Management of Alzheimer’s Disease in Primary Care Practice: Relative Efficacy of Pharmacologic Options
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An estimated 22% of adults 65 years of age or older have Alzheimer’s disease (AD).1 Because the incidence of AD doubles every 5 years after age 65, its prevalence is expected to increase as the United States population ages.2 The impact of this neurodegenerative disease encompasses a range of symptoms affecting cognition, function, and behavior.
Like many other diseases, there is a spectrum of continuum for AD, and there are different features at each stage. Artificially, the spectrum has been divided into mild, moderate, and severe stages. In the mild stage (Mini-Mental State Examination [MMSE] 21-26), cognitive and memory deficits are the most apparent symptoms. Behavioral changes, such as depression, begin to appear but may remain subtle.3 As the disease progresses to the moderate stage (MMSE 10-20), cognitive losses are striking. The ability to perform instrumental activities of daily living (ADLs), such as cooking or handling finances, declines rapidly, and behavioral symptoms increase in number and severity.3 In the severe stage (MMSE < 10), the ability to use expressive language declines and basic ADLs, such as feeding or dressing oneself, are lost (Figure 1).3 Behavioral disturbances may decrease in number; however, agitation, dysphoria, anxiety, apathy, and aberrant motor behavior tend to increase in the severe stage.4
Although AD is a complex disorder, much of its treatment can be managed successfully by primary care physicians, who can improve the lives of patients with AD with the appropriate use of treatments that maximize cognition and function while minimizing behavioral symptoms.5 Increased cognitive and functional impairment has been associated with a higher incidence of medical comorbidities.6 Effective treatment of AD may reduce the risk of comorbidities by ameliorating the deficits that mask other conditions. Clinical practice guidelines exist for the screening and diagnosis, as well as for the nonpharmacologic management, of AD.7,8 However, practical guidelines for the pharmacologic management of the disease have yet to be developed. This review focuses on the efficacy data for currently prescribed AD treatments and factors that may affect the choice of pharmacologic agent in the primary care setting.
CLINICAL ASSESSMENTS AND EXPECTATIONS
The symptoms of AD can be classified into those that affect cognition, those that affect function, and those that affect behavior. Hence, tools were developed to assess these three domains to help in the diagnosis and staging of the disease. These same tools can help to assess potential treatment effects of our therapies. Although these tools are primitive, they are often sufficient to detect a treatment signal. Relatively easy-to-administer scales that measure cognition,9 function,10 and behavioral symptoms11 have been developed, and they provide reliable indications of disease severity and symptom progression (Table).9-16 The MMSE,9 for example, can be administered readily by a trained assistant.17 This test relies on simple questions and thought exercises to measure the severity of cognitive impairment. Questions such as “What is the year? The season? The date?” measure the patient’s orientation, while attention and calculation are measured by asking the patient to spell world backwards. Similarly, functional dependence can be measured by asking a family member or other caregiver simple questions about the patient’s ability to perform tasks. The Functional Activities Questionnaire10 rates patient independence based on observer responses to questions such as “Is the patient able to keep track of current events?” These tools can also provide physicians with practical ways to measure the effects of therapy. If a patient regains or retains the ability to dress himself/herself or to work on his/her hobby, that outcome has real meaning for the patient.
REFERENCES
1. Evans DA, Funkenstein HH, Albert MS, et al. Prevalence of Alzheimer’s disease in a community population of older persons. Higher than previously reported. JAMA 1989;262(18):2551-2556.
2. Ott A, Breteler MM, van Harskamp F, et al. Prevalence of Alzheimer’s disease and vascular dementia: Association with education. The Rotterdam study. BMJ 1995;310(6985):970-973.
3. Galasko D. An integrated approach to the management of Alzheimer’s disease: Assessing cognition, function and behaviour. Eur J Neurol 1998;5(suppl 4):S9-S17.
4. Mega MS, Cummings JL, Fiorello T, Gornbein J. The spectrum of behavioral changes in Alzheimer’s disease. Neurology 1996;46(1):130-135.
5. Small GW, Rabins PV, Barry PP, et al. Diagnosis and treatment of Alzheimer disease and related disorders. Consensus statement of the American Association for Geriatric Psychiatry, the Alzheimer’s Association, and the American Geriatrics Society. JAMA 1997;278(16):1363-1371.
6. Doraiswamy PM, Leon J, Cummings JL, et al. Prevalence and impact of medical comorbidity in Alzheimer’s disease. J Gerontol A Biol Sci Med Sci 2002;57(3):M173-M177.
7. Knopman DS, DeKosky ST, Cummings JL, et al. Practice parameter: Diagnosis of dementia (an evidence-based review). Report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology 2001;56:1143-1153.
8. Cummings JL, Frank JC, Cherry D, et al. Guidelines for managing Alzheimer’s disease: Part I. Assessment. Am Fam Physician 2002;65(11):2263-2272.
9. Folstein MF, Folstein SE, McHugh PR. “Mini-mental state.” A practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res 1975;12(3):189-198.
10. Pfeffer RI, Kurosaki TT, Harrah CH Jr, et al. Measurement of functional activities in older adults in the community. J Gerontol 1982;37(3):323-329.
11. Teri L, Truax P, Logsdon R, et al. Assessment of behavioral problems in dementia: The revised memory and behavior problems checklist. Psychol Aging 1992;7(4):622-631.
12. Alzheimer’s Association. 10 warning signs of Alzheimer’s disease. Available at: www.alz.org/aboutAD/warning.asp. Accessed August 25, 2005.
13. Chronic Care Networks for Alzheimer’s Disease. A Joint Initiative of the Alzheimer’s Association and the National Chronic Care Consortium. Available at: www.nccconline.org/about/ alzheimers.htm. Accessed August 25, 2005.
14. Lawton MP, Brody EM. Assessment of older people: Self-maintaining and instrumental activities of daily living. Gerontologist 1969;9(3):179-186.
15. Wolf-Klein GP, Silverstone FA, Levy AP, Brod MS. Screening for Alzheimer’s disease by clock drawing. J Am Geriatr Soc 1989; 37(8):730-734.
16. Borson S, Scanlan J, Brush M, et al. The Mini-Cog: A cognitive ‘vital signs’ measure for dementia screening in multi-lingual elderly. Int J Geriatr Psychiatry 2000;15(11):1021-1027.
17. Christensen DD. Practical principles for the management of Alzheimer’s disease. Prim Care Companion J Clin Psychiatry 2002;4(2):63-69.
18. Salloway S, Ferris S, Kluger A, et al. Efficacy of donepezil in mild cognitive impairment: A randomized placebo-controlled trial. Neurology 2004;63:651-657.
19. Burns A, Rossor M, Hecker J, et al. The effects of donepezil in Alzheimer’s disease—Results from a multinational trial. Dement Geriatr Cogn Disord 1999;10(3):237-244.
20. Winblad B, Engedal K, Soininen H, et al; Donepezil Nordic Study Group. A 1-year, randomized, placebo-controlled study of donepezil in patients with mild to moderate AD. Neurology 2001;57(3):489-495.
21. Doody RS, Geldmacher DS, Gordon B, et al; Donepezil Study Group. Open-label, multicenter, phase 3 extension study of the safety and efficacy of donepezil in patients with Alzheimer disease. Arch Neurol 2001;58:427-433.
22. Rogers SL, Doody RS, Pratt RD, Ieni JR. Long-term efficacy and safety of donepezil in the treatment of Alzheimer’s disease: Final analysis of a US multicentre open-label study. Eur Neuropsychopharmacol 2000;10:195-203.
23. Mohs RC, Doody RS, Morris JC, et al; “312” Study Group. A 1-year, placebo-controlled preservation of function survival study of donepezil in AD patients. Neurology 2001;57(3):481-488. Erratum in: Neurology 2001;57(10):1942.
24. Courtney C, Farrell D, Gray R, et al; AD2000 Collaborative Group. Long-term donepezil treatment in 565 patients with Alzheimer’s disease (AD2000): Randomised double-blind trial. Lancet 2004;363(9427):2105-2115.
25. Feldman H, Gauthier S, Hecker J, et al; Donepezil MSAD Study Investigators Group. A 24-week, randomized, double-blind study of donepezil in moderate to severe Alzheimer’s disease. Neurology 2001;57(4):613-620. Erratum in: Neurology 2001;57(11):2153.
26. Gauthier S, Feldman H, Hecker J, et al; Donepezil MSAD Study Investigators Group. Efficacy of donepezil on behavioral symptoms in patients with moderate to severe Alzheimer’s disease. Int Psychogeriatr 2002;14(4):389-404.
27. Wilcock GK, Lilienfeld S, Gaens E. Efficacy and safety of galantamine in patients with mild to moderate Alzheimer’s disease: Multicentre randomised controlled trial. Galantamine International-1 Study Group. BMJ 2000;321(7274):1445-1449. Erratum in: BMJ 2001;322:405.
28. Reminyl [package insert]. Titusville, NJ: Janssen Pharmaceutica; 2002.
29. Tariot PN, Solomon PR, Morris JC, et al. A 5-month, randomized, placebo-controlled trial of galantamine in AD. The Galantamine USA-10 Study Group. Neurology 2000;54(12):2269-2276.
30. Raskind MA, Peskind ER, Wessel T, Yuan W. Galantamine in AD: A 6-month randomized, placebo-controlled trial with a 6-month extension. The Galantamine USA-1 Study Group Neurology 2000;54(12):2261-2268.
31. Wilcock G, Howe I, Coles H, et al; GAL-GBR-2 Study Group. A long-term comparison of galantamine and donepezil in the treatment of Alzheimer’s disease. Drugs Aging 2003;20(10):777-789.
32. Blesa R, Davidson M, Kurz A, et al. Galantamine provides sustained benefits in patients with ‘advanced moderate’ Alzheimer’s disease for at least 12 months. Dement Geriatr Cogn Disord 2003(2):79-87.
33. Wilkinson DG, Hock C, Farlow M, et al. Galantamine provides broad benefits in patients with ‘advanced moderate’ Alzheimer’s disease (MMSE £12) for up to six months. Int J Clin Pract 2002;56(7):509-514.
34. Corey-Bloom J, Anand R, Veach J, for the ENA 713 B352 Study Group. A randomized trial evaluating the efficacy and safety of ENA 713 (rivastigmine tartrate), a new acetylcholinesterase inhibitor, in patients with mild to moderately severe Alzheimer’s disease. Int J Geriatr Psychopharmacol 1998;1:55-65.
35. Rösler M, Anand R, Cicin-Sain A, et al. Efficacy and safety of rivastigmine in patients with Alzheimer’s disease: International randomised controlled trial. BMJ 1999;318(7184):633-638. Erratum in: BMJ 2001;322(7300):1456.
36. Farlow M, Anand R, Messina J Jr, et al. A 52-week study of the efficacy of rivastigmine in patients with mild to moderately severe Alzheimer’s disease. Eur Neurol 2000;44(4):236-241.
37. Doraiswamy PM, Krishnan KR, Anand R, et al. Long-term effects of rivastigmine in moderately severe Alzheimer’s disease: Does early initiation of therapy offer sustained benefits? Prog Neuropsychopharmacol Biol Psychiatry 2002;26(4):705-712.
38. Reisberg B, Doody R, Stöffler A, et al; Memantine Study Group. Memantine in moderate-to-severe Alzheimer’s disease. N Engl J Med 2003;348(14):1333-1341.
39. Tariot PN, Farlow MR, Grossberg GT, et al; Memantine Study Group. Memantine treatment in patients with moderate to severe Alzheimer’s disease already receiving donepezil: A randomized controlled trial. JAMA 2004;291(3):317-324.
40. Winblad B, Poritis N. Memantine in severe dementia: Results of the 9M-Best Study (benefit and efficacy in severely demented patients during treatment with memantine). Int J Geriatr Psychiatry 1999;14:135-146.
41. Lanctôt KL, Herrmann N, Yau KK, et al. Efficacy and safety of cholinesterase inhibitors in Alzheimer’s disease: A meta-analysis. CMAJ 2003;169(6):557-564.
42. Wilkinson DG, Passmore AP, Bullock R, et al. A multinational, randomised, 12-week, comparative study of donepezil and rivastigmine in patients with mild to moderate Alzheimer’s disease. Int J Clin Pract 2002;56(6):441-446.
43. Exelon [package insert]. East Hanover, NJ: Novartis; 2001.
44. Babic T, Banfic L, Papa J, et al. Spontaneous rupture of oesophagus (Boerhaave’s syndrome) related to rivastigmine. Age Ageing 2000;29(4):370-371.
45. Aricept [package insert]. Teaneck, NJ: Eisai Inc.; 2001.
46. Broderick W, Solis A, McRae T, Mastey V, Shah S. Donepezil versus rivastigmine utilization patterns in retrospective claims analysis. J Am Geriatr Soc 2003;51(4):S121-S122.
47. Francis PT, Palmer AM, Snape M, Wilcock GK. The cholinergic hypothesis of Alzheimer’s disease: A review of progress. J Neurol Neurosurg Psychiatry 1999;66(2): 137-147.
48. Doody RS, Stevens JC, Beck C, et al. Practice parameter: Management of dementia (an evidence-based review). Report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology 2001;56(9):1154-1166.
