In the severe stages of Alzheimer's disease, functional autonomy is lost, psychiatric and behavioral symptoms become increasingly troublesome, and cognitive deficits increase until most patients require complete care, usually in specialized nursing homes. Consequently, some health care professionals question the benefits of pharmacologic intervention during these later stages. Since primary care physicians are often first to see these patients, they have key roles in recognizing the benefits of treatment and initiating appropriate management and referral. Three prospective randomized clinical trials of donepezil in severe Alzheimer's disease have been conducted; these show donepezil treatment is associated with functional and cognitive benefits, although behavioral benefits were not consistently observed. Donepezil was well tolerated; side effects were transient, mild to moderately severe, and cholinergic in nature. Donepezil has strong data throughout the Alzheimer's disease spectrum and, therefore, represents a first-line monotherapy that can provide benefits to patients in all stages of Alzheimer's disease.
Feldman HH, Woodward M.The staging and assessment of moderate to severe Alzheimer disease. Neurology. 2005;65:S10-S17.
2.
National Institute of Clinical Excellence.Appraisal Consultation Document: Donepezil, galantamine, rivastigmine (review) and memantine for the treatment of Alzheimer's disease. Available at: http://www.nice.org.uk/Guidance/TA111. Accessed September 12, 2008.
3.
Hebert LE, Scherr PA, Bienias JL, Bennett DA, Evans DAAlzheimer disease in the US population: prevalence estimates using the 2000 census. Arch Neurol. 2003;60:1119-1122.
4.
Wilkinson D., Sganga A., Stave C., O'Connell B.Implications of the Facing Dementia Survey for health care professionals across Europe. Int J Clin Pract. 2005;59(suppl 146):27-31.
Winblad B., Wimo A., Engedal K., et al. 3-year study of donepezil therapy in Alzheimer's disease: effects of early and continuous therapy. Dement Geriatr Cogn Disord . 2006;21:353-363.
7.
Doody RS, Geldmacher DS, Gordon B., Perdomo CA, Pratt RD, and 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.
8.
Mohs RC, Doody RS, Morris JC, et al, and for the ``312'' Study Group.A 1-year, placebo-controlled preservation of function survival study of donepezil in AD patients. Neurology. 2001;57:481-488.
9.
Holmes C., Wilkinson D., Dean C., et al. The efficacy of donepezil in the treatment of neuropsychiatric symptoms in Alzheimer disease. Neurology. 2004;63:214-219.
10.
Geldmacher DS, Provenzano G., McRae T., Mastey V., Ieni JRDonepezil is associated with delayed nursing home placement in patients with Alzheimer's disease. J Am Geriatr Soc. 2003;51:937-944.
11.
Rimmer E., Wojciechowska M., Stave C., Sganga A., O'Connell B.Implications of the Facing Dementia Survey for the general population, patients and caregivers across Europe. Int J Clin Pract. 2005;59(suppl 146):17-24.
12.
Caltagirone C., Bianchetti A., Di Luca M., et al, and Italian Association of Psychogeriatrics. Guidelines for the treatment of Alzheimer's disease from the Italian Association of Psychogeriatrics. Drugs Aging. 2005;22(suppl 1):1-26.
13.
Fillit HM, Doody RS, Binaso K., et al. Recommendations for best practices in the treatment of Alzheimer's disease in managed care. Am J Geriatr Pharmacother. 2006;4(suppl A):S9-S24.
14.
Waldemar G. , Dubois B., Emre M., et al. Recommendations for the diagnosis and management of Alzheimer's disease and other disorders associated with dementia: EFNS guideline. Eur J Neurol. 2007 ;14:e1-e26.
15.
Winblad B., Kilander L., Eriksson S., et al, and Severe Alzheimer's Disease Study Group.Donepezil in patients with severe Alzheimer's disease: double-blind, parallel-group, placebo-controlled study. Lancet . 2006;367: 1057-1065.
16.
Black SE, Doody RS, Li H., et al. Donepezil preserves cognition and global function in severe Alzheimer's disease patients. Neurology. 2007 ;69:459-469.
17.
Homma A., Imai Y., Tago H., et al. Donepezil treatment of patients with severe Alzheimer's disease in a Japanese population: results from a 24-week, double-blind, placebo-controlled, randomized trial. Dement Geriatr Cogn Disord. 2008;25:399-407.
18.
Karaman Y., Erdoğan F., Köseoğlu E., Turan T., Ersoy AOA 12-month study of the efficacy of rivastigmine in patients with advanced moderate Alzheimer's disease. Dement Geriatr Cogn Disord. 2005;19:51-56.
19.
Cummings JL , Koumaras B., Chen M., Mirski D., for the Rivastigmine NursingHome Study Team.Effects of rivastigmine treatment on the neuropsychiatric and behavioral disturbances of nursing home residents with moderate to severe probable Alzheimer's disease: a 26-week, multicenter, open-label study. Am J Geriatr Pharmacother . 2005;3:137-148.
20.
Burns A., Spiegel R., Quarg P.Efficacy of rivastigmine in subjects with moderately severe Alzheimer's disease . Int J Geriatr Psychiatry. 2004;19:243-249.
21.
Blesa R., Davidson M., Kurz A., Reichman W., van Baelen B., Schwalen S.Galantamine provides sustained benefits in patients with `advanced moderate' Alzheimer's disease for at least 12 months. Dement Geriatr Cogn Disord. 2003;15:79-87.
22.
Wilkinson DG , Hock C., Farlow M., van Baelen B., Schwalen S.Galantamine provides broad benefits in patients with `advanced moderate' Alzheimer's disease (MMSE < or = 12) for up to six months. Int J Clin Pract. 2002;56:509-514.
23.
Reisberg B. , Doody R., Stoffler A., et al, and Memantine Study Group.Memantine in moderate-to-severe Alzheimer's disease . N Engl J Med. 2003;348:1333-1341.
24.
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.
25.
van Dyck CH , Tariot PN, Meyers B., Malca Resnick E., for the Memantine MEM-MD-01 Study Group.A 24-week randomized, controlled trial of memantine in patients with moderate-to-severe Alzheimer disease. Alzheimer Dis Assoc Disord. 2007;21:136-143.
26.
Tariot PN, Farlow MR, Grossberg GT, et al, and Memantine Study Group.Memantine treatment in patients with moderate to severe Alzheimer disease already receiving donepezil: a randomized controlled trial. JAMA. 2004;291:317-324.
27.
Feldman H., Gauthier S., Hecker J., et al, and Donepezil MSAD Study Investigators Group.Efficacy and safety of donepezil in patients with more severe Alzheimer's disease: a subgroup analysis from a randomized, placebo-controlled trial. Int J Geriatr Psychiatry. 2005;20: 559-569.
28.
Byrne EJ, Collins D., Burns A.Behavioural and psychological symptoms of dementia-agitation. In: Burns A, Winblad B, eds. Severe Dementia. Chichester, England: John Wiley & Sons;2006:51-61.
29.
Gauthier S., Feldman H., Hecker J., et al, and Donepezil MSAD Study Investigators Group.Efficacy of donepezil on behavioral symptoms in patients with moderate to severe Alzheimer's disease. Int Psychogeriatr . 2002;14: 389-404.
30.
Feldman H., Gauthier S., Hecker J., et al, and Donepezil MSAD Study Investigators Group.Efficacy of donepezil on maintenance of activities of daily living in patients with moderate to severe Alzheimer's disease and the effect on caregiver burden. J Am Geriatr Soc. 2003 ;51: 737-744.
31.
Rogers SL, Farlow MR, Doody RS, Mohs R., Friedhoff LTA 24-week, double-blind, placebo-controlled trial of donepezil in patients with Alzheimer's disease. Donepezil Study Group. Neurology . 1998;50: 136-145.
32.
Feldman H., Gauthier S., Hecker J., et al, and Donepezil MSAD Study Investigators Group.A 24-week, randomized, double-blind study of donepezil in moderate to severe Alzheimer's disease [published erratum appears in Neurology 2001;57(11):2153]. Neurology. 2001;57: 613-620.
