Supportive Care for the Patient With Alzheimer's Disease Although Alzheimer's disease cannot be cured, pharmacists can assist in providing supportive care to reduce the burden on patients, caregivers, and families.
Alzheimer's disease (AD), the most common fonn of dementia, is a progressive neurodegenerative disease that is typically characterized by memory impairment. Other common features include changes in the patient's personality, behavior, andjudgment, and a diminished ability to perform daily activities. About 4 million Americans are currently diagnosed with AD, but this number is projected to at least double by 2020 as baby boomers age and enter the peak years for AD onset. Although no cure for AD exists, appropriate disease management can ease the burdens on the patient, caregivers, and family. As this session highlighted, a tremendous amount of infonnation about AD has been elucidated in the past decade. Pharmacists can use these clinical insights to provide supportive care for AD patients and their caregivers.
Disease Risk Factors and Characteristics Although the cause of AD is unknown, a number of risk factors have been identified, such as aging. Epidemiological data have shown that the incidence of AD is about 3 % of persons aged 65 to 74 years, 18% of those aged 75 to 84 years, and 47% of those 85 years and older. Other risk factors for AD include a positive family history, genetic predisposition (APO E4 or other genes), and head trauma. The pathogenesis of AD involves the formation of abnonnal structures in the brain called plaques and tangles. As these accumulate, nerve cell connections become impaired. The presence of beta-amyloid protein and neurofibrillary tangles in the brain, which can be detected upon autopsy, are hallmark features of the disease. The neurons that are most affected in AD Based on presentations by Michael W iann, PharmD, professor and director, Mercer University Southern School of Pharmacy, Atlanta, Ga.; and Nicki Brandt, PharmD, assistant professor and deputy director, Lamy Center, University of Maryland School of Pharmacy, Baltimore.
Supplement to the Journal of the American Phannaceutical Association
are cholinergic and innervate a variety of brain areas, including the hippocampus, frontal cortex, and parietal cortex. These brain centers are involved with memory, cognition, language, personality, and many other functions.
Assessment and Management of AD No single clinical test is available to identify AD. Early diagnosis is important to rule out other fonns of dementia, some of which may be reversible with treatment (see Figure 1). Patients require a comprehensive evaluation that includes a complete health history, physical examination, neuropsychological assessments, and other tests, such as blood and urine analyses, and a scanning exam with magnetic resonance imaging or computer tomography. With a thorough evaluation, a positive clinical diagnosis of probable AD can be established with an accuracy of about 90%. Absolute confirmation, however, requires examination of brain tissue at autopsy. Presently, the only medications that are approved by the U.S. Food and Drug Administration (FDA) for the treatment of AD are cholinesterase inhibitors (ChEls). This drug class works by blocking the acetylcholinesterase and butrylcholesterase enzymes. The primary effect of these medications is to increase levels of acetylcholine, an important neurotransmitter that is depleted in AD patients. The overall goal of AD treatment is to maintain quality of life, and ChEls can have a significant benefit in this regard for patients and their caregivers. Marketed drugs in this class are tacrine (Cognex-First Horizon Pharmaceuticals), donepezil (Aricept-Pfizer), and rivastigmine (Exelon-Novartis), the most recently FDA-approved agent. ChEls can be divided into three pharmacological classesshort, intennediate, and long-based on the time for regeneration of the cholinesterase enzyme. Tacrine and donepezil are short-acting agents. Rivastigmine is an intermediate-acting agent, with a single dose inhibiting enzyme activity for up to 10 hours. Tacrine and donepezil are metabolized by hepatic cytochrome P-450 isozymes, but rivastigmine is not. September/October 2000
Vol. 40, No.5, Suppl. 1
Supportive Care for the Patient With Alzheimer's Disease
Figure 1. Major Causes of Dementia
Reversible and other causes (metabolic, drug induced) 7%
Other progressive disorders (eg, Parkinson1s disease) 17% Vascular (stroke) 11%
Clinical assessments accepted by the FDA for the evaluation of dementia drugs include the Alzheimer's Disease Assessment Scale (ADAS) and the Clinician's Global Impression of Change. Other assessments include the Mini-Mental Status Exam and Progressive Deterioration Scale (PDS). In clinical trials comparing donepezil versus placebo, the placebo-treated subjects declined in their ADAS scores during a 6-month study period, whereas patients treated with donepezil did not decline. Upon drug discontinuation, donepezil-treated subjects also declined. Similar findings were demonstrated with rivastigmine in a multicenter clinical trial that assessed changes in ADAS. Rivastigmine also has been shown to maintain subjects' daily functioning, as assessed by the PDS. The main adverse effects associated with ChEIs include gastrointestinal disturbances, bradycardia, and occasional leg cramps. A number of investigational therapies, including certain herbal remedies, are being evaluated for their efficacy and safety in AD. Although more research needs to be done, a meta-analysis showed that gingko biloba may be beneficial in treating individuals with mild to moderate AD. Conversely, a recent report showed that estrogen is not beneficial in individuals with mild to moderate AD.
Behavioral Problems in AD Behavioral problems in patients with AD are a major source of caregiver "burnout" or stress and are a major reason for patient admission to long-term care facilities. Up to 62% of nursing home residents and at least 50% of outpatients with dementia experience behavioral disturbances. Identifying and treating these behavioral abnormalities can significantly improve the quality of life of patients and caregivers. Vol. 40, No.5, Suppl. 1
Behavioral changes in AD include agitation, aggression, psychosis, wandering, "sundowning" (the onset or exacerbation of delirium during the evening or night), and sleep disturbances. Identifying behavioral manifestations and clustering them into related behaviors can help clinicians to develop a more systematic approach to treatment. Often, patients' behaviors are indicative of depression, mania, psychosis, or anxiety. Other times, the patient may be agitated, as evidenced by inappropriate verbal, vocal, or motor activity that cannot be explained by his or her apparent needs. Aggression, a type of agitation, involves hostile actions directed toward others, self, or objects. It is important to differentiate these types of behaviors and rule out a possible underlying medical etiology or environmental causes. Both nonpharmacologic and pharmacologic interventions can be used to manage behavior difficulties. Pharmacists need to understand the benefits and limitations of these various interventions, what to monitor, and when to expect therapeutic effects. For instance, antipsychotics are often prescribed for AD patients, but improvement is seen in only 20% to 30% of agitated patients with dementia. Pharmacists also should be aware that newer antipsychotics have similar efficacy to traditional agents, such as haloperidol, but are better tolerated.
Support for Caregivers Pharmacists can help to ease caregiver stress by informing these individuals about support groups in the community and providing contact information for national advocacy organizations, such as the Alzheimer's Association (http://www.alz.org) and the Alzheimer's Disease Education and Referral Center (http://www.alzheimers.org). By educating and supporting caregivers, pharmacists and other health care providers can help to delay institutionalization of patients and reduce health care expenses. Pharmacists also need to follow up on interventions for AD patients and help establish a treatment plan with the patient, caregivers, and family to provide comprehensive supportive care.
Summary • The prevalence of AD, the most common form of dementia, is likely to double in the next 20 years. • Although the cause of AD is unknown, risk factors include aging, genetic predisposition, and head trauma. • The cholinesterase inhibitors (tacrine, donepezil, and rivastigmine) are the only FDA-approved class of medications for AD. • Behavioral problems associated with AD are a major reason for admission to long-term care facilities and a common cause of caregiver "burnout" or stress. This symposium was made possible by an unrestricted educational grant from Novartis Pharmaceuticals Corporation.
Supplement to the Journal of the American Phannaceutical Association