- An estimated 4 million Americans have Alzheimer’s disease, a progressive, degenerative disorder. (CDC 1999)
- Approximately 10 percent of people older than 65 years and 47 percent of those older than 85 years have the disease.
- New therapies to reduce the morbidity and mortality of Alzheimer’s disease are in development.
Symptoms of Alzheimer’s disease may include memory loss, cognitive deficits in language, object recognition and executive functioning, and behavioral symptoms such as psychosis, agitation, depression, and wandering. The death rate for people with Alzheimer’s disease is twice as great as the rate among those of the same age without the disease. Although less than three percent of the population has Alzheimer’s disease at age 65, the prevalence doubles every five years thereafter. Because the risk of Alzheimer’s disease increases with age, the prevalence of the disease is anticipated to increase as the U.S. population ages. This will incur a substantial economic and social burden. The estimated annual economic toll of health care expenses due to Alzheimer’s patients and caregivers in the U.S. is $80 to $100 billion. (CDC 1999) This estimate includes both direct and indirect costs for medical and long-term care, home care, and loss of productivity for caregivers. Costs are especially high among patients with behavioral symptoms, who often require earlier or more frequent institutionalization.
Percentage of Older Adults who have Alzheimer's Disease, by Age
Source: D. Evans, et. al., JAMA, vol. 262, no. 18, 1989.
Pharmaceutical treatment of Alzheimer’s disease
Early Alzheimer’s disease is marked by a deficiency of acetylcholine in critical areas of the brain which is believed to account for some of the clinical manifestations of mild to moderate dementia. Cholinesterase inhibitors act to raise the concentration of acetylcholine in the brain by slowing the degradation of acetylcholine. Newer drugs included in this category are donepezil, tacrine, galantamine, and rivastigmine. Treating persons suffering with Alzheimer’s disease with these new drugs may help to maintain function and may ease the burden on caregivers for a limited period of time.
Donepezil (Aricept®) is not approved for coverage in Quebec, Canada or New Zealand. (Quebec Prescription Drug Insurance Plan 2002; PHARMAC 2002) Tacrine, an acetyl cholinesterase inhibitor available in the U.S., is currently not registered for use in New Zealand. (New Zealand Guidelines Group 2002)
Drugs in the pipeline to treat Alzheimer’s disease
Over 20 clinical trials of new drugs to treat Alzheimer’s disease were underway in 2001 (PhRMA 2002) and a similar number were funded by the NIH. These include:
- A new approach under development for the treatment of Alzheimer’s disease is to use drugs to limit the neurotoxicity mediated by microglia. (NIH 2002)
- Anti-oxidants and anti-inflammatory agents are being tested for effectiveness in treating Alzheimer’s disease. (NIH 2002, Alzheimer’s Research Forum 2002)
- A compound that activates neural growth factors in the brain is being tested. (Alzheimer’s Association 2002)
- A drug that increases signaling between nerve cells is also under study. (NIH 2002, Alzheimer’s Research Forum 2002)
Ideas for drugs that may be useful for the treatment and prevention of the cognitive and behavioral symptoms of Alzheimer’s disease have come from a variety of sources. Clinical-pathological studies have indicated that there are a variety of brain mechanisms that may lead to or exacerbate the nerve cell dysfunction and death and loss of connections among nerve cells seen in Alzheimer’s disease, including abnormal processing of proteins such as the amyloid precursor protein, beta-amyloid; oxidative damage; inflammation; and neurotrophic support of brain cells. (NIH 2002) Studies in test tubes and in animals have indicated that many of these mechanisms are potential targets for new drug discovery and development. A number of drugs targeting these mechanisms involved in Alzheimer’s disease pathogenesis are currently in preclinical development or clinical testing.
Some of the drugs being investigated are new agents; others are compounds such as vitamins that are already on the market for other indications or uses, but may be effective against Alzheimer’s disease. Epidemiological studies have suggested that some medications such as anti-inflammatory drugs, anti-oxidant vitamins, statins, and hormone replacement therapy may reduce the risk of developing Alzheimer’s disease (NIH 2002)
One new approach to treating Alzheimer’s disease is to disrupt the formation of plaques, the telltale sign of the disease. In the brains of Alzheimer’s disease patients, certain proteins cleave the amyloid precursor protein (APP) into beta-amyloid fragments, which then aggregate into the characteristic plaques of the disease. Several drugs currently in development are targeted at the steps involved in this process. These include drugs that inhibit proteins that cleave the APP; a variety of agents that are proposed to inhibit the aggregation of beta-amyloid into plaques, including a plant extract from cat’s claw; and immuno-therapeutic agents such as beta-amyloid vaccines. (NIH 2002)
A related strategy against Alzheimer’s disease is the development of compounds proposed to be neurotrophic (i.e., facilitating the health of nerve cells) or neuroprotective against mechanisms that kill nerve cells. There are several of these types of agents in pre-clinical and clinical trials. (NIH 2002)
In addition, researchers are conducting clinical trials of drugs targeted at the behavioral symptom of agitation in people with Alzheimer’s disease. Finally, substances that may protect against the development of Alzheimer’s disease are in clinical trials. (NIH 2002)