Abstract
Early diagnosis and treatment of Alzheimer's disease, a chronic, debilitating disease, can delay cognitive, functional, and behavioral declines in afflicted patients. Here, learn how to diagnose and manage the disease with the latest pharmacologic approaches. Early diagnosis and treatment, coupled with caregiver support, can delay nursing home placement, improving patient well-being.
A decline in cognitive abilities, a decreased ability to perform activities of daily living (ADL), and behavioral disturbances characterize Alzheimer's disease, a chronic, debilitating disease.1,2 Although 360,000 new cases occur annually,3 primary care clinicians fail to recognize about 50% of these cases.5 Several factors hamper diagnosis: unfamiliarity with assessment tools, ambivalence toward making a specific diagnosis, stigmatizing the diagnosis, and attributing symptoms to the normal aging process.4
Approximately 4 million Americans suffer from the disease, and 14 million may have it by 2050. Disease incidence increases with age, with a prevalence of nearly 50% in those age 85 and older.1 Although the etiology remains unclear, a decrease in cholinergic neurotransmission may account for the cognitive and behavioral disturbances characteristic of the disease.2 Amyloid plaques and neurofibrillary tangles in the brain are hallmarks of the disease.2
* Diagnosing Alzheimer's Disease
Because Alzheimer's disease has a relatively consistent onset and course, a well-defined set of clinical features help render the diagnosis. Base diagnosis on a comprehensive history and physical examination and laboratory and neuropsychiatric testing. Using clinical criteria, clinicians can accurately diagnose Alzheimer's disease in 75% to 97% of cases.6,7 Table 1, "Using Clinical Criteria to Form a Diagnosis," features recommendations from the 1996 Agency for Health Care Policy and Research, guidelines of the National Institute of Neurological Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association Working Group, and criteria in the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition (DSM-IV).8
When considering an Alzheimer's disease diagnosis, neuropsychological assessment tools help monitor shortand long-term memory, cognition (intelligence, attention span, judgment, orientation, perception, problem-solving, learning abilities, social intactness, and behavioral problems), and neurologic function (apraxia, aphasia, and agnosia). Assessment tools that measure cognition include the Mini-Mental State Examination (MMSE),9 the clock drawing test,10 and the Alzheimer's Disease Assessment Scale-- cognitive subscale (ADAS-cog).11 Because impairment of ADLs supports Alzheimer's disease criteria,12 the Nurses' Observation Scale for Geriatric Patients (NOSGER)13 or the Functional Assessment Questionnaire (FAQ)14 can help assess functional ability.
* Benefits of Early Diagnosis
The slow and progressive onset of symptoms may frustrate patients and their families who often misinterpret the cognitive and behavioral changes. After receiving the diagnosis, the patient and family usually respond with denial, and they frequently seek a second opinion. Once the patient and family accept the diagnosis, however, they can begin to consider treatment options and prepare for the future.
Early diagnosis has ramifications for financial and legal issues associated with the disease. If the diagnosis is made before onset of significant cognitive impairment, the patient may contribute to decisions regarding long-term care, power of attorney, disability coverage, and a living will. The patient may find making decisions empowering, while allowing some stress relief for the caregiver.
An early diagnosis also allows early therapy. Data suggest that when treatment initiation is delayed, patients may not attain maximum treatment benefits.15 Cholinesterase (ChE) inhibitor treatment positively affects the cognitive and functional symptoms associated with the disease.16-18 Early support, care, and treatment may allow patients and caregivers to receive optimal therapeutic benefits, especially when treatment begins before significant cognitive or functional deterioration.
Early treatment may impact costs associated with the disease, which are $100 billion per year.1 Early treatment with costeffective drug therapy may provide pharmacoeconomic benefits for patients, caregivers, and society.19,20 Because patients require costly care settings as the disease progresses, timely treatment that improves cognition, function, and behavior may lead to cost savings by extending the time patients can be at home.21
* Guidelines for Diagnosing AD
Several warning signs signal Alzheimer's disease (see Table 2, "Early Warning Signs of Alzheimer's Disease"). Once you detect early warning signs, arrange office visits for diagnostic purposes. Use three office visits to administer a stepwise assessment of dementia symptoms, ruling out reversible causes during the first two visits. This structure allows ample time for testing, while keeping patient distress to a minimum. Because the reimbursement structure allows NPs to recover expenses for the first 30 minutes of an office visit, each diagnostic visit should last 30 to 45 minutes.
First Office Visit
Obtain a clinical history from the patient and a family member or close friend. The clinical history should detail the pabent's prior health status and when symptoms began (see Table 3, "Taking the History"). You can explore many of the diagnostic criteria through the clinical history. Then have the patient's family complete a NOSGER at home. This tool, which can detect symptoms not present during the office visit, helps assess memory, ADL, self-care, mood, social behavior, and disturbing behavior (see Table 4, "Nurses' Observation Scale for Geriatric Patients").13
Perform a thorough physical examination and diagnostic laboratory tests to help rule out other underlying conditions that cause cognitive impairment. A complete blood count and chemistry can indicate infection or serum B 12 and folate deficiencies; rapid plasma reagin can identify tertiary syphilis; and thyroid-stimulating hormone can identify hypothyroidism. In addition, tumors, stroke, and polypharmacy can affect cognition: Rule these out before diagnosing Alzheimer's disease.
Second Office Visit
Cognitive impairment is the hallmark symptom of Alzheimer's disease. During the second visit, you can use the clock drawing test and the MMSE to assess cognitive function (see Table 5, "Assessing Cognitive Function"). The clock drawing test measures visuospatial ability and executive functioning (high-level cognitive skills, such as concentration, planning, and problem solving). The MMSE measures five areas of cognition: orientation, registration, attention and calculation, recall, and language.9 Although clinical experience varies, MMSE scores may reflect mild (>20), moderate (10-- 20), or severe (
Functional ability declines as a result of cognitive impairment. Initially, the patient exhibits impairment in high-level functions, such as balancing a checkbook or shopping. As the disease progresses, functional ability continues to decline. Eventually, the patient can no longer manage basic ADLs such as dressing or feeding. Assess the patient's functional ability by administering the questionnaire in Table 6 ("Determining Function") to the patient's family. Patients with normal function can perform all tasks; patients with Alzheimer's disease may have difficulty completing one or more tasks.
Following a chief complaint of memory loss or a decline in cognitive function, a history, physical examination, laboratory tests, and neuropsychological assessment can help render an appropriate diagnosis (see Figure 1, "Diagnosing Alzheimer's Disease"). Computed tomography and magnetic resonance imaging can also help rule out other causes of dementia, such as brain tumors and subdural hematoma. When the presentation is atypical, refer the patient to a specialist.
Third Office Visit
Once you've confirmed a diagnosis of Alzheimer's disease, advise the patient and family of the diagnosis. When discussing the diagnosis, use sensitivity and thoroughness. Patients and families often accept results from objective measures, such as assessment tools, more readily than subjective measures, such as interview findings. After disclosing the diagnosis, immediately discuss disease-related information, including treatment options, the need for immediate treatment, treatment adherence, and treatment expectations. Provide information on support groups and local and national associations and agencies that offer education and programs to patients and caregivers.
If the patient has an atypical presentation or evaluation results are equivocal, refer the patient to a specialist. Patients may request a second opinion from a specialist as well.
The complex nature of Alzheimer's disease requires the involvement of different specialists and health professionals. A multidisciplinary approach includes addressing medical, psychosocial, nutritional, safety, and financial issues, physical and occupational therapies, living arrangements, social services, and caregiver needs.
* Treating Alzheimer's Disease
A treatment that restores patients to a premorbid disease state doesn't exist. Successful management of Alzheimer's disease must address the cognitive, functional, and behavioral symptoms of this disease.22 A positive treatment outcome includes improvement or stabilization of signs and symptoms or a slower rate of decline.
Researchers have studied estrogens, anti-inflammatory drugs, and antioxidants with varying success.1 ChE inhibitors (tacrine [Cognex],donepezil [Aricept],rivastigmine [Exelon], and galantamine [Reminyl]) are the only Food and Drug Administration-approved drugs for treating mild to moderate Alzheimer's disease. Although these drugs don't stop disease progression, they improve cognition and overall function. Numerous clinical trials show that second-generation ChE inhibitors (donepezil, rivastigmine, and galantamine) have beneficial effects on the cognitive,18,24-26 functional,18,24-26 and behavioral25,26 symptoms of Alzheimer's disease and may benefit both patients and their caregivers.
* Benefits of Early Treatment
Effective treatment of symptoms can make a meaningful difference in the lives of patients and their caregivers. In clinical trials, donepezil treatment resulted in significant improvements in ADAS-cog and MMSE scores.16,24 Clinical studies also demonstrate that rivastigmine and galantamine significantly improve cognition compared with placebo.18,26
Assessing global function requires input from caregivers and clinicians and is based on perceived changes from baseline in the patient's cognition, daily function, and behavior. ChE inhibitor treatment stabilizes or improves global function as measured by the clinician's interview-based impression of change scores (CIBIC).16,18,25,27 In addition, clinical studies demonstrate that ChE inhibitors attenuate the loss of function that occurs with Alzheimer's disease.18,26,28 Presumably, ChE inhibitors positively affect function by improving cognitive performance. By attenuating functional decline, ChE inhibitors may enable patients to remain self-sufficient longer.
As the disease progresses, increasingly distressing behavioral disturbances often lead to nursing home placement.29 Attenuating these disturbances may allow patients to stay at home, which is important to their sense of orientation and well-being. Treatment with donepezil can improve behavior25 and delay nursing home placement.30 Reducing behavioral problems and delaying institutionalization affect patient and caregiver quality of life and utilization of health care resources.31
* Caring for the Caregiver
The emotional, physical, and financial burdens of caregiving can result in physical and mental illness for the caregiver. For example, clinical depression occurs in 50% of caregivers.32 Because stressed caregivers may find it difficult to maintain appropriate patient care, caregiver health is vital.
Monitor caregivers for signs of depression and other disease states. Prompt attention and treatment can improve the caregivers' ability to care for themselves and patients. Treatments that delay patient dependence and improve behavioral symptoms may benefit caregiver health by reducing caregiver stress and burden.
* Consider Safety and Tolerability
Consider compliance, safety, and tolerability when initiating pharmacologic therapy, as normal, age-related pharmacokinetic and pharmacodynamic changes may impact drug efficacy and tolerability.33
The safety and tolerability profiles of ChE inhibitors vary (see Table 7, "Pharmacologic Properties of ChE Inhibitors"). Common adverse effects include headache, nausea, vomiting, diarrhea, and dizziness.34-36 Activation of the widespread cholinergic fibers in the peripheral and central nervous system may cause many of these effects.
In a comparison of donepezil and rivastigmine, patients taking rivastigmine had three to four times the incidence of gastrointestinal adverse effects compared with patients taking donepezil.37 Slower dose escalation schedules have a lower incidence of adverse effects than reported in initial clinical trials.15,26,34,38 Dosing guidelines recommend these slower schedules.34-36
The manufacturer changed rivastigmine's package labeling in response to esophageal rupture in a patient who restarted therapy at a high dose following treatment interruption.39 The package insert for galantamine also notes to reinitiate therapy at the lowest dose following drug interruption. Galantamine is not recommended in patients with severe hepatic or renal impairment.
Additional adverse effects related to the cholinomimetic effects of ChE inhibitors include increased risk of peptic ulcer disease, occult gastrointestinal bleeding, bradycardia, and bronchoconstriction. Monitor patients for these effects.34-36
* Considerations for Long-term ChE Inhibitor Treatment
Typically, patients with Alzheimer's disease who don't receive treatment have declines of 2 to 4 points per year in MMSE scores.40 Long-term ChE inhibitor therapy has provided long-term benefits for cognition and global function in double-blind24,28 and open-label studies.15,27 In a longterm, double-blind trial, sustained donepezil treatment maintained patients' cognitive scores at or near baseline for 52 weeks.24
Clinical trial data suggest that patients experience optimal benefits when they receive uninterrupted, long-term ChE inhibitor therapy.15 Deciding to continue ChE inhibitor treatment may depend on caregiver expectations and perceived treatment benefit. In an open-label extension of two double-blind trials of donepezil, the cognitive and functional benefits gained following 24 weeks of treatment with donepezil were lost in patients who stopped therapy for 6 weeks. This finding underscores the importance of communicating to the caregiver that discontinuing treatment may jeopardize benefits gained. Discuss realistic treatment expectations and the benefits of continuous treatment with patients and caregivers at follow-up visits.
* The Future of Treatment
We have reason to be optimistic about the future of Alzheimer's disease treatment. Researchers continue to investigate new pharmacologic approaches, a vaccine, and neurotrophins. Combination therapies, such as ChE inhibitors and anti-inflammatory drugs, are also under investigation. As advances in diagnosis and treatment continue, we can provide the latest in resources, treatment options, and care to patients and caregivers, helping to alleviate some of their burden.
Rx Of the 1.5 ANCC contact hours awarded for this activity, 0.5 is applicable toward a pharmacology requirement.
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Veronica T. Griffith, FNP, GNP
ABOUT THE AUTHOR
Veronica T. Griffith is a family NP, Internal Medicine Clinic, Jacksonville, Fla.
Copyright Springhouse Corporation Dec 2002
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