How do they work?
Alzheimer's medications raise the level of a brain chemical
that certain brain cells (neurons)
need to function properly. They do this by blocking an enzyme
which normally recycles "used" acetylcholine between
neurons. This increases the amount of acetylcholine in the
brain, which appears to counteract some of the effects of
Alzheimer's disease on memory
and thinking. "They all can improve behavior and physical
functioning and for that reason the medical profession agrees
that they're warranted," says Robert M. Palmer, M.D.,
a geriatrician at The Cleveland Clinic in Cleveland, Ohio.
The effect is modest-an average of 4 points of improvement
on a 70-point scale of cognitive function. That said, those
modest effects can be important on a personal level. Taking
the drug upon diagnosis may allow a person with Alzheimer's
to participate more fully in day-to-day activities, such as
attending family gatherings and cooking and cleaning. This
means a person with the disease could continue to function
longer without the need for a full-time caregiver
or admission to a nursing facility.
Staking a claim
The manufacturers of Reminyl and Exelon are working double-time
to convince doctors to prescribe their products rather than
Aricept, the leading medication right now. The most convincing
way would be to conduct a large "head-to-head" clinical
trial to directly compare the effects of the competing
drugs. That hasn't happened yet, so most doctors are content
to dispense Aricept. "There's really no convincing evidence
that any one drug is superior in its effectiveness,"
However, laboratory and animal research suggests that slight
differences in the way the drugs work, compared to the older
inhibitors, may offer certain extra benefits to patients.
For example, the manufacturer of Reminyl, Janssen Pharmaceutica,
maintains that its product has a duel mechanism of action
that may increase its effect on the brain.
Reminyl: sensitizing the brain?
Like the other cholinesterase inhibitors, Reminyl helps to
maintain a higher level of acetylcholine in the brain for
a longer period of time. Laboratory experiments suggest that
Reminyl may also increase the sensitivity of neurons to acetylcholine.
So not only is there more acetylcholine available, but Reminyl
may boost the response of the brain to it. "It is Reminyl
alone that has this second mechanism of action," asserts
Sean Lillienfeld, M.D., a neurologist and senior Janssen researcher
based in the company's U.S. headquarters in Titusville, New
Right now, it's not known what the alleged duel action of
Reminyl means for patients. Lillienfeld says that evidence
is accumulating that Reminyl may be more effective than the
other drugs. However, in the absence of head-to-head trials,
that remains a matter of speculation.
Exelon: broader action?
Novartis, the manufacturer of Exelon, has also identified
an aspect of its drug that could, hypothetically, offer extra
benefits to patients. Exelon appears to block a form of the
cholinesterase enzyme that becomes more important in the brain
chemistry of Alzheimer's later in the progression of the disease.
As a result, patients may benefit more over the long run from
Exelon, even if in the short term the drug is no more effective
than the others.
But again, there is no evidence from human clinical trials
that Exelon does, in fact, have any special benefit compared
to its competitors. "Theoretically that might be an advantage,"
notes Palmer, "but it remains to be seen if it actually
means anything at all."
Besides trying to prove that the new Alzheimer's drugs work
better, research is also underway to justify their use for
additional brain diseases and conditions. A study published
in the April 13, 2002, issue of the British medical journal
Lancet suggests that Reminyl may help people with vascular
dementia-a condition caused by small strokes
in the brain that has symptoms similar to those of Alzheimer's
Clinical trials are also underway to see if cholinesterase
inhibitors can help people with mild
cognitive impairment (MCI), whose impairments in memory
and thinking are noticeable but not severe enough for a diagnosis
of Alzheimer's disease. Studies show that over a period of
five to 10 years, most people with MCI go on to develop full-blown
Alzheimer's. The hope is that starting someone with MCI on
cholinesterase inhibitors will prevent or delay the progression
Trials are also underway to establish whether the cholinesterase
inhibitors are effective in later stages of Alzheimer's. Right
now, the drugs are typically prescribed for mild to moderate
stages of the disease, although patients are usually kept
on the medications as long as they can continue to benefit
It will be years before all these questions are worked out,
if at all. In the meantime, the good news for patients is
that early diagnosis and treatment of Alzheimer's disease
can buy them precious extra time to live a relatively normal,
functional life. Recent changes in Medicare policy also mean
that more people with Alzheimer's can benefit from helpful
measures that don't come from a pill bottle. Physical therapy,
for example, can help a person with Alzheimer's to maintain
the ability to move around freely and avoid disabling falls.
For the latest on Alzheimer's treatment and resources available
in your area, contact the Alzheimer's Disease Education and
Referral Center (ADEAR) at 800-438-4380 or www.alzheimers.org.
Alzheimer's Early Stages: First Steps In Care and Treatment,
by Daniel Kuhn and David A. Bennett. (Hunter House, 1999 (1st
edition) , 274 pp., $14.95). This guidebook focuses on the
medical aspects of the disease and includes a comparison of
the normal aging pattern of the brain and the effects of Alzheimer's.
Discusses long-term planning, relationships, communication,
and how to stay healthy while caring for someone with Alzheimer's.
"Guidance on the use of donepezil, rivastigmine,
and galantamine for the treatment of Alzheimer's disease,"
by the National Institute for Clinical Excellence (NICE).
(Technology Appraisal Guidance No. 19, January 2001. Available
"Efficacy of galantamine in probable vascular dementia
and Alzheimer's disease combined with cerebrovascular disease:
a randomized trial," by Timo Erkinjuntti, et
al. (Lancet, April 13, 2002, Volume 359, pp. 1283-1290.
"Galantamine for Alzheimer's disease (Cochrane
Review)," by J. Olin and L. Schneider. (Cochrane
Database Systematic Review 2001; 4: CD001747.)
"Practice parameter: management of dementia (an
evidence-based review)," by the Quality Standards
Subcommittee of the American Academy of Neurology. (Neurology,
2001, Volume 56, pp. 1154-1166.)
"Use of acetylcholinesterase inhibitors in Alzheimer's
disease," by Shehram Moghul and David Wilkinson.
(Expert Reviews in Neurotherapeutics, 2001, Volume 1, Number
1, pp. 61-69.) Available online: www.future-drugs.com