with a significant melatonin deficiency.  However, melatonin is an excellent anti-oxidant and some recent laboratory evidence has suggested that melatonin may prevent the formation of toxic amyloid fibrils in the brain, and these fibrils may be the primary cause of Alzheimer’s disease. 

10) If you have significant difficulty with your memory, talk to your doctor about cholinesterase inhibitors.  Several drugs from this class, including tacrine (Cognex), donepezil (Aricept), rivastigmine (Exelon), and galantamine (Reminyl), have been approved by the FDA for treating Alzheimer patients with mild dementia.  While the primary evidence suggests that these drugs have only a modest benefit on cognition, there have been several studies that have suggested that these drugs may slow down the progression of Alzheimer’s disease.  Note that these studies are only suggestive, not conclusive, but many physicians agree with this suggestion based on their own observations.  Importantly, if these drugs can slow Alzheimer progression, then they may have their biggest advantage very early in the disease course.  While doctors are not prescribing these drugs for preventing Alzheimer’s disease, many physicians are prescribing these drugs beneficially for patients with mild memory problems.  It is possible that these drugs may become a central part of preventive therapy for Alzheimer’s disease in the future.  

There are several treatments in addition to those listed above that have been recommended for Alzheimer’s disease as treatment or preventive agents.  At this point, there is not enough data to make more explicit recommendations.  For example, a recent review of Ginkgo Biloba suggested that the recommendations for this substance “remain ambiguous” (Sommer & shatzberg, 2002, Psychiatric Annals).  Co-enzyme Q-10 has also been recommended without wide support.  There is not enough evidence that aluminum is associated with Alzheimer’s disease to recommend throwing out your aluminum pots, but you probably shouldn’t cook tomato sauce in them.  Tobacco was shown in some studies to protect against Alzheimer’s disease, but later analyses have suggested that it is not preventive.  Alcohol in very low quantities may protect against heart disease and has been suggested to protect against Alzheimer’s disease as well, but anything more than minimal use is not wise. 

Several studies are exploring potential new preventions and treatments for Alzheimer’s disease.  The “amyloid vaccine” is one of the most interesting, but the development of this treatment has suffered a recent setback because some of the volunteers trying the treatment developed brain inflammation.  Also, there may be specific drugs now available that might slow Alzheimer pathology.  For example, lithium and valproic acid, two drugs used to treat manic-depression, may inhibit a brain enzyme (glycogen-synthase-kinase-3-beta), which could prevent the development of neurofibrillary tangles, a late Alzheimer pathology. 

Many patients with Alzheimer’s disease, including those in very early phases, have problems with depression and paranoid ideas.  These symptoms can and should be treated. 

Another critical question in Alzheimer’s disease, especially if early treatment can slow progression and delay dementia, is early recognition.  Screening tests to be used routinely in doctors’ offices for patients over 60 years of age are now being developed and may help many patients to get help sooner. 

At this time, there are many genes being uncovered that appear to be associated with Alzheimer’s disease.  In the future, it is likely that specific individuals will be told not only what their risk is for developing Alzheimer’s disease, but also how they can modify their life to prevent it completely.  There are so many indications that Alzheimer’s disease might be prevented that there is hope mounting that we may be able to end this disease in the near future.