Pharmacy and Medications

Supplemental Treatment of Alzheimer Disease

12/30/2002

Question:

My mother has alzheimer disease and is still functioning pretty well. Her doctor has started her on aricept. I am wondering if there is anything else she can take like vitamin E to help stop the disease. I am also wondering if there is anything I can take to decrease my chances of having it later in life.

Answer:

Alzheimer’s Disease (AD) is a common age-related progressive neurodegenerative disorder that causes memory loss and reduced cognitive functioning, which impair the patient’s activities of daily living, and cause various behavioral and psychiatric problems. The onset of the disease is subtle. Memory loss is the most common presenting complaint and this symptom is often brought to the attention of the patient’s physician by a family member. A number of markers for the disease have been identified, but the exact cause is unknown. Genetic factors may play a role in up to 30% of cases. Environmental factors such as alcohol abuse, head trauma, and stroke may also play a role in the development of the disease. Patients with Alzheimer`s Disease have widespread disruption of a number of different neuronal pathways as well as disruption of most neurotransmitter systems. The identification of large losses in cholinergic neurons in these patients led to the cholinergic theory of Alzheimer Disease. Subsequently, much of the work on developing a treatment has focused on developing drugs that increase acetylcholine in the brain. The prescription medications Aricept, Reminyl, and Exelon all work by increasing the availability of acetylcholine in the brain. One of the main problems with Alzheimer`s Disease is that most patients have already sustained significant brain damage by the time they develop symptoms. The goal of therapy is to maintain patient functioning as long as possible. There is no cure and at present, disease progression is inevitable. Significant research efforts focus on determining the underlying cause, identifying individuals at increased risk of developing the disease, and attempting to determine strategies to prevent the at-risk population from developing the disease. There is growing evidence that oxidative stress is a significant factor in the pathogenesis of Alzheimer`s Disease. Accumulated damage to lipid membranes and DNA by oxygen free radicals and reactive oxygen species is thought to disrupt normal cell functioning and lead to neuronal cell death. There is some evidence that adding vitamin E, an antioxidant, to a standard Alzheimer disease treatment regimen could delay symptom progression. The American Psychiatric Association Alzheimer Disease Treatment Guidelines recommend that initial treatment include vitamin E. Many clinicians recommend that Alzheimer disease patients take 2000 units of vitamin E per day. However, a government advisory group recently has recommended that vitamin E be given in daily dosages between 60 and 1,000 units, and suggested that higher dosages may increase the risk for coagulation disorders. More work is needed to define the exact role of vitamin E and other anti-oxidants in treating Alzheimer disease. Because patients typically present after significant brain damage occurs, defining the “at risk” population and determination of effective preventative measures is a key consideration. A genetic marker of increased risk of late onset Alzheimer`s Disease has been identified, but the presence of this marker is not diagnostic of the disease nor does its absence rule out the disease. It is unlikely that knowledge of the presence of this marker in an individual patient would confer any benefit. Regarding prevention of the disease, there is little evidence that anything works. Based on the current thinking, measures aimed at reducing oxidative stress may be useful. A recent journal article suggests that restricting daily caloric intake to 1800 – 2000 calories, taking antioxidants (vitamins E and C and fresh fruits and vegetables), and engaging in regular moderate physical exercise is a good preventative strategy. Huperzine A is sold as a dietary supplement for improving mental ability. It blocks the breakdown of acetylcholine like Aricept and the other first line drugs used to treat Alzheimer`s Disease. Studies indicate that it is slightly more potent than Aricept. It is unlikely that this dietary supplement prevents Alzheimer`s Disease. However, studies might prove it to be a useful treatment. Ginkgo biloba is another dietary supplement. It may act by reducing the oxidative stress in the brain. In addition, gingko may have anti-platelet activity and improve blood flow. Positive effects on cognition compared to placebo have been shown in clinical trials in patients with dementia. However, no large clinical trails have been completed. A number of animal models predict that estrogen replacement therapy should provide protection against the occurrence of Alzheimer`s Disease. However, small studies in humans have been inconclusive. A recent large study provides evidence that prolonged estrogen replacement therapy (more than 10 years duration) could reduce or delay the occurrence of Alzheimer`s Disease. Prolonged estrogen replacement therapy may increase the risk of developing other potentially life-threatening diseases.
Antioxidant vitamins: By preventing the progressive oxidative damage of free-radicals, vitamins E, B6, B12, and folic acid may be beneficial to the prevention of AD. Vitamin E can reduce the production of free radicals in the brain. Vitamins B6, B12, and folic acid lower homocysteine levels. A recent study of 1092 individuals showed that an increase in plasma homocysteine levels could increase the risk of developing Alzheimer`s Disease by as much as two-fold. A number of epidemiological studies reported a lower incidence of Alzheimer`s Disease in patients taking nonsteroidal anti-inflammatory drugs (NSAID) (e.g. ibuprofen) on a regular basis. In one small study, Alzheimer patients treated with indomethacin did not have cognitive decline over the 6-month study interval, but about a third of the patients dropped out of the study due to intolerable gastrointestinal side effects. At present there is little clinical evidence of benefit with these drugs and their gastrointestinal side effects are likely to be intolerable in these patients. At present they are not indicated for either prevention or treatment of Alzheimer`s Disease. The newer COX-2 NSAIDs are less likely to cause gastrointestinal complaints, and clinical trials of their use in Alzheimer `sDisease are currently in progress. Prednisone, a steroid anti-inflammatory drug actually worsened symptoms in Alzheimer patients. Prescription medications have been helpful in slowing symptom progression in Alzheimer patients, but typically they become ineffective within a year. Many medications and supplements have been tested and theorized to be beneficial but most lack sufficient data to prove their effectiveness. Current evidence indicates that vitamin E may be useful for prevention and treatment of the disease, but the high doses (up to 2,000 IU per day) may cause bleeding problems in some patients and should not be used unless approved by a physician. Maintaining a healthy lifestyle seems to be a reasonable approach to the prevention of Alzheimer`s and other diseases.
This response was prepared in part by Matthew Everly, a Pharm.D. student at the University of Cincinnati College of Pharmacy.

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Response by:

Robert James Goetz, PharmD, DABAT
Assistant Professor of Pharmacy Practice
Drug and Poison Information Center
Cincinnati Children’s Hospital Medical Center
University of Cincinnati