Memory Screening Aids Diagnosis of AD
Alzheimer's disease (AD) isthe most common form ofdementia. Age is the greatestrisk factor for dementia. Dementiaaffects ~1% of individualsaged 60 to 64 years and between24% and 33% of individuals over theage of 85.1
The main pathologic componentsof the AD brain are neuritic plaquesand neurofibrillary tangles. Theneuritic plaques are composed of?-amyloid peptides, sometimes referredto as ?-amyloid plaques. Theneurofibrillary tangles are composedof protein called tau, whichforms insoluble filaments that leadto cell death in large numbers andresult in atrophy of the cerebralhemispheres.2
Diagnosis of AD is one of exclusionbased on the presence of certainclinical findings. The primaryclinical finding is a loss of cognitivefunction?a decline from a previoushigher level of functioning that distinguishesdementia from mentalretardation or other developmentaldelays.3 The primary cognitive findingis short-term memory loss or, inparticular, the inability to learn anythingnew. AD patients often havedifficulty keeping track of the date,remembering recent conversations,or recalling where they recently leftan item. The diagnosis is made asthese symptoms become more evident,but often after much delay.
AD often is described in stages.The 2 most common staging methodsinvolve a 3-stage system and a7-stage system. Staging of AD providesthe patient and/or familymembers and caregivers a frame ofreference for understanding the diseaseprocess and for future planning.4 AD is a continuing diseaseprocess in which individuals maynot experience all symptoms ateach stage, and symptoms mayoccur at different times. After diagnosis,patients live an average of 8years, with a range of 3 to 20 years.4
Current drugs used in the treatmentof AD are (1) the cholinesteraseinhibitors donepezil,galantamine, and rivastigmine and(2) memantine, an N-methyl-Daspartate(NMDA) receptor antagonist.Donepezil is currently indicatedfor mild, moderate, and severe AD,and galantamine and rivastigmineare indicated for mild-to-moderateAD. Memantine is indicated formoderate-to-severe AD. Trials ofcholinesterase inhibitors show thatlong-term use will result in modeststabilization of cognitive and functionalstatus in AD patients for up to1 year.3
Memantine can delay symptomprogression in moderate-to-severestageAD patients. One study hasindicated that combination treatmentwith memantine anddonepezil in moderate-to-severe ADis more effective than donepeziltherapy alone.5 Therefore, combinationtherapy with memantine and acholinesterase inhibitor may proveto be beneficial.
Data indicate that early and continued therapy with a cholinesteraseinhibitor (possibly combinedwith memantine) can delay or slowthe inevitable cognitive and functionaldecline in AD patients.6 Early,continued treatment of AD translatesinto longer periods of higherfunctioning, which may mean increasedquality of life for patients,less caregiver burden or stress, anddelayed institutionalization. Therefore,early recognition of the signsand symptoms of AD is critical tomaximize the benefits of currentdrug treatment for AD.
Although a randomized trial doesnot exist for definitive evaluation,screening programs should be beneficial.The prevalence of undiagnoseddementia, the accuracy ofthe screening tools, the efficacy oftreatment for mild-to-moderate dementia,and whether screeningactually could be harmful are importantfactors in determining the benefitsof a screening program.7 Oneevaluation of the body of literatureon undiagnosed dementia foundthat 50% to 66% of all patientswho had not receiveda diagnosis of dementiadid, in fact, have mild-tomoderatedementia.7 Thus,a screening program forpatients 65 years and oldercould double the number ofdiagnosed dementia patients.
Among the memoryscreeninginstruments, theMini-Mental StateExamination (MMSE) is themost widely used. It hasbeen used for screening inepidemiologic studies. Itassesses attention, orientation,short-term recall, language,and an ability to followverbal and written commandson a 30-point scale.8The MMSE may be lessaccurate when detectingmild dementia, and it requires specialadjustments for variations inage and educational level.9 Thegroups most appropriate for the useof the MMSE are Caucasians with atleast a high school education.7
Other memory-screening toolsinclude the Memory ImpairmentScreen (MIS) and the Short BlessedTest.10,11 During the MIS, patients aregiven the names of items in 4 differentcategories and are asked toname each item after a short delay.The Short Blessed Test has 6 items:the patient is asked to identify theyear, month, and time of day; tocount from 20 backwards; to recitethe months backwards; and torecall a phrase.11 A Web-based ADscreener contains a list of 11 questions,adapted from a validatedquestionnaire that describes symptomsof AD.12
The risks of screening programsare relatively few, but they include arisk for causing anxiety or depressionand, of course, adverse effectsfrom medications if drugs are subsequentlyemployed.7 Surveys reveal,however, that most patientswith AD want to be told of a dementiadiagnosis.13,14
Another risk is identifying falsepositives. Screening tests may yieldmore than 50% of patients with apositive result that will not meet thecriteria for dementia. Thus, thescreening program must be linkedwith a good referral system to aprovider for follow-up.7
When counseling a patient showingsigns of memory impairment, itis important to point out that,although memory impairment is ahallmark feature of AD, it does notmean that the patient has AD. Apatient showing signs of dementiashould follow up with a physician torule out potential reversible causes.Potential medical causes may includedepression, vitamin B12 deficiency,and certain medications.2Medications that possess anticholinergicactivity may impair memoryand cognitive functioning, and theiruse in older patients should beavoided if medically possible.
Because drug therapy can delaythe progression of impairment, thepharmacist can play a pivotal role inscreening, educating, and referringpatients to their physician for follow-up. Maximizing the effectivenessof drug therapy for AD includesinitiating early treatment, maximizingthe dose, and continuing treatment.In all 3 areas, the pharmacistcan play an active role. Screeningpatients for memory impairmentand referral can lead to early initiationof therapy. Education of patients,caregivers, and physiciansregarding dose maximization andcontinuation of treatment also canlead to more effective drug treatmentof 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 Delphiconsensus 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. ACPMedicine. Available at: www.medscape.com/viewarticle/530672. Accessed May10, 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 diseasealready receiving donepezil: a randomized controlled trial. JAMA.2004;291(3):317-324.
6. Seltzer B. Cholinesterase inhibitors in the clinical management of Alzheimer'sdisease: 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 inprimary care: a summary of the evidence for the US Preventive Services TaskForce. Ann Intern Med. 2003;138:927-937.
8. Stern RG, Mohs RC, Davidson M, et al. A longitudinal study of Alzheimer'sdisease: measurement, rate, and predictors of cognitive deterioration. Am JPsychiatry. 1994;151:390-396.
9. Crum RM, Anthony JC, Bassett SS, Folstein MF. Population-based norms for theMini-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 memoryimpairment screen. Neurology. 1999;52(2):231-238.
11. Katzman R, Brown T, Fuld P, Peck A, Schechter R, Schimmel H. Validation of ashort Orientation-Memory-Concentration test of cognitive impairment. Am JPsychiatry. 1983;140(6):734-739.
12. Alzheimer's and Your Loved One: Concerned a Loved One Has Alzheimer's? EisaiInc. Available at: http://aricept.com/your_loved_one/does_loved_one.aspx. AccessedNovember 8, 2006.
13. Drickamer MA, Lachs MS. Should patients with Alzheimer's disease be told theirdiagnosis? 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.