Alzheimer's disease (AD) is the most common form of dementia. Age is the greatest risk factor for dementia. Dementia affects ~1% of individuals aged 60 to 64 years and between 24% and 33% of individuals over the age of 85.1
The main pathologic components of the AD brain are neuritic plaques and neurofibrillary tangles. The neuritic plaques are composed of ?-amyloid peptides, sometimes referred to as ?-amyloid plaques. The neurofibrillary tangles are composed of protein called tau, which forms insoluble filaments that lead to cell death in large numbers and result in atrophy of the cerebral hemispheres.2
Diagnosis of AD is one of exclusion based on the presence of certain clinical findings. The primary clinical finding is a loss of cognitive function?a decline from a previous higher level of functioning that distinguishes dementia from mental retardation or other developmental delays.3 The primary cognitive finding is short-term memory loss or, in particular, the inability to learn anything new. AD patients often have difficulty keeping track of the date, remembering recent conversations, or recalling where they recently left an item. The diagnosis is made as these symptoms become more evident, but often after much delay.
AD often is described in stages. The 2 most common staging methods involve a 3-stage system and a 7-stage system. Staging of AD provides the patient and/or family members and caregivers a frame of reference for understanding the disease process and for future planning. 4 AD is a continuing disease process in which individuals may not experience all symptoms at each stage, and symptoms may occur at different times. After diagnosis, patients live an average of 8 years, with a range of 3 to 20 years.4
Current drugs used in the treatment of AD are (1) the cholinesterase inhibitors donepezil, galantamine, and rivastigmine and (2) memantine, an N-methyl-Daspartate (NMDA) receptor antagonist. Donepezil is currently indicated for mild, moderate, and severe AD, and galantamine and rivastigmine are indicated for mild-to-moderate AD. Memantine is indicated for moderate-to-severe AD. Trials of cholinesterase inhibitors show that long-term use will result in modest stabilization of cognitive and functional status in AD patients for up to 1 year.3
Memantine can delay symptom progression in moderate-to-severestage AD patients. One study has indicated that combination treatment with memantine and donepezil in moderate-to-severe AD is more effective than donepezil therapy alone.5 Therefore, combination therapy with memantine and a cholinesterase inhibitor may prove to be beneficial.
Data indicate that early and continued therapy with a cholinesterase inhibitor (possibly combined with memantine) can delay or slow the inevitable cognitive and functional decline in AD patients.6 Early, continued treatment of AD translates into longer periods of higher functioning, which may mean increased quality of life for patients, less caregiver burden or stress, and delayed institutionalization. Therefore, early recognition of the signs and symptoms of AD is critical to maximize the benefits of current drug treatment for AD.
Although a randomized trial does not exist for definitive evaluation, screening programs should be beneficial. The prevalence of undiagnosed dementia, the accuracy of the screening tools, the efficacy of treatment for mild-to-moderate dementia, and whether screening actually could be harmful are important factors in determining the benefits of a screening program.7 One evaluation of the body of literature on undiagnosed dementia found that 50% to 66% of all patients who had not received a diagnosis of dementia did, in fact, have mild-tomoderate dementia.7 Thus, a screening program for patients 65 years and older could double the number of diagnosed dementia patients.
Among the memoryscreening instruments, the Mini-Mental State Examination (MMSE) is the most widely used. It has been used for screening in epidemiologic studies. It assesses attention, orientation, short-term recall, language, and an ability to follow verbal and written commands on a 30-point scale.8 The MMSE may be less accurate when detecting mild dementia, and it requires special adjustments for variations in age and educational level.9 The groups most appropriate for the use of the MMSE are Caucasians with at least a high school education.7
Other memory-screening tools include the Memory Impairment Screen (MIS) and the Short Blessed Test.10,11 During the MIS, patients are given the names of items in 4 different categories and are asked to name each item after a short delay. The Short Blessed Test has 6 items: the patient is asked to identify the year, month, and time of day; to count from 20 backwards; to recite the months backwards; and to recall a phrase.11 A Web-based AD screener contains a list of 11 questions, adapted from a validated questionnaire that describes symptoms of AD.12
The risks of screening programs are relatively few, but they include a risk for causing anxiety or depression and, of course, adverse effects from medications if drugs are subsequently employed.7 Surveys reveal, however, that most patients with AD want to be told of a dementia diagnosis.13,14
Another risk is identifying false positives. Screening tests may yield more than 50% of patients with a positive result that will not meet the criteria for dementia. Thus, the screening program must be linked with a good referral system to a provider for follow-up.7
When counseling a patient showing signs of memory impairment, it is important to point out that, although memory impairment is a hallmark feature of AD, it does not mean that the patient has AD. A patient showing signs of dementia should follow up with a physician to rule out potential reversible causes. Potential medical causes may include depression, vitamin B12 deficiency, and certain medications.2 Medications that possess anticholinergic activity may impair memory and cognitive functioning, and their use in older patients should be avoided if medically possible.
Because drug therapy can delay the progression of impairment, the pharmacist can play a pivotal role in screening, educating, and referring patients to their physician for follow-up. Maximizing the effectiveness of drug therapy for AD includes initiating early treatment, maximizing the dose, and continuing treatment. In all 3 areas, the pharmacist can play an active role. Screening patients for memory impairment and referral can lead to early initiation of therapy. Education of patients, caregivers, and physicians regarding dose maximization and continuation of treatment also can lead to more effective drug treatment of AD.
Dr. Nickelson is an assistant professor of pharmacy practice and Dr. Sherman is an associate professor of pharmacy practice at the University of Louisiana at Monroe College of Pharmacy.
1. Ferri CP, Prince M, Brayne C, et al. Global prevalence of dementia: a Delphi consensus study. Lancet. 2005;366:2112-2117.
2. Blennow K, de Leon MJ, Zetterberg H. Alzheimer's disease. Lancet. 2006;368:387-403.
3. Alzheimer disease and other major dementing illnesses. Knopman DS. ACP Medicine. Available at: www.medscape.com/viewarticle/530672. Accessed May 10, 2006.
4. Stages of Alzheimer's Disease. Alzheimer's Association Web site. Available at: www.alz.org/AboutAD/Stages.asp. Accessed November 1, 2006.
5. Tariot PN, Farlow MR, Grossberg GT, Graham SM, McDonald S, Gergel I. Memantine treatment in patients with moderate to severe Alzheimer disease already receiving donepezil: a randomized controlled trial. JAMA. 2004;291(3):317-324.
6. Seltzer B. Cholinesterase inhibitors in the clinical management of Alzheimer's disease: importance of early and persistent treatment. J Int Med Res. 2006;34(4):339-347.
7. Boustani M, Peterson B, Hanson L, Harris R, Lohr KN. Screening for dementia in primary care: a summary of the evidence for the US Preventive Services Task Force. Ann Intern Med. 2003;138:927-937.
8. Stern RG, Mohs RC, Davidson M, et al. A longitudinal study of Alzheimer's disease: measurement, rate, and predictors of cognitive deterioration. Am J Psychiatry. 1994;151:390-396.
9. Crum RM, Anthony JC, Bassett SS, Folstein MF. Population-based norms for the Mini-Mental State Examination by age and educational level. JAMA. 1993;269(18):2386-2391.
10. Buschke H, Kuslansky G, Katz M, et al. Screening for dementia with the memory impairment screen. Neurology. 1999;52(2):231-238.
11. Katzman R, Brown T, Fuld P, Peck A, Schechter R, Schimmel H. Validation of a short Orientation-Memory-Concentration test of cognitive impairment. Am J Psychiatry. 1983;140(6):734-739.
12. Alzheimer's and Your Loved One: Concerned a Loved One Has Alzheimer's? Eisai Inc. Available at: http://aricept.com/your_loved_one/does_loved_one.aspx. Accessed November 8, 2006.
13. Drickamer MA, Lachs MS. Should patients with Alzheimer's disease be told their diagnosis? N Engl J Med. 1992;326:947-951.
14. Jha A, Taber N, Orrell M. To tell or not to tell?comparison of older patients' reaction to their diagnosis of dementia and depression. Intl J Geriatr Psychiatry. 2001;16:879-885.
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