Dementia is a gradual progressive decrease in mental capacity in which memory, decision-making skills, and the ability to learn become impaired. One of the most challenging conditions to affect our rising aging population is Alzheimer's disease (AD). This disease is the most common form of dementia and accounts for more than 65% of all forms of dementia in the elderly.1
AD is the 8th leading cause of death in the United States. It affects approximately 4.2 million to 5.8 million individuals. Approximately 1 person in 10 over 65 years of age is affected, and 5 out of 10 individuals 85 years old or older are affected. In addition, a very small percentage of individuals in their 40s may be diagnosed with AD.2 Since 1980, the number of Americans with AD has more than doubled, and unfortunately the number is expected to continue to increase.3 It is estimated that by the year 2050 the number of individuals with AD could range from 11.3 million to 16 million.3
On average, an individual will live 8 years after diagnosis or as many as 20 years from the onset of symptoms.2,3 Caring for individuals with AD requires significant resources. For instance, it is estimated that 1 to 4 family members act as caregivers for an individual with AD. According to the Alzheimer's Association and the National Institute on Aging, the national direct and indirect costs attributed to caring for individuals with AD are at least $100 billion. The average lifetime cost for an individual with AD is $174,000.2
What Is AD?
AD is a progressive and degenerative condition that is characterized by a loss of mental function.1
Although the exact cause is unknown, theories suggest that AD can be due to both inherited and environmental factors. The disease appears to run in some families. In AD, certain components of the brain degenerate, thus destroying nerve cells and reducing the responsiveness of the unaffected brain cells to the neurotransmitters in the brain. Research has shown that patients with AD exhibit 2 types of abnormalities in the brain tissue: amyloid plaques and neurofibrillary tangles. Researchers are still unclear as to whether these structures cause AD or are a result of it.2 The progression of AD often is unpredictable, and severity varies from patient to patient.
There are 2 distinct types of AD: familial AD and sporadic AD. Familial AD follows an obvious inheritance pattern. This is a very rare form of AD and may be responsible for less than 10% of all AD cases. Familial AD typically occurs before the age of 60, so it is also referred to as early-onset AD. With regard to sporadic AD, genes may not be the direct cause of the disease but may influence the risk of developing AD. Sporadic AD is sometimes referred to as late-onset AD, because many cases occur in individuals after the age of 60, with the vast majority of individuals in their 70s and 80s.4,5 There are, however, exceptions to the general observations regarding age at onset.4,5 Three genetic mutations (amyloid precursor protein [APP], presenilin 1 [PS1], and presenilin 2 [PS2]) are known to cause a small number of early-onset forms of AD. Furthermore, the apolipoprotein E gene may increase an individual's chance of developing late-onset AD.4,5
Current research indicates that AD may be triggered by several factors, including age, genetics, serious head injuries, and inflammation of the brain, as well as environmental factors.2,4 Age is the most important known risk factor.
Most patients' symptoms progress gradually over a number of years and may not be noticeable early on. Symptoms can be classified into 2 categories2:
The disease customarily is marked by 3 general stages: mild, moderate, and severe (Table 1).As the disease progresses from the mild to the moderate stage, the signs of AD may become more noticeable to family members and friends. Usually at this stage, the need for caregiver assistance becomes essential for the safety of the individual. In the severe stage of AD, individuals usually are solely dependent upon the caregiver.6
There is no definitive diagnostic test to determine whether an individual has AD. Diagnosis of AD, however, can be determined through the symptoms illustrated by the patient, by assessment of the patient through medical history from family members, and by a thorough neurologic examination. Today, clinicians can diagnose AD with up to 90% accuracy, but a confirmation of the diagnosis can be made only at the time of autopsy.2
Currently, the FDA has approved 2 classes of drugs to treat cognitive symptoms of AD, such as memory problems and other mental deficits (Table 2).
The first medications to be approved were cholinesterase inhibitors. Three of these drugs are commonly prescribed: donepezil (Aricept), approved in 1996; rivastigmine (Exelon), approved in 2000; and galantamine (Razadyne; formerly Reminyl), approved in 20016 (Table 2). Tacrine (Cognex), the first cholinesterase inhibitor, was approved in 1993, but it is rarely prescribed today because of its associated side effects, including possible liver damage.7
NMDA Receptor Antagonist
In October 2003, the FDA approved memantine (Namenda), the only approved agent for the treatment of moderate-to-severe AD. This agent is classified as the first N-methyl-D-aspartate (NMDA) receptor antagonist. It aids in protecting nerve cells in the brain from excess glutamate, which is the neurotransmitter that plays a role in neurodegenerative diseases such as AD. It is presumed that this agent exerts its action as an uncompetitive openchannel NMDA receptor antagonist that binds to the NMDA receptor-operated cation channels.8
Clinical studies have shown that memantine actually may improve memory function and prolong independence and quality of life in some AD patients.8 This agent can be used as monotherapy or in conjunction with cholinesterase inhibitors. It is available in 5- and 10-mg tablets. The usual starting dosage is 5 mg once daily, titrated eventually up to the desired dose of 20 mg per day. The dosage is increased in increments of 5 to 10 mg per day in 2 divided doses, then 15 mg per day (administered as 5 and 10 mg as separate doses), then 20 mg daily as 10 mg bid. This agent can be taken with or without meals. The recommended minimal time interval between dosage increases is 1 week.
Following administration, memantine is highly absorbed, with peak concentrations reached in 3 to 7 hours. The manufacturer cautions that, in certain cases, some agents, such as carbonic anhydrase inhibitors and sodium bicarbonate, which increase urinary pH, may decrease the urinary elimination of memantine, resulting in increased plasma levels of this agent.8 The most frequently reported side effects include ataxia, hypokinesia, anemia, dizziness, headache, and constipation.
What Other Therapy May Be Needed?
It may be necessary to use other agents such as antidepressants, antianxiety agents, and antipsychotics to treat such specific behavioral symptoms as agitation, hallucinations, or sleep disturbances often associated with AD that may not respond to nonpharmacologic behavioral strategies. These agents are prescribed based upon specific patient need. Most individuals with AD do not die from the disease itself but rather from complications of a secondary illness such as pneumonia. In some cases, when AD patients are unable to care for themselves, this inability may increase the risk for developing other health concerns, including pneumonia, infections, and injuries or complications due to falls.4
Managing the care of an individual with AD can be difficult and overwhelming at times. All caregivers should be encouraged to participate in some form of support network. Because AD is a progressive disease, decisions about care need to be planned in advance. These decisions depend upon the home environment, the availability of family members and/or other caregivers able to assist, financial resources, and the presence of other physiologic conditions in the patient.
The Role of the Pharmacist
Each case of AD presents a unique set of circumstances and challenges. Pharmacists can be a fundamental source of information and support for those diagnosed with the disease and their caregivers. Caring for a patient with AD involves more than drug treatment. Caregivers should be encouraged to join local support groups and to take care of themselves as well.
Pharmacists are crucial members of the health care team and should thoroughly counsel AD patients and their caregivers on the agents currently prescribed for this disease. Pharmacists can monitor drug regimens for drug interactions and contraindications. More importantly, pharmacists should demonstrate empathy toward patients with AD and their caregivers. They should keep caregivers updated on new developments in the fight against this condition and suggest sources of information for them. Although at the present time there are no cures for AD, the hope for these patients lies in the ongoing research. Maybe one day that hope will become a reality and benefit the millions of individuals affected by AD.
Ms. Terrie is a clinical pharmacy writer based in Haymarket,VA.
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