Buying time for Alzheimer's patients - Alzheimer's Trea...

Buying time for Alzheimer's patients

When a loved one has Alzheimer's disease, time takes on new significance. Every day that he or she can hold onto old memories or stay out of a nursing home becomes a gift. Thanks to new treatments and a growing understanding of the disease, families and patients can enjoy more of those gifts than ever before. For some patients, new drugs can delay the advance of the disease for months, or even years. Meanwhile, families everywhere are learning how to keep their loved ones as healthy as possible for as long as possible. It's called buying time, and it's hard to think of a better investment.

A slow road

The progression of Alzheimer's disease is usually slow, but devastating. For reasons that have so far eluded scientists, the brain of a person with Alzheimer's gradually develops strange deposits of tangles (twisted protein fibers inside brain cells, or neurons) and sticky plaques outside those cells. Studies now suggest that the disease is caused by the shrinkage and death of brain cells and their synapses, rather than the actual plaques and tangles. The latest thinking is that the abnormal processing of a normally harmless protein called beta-amyloid triggers a set of events that causes the neurons to shrink and die.

These changes in the brain soon lead to subtle changes in the person. Long before receiving the diagnosis of Alzheimer's disease, a person may feel his memory is slipping away. He may stumble over familiar words, miss appointments, or lose things more often than usual. Within a few years, someone with Alzheimer’s may get lost in familiar neighborhoods. Eventually, even simple tasks such as cooking and dressing normally become a challenge. By this time, many friends and family members aren't surprised when a doctor finally makes the diagnosis of Alzheimer's disease.

As the years go by, Alzheimer's disease will tighten its grip. Patients start to forget basic facts, from the current year to the names of their siblings. No matter what course the disease follows, patients and their families have the same goal: Hold on to the good times for as long as possible. The longer a person can do things for himself, the longer he can enjoy his favorite activities, and the longer he can maintain some independence while living with his family, the better it is for everyone.

Time in a pill

For some patients, buying time may be as easy as taking a pill. A class of drugs known as cholinesterase inhibitors -- including Aricept (donepezil), Exelon (rivastigmine), and Razadyne (galantamine) -- can delay the progression of Alzheimer's for months or, in a few cases, years, says Vincent DeLaGarza, MD, an associate professor and author of a comprehensive article on Alzheimer's medications that appeared in the American Family Physician in 2003. The first drug of this type was called Cognex (tacrine), and had the potential to cause liver damage, so it has been largely supplanted by the newer drugs in the class, which have a better safety record.

Cholinesterase inhibitors were developed after scientists found that people with Alzheimer's have lower levels of an important neurotransmitter in their brains (acetylcholine) than people without the disease. The medications are designed to keep nerve impulses moving by preserving more acetylcholine, which is crucial to memory; they do so by inhibiting an enzyme (acetylcholinesterase) that causes the neurotransmitter to break down.

Studies suggest that fewer than half of all people in the early stages of Alzheimer's respond to the drugs, but they may prove important for those who do by delaying the symptoms of mental decline for several months, or even a year or two, for example. The patient may be able to recall recent events and to take care of himself and household tasks more easily; this may correspond to an improvement in mood as well. Nobody knows if the drugs actually affect the buildup of proteins in the brain, but they can slow symptoms of mental decline, at least in the patients who are lucky enough to respond. Side effects can include nausea, vomiting and diarrhea.

And the sooner treatment begins, the better. In July 2004, researchers at the 9th International Conference on Alzheimer's Disease and Related Disorders announced that Aricept could delay the progression of Mild Cognitive Disorder to Alzheimer's by as much as 18 months. Another recent study of 565 patients with early Alzheimer's disease found that a two-year course of Aricept slowed symptoms of mental decline for some patients.

A weapon against advanced Alzheimer's

In 2003, the Food and Drug Administration approved the first drug to treat moderate to advanced Alzheimer's: Namenda (memantine). The newest U.S. drug in the arsenal against Alzheimer's, memantine was used in Europe to treat various types of dementia long before it was approved here. Unlike cholinesterase inhibitors, memantine protects brain cells from damage caused by the chemical messenger glutamate, that, when produced in excess, can lead to the death of brain cells. In cases of severe Alzheimer's, it's the only treatment available.

Memantine, which can be prescribed in addition to Aricept or another cholinesterase inhibitor, may help some patients with moderate to severe Alzheimer's hold on to their ability to perform daily tasks and maintain some independence. A U.S. study of 252 outpatients with Alzheimer's found that those using memantine were better able to use the phone, pay attention to conversation, get around outside the home, and perform daily tasks such as clearing the dishes after eating. These gains might seem modest, but to families dealing with Alzheimer's, they can be gratifying beyond measure.

And caregivers, take note: There's some evidence that the drug helps in very advanced cases of Alzheimer's. One European study that focused on nursing-home patients with severe dementia found that those who took the drug were more likely to be able to stand up, move, eat and drink, dress themselves, and use the toilet. Not only can these basic skills help preserve a person’s last remnants of precious independence, but they can help relieve the burden on caregivers. According to data presented at the 8th International Conference on Alzheimer's and Related Disorders, a different study suggests that treatment with memantine may reduce caregiver time by nearly 50 hours a month, compared to a placebo. (However, the consumer watchdog group Public Citizen has criticized the methodology of the study, whose findings it calls "suspect.")

Memantine even shows some potential for treating the earlier stages of the disease, DeLaGarza says. In fact, a combination of Namenda and a cholinesterase inhibitor -- like Razadyne or Aricept -- may prove to be more effective for early-stage Alzheimer's than the cholinesterase inhibitor alone. An observational study published in 2009 found that Alzheimer’s patients who used cholinesterase inhibitors and memantine were able to postpone nursing home admission significantly longer than those who only took cholinesterase inhibitors.

However, Public Citizen recommends against the use of memantine, saying there is little persuasive evidence that it improves functioning in Alzheimer's patients. The organization also notes that the manufacturer has received adverse event reports from Germany that include seizures and circulatory failure.

Drug therapy for Alzheimer's behaviors

The slow mental decline wrought by Alzheimer's may be hard to witness, but it's the disturbing behaviors -- wandering, paranoia, violent outbursts, and so on -- that often put family members over the edge. Anything that will control these behaviors can go a long way toward helping a patient stay at home for as long as possible. For this reason, more doctors -- including DeLaGarza -- are looking beyond Alzheimer's medications for treatment options.

Many Alzheimer's behaviors can be controlled by keeping patients' environment as calm, nonthreatening, and familiar as possible. In cases of persistent and highly disturbing behaviors, however, doctors sometimes prescribe sleeping pills, antianxiety medication, and even antipsychotic drugs such as Zyprexa (olanzapine) and Risperdal (risperidone). Although the last two drugs have FDA approval only for schizophrenia and other psychiatric disorders, there is some evidence that they may reduce aggression in people with Alzheimer's.

However, these drugs should not be prescribed lightly. Doctors should only consider prescribing the drugs when a person's behaviors are causing serious distress, and any patients taking the drugs still need to be closely monitored by doctors and family members alike. Studies have long shown that the negative side effects of antipsychotic drugs for Alzheimer’s patients – like sedation, confusion and weight gain – may outweigh the benefits. And now data also show that Alzheimer’s patients prescribed antipsychotic drugs do not live as long as those who do not take these medications.

Early-stage Alzheimer's patients capable of learning

Drugs aren't the only way patients and family members can buy time: According to two recent studies supported by the National Institute on Aging, people who have early-stage Alzheimer's disease have far more capacity to learn new things than previously thought.

Researchers in Miami, Florida found that mildly impaired Alzheimer's patients who took three to four months of "cognitive rehabiliation" classes had an 170 percent improvement in their ability to recall faces and names, along with a 71 percent improvement in their skill at giving the proper change for a purchase. The findings were published in the July-August 2004 issue of the American Journal of Geriatric Psychiatry.

This report followed on the heels of an earlier study from Washington University in St. Louis, which found that older people in the early stages of Alzheimer's retained working levels of "implicit memory" similar to that in young and older adults who were free of Alzheimer's. Implicit memory, researchers noted, is largely automatic and unconscious, surfacing in skills such as speaking a language and riding a bicycle.

"Taken together, these studies introduce the exciting notion that older people in the early stages of Alzheimer's can be taught techniques that help them stay engaged in everyday life," said Neil Buckholtz, PhD, head of the Dementias of Aging Branch of the NIA, discussing the research with an Alzheimer's organization. These findings suggest it's possible to pinpoint the memory capabilities that are preserved in early Alzheimer's, he added, "and make the most of them."

Walking and weaving

One way to make the most of these capabilities may be reality orientation therapy, which focuses on helping patients relearn new information such as dates, times of day, and location. One meta-analysis of six controlled trials found that classroom reality orientation produced modest cognitive gains in 125 Alzheimer's patients, and improved behavior in 48 -- benefits that in one study persisted a month after participants stopped attending the sessions.

Many families and caregivers can adapt the techniques used by researchers by hanging a blackboard or bulletin board where the patient can read it, and posting the day of the week, date, weather, season, and name and time of the person's next meal. (Books on caregiving show that, in fact, some families have long used similar techniques to help their loved ones.) Keeping a large clock, calendar, and schedule can also help people with Alzheimer's keep current; some may even review the calendar daily to remind themselves what happened the day or week before.

These techniques should be adapted to the individual, however, and in no cases should someone be "forced" into the present if he or she becomes disturbed or agitated. In addition, if the patient regularly mentions recent visits by a sister that died years ago, the latest thinking is that caregivers should simply acknowledge how much she loves her sister. Reality orientation is only valuable when it benefits the patient: Forcing someone to continually relive a painful loss would be cruel rather than helpful.

Exercise Rx for Alzheimer's?

And some of the best therapies around can't top good old-fashioned exercise, says Eric Larson, MD, a professor of medicine at the University of Washington in Seattle. A simple 30-minute walk around the neighborhood every day (with a caregiver, of course) can help slow the "downward spiral" of Alzheimer's, he says.

In a study of Alzheimer's patients published in the Journal of the American Medical Association in 2003, Larson and colleagues found that a three-month exercise program improved physical functioning, eased depression, and helped keep people out of nursing homes. Larson has seen similar results many times in his practice, and he knows how much these improvements can mean to patients and their families. Exercise greatly prolongs the time that patients can get out of bed by themselves, he says. It also helps them burn the nervous energy that could otherwise lead to nighttime wandering and other troubling behaviors. As a result, patients sleep better at night, which is a triumph for the whole family.

Larson says any type of walking will do the trick, whether it's a lap around the neighborhood or 30 minutes on a treadmill. Still, he says, it's hard to beat a stroll outdoors. The patient gets some fresh air and a chance to get reacquainted with the surroundings, and, just as important, caregivers (who often have trouble getting exercise themselves) get a chance to be physically active, too. A daily walk can help undo some of the stress of caregiving, he says.

The daily walk may soon turn into a high point in the patient's day, but it shouldn't be the only moment of peace and satisfaction. Larson says families should strive to create "pleasant events" for their loved ones, whether it's looking through a favorite photo album, getting a milkshake, or drawing a picture. "If you know someone well, you know what they like to do," he says. "The goal is to keep them doing it for as long as possible." Larson's own father is 88 years old and starting to slip into the middle stages of Alzheimer's. Larson doesn't want him to stare into space all day, so he buys kits for making Scandinavian rugs, something his father still enjoys.

Family members should resist the temptation to "sharpen" their loved one's mind with new puzzles and games, Larson says. "You don't want to force them to try anything new or anything they're not capable of doing," Larson says. "If you're trying to retrain the brain, it can be very frustrating."

Every family eventually finds its own approach to Alzheimer's. The most successful approaches combine quality medical care with regular exercise and a healthy dose of compassion. As the disease progresses and new problems arise, family members will naturally have fresh questions and doubts. At these times, families can turn to their local chapter of the Alzheimer's Association for guidance and support, Larson says. Buying time isn't always easy, but those extra days and months and years will be a family treasure.


-- Chris Woolston, MS, is a health and medical writer with a master's degree in biology. He is a contributing editor at Consumer Health Interactive, and was a staff writer at Hippocrates, a magazine for physicians.


Further Resources

Alzheimer's Association: http://www.alz.org/index.asp
This Web site has resources for people living with Alzheimer's, their caregivers, and professionals who want to keep up with the latest medical advances.

Family Caregiver Alliance: http://www.caregiver.org/caregiver/jsp/home.jsp
This site has information on services, research, and education for those caring for loved ones with chronic health conditions.


References

Interview with Vincent DeLaGarza, MD, an associate professor and author of a comprehensive article on Alzheimer's medications

Interview with Eric Larson, MD, a professor of medicine at the University of Washington in Seattle

Aricept may temporarily delay Alzheimer's in those at high risk. Alzheimer's Association. 2004.

Long-term donepezil treatment in 565 patients with Alzheimer's disease (AD2000): randomised double-blind trial.

DeLaGarza, VW. Pharmacologic treatment of Alzheimer's Disease: An update. American Family Physician. October 1, 2003.

Doody R et al (2004). Specific functional effects of memantine treatment in patients with moderate to severe Alzheimer's Disease. Dementia and Geriatric Cognitive Disorders. 18 (2); 227-32.

Winblad B et al. Memantine in severe dementia. Results of the M-BEST study (benefits and efficacy in severely demented patients during treatment with menantine). Int J Geriatr Psychiatry 1999; 14:135-146.

HutmanS et al. Tolerability of memantine in combination with cholinesterase inhibitors in dementia therapy. Int Clin Psychopharmacol 2003;18:81-85.

Teri L et al. Exercise plus behavioral management in patients with Alzheimer Disease. Journal of the American Medical Association. October 15, 2003.

Lowenstein, David, et al. American Journal of Geriatric Psychiatry, July-August 2004

Lustig, Cindy, et al. Neuron. June 10, 2004

Medical Encyclopedia: Alzheimer’s Disease. MedlinePlus. U.S. National Library of Medicine and the National Institutes of Health.

A Guide to Alzheimer’s Disease, a Special Health Report. Harvard Medical School. 2002.

10 warning signs of Alzheimer’s disease. Alzheimer’s Association. 2004.

Understanding Alzheimer’s. Fisher Center for Alzheimer’s Research Foundation.

Fact sheet: cholinesterase inhibitors. Alzheimer’s Association.
Masterman D. Role of cholinesterase inhibitors in managing behavioral problems in Alzheimer’s disease. Primary Care Companion to the Journal of Clinical Psychiatry. 2004;6(3).

Fact sheet: memantine. Alzheimer’s Association.

Alzheimer’s disease medications fact sheet. Alzheimer’s Disease Education and Referral Center. National Institute on Aging.

Wimo A, et al. Resource utilization and cost analysis of memantine in patients with moderate to severe Alzheimer’s disease. Pharmacoeconomics. 2003;21(5):327-40.

Modifying the home. Fisher Center for Alzheimer’s Research Foundation.

Medications used to manage behavioral symptoms of Alzheimer’s. Fisher Center for Alzheimer’s Research Foundation.

Memory. Johns Hopkins White Papers. The Johns Hopkins Medical Institutions. 2003.

National Institute of Mental Health. Antipsychotic Medications Used to Treat Alzheimer's Patients Found Lacking. October 11, 2006. http://www.nimh.nih.gov/science-news/2006/antipshotic-medications-used-to-treat-alzheimers-patients-found-lacking.shtml

Lopez, O, et al. Memantine augments the effects of cholinesterase inhibition in the treatment of Alzheimer’s disease. Journal of Neurology, Neurosurgery and Psychiatry. 9 February 2009.

Ballard, C, et al. The dementia antipsychotic withdrawal trial (DART-AD): long-term follow-up of a randomised placebo-controlled trial. Lancet Neurology. 2009 Feb;8(2):125.


Written by Chris Woolston, MS.

Reviewed by Michael Potter, MD, an attending physician and associate clinical professor at the University of California, San Francisco. He is board-certified in family practice.

Our reviewers are members of Consumer Health Interactive's medical advisory board.
To learn more about our writers and editors, [go to the original article and] click here.

First published September 22, 2004
Last updated February 26, 2009
Copyright © 2004 Consumer Health Interactive


All contents copyright © 2000 - 2009 Vhi Healthcare. All rights reserved. Vhi Healthcare makes this Web site available free to residents of Ireland and for the sole purposes of providing educational information on health-related issues and providing access to health-related resources. This Web site's health-related information and resources are not intended to be a substitute for professional medical advice or for the care that patients receive from their doctors. Please review the Terms of Use before using this Web site. Your use of this Web site indicates your agreement to be bound by the Terms of Use.