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Effective Pharmacologic Management of Alzheimer’s Disease

      Abstract

      In order to assist physicians in the effective pharmacologic management of this challenging population, evidence-based pharmacologic treatment algorithms for the different stages of Alzheimer’s disease have been developed. Evidence-based guidelines outlining pharmacotherapeutic strategies can be systematically implemented to optimize outcomes for patients in different stages of Alzheimer’s disease. The first step toward the best possible long-term management is early diagnosis of Alzheimer’s disease, thereby facilitating early initiation of cholinesterase inhibitor treatment, which may stabilize/reduce the rate of symptomatic cognitive and functional decline. Cholinesterase inhibitor therapy with rivastigmine, donepezil, or galantamine is endorsed as standard first-line therapy in patients with mild-to-moderate Alzheimer’s disease. The N-methyl-D-aspartate receptor-antagonist, memantine, may be used as monotherapy or in combination with a cholinesterase inhibitor for patients with moderate Alzheimer’s disease, and as monotherapy for patients with severe Alzheimer’s disease. During treatment, cognitive and functional status should be monitored over 6-month intervals, and pharmacologic therapy should ideally be continued until there are no meaningful social interactions and quality of life has irreversibly deteriorated.

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      References

        • Geldmacher D.S.
        Long-term cholinesterase inhibitor therapy for Alzheimer’s disease: practical considerations for the primary care physician.
        Prim Care Companion J Clin Psychiatry. 2003; 5: 251-259
        • Small G.W.
        • Rabins P.V.
        • Barry P.P.
        • et al.
        Diagnosis and treatment of Alzheimer disease and related disorders.
        JAMA. 1997; 278: 1363-1371
      1. Practice guideline for the treatment of patients with Alzheimer’s disease and other dementias of late life.
        Am J Psychiatry. 1997; 154: 1-39
        • Doody R.S.
        • Stevens J.C.
        • Beck R.N.
        • et al.
        Practice parameter: management of dementia (an evidence-based review).
        Neurology. 2001; 56: 1154-1166
        • Cummings J.L.
        • Frank J.C.
        • Cherry D.
        • et al.
        Guidelines for managing Alzheimer’s disease: part II.
        Am Fam Physician. 2002; 65: 2525-2534
        • Cummings J.L.
        • Frank J.C.
        • Cherry D.
        • et al.
        Guidelines for managing Alzheimer’s disease: part I.
        Am Fam Physician. 2002; 65: 2263-2272
      2. Alzheimer’s disease: risk stratification, patient evaluation, and outcome-effective pharmacologic therapy—year 2004 clinical update. Available at: http://www.ahcpub.com. Accessed June 9, 2005.

        • Doody R.S.
        • Geldmacher D.S.
        • Gordon B.
        • Perdomo C.A.
        • Pratt R.D.
        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
        • Farlow M.R.
        • Anand R.
        • Messina Jr, J.
        • Hartman R.
        • Veach J.
        A 52-week study of the efficacy of rivastigmine in patients with mild to moderately severe Alzheimer’s disease.
        Eur Neurol. 2000; 44: 236-241
        • Raskind M.A.
        • Peskind E.R.
        • Wessel T.
        • Yuan W.
        Galantamine in AD: a 6-month randomized, placebo-controlled trial with a 6-month extension.
        Neurology. 2000; 54: 2261-2268
        • Raskind M.A.
        • Peskind E.R.
        • Truyen L.
        • Kershaw P.
        • Damaraju C.V.
        The cognitive benefits of galantamine are sustained for at least 36 months: a long-term extension trial.
        Arch Neurol. 2004; 61: 252-256
      3. Diagnostic and Statistical Manual of Mental Disorders. 4th ed. American Psychiatric Association, Washington, DC1994
        • Francis P.T.
        • Palmer A.M.
        • Snape M.
        • Wilcock G.K.
        The cholinergic hypothesis of Alzheimer’s disease: a review of progress.
        J Neurol Neurosurg Psychiatry. 1999; 66: 137-147
        • Lemiere J.
        • Van Gool D.
        • Dom R.
        Treatment of Alzheimer’s disease: an evaluation of the cholinergic approach.
        Acta Neurol Belg. 1999; 99: 96-106
        • Mesulam M.
        • Guillozet A.
        • Shaw P.
        • Quinn B.
        Widely spread butyrylcholinesterase can hydrolyze acetylcholine in the normal and Alzheimer brain.
        Neurobiol Dis. 2002; 9: 88-93
        • Ballard C.G.
        Advances in the treatment of Alzheimer’s disease: benefits of dual cholinesterase inhibition.
        Eur Neurol. 2002; 47: 64-70
        • Hynd M.R.
        • Scott H.L.
        • Dodd P.R.
        Glutamate-mediated excitotoxicity and neurodegeneration in Alzheimer’s disease.
        Neurochem Int. 2004; 45: 583-595
        • Farlow M.R.
        NMDA receptor antagonists.
        Geriatrics. 2004; 59: 22-27
        • Corey-Bloom J.
        • Anand R.
        • Veach J.
        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 Psychopharmacol. 1998; 2: 55-65
        • Rosler 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: 633-638
        • Tariot P.N.
        • Solomon P.R.
        • Morris J.C.
        • Kershaw P.
        • Lilienfeld S.
        • Ding C.
        A 5-month, randomized, placebo-controlled trial of galantamine in AD.
        Neurology. 2000; 54: 2269-2276
        • Wilcock G.K.
        • Lilienfeld S.
        • Gaens E.
        Efficacy and safety of galantamine in patients with mild to moderate Alzheimer’s disease: multicentre randomised controlled trial.
        BMJ. 2000; 321: 1-7
        • Rogers S.L.
        • Farlow M.R.
        • Doody R.S.
        • Mohs R.
        • Friedhoff L.T.
        A 24-week, double-blind, placebo-controlled trial of donepezil in patients with Alzheimer’s disease.
        Neurology. 1998; 50: 136-145
        • 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: 237-244
        • Mohs R.C.
        • Doody R.S.
        • Morris J.C.
        • et al.
        A 1-year, placebo-controlled preservation of function survival study of donepezil in AD patients.
        Neurology. 2001; 57: 481-488
        • Winblad B.
        • Engedal K.
        • Soininen H.
        • et al.
        A 1-year, randomized, placebo-controlled study of donepezil in patients with mild to moderate AD.
        Neurology. 2001; 57: 489-495
        • Cummings J.L.
        • Schneider L.
        • Tariot P.N.
        • Kershaw P.R.
        • Yuan W.
        Reduction of behavioral disturbances and caregiver distress by galantamine in patients with Alzheimer’s disease.
        Am J Psychiatry. 2004; 161: 532-538
        • Feldman H.
        • Gauthier S.
        • Hecker J.
        • Vellas B.
        • Subbiah P.
        • Whalen E.
        A 24-week, randomized, double-blind study of donepezil in moderate to severe Alzheimer’s disease.
        Neurology. 2001; 57: 613-620
        • Cummings J.L.
        • Anand R.
        • Koumaras B.
        • Hartman R.
        Behavioral benefits in Alzheimer’s disease patients residing in a nursing home following 52 weeks of rivastigmine treatment.
        American Psychiatric Association 2000 Annual Meeting: The Doctor-Patient Relationship: New Research Abstracts. 2000; : 212-213
        • Marin D.
        • Amaya K.
        • Casciano R.
        • et al.
        Impact of rivastigmine on costs and on time spent in caregiving for families of patients with Alzheimer’s disease.
        Int Psychogeriatr. 2003; 15: 385-398
        • Wimo A.
        • Winblad B.
        • Shah S.N.
        • Chin W.
        • Zhang R.
        • McRae T.
        Impact of donepezil treatment for Alzheimer’s disease on caregiver time.
        Curr Med Res Opin. 2004; 20: 1221-1225
        • Lopez O.L.
        • Becker S.
        • Wisniewski S.
        • Saxton J.
        • Kaufer D.I.
        • DeKosky S.T.
        Cholinesterase inhibitor treatment alters the natural history of Alzheimer’s disease.
        J Neurol Neurosurg Psychiatry. 2002; 72: 310-314
        • Geldmacher D.S.
        • Provenzano G.
        • McRae T.
        • Mastey V.
        • Ieni J.R.
        Donepezil is associated with delayed nursing home placement in patients with Alzheimer’s disease.
        J Am Geriatr Soc. 2003; 51: 937-944
        • Wimo A.
        • Winblad B.
        • Engedal K.
        • et al.
        An economic evaluation of donepezil in mild to moderate Alzheimer’s disease: results of a 1-year, double-blind, randomized trial.
        Dement Geriatr Cogn Disord. 2003; 15: 44-54
        • Auriacombe S.
        • Pere J.-J.
        • Loria-Kanza Y.
        • Vellas B.
        Efficacy and safety of rivastigmine in patients with Alzheimer’s disease who failed to benefit from treatment with donepezil.
        Curr Med Res Opin. 2002; 18: 129-138
        • Reisberg B.
        • Doody R.
        • Stoffler A.
        • Schmitt F.
        • Ferris S.
        • Mobius H.J.
        Memantine in moderate-to-severe Alzheimer’s disease.
        N Engl J Med. 2003; 348: 1333-1341
      4. Forest Laboratories. Namenda [package insert]. St. Louis, MO, 2003.

        • Reisberg B.
        • Doody R.
        • Stoffler A.
        • Schmitt F.
        • Ferris S.
        • Mobius H.J.
        A 24-week open-label extension study of memantine in moderate to severe Alzheimer disease.
        Arch Neurol. 2006; 63: 49-54
        • Tariot P.
        • Cummings J.L.
        • Katz I.R.
        • et al.
        A randomized, double-blind, placebo-controlled study of the efficacy and safety of donepezil in patients with Alzheimer’s disease in the nursing home setting.
        J Am Geriatr Soc. 2001; 49: 1590-1599
        • Feldman H.
        • Gauthier S.
        • Hecker J.
        • et al.
        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
        • 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
        • Cummings J.L.
        • Koumaras B.
        • Chen M.
        • Mirski D.
        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
        • Tariot P.N.
        • Farlow M.R.
        • Grossberg G.T.
        • Graham S.M.
        • McDonald S.
        • Gergel I.
        Memantine treatment in patients with moderate to severe Alzheimer disease already receiving donepezil: a randomized controlled trial.
        JAMA. 2004; 291: 317-324
      5. Eisai Inc. Aricept [package insert]. Teaneck, NJ, 2000.

      6. Novartis Pharmaceuticals Corp. Exelon [package insert]. East Hanover, NJ, 2001.

      7. Ortho-McNeil Neurologics Inc. Razadyne [package insert]. Titusville, NJ, 2005.

      8. Ortho-McNeil Neurologics Inc. Razadyne ER [package insert]. Titusville, NJ, 2005.

        • Defilippi J.L.
        • Crismon M.L.
        Drug interactions with cholinesterase inhibitors.
        Drugs Aging. 2003; 20: 437-444
        • Grossberg G.T.
        • Stahelin H.B.
        • Messina J.C.
        • Anand R.
        • Veach J.
        Lack of adverse pharmacodynamic drug interactions with rivastigmine and twenty-two classes of medications.
        Int J Geriatr Psychiatry. 2000; 15: 242-247
        • Kaduszkiewicz H.
        • Zimmermann T.
        • Beck-Bornholdt H.P.
        • van den Bussche H.
        Cholinesterase inhibitors for patients with Alzheimer’s disease: systematic review of randomised clinical trials.
        BMJ. 2005; 331: 321-327
        • Petersen R.C.
        • Thomas R.G.
        • Grundman M.
        • et al.
        Vitamin E and donepezil for the treatment of mild cognitive impairment.
        N Engl J Med. 2005; 352: 2379-2388
        • 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
        • Loy C.
        • Schneider L.
        Galantamine for Alzheimer’s disease and mild cognitive impairment.
        Cochrane Database Syst Rev. 2006; : CD001747
      9. Press release: NICE consults on revised first draft guidance on the use of drugs to treat Alzheimer’s disease (including a review of existing guidance no. 19). Available at: http://www.nice.org.uk/page.aspx?o=289014. Accessed June 8, 2006.

        • Diamond B.
        • Johnson S.
        • Torsney K.
        • et al.
        Complementary and alternative medicines in the treatment of dementia: an evidence-based review.
        Drugs Aging. 2003; 20: 981-998
        • Sierpina V.S.
        • Sierpina M.
        • Loera J.A.
        • Grumbles L.
        Complementary and integrative approaches to dementia.
        South Med J. 2005; 98: 636-645
        • Birks J.
        • Grimley E.V.
        • Van Dongen M.
        Ginkgo biloba for cognitive impairment and dementia.
        Cochrane Database Syst Rev. 2002; : CD003120
        • Schneider L.S.
        • DeKosky S.T.
        • Farlow M.R.
        • Tariot P.N.
        • Hoerr R.
        • Kieser M.
        A randomized, double-blind, placebo-controlled trial of two doses of Ginkgo biloba extract in dementia of the Alzheimer’s type.
        Curr Alzheimer Res. 2005; 2: 541-551
        • Fioravanti M.
        • Yanagi M.
        Cytidinediphosphocholine (CDP-choline) for cognitive and behavioural disturbances associated with chronic cerebral disorders in the elderly.
        Cochrane Database Syst Rev. 2005; : CD000269
        • Sano M.
        • Ernesto C.
        • Thomas R.G.
        • et al.
        A controlled trial of selegiline, alpha-tocopherol, or both as treatment for Alzheimer’s disease.
        N Engl J Med. 1997; 336: 1216-1222
        • Boothby L.A.
        • Doering P.L.
        Vitamin C and vitamin E for Alzheimer’s disease.
        Ann Pharmacother. 2005; 39: 2073-2080
        • Henderson V.W.
        Estrogen-containing hormone therapy and Alzheimer’s disease risk: understanding discrepant inferences from observational and experimental research.
        Neuroscience. 2006; 138: 1031-1039
        • Almeida O.P.
        • Flicker L.
        Association between hormone replacement therapy and dementia: is it time to forget?.
        Int Psychogeriatr. 2005; 17: 155-164
        • Reines S.A.
        • Block G.A.
        • Morris J.C.
        • et al.
        Rofecoxib: no effect on Alzheimer’s disease in a 1-year, randomized, blinded, controlled study.
        Neurology. 2004; 62: 66-71
        • Thal L.J.
        • Ferris S.H.
        • Kirby L.
        • et al.
        A randomized, double-blind, study of rofecoxib in patients with mild cognitive impairment.
        Neuropsychopharmacology. 2005; 30: 1204-1215
        • Higgins J.P.
        • Flicker L.
        Lecithin for dementia and cognitive impairment.
        Cochrane Database Syst Rev. 2003; : CD001015
        • Hudson S.
        • Tabet N.
        Acetyl-L-carnitine for dementia.
        Cochrane Database Syst Rev. 2003; : CD003158
        • Jansen S.L.
        • Forbes D.A.
        • Duncan V.
        • Morgan D.G.
        Melatonin for cognitive impairment.
        Cochrane Database Syst Rev. 2006; : CD003802
        • Malouf R.
        • Areosa Sastre A.
        Vitamin B12 for cognition.
        Cochrane Database Syst Rev. 2003; : CD004326
        • Malouf R.
        • Grimley Evans J.
        The effect of vitamin B6 on cognition.
        Cochrane Database Syst Rev. 2003; : CD004393
        • Areosa S.A.
        • McShane R.
        • Sherriff F.
        Memantine for dementia.
        Cochrane Database Syst Rev. 2004; : CD003154
        • Folstein M.F.
        • Folstein S.E.
        • McHugh P.R.
        ″Mini-mental state.
        J Psychiatric Res. 1975; 12: 189-198
        • Lawton M.P.
        • Brody E.M.
        Assessment of older people: self-maintaining and instrumental activities of daily living.
        Gerontologist. 1969; 9: 179-186
        • Morris J.C.
        • Edland S.
        • Clark C.
        • et al.
        The consortium to establish a registry for Alzheimer’s disease (CERAD). Part IV. Rates of cognitive change in the longitudinal assessment of probable Alzheimer’s disease.
        Neurology. 1993; 43: 2457-2465
        • Schneider L.S.
        • Olin J.T.
        • Doody R.S.
        • et al.
        Validity and reliability of the Alzheimer’s disease Cooperative Study-Clinical Global Impression of Change.
        Alzheimer Dis Assoc Disord. 1997; 11: S22-S32
        • Pfeffer R.I.
        • Kurosaki T.T.
        • Harrah Jr, C.H.
        • Chance J.M.
        • Filos S.
        Measurement of functional activities in older adults in the community.
        J Gerontol. 1982; 37: 323-329
        • Kaufer D.I.
        • Cummings J.L.
        • Ketchel P.
        • et al.
        Validation of the NPI-Q, a brief clinical form of the Neuropsychiatric Inventory.
        J Neuropsychiatry Clin Neurosci. 2000; 12: 233-239
        • Gauthier S.
        • Emre M.
        • Farlow M.R.
        • Bullock R.
        • Grossberg G.T.
        • Potkin S.G.
        Strategies for continued successful treatment of Alzheimer’s disease: switching cholinesterase inhibitors.
        Curr Med Res Opin. 2003; 19: 707-714