Rx CARE

Alzheimer's drugs can work for severe disease, too

As baby boomers age, the United States could be hit with an epidemic of Alzheimer's disease (AD). The number of people diagnosed with the crippling disorder is expected to triple over the next 30 to 40 years. Is the United States prepared to handle this looming crisis? Not at all, according to the experts who spoke recently at a briefing sponsored by the American Medical Association.

"The boomers are going to be the healthiest cohort of people ever to hit their 70s and 80s," said Steven DeKosky, M.D., director of the Alzheimer's Disease Research Center in Pittsburgh. Ironically, since the risk of AD increases with age, this will correlate with more cases being diagnosed. According to the Alzheimer's Association, one in 10 persons over 65 years of age and nearly half of those over 85 have AD. Approximately four million Americans have AD, and DeKosky cautioned that unless a cure or prevention for AD is found, the number of Americans diagnosed with AD could reach 14 million by the middle of this century (2050).

According to DeKosky, the current pace of research will not keep up with demand. Results from studies now under way are not expected until 2005. He would like to see the launching of several parallel trials of potential therapies as soon as possible. Therapeutic strategies that look promising include methods of diminishing or preventing amyloid protein deposition in the brain. These include enzyme inhibitors (secretase inhibitors) and beta amyloid immunization strategies. These medications are now nearing use in human safety trials.

However, before we begin to worry about the coming epidemic, what about the here and now? Alzheimer's disease is treatable, yet "fewer than half of patients diagnosed with AD are ever offered therapy for their disease," declared Rachelle Doody, M.D., Ph.D., of the Alzheimer's Disease Research Center at Baylor College of Medicine in Houston.

New evidence-based Alzheimer's disease guidelines, published in the May 8 issue of Neurology, advocate the use of cholinesterase inhibitors as "standard of care" for the treatment of mild to moderate patients.

"We're finding that the treatments we have now do more than we ever thought they would do," continued Doody. She explained that the older way of thinking was that the cholinesterase inhibitors would lose their effectiveness rapidly over time as the disease progressed. This has not turned out to be the case and, she added, newer research suggests you'd be doing more harm to the patient by discontinuing therapy too early.

Evidence to substantiate the long-term effectiveness of cholinesterase inhibitors in patients with AD was published in the March issue of the Archives of Neurology. The results of the study strongly suggest that donepezil (Aricept, Eisai) is an effective agent for long-term treatment of mild to moderately severe AD, based on clinical data up to 144 weeks (2.8 years). The study also demonstrated that donepezil treatment effects that are lost after prolonged discontinuation are not fully recovered when drug treatment is restarted.

"The cholinesterase inhibitors [appear] to be effective across the spectrum of the disease," noted Doody. The agents currently available are approved for mild to moderate stages of AD, but she explained that that's because it's easier to conduct trials in this group of patients. In fact, these agents are also beneficial for patients with severe disease. These are important findings because if third-party payers believe therapy is effective only for six months for mild to moderate AD patients, then they will discontinue or deny coverage for patients who do not meet these criteria.

The degree of benefit with the cholinesterase inhibitors may vary, commented Doody. But 80% of patients respond to therapy with either stabilization of disease or improvement in cognition, behavior, and functionality. This underscores the importance of early diagnosis and treatment. The cholinesterase inhibitors are under evaluation in patients with mild cognitive impairment (MCI) and severe dementia. According to Doody, patients meeting the criteria for MCI will progress to AD at a rate of about 15% per year, which is why the medical community needs to think about AD as a disease across the life span.

The guidelines also recommend the use of vitamin E to help delay the progression of the disease. Vitamin E needs to be given "in brain doses"—1,000 IU twice daily—because lower doses will not reach the brain in appropriate levels, noted Doody.

Doody also remarked that strong evidence exists for the use of antipsychotics in AD patients exhibiting signs of psychosis or agitation not caused by environmental factors and that antidepressants may also help some patients. However, she cautioned about the use of any medication that may have anticholinergic side effects since these agents will counteract some of the benefits of the cholinesterase inhibitors.

Tammy Chernin, R.Ph.

CURRENTLY AVAILABLE CHOLINESTERASE INHIBITORS

Tammy Chernin. Alzheimer's drugs can work for severe disease, too.

Drug Topics

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